INTRODUCTION

Pharmacy teams understand pain is on the nation's radar, and the nuances of pain management can be challenging for the clinical team and the patient. Pain is among the most common reasons why people seek medical care. Conditions like osteoarthritis, back pain, and headaches consistently land in the top ten reasons someone would see a doctor.¹ Statisticians estimate that more than 30% of people worldwide are affected by some variation of chronic pain. It exerts a substantial personal and economic burden; three of the four leading causes of years lost to disability are chronic pain conditions (back pain, neck pain, musculoskeletal disorders).² A 2010 Institute of Medicine review estimated that chronic pain afflicts one in three Americans, costing between $560 billion and $635 billion annually in medical costs and lost productivity. It is worth noting that this estimation did not include institutionalized individuals (i.e., prisoners, nursing home patients), military personnel, or children.³

 

A few fun facts are planted along the way in this activity, so watch for interesting information about redheads, snakes, and social anxiety. Pain is the appropriate response of an intact nervous system, serving as a protective mechanism crucial to function. It is an adaptive tool that grants insight to the nature of a disease state and the healing process, until it doesn’t. In 1953, John J. Bonica, the “father of pain medicine,” described pain’s complexity, stating that when pain is intractable (not able to be managed or controlled), it no longer serves a useful purpose. Through both mental and physical effects, it becomes destructive.⁴ While the general consensus on pain has graduated from being considered a mere symptom of disease, most practitioners still fail to recognize the condition as its own distinct disease state.

 

Pain can range widely in intensity, quality, and duration and has diverse pathophysiologic mechanisms and meanings, making it difficult to define concisely.⁵ In 2020, the International Association for the Study of Pain (IASP) produced a revised definition of pain supplemented with additional clarifications. The list below outlines the major takeaways:⁶

• Pain, an unpleasant sensory and emotional experience, is associated with or resembles actual or potential tissue damage.
• Biologic, psychologic, and social factors influence pain perception, making it a highly personal experience.
• Respecting a person’s narrative of his or her pain experience is a healthcare team responsibility.
• Pain and nociception are different, so clinicians shouldn’t infer that a patient is having pain exactly where the patient reports the pain.
• Although pain is usually adaptive, it may adversely affect a patient’s functioning and social and psychologic well-being.
• Each individual’s life experiences develop their own notion of pain.
• Patients use several behaviors to express pain, not just their words; people who cannot communicate (i.e., have dementia or cognitive compromise) can and do experience pain.

The recent modifications propose a more individualized and holistic comprehension of pain and further solidify the case for pain as a disease state.⁶

PAUSE AND PONDER: A patient walks up to your pharmacy counter and asks for help picking out an over-the-counter medication for his chest pain. What questions might you ask before recommending a product?

 

NOCICEPTIVE PAIN

Pain specialists define nociceptive pain as normal neural activity in response to noxious (harmful) stimuli damaging tissue. ⁷  Physical or chemical assaults such as trauma, surgery, or chemical burns stimulate nociceptors (pain receptors) found in the skin, organs, joints, bones, and muscles. The presence of a noxious stimuli triggers the basic pain mechanism, which can be broken down into three stages: transduction, transmission, and modulation. Transduction begins with the conversion of the inciting stimulus to chemical tissue and synaptic cleft events. Neurons propagate these events as electrical signals to be transduced as chemical events at the synapses. Transmission conveys the peripheral nociceptor activation to the central nervous system (CNS) using electrical impulses and neurotransmitter release along the neurons in the spinal cord.⁷ Once the signal reaches the somatosensory cortex of the brain, the individual perceives pain. In other words, once an event occurs, a chemical process starts and travels through the tissue and synapses. Next, an electrical system takes over and eventually conveys the message that the patient needs to feel pain to the CNS.

 

Perception of pain also plays a role in the brain’s ability to generate alerts for future avoidance behaviors.⁸ The sensation of nociceptive pain continues as long as the offending stimuli remains present. Pain modulation occurs at every level of the nociceptive pathway. The body’s ability to alter pain signaling partially explains why the same noxious stimulus may elicit different individual responses.⁹

 

The two subtypes of nociceptive pain are somatic and visceral. Somatic pain occurs due to injury to the skin, bones, joints, or soft tissue.¹⁰ This pain is localized, often manifesting as an ache, a dull discomfort, or a sensation of soreness. Visceral pain arises from damage to visceral organs (e.g., heart, kidney, liver, lungs). Direct stimulation of afferent nerves (nerves that relay sensory information from the organ to the CNS) due to tumor, distention (swelling), or ischemia (restricted blood supply) of viscera results in this cramping/squeezing pain sensation. Visceral pain often presents as diffuse and poorly localized in space and time.¹⁰

 

The lack of sensory nerves in organs and blood vessels often results in referred pain (discussed below).¹⁰ Pain signals from viscera are transmitted over common nerve pathways used in somatic pain responses. For example, during a heart attack, pain may initially present in the neck, jaw, shoulder, or medial arm before the patient feels it in the chest. Visceral pain is also commonly associated with nausea/vomiting, tachycardia, and other vital sign changes due to its non-specific involvement of the autonomic system.¹⁰

 

NEUROPATHIC PAIN

Neuropathic pain can be defined as a process occurring after a primary lesion or disease of the somatosensory system (the body’s system for sensing touch, pain, and temperature). The injury results in improper excitatory and inhibitory somatosensory signaling, maladaptive changes to ion channels, and increased variability of pain modulation across the CNS.¹¹ Prolonged exposure to a neuropathic event often results in sensitization (increased sensitivity to stimuli in the peripheral or central nervous system). When involving a noxious stimulus, sensitization is a normal response. Due to some outside force, the body becomes hyperaware of potential future damage. Sensitization, however, becomes a significant issue in chronic pain cases because it eventually produces painful stimuli even if no apparent harm is present.¹²

 

Peripheral sensitization describes a reduction in action potential threshold causing an amplified response of nociceptors.¹² A stimulus of a lower magnitude creates more pain than one would expect. This occurs when primary sensory neurons’ peripheral terminals are exposed to inflammatory mediators and damaged tissue, localizing the dysfunction to the site of tissue injury. Nociceptors still initiate this pain response, but these nociceptors now require much less input to trigger pain signals. Central sensitization results from changes in the neurons’ properties in the CNS. The result: the nociceptive system becomes abnormally responsive and overexerts itself. These CNS changes alter response to sensory inputs, no longer requiring the presence of peripheral noxious stimuli. Pain experts describe the process as sensory illusion, where pain sensation occurs even in the absence of noxious stimuli or peripheral pathologies.¹²

 

Common signs and symptoms associated with neuropathic pain include:¹³

• Allodynia (pain due to a stimulus that does not normally provoke pain)
• Hyperalgesia (increased sensitivity to feeling pain and an extreme response to pain)
• Paresthesia (abnormal touch sensation, such as burning or prickling)

 

While nociceptive pain is understood best by its inherent “detect and protect” mechanism, neuropathy has no benefit or protective function.¹⁴ This condition’s pathology can originate from a number of different mechanisms best described by anatomic location or etiology.¹⁵ Neuropathy’s variable etiology makes it more difficult to treat than nociceptive pain. Neuropathic pain syndromes are divided into those representing a peripheral or central lesion or disease. Peripheral nerve damage may stem from a number of potential causes including mechanical, chemical, or infectious offenders. Metabolic dysfunction, medications, toxins, or inflammatory mediators can change the density of fibers involved in neuronal signaling resulting in hyperexcitability. Injuries along the axon including trauma, compression, hypoxia, or chemical damage can result in fiber degeneration and faulty signal transmission. Some examples of common peripheral neuropathies include:¹⁵

• Carpal tunnel syndrome
• Chemotherapy-induced peripheral neuropathy
• Diabetic neuropathy
• Post-herpetic neuralgia

 

Central neuropathy is associated with traumatic injury to the brain or the spinal cord, a stroke, or multiple sclerosis. In some cases, patients may not experience the total manifestation of central neuropathy until months after a CNS injury.¹⁵

 

NOCIPLASTIC PAIN

In 2017, the IASP introduced nociplastic pain as the third mechanistic pain descriptor, indicating significant differentiation from well-established nociceptive and neuropathic pain. ¹⁶  Nociplastic pain arises from altered nociception despite no clear evidence of actual or threatened damage to tissue or the somatosensory system. Before establishing nociplastic pain as its own entity, the IASP referred to this class as predominant central sensitization (CS) pain. CS is understood as an amplification of neural signaling within the CNS that results in various forms of dysfunction that induce pain hypersensitivity. Examples of dysfunction include:¹⁶

• Altered sensory processing in the brain in resting state
• Increased brain activity in areas involved in acute pain sensation (e.g., prefrontal cortex)
• Altered activity in brain-orchestrated nociceptive facilitatory pathway
• Decreased or improper endogenous analgesia activity

 

In 2021, the IASP developed clinical criteria and a grading scale for nociplastic pain. Table 1 lists nociplastic pain’s criteria components.¹⁶

 

Table 1. IASP Criteria for a Nociplastic Pain Diagnosis ¹⁶

 

Pain lasting at least 3 months in duration (chronic)*

Regional rather than discrete pain distribution*

Pain cannot be explained entirely by nociceptive or neuropathic mechanisms*

Patient must display clinical signs of pain hypersensitivity (e.g., thermal or mechanical allodynia) at least in the reported region of pain*

History of pain hypersensitivity in the region of pain

Patient presents with at least 1 of the defined comorbidities: increased sensitivity to light/sound/color, sleep disturbance with frequent nocturnal awakenings, fatigue, or cognitive problems with attention or memory

*Mandatory for “possible nociplastic pain” diagnosis

 

This criteria’s establishment by a worldwide scientific organization helps recognize nociplastic pain as the third mechanistic pain descriptor along with nociceptive and neuropathic pain. The stressed importance of assessing comorbidities with non-pain symptoms and sensory hypersensitivity highlights the notion that CS, a key underlying mechanism of nociplastic pain, goes beyond the nociceptive system.¹⁶

 

Some common disease states recognized as nociplastic include fibromyalgia, irritable bowel syndrome, and chronic headache.¹⁷ These conditions highlight the nuance required to assess chronic pain thoroughly. Typically, an individual with a chronic condition will either have mixed pain clearly involving all three pain types or a nociplastic condition disguised as neuropathy or visceral pain. Pain categorization guides its pharmacologic treatment approach and jumpstarts the pain assessment triage.¹⁷

 

PAUSE AND PONDER: Now that a third type of pain has been globally defined, how has your overall perception of pain changed?

 

PAIN ASSESSMENT

As recently clarified by the IASP, healthcare providers should recognize and treat pain as a unique, individual experience.¹ Chronic pain does not impact all people equally. According to the Centers for Disease Control and Prevention (CDC), the highest prevalence rates of chronic pain are seen in women, military veterans, individuals from lower socioeconomic backgrounds, and people residing in rural areas. With regard to race and ethnicity, studies are mixed; however, most have reported higher incidence in racial and ethnic minorities (e.g., African American, indigenous people). Research attributes these differences to enhanced physiologic pain sensitivity, cultural differences, and reduced access to care.¹

 

To create a more holistic approach to patient assessment, healthcare providers must first categorize and classify pain, then cross-reference these factors against personal lifestyle factors. Upon determining which of the three major pain types a person is experiencing, the pain management team must consider other more general features of the pain before making a specific diagnosis. The other components of the classification system include duration, actual or perceived location, and intensity.¹⁸

 

DURATION AND LOCATION OF PAIN

Providers typically describe pain as acute or chronic. According to the IASP, acute pain is commonly associated with actual or threatened tissue damage that lasts from a few seconds to three months. Chronic pain persists or recurs for more than three months. It is sometimes further differentiated by considering if the chronic condition is cancer-related, non-cancerous, or episodic.⁶

 

Over the last few years, the IASP has fought alongside the World Health Organization (WHO) to change the way the healthcare system recognizes chronic pain conditions.⁶ They advocate a shift to considering chronic pain as a disease in its own right rather than an underlying consequence of another affliction. In 2015, the IASP Task Force proposed updated categorization of pathologic pain conditions for the 11^th Revision of the International Classification of Diseases (ICD-11). The revamped definition supported with adequate coding would grant pain sufferers greater access to proper care. This in turn improves epidemiological data regarding chronic pain and helps address some of the shortcomings that have plagued pain management.⁶

 

The actual or perceived location of pain can help with treatment selection and/or prognosis in an emergent situation. For example, if a patient has left arm pain, it would be vital to differentiate a fractured humerus bone from referred cardiac pain sometimes associated with a heart attack. Although etiology may not always match with sensory information, perceived location of pain helps initiate the diagnostic process and establishes a patients’ baseline pain pattern.¹⁸

 

Pain intensity is a subjective but valuable diagnostic element. Unidimensional pain assessment tools such as verbal rating scales (VRS), numerical rating scales (NRS), and visual analog scales (VAS) provide a baseline pain score dictating the level of analgesia necessary to achieve an optimal pain response.¹⁹ Providers combine these rating scales with multi-dimensional pain assessment tools (e.g., Brief Pain Inventory, McGill Pain Questionnaire) to capture comprehensive understanding of the complaint and guide treatment.²⁰

 

THE BIOPSYCHOSOCIAL MODEL
The biopsychosocial model of pain demonstrates the dynamic interaction of physical symptoms combined with biologic, psychologic, and social factors. Some contributing biologic factors considered include age, sex, genetics, and other predisposing conditions (i.e., hormone abnormalities, nervous system sensitization).²¹

 

Psychologic factors corresponding to chronic pain include depression, anxiety, post-traumatic stress, diminished coping skills, and somatization (expression of psychologic or emotional factors as physical symptoms), among others.²¹ If a disease state significantly impairs a patient’s ability to work, a state of helplessness often follows. A chronic pain condition can rapidly diminish self-esteem, which in turn can negatively impact interpersonal relationships. Higher rates of divorce, substance abuse, and suicide are often seen in those battling chronic pain conditions.²¹

 

Sociocultural factors linked to chronic pain include low education status, job dissatisfaction, lack of social support, and fundamental cultural differences.²¹

 

ELEMENTS OF A MULTIDIMENSIONAL ASSESSMENT

Chronic pain can detrimentally affect a number of social conditions in one’s life.²² Providers must be cognizant of the evolving picture of health to provide well rounded care. They should acknowledge that the cause-and-effect relationship between pain and lifestyle is bidirectional. A patient’s sub-optimal living condition may increase the likelihood of a condition developing into a chronic problem. Underlying depression, anxiety, or poor sleep habits may exacerbate an injury’s severity or even predispose individuals to pain. Health care providers should increase efforts to promote each pain patient’s resiliency. Two ways of doing this are strengthening emotional support systems and promoting positive health practices. Both interventions can expedite restoration and hinder chronification.²²

 

In addition to the unidimensional scales and questionnaires, healthcare practitioners use multidimensional assessment to address the eight elements of a pain complaint. Practitioners often use the mnemonic PQRSTU, described in Table 2, to help guide this systematic approach.²³

 

Table 2. The PQRSTU Mnemonic for Pain Assessment

P	Precipitating or Provocative Factors “What brings on the pain? What makes it worse?” Changes in position, bowel movements, and even eating habits can sometimes alter the level of pain.
	Palliative Factors “What relieves the pain? What makes it better?” This is strictly in reference to non-pharmacologic aids, including ice or heat application, sleeping, or any distraction strategies.
	Previous Therapy “What have you used for pain control in the past? How well did the medication work? Did you experience any side effects?” Consider all prescription, over-the-counter, and homeopathic remedies.
Q	Quality of Pain “What does the pain feel like?” It is best practice to ask patients to try and describe it in their own words and only prompt with suggestions if they are struggling to explain the sensation (e.g., aching, stabbing, burning).
R	Region/Radiation of Pain “Where do you feel the pain? Does it spread to other areas or remain in the same place?” Always try and have patients show you where they perceive the pain. This may provide greater context as to the pain being referred or localized.
S	Severity of Pain “How bad is the pain?” The use of a VRS is crucial for establishing a baseline and indicating if specific interventions should be implemented for pain control.
T	Temporal Aspects of Pain “When did the pain start? Is the pain constant or intermittent? How long does the pain last or how frequently does it occur?” Duration of pain and time since pain onset are crucial to differentiating an acute or chronic pain condition.
U	YoU-Associated Symptoms of Pain “How does the pain affect your everyday life? What do you want to be doing right now that you cannot because of your pain?” Consider how significantly quality of life might be decreased if the patient is now unable to work or exercise because of their condition.

VRS, verbal rating scale.

 

PAUSE AND PONDER: What is the pharmacist's role in the multidisciplinary approach to pain management?

 

GOALS OF PAIN MANAGEMENT

The 3 basic goals of a successful pain management plan are

1. To relieve pain! Identify and treat the cause of pain (when possible) by matching the analgesic with the pathogenesis.
2. To restore function. Improve the patient’s ability to perform every day activities without exceeding limits of pain and discomfort.
3. To prevent pain from becoming chronic. If pain becomes chronic, optimize therapies by titrating to the lowest dose that improves pain without unacceptable side effects.

 

To achieve these goals, a well-constructed pain team monitors the situation from all angles. A multidisciplinary approach is a standard of care; nurses, pharmacists, physicians, social workers, and therapists all pool their expertise with the common objective of pain control. The pain team does not just include healthcare professionals. Family members or caregivers can also significantly contribute on the road to recovery. The unique support that they provide can add a familiar layer of comfort for patients in an unfamiliar situation.²⁴

 

In 1986, WHO designed an analgesic ladder (see Figure 1) as a tool to aid in the development of cancer pain treatment plans. The simple, stepwise approach to addressing pain severity while considering adverse effects of pharmacologic agents revolutionized pain management. It was immediately clear that this conservative protocol was not limited to cancer pain and could be applied to most acute or chronic conditions.

 

<<< Insert Figure 1 Near Here >>>

 

In 2020, clinicians from the Mayo Clinic considered updates from the CDC Guideline for Prescribing Opioids for Chronic Pain and the American Society of Interventional Pain Physicians to modernize the analgesic ladder. The three modifications are as follows:²⁵

1. Attempt to employ integrative medical treatments at each step of the ladder. Therapies including yoga, acupuncture, tai chi, and spinal manipulation have demonstrated a positive effect on patient outcomes. Acupuncture as a complementary treatment for chronic pain displays evidence of decreasing required opioid analgesic dosages and, in some cases, eliminating the need for opioids all together.
2. Consider minimally invasive interventions at step 3 when non-opioids or weak opioids have failed to control the pain. Procedures such as nerve blocks, epidural or subarachnoid administration of local anesthetics, and spinal cord stimulation may slow the progression to the need for strong opioid medications.
3. Prescribe strong opioid medications at step 4 only as a last resort after all other modalities fail.

 

PAUSE AND PONDER: Consider a time when a patient has told you that they do not even know what the medication they are taking is for. Or maybe they asked why they take an anti-seizure medication and have never had a seizure in their life. How can you bridge the knowledge gap?

 

TREATMENT OPTIONS FOR NOCICEPTIVE PAIN

First line treatments for somatic or visceral nociceptive pain include non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (aspirin; ASA), acetaminophen (APAP), and steroids.

 

Providers prescribe NSAIDs (e.g., celecoxib, diclofenac, ibuprofen, indomethacin, naproxen) largely due to their analgesic properties, anti-inflammatory mechanism, and antipyretic (fever reducing) effect.²⁶ This class of drugs exerts its effects by inhibiting the enzyme cyclooxygenase (COX). COX is responsible for the conversion of arachidonic acid into thromboxanes, prostaglandins, and prostacyclins. Thromboxanes are involved in platelet adhesion following tissue injury. Prostaglandins and prostacyclins cause vasodilation and play a role in anti-nociception.²⁶

 

The two isoenzymes of COX (COX-1 and COX-2) exert different effects that help explain the class’s adverse effect profile.²⁶ COX-1 is the prime mediator for maintaining gastrointestinal tract lining. Inflammatory conditions induce COX-2 expression. Due to most NSAIDs’ nonselective nature, gastric distress is a common adverse effect of these drugs. COX inhibitors with selectivity to COX-2 (e.g., celecoxib) significantly limit damage to the digestive tract. Other significant adverse drug reactions (ADRs) include renal damage and antiplatelet function.²⁶

 

Although ASA is considered an NSAID, its unique mechanism of action is worth noting. The drug simultaneously modifies both COX-1 and COX-2. The interaction with COX-2 is believed to turn off prostaglandin production but triggers the creation of novel protective lipid mediators.²⁶

 

It is important to recognize that while APAP has analgesic and antipyretic properties, it is considered to be at best a weak anti-inflammatory agent. A study showed that daily doses of APAP may reduce neural activity related to the emotional pain associated with social rejection. Participants’ brain activity were measured and found that APAP decreased neural response in areas associated with distress caused by social pain.²⁷ Despite its long history of use, APAP’s mechanisms are still not completely understood. It is widely accepted that its metabolite, N-acylphenolamine, works on receptors in the brain and the dorsal horn. The ADR of highest concern associated with APAP is liver damage. Healthy adults should not take more than 4 grams of APAP daily and should avoid extended exposures to high dose therapy.²⁸ Older patients and individuals with liver disease or chronic alcohol use should limit APAP use to 3 grams daily.

 

An adjuvant therapy is a drug that is not primarily recognized as an analgesic based on its pharmacologic class but has been shown in clinical practice to either demonstrate some independent analgesic effect or provide a synergistic effect when combined with opioids.²⁹ The adjuvant will act on excitatory neurotransmitters (e.g., glutamate, substance P), inhibitory transmitters (e.g., GABA), or neurotransmitters that modulate the experience of pain (e.g., serotonin, norepinephrine). Drug classes commonly used as adjuvant therapies for pain management include:³⁰

• Skeletal muscle relaxants (e.g., carisoprodol, baclofen)
• Tricyclic antidepressants (TCAs; e.g., amitriptyline)
• Serotonin norepinephrine reuptake inhibitors (e.g., venlafaxine, duloxetine)
• Anti-epileptics (e.g., carbamazepine)

 

Opioids’  (e.g., codeine, hydrocodone, methadone, morphine, oxycodone, tramadol) role in pain management is paradoxical. Opioids are a mainstay in perioperative and palliative care settings. However, their use and effectiveness in chronic pain cases becomes increasingly controversial over time due to their problematic set of short-term and long-term adverse effects.³¹ A solution may be on the way in the form of snake venom. Researchers reported that the isolation of a specific class of peptides from the African black mamba snake were found to have analgesic effects comparable to morphine in mice.³²

 

Opioids exhibit their effects by binding to the three categories of opioid receptor subtypes: mu (µ), delta (δ), and kappa (Κ) found across the CNS and other tissues. Each subtype (see Table 3) is capable of producing spinal or supra-spinal analgesia, but their specific localizations provide insight into the adverse effect profile of this drug class. For example, µ receptors are found in the small intestine and function to decrease intestinal transit rate, which often results in the commonly seen adverse effect of constipation.

 

Table 3. Opioid Receptor Subtypes^33,34

RECEPTOR	UNIQUE FUNCTIONS	LOCATIONS
µ	·        Sedation ·        Inhibition of respiration ·        Decreased intestinal transit rate ·        Regulation of hormone and neurotransmitter secretion	·        Brain (thalamus, caudate, amygdala, raphe nuclei, gray matter, hippocampus) ·        Dorsal horn ·        Peripheral terminals ·        Small intestine
δ	·        Regulation of hormone and neurotransmitter secretion	·        Brain (cortex, amygdala, hypothalamus, midbrain) ·        Spinal cord
Κ	·        Psychotomimetic effects ·        Decreased gastrointestinal transit	·        Brain (cortex, thalamus, hypothalamus, gray matter, black matter, caudate, and putamen)

 

 

Opioids may be classified as agonists (full or partial receptor activators), antagonists (receptor blockers), partial agonists (submaximal receptor activators), or mixed agonist-antagonists (activate one receptor subtype while blocking another).³³ The varying potency at which different opioids act at one or more of their receptors also contributes to their wide array of pharmacologic effects.³⁴ Table 4 provides examples of each opioid classification relative to its receptor affinity.

 

Table 4. Opioid Affinity and Activity³⁵

	RECEPTOR SUBTYPE
	µ	δ	Κ
Morphine (agonist)	Affinity: +++ Activity: ***	Affinity: + Activity: *	Affinity: + Activity: *
Buprenorphine (partial/mixed agonist)	Affinity: ++ Activity: (***)	Affinity: - Activity: -	Affinity: + Activity: XX
Naltrexone (antagonist)	Affinity: +++ Activity: XXX	Affinity: ++ Activity: X	Affinity: ++ Activity: XXX

+, low affinity; ++, moderate affinity; +++, high affinity; -, negligible affinity/activity; *, agonist activity; ( ), partial agonist activity; X, antagonist activity.

 

Opioids’ common adverse effects include constipation, dependence and tolerance, CNS impairment, and respiratory depression. Counseling patients on what to watch for and how to mitigate these adverse effects when they occur improves their quality of life. Recommendations when discussing potential drawbacks of opioid therapies include:^11,36,37,38

1. Confirm a bowel regimen is in place that includes both drug and nondrug treatments. Using a stool softener, stimulant and/or osmotic laxative combined with increased physical activity, fluid intake, and dietary fiber intake can minimize constipation.
2. Establish a baseline cognitive level. Sedation and decreased cognition can occur with initiation of opioid therapy or when increasing the dose. Pharmacists should perform a thorough medication review to modify or eliminate unnecessary medications that synergize CNS effects (e.g., antihistamines, antidepressants).
3. Differentiate between dependence and tolerance. Physical dependence is the result of an altered physiologic state due to chronic drug exposure. Tolerance describes the need for a dose increase to achieve desired analgesic effect. Clinicians should also recognize the lack of complete cross tolerance with opioids. Tolerance with one opioid does not mean tolerance to all, and titrating a new opioid to the target equianalgesic dose is crucial in the prevention of an overdose.
4. Identify risk factors for opioid-induced respiratory depression. Advanced age, female sex, and comorbidities (e.g., diabetes, sleep apnea) increase the likelihood of this potentially fatal adverse effect. The simultaneous use of multiple opioid drugs or modified-release opioid formulations can also put patients at higher risk.

 

Opioid use in patients with hepatic or renal insufficiency must be closely monitored. Opioids undergo phase 1 metabolism via the cytochrome P450 (CYP) pathway and/or phase 2 glucuronidation in the liver.³⁹ Primary metabolic enzymes include CYP3A4 and CYP2D6, resulting in substantial interaction potential with a number of commonly used drugs (e.g., cardiovascular agents, antibiotics, statins). Moderate to severe liver disease can result in higher peak plasma levels of opioids and their metabolites, which is associated with an increased incidence of adverse events. Primary elimination of opioids through urine necessitates dose adjustment in the renally impaired population. The impact of kidney dysfunction on opioid excretion is not uniform. For example, while morphine only sees its clearance decrease slightly, the clearance of morphine’s active metabolites decreases significantly. Accumulation of these metabolites correlates with serious CNS adverse effects and respiratory depression. Hepatic or renal impairment impact fentanyl and methadone, two commonly used opioids, least. Clinicians should consider low and slow dose titration, dose reduction, and extension of dosing intervals when treating people with hepatic or renal impairment.³⁹

 

Designation of opioids based on potency is of limited practical use and often can perpetuate misperception among prescribers. The notion that a “weak” opioid (e.g., tramadol, codeine) is less likely to result in dependence or withdrawal symptoms compared to a “strong” opioid is false. Prescribers need to consider the potential harm of opioid use and misuse regardless of the drug’s classified potency.⁴⁰

 

In the United States, the number of patients taking opioids regularly is equal to the number of patients diagnosed with psoriatic arthritis, epilepsy, and obsessive-compulsive disorder combined. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) defines opioid use disorder (OUD) as repeated opioid use within 12 months resulting in problems or distress including two or more of the following:⁴¹

1. Continued opioid use despite worsening physical or psychological health
2. Continued opioid use despite social and interpersonal consequences
3. Decreased social or recreational activities
4. Difficulty fulfilling professional duties at school or work
5. Excessive time spent obtaining or recovering from taking opioids
6. Taking more opioids than intended
7. Experiencing opioid cravings
8. Inability to decrease the amount of opioids used
9. Development of opioid tolerance
10. Continued opioid despite the dangers it poses to the user
11. Experiencing withdrawal or continuing to take opioids to avoid withdrawal

 

Congress enacted the Drug Addiction Treatment Act of 2000 (DATA 2000) to allow qualified practitioners to prescribe buprenorphine outside of opioid treatment programs in an effort to increase access to medication-assisted treatment.⁴² Interested prescribers needed to obtain the DATA-Waiver (a document to allow prescribing of opioid treatment products outside of parameters established by existing law. As of December 2022, the DATA-Waiver previously necessary to prescribe medications for OUD treatment no longer exists, and any provider with a standard DEA number may prescribe buprenorphine products. Pharmacists play a versatile role in combatting the opioid epidemic by using prescription drug monitoring programs, providing education, dispensing naloxone, and referring patients or loved ones to resources and treatment services.⁴²

 

PAUSE AND PONDER: You have noticed that a patient is asking for a refill on their opioid prescription a week early for the third consecutive month. What questions might you have for the patient? The prescriber?

 

NEUROPATHIC PAIN TREATMENT OPTIONS

When considering neuropathic pain treatment, guidelines recommend first considering the patient’s report of negative (e.g., reduced sensation to touch, vibration, pin prick, and temperature) or positive sensory symptoms (e.g., spontaneous or evoked pain). Spontaneous pain includes dysesthesia (abnormal sensation), paresthesia, or superficial burning pain. Evoked pain symptoms include touch-induced hyperalgesia, thermal hyperalgesia, or a prolonged sensation of pain after the stimuli is removed (aftersensation).⁴³

 

First line treatments for neuropathic pain include serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentinoids, TCAs, and topical medications.

 

Duloxetine and venlafaxine are the most common SNRIs used to treat pain.⁴³ These drugs exhibit some staying power when considering neuropathic pain first line options. The class has demonstrated effectiveness in both peripheral and central neuropathies, including peripheral diabetic neuropathy, painful peripheral neuropathy, and central neuropathic pain secondary to multiple sclerosis. Compared to TCAs and selective serotonin reuptake inhibitors, patients tolerate SNRIs better, with the most common adverse effects including nausea, headache, and drowsiness. Beyond neuropathic pain, SNRIs have also provided benefit in a number of potentially concurrent chronic pain conditions including osteoarthritis, chronic low back pain, and fibromyalgia.⁴³

 

Long recognized as the cornerstone of nerve pain treatment are gabapentinoids: gabapentin and pregabalin. This notion has recently fallen under a heightened scrutiny due to a lack of strong data. A recent study found around 50% of patients treated with gabapentin will not derive meaningful pain relief but will likely experience adverse events.⁴⁴ While sometimes mistaken as benign drugs, gabapentinoids carry significant risks and have been moved onto the controlled substance schedule (drugs that carry the potential risk for addiction/use disorder) in many states. CNS effects such as dizziness, sedation, and gait instability occur in roughly every third patient, even when taken at a therapeutic dosage. This creates additional concern when prescribers use them with opioids. Concomitant gabapentinoid and opioid use increases risk of hospitalization and opioid-related death compared to gabapentinoid or opioid monotherapy. The updated Beers criteria list cautions against the use of this dual therapy regimen in older adults.⁴⁵

 

TCAs impact pain through multiples mechanisms of action. Serotonin and norepinephrine reuptake inhibition serves as the primary pain-relieving effect.⁴³ In addition, drugs like amitriptyline and nortriptyline block other neurotransmitters and neuromodulators involved in the pain response, including histamine, acetylcholine, and epinephrine. This wide-spread, non-specific activity also contributes to TCAs’ broad adverse effect profile. Significant incidence of anticholinergic effects (e.g., dry mouth, constipation, urinary retention) combined with cardiotoxic potential create legitimate concern when using these drugs in older adults.⁴⁶ The fact that only 20% to 30% of the dose normally used in effective anti-depressant treatment is necessary for pain relief may mitigate these concerns slightly.⁴³

 

Topical lidocaine or capsaicin circumvent the cautious dosing regimens of previously discussed classes.⁴³ Although lidocaine is considered first or second line therapy only in post herpetic neuralgia, its safety and tolerability establish the drug as a viable adjunct option for other neuropathic pain causes. A three-week trial period may provide the patient with modest pain relief while using a non-systemic mechanism of action, so long as that person does not have red hair. Studies show that redheads are more sensitive to thermal pain and more resistant to the effects of topical anesthetics like lidocaine.⁴⁷ Success of capsaicin is dependent on consistent use, however, pharmacists should caution patients against overuse due to nerve desensitization risk.⁴³

 

NOCIPLASTIC PAIN TREATMENT OPTIONS

Non-pharmacologic interventions are first line for nociplastic pain. The pain management plan should include:⁴⁸

• Routine, aerobic and mind-body exercises
• Cognitive behavioral therapy and/or acceptance commitment therapy
• Strict sleep hygiene practices
• Physical/occupational therapy
• Keeping a pain journal to track goals and identify potential barriers

 

A positive patient-provider relationship is crucial due to the complex nature of the disease states that cause nociplastic pain. Providers must communicate to patients that pain may not be a true representation of underlying inflammation and/or joint damage. Explanation and identification of nociplastic pain may validate the patient experience and improve the withdrawn and dismissive affect associated with this population.⁴⁸

 

Data on effective pharmacologic treatment options for nociplastic pain is limited. The main objectives of treatment are to reduce symptoms and improve quality of life. Most first line and adjuvant drugs used in nociceptive pain are considered marginally effective at best. Codeine provides weak analgesia in regards to fibromyalgia but not without the increased risk of prescription opioid misuse seen in nociplastic pain patients. TCAs, SNRIs, and gabapentinoids have shown some efficacy in nociplastic pain, but are not without concern due to the high incidence of adverse effects linked to these drug classes.¹⁷

 

It is worth mentioning that ketamine has shown promise in complex regional pain syndrome (CRPS), making a case for trial in other nociplastic pain conditions. CRPS occurs after a stroke, heart attack, or injury that presents as severe extremity pain disproportionate to the inciting event. Ketamine primarily works in the CNS to decrease neuronal activity, and secondarily through other pathways that affect pain and mood regulation.⁴⁹

 

CONCLUSION

Successful pain management demands collaboration. Consider the work that you do every day. Whether pain is the chief complaint or a secondary issue, odds are that it will be a factor in your clinical decision making. A comprehensive pain assessment starts this process. Understanding the different pain classifications enables the assessment to guide next steps in care. Healthcare providers formulate and modify a treatment plan as more information rolls in. Pain does not follow an algorithm; it is an individual experience that requires nuance and balance. How can you make an impact? Figure 1 lists ways to improve your practice.

Download CE Activity

INTRODUCTION

Interprofessional collaboration crops up as a topic in many healthcare facility staff meetings. However, team members often don’t know how to collaborate effectively, so the conversation quickly trails off. Before you know it, everyone’s talking about the new espresso machine in the break room, and attendees are leaving the meeting without practicable advice.

Insufficient guidance on how to work together results in lost opportunities to improve patient outcomes. Consider the heart failure medication titration clinic that tested a pharmacist-driven titration protocol. Pharmacists collected data from vital signs and patient interviews to optimize drug dosages in heart failure, with statistically significant improvements in dosages.¹ There was a key opportunity to collaborate here. The job description of someone on your team includes taking vitals and interviewing patients: the registered nurse (RN)!

Step one of effective teamwork is recognizing opportunities to put your heads together. Pain management took center stage when the multi-wave opioid overdose epidemic began in the 1990s.² Plus, pain is an intrinsic characteristic of nearly all physical afflictions. What do you get when you combine these facts? An issue that’s causing significant problems and is ubiquitous— it’s ripe for collaboration.

What do RNs do? How can you partner with them? And what is this about pie?! This continuing education activity will guide you through those questions and provide an overview of trends in pharmacologic pain management. You’ll also learn several nonpharmacologic pain management strategies.

Note: “RN” and “nurse” are used interchangeably in this activity. Many of an RN’s responsibilities (comprehensive assessment and care plan creation in particular) are outside the scope of practice of, for example, a Licensed Practical Nurse (LPN).^3,4,5

Furthermore, RNs are as ubiquitous as pharmacy professionals. Pieces of this activity apply mostly to RNs in specific settings such as hospitals. However, it’s helpful to keep in mind that RNs work in skilled nursing facilities, telehealth, schools, home healthcare, correctional facilities, and more. Considering these different areas can keep your gears turning when deducing how to crack the nut of collaboration.

THE NURSE’S ROLE

Working with every member of the healthcare team necessitates understanding everyone’s role. Ask five people what an RN does, and you’ll probably hear five different answers. One misconception is that the nurse is an extension of the doctor. On the contrary, nurses have their own chain of command and overarching objectives in patient care. The doctor’s focus centers around an injury's or illness’ physiological implications, whereas the nurse manages how the condition affects the patient.^6,7,8 The SIDEBAR about nursing diagnoses later in the activity differentiates these concepts.

What nurses do is part of the picture—the other part is how they do it. RNs use communication and four of their five senses (hopefully they’re not tasting anything, anyway…) to establish and continually revise a care plan. The framework for a care plan is known as ADPIE.^4,8

We’ll circle back to RNs, care plans, and that pie you were promised. Let’s look at pharmacologic and nonpharmacologic pain management methods first, and we’ll connect the dots later.

PAIN MANAGEMENT

At its most fundamental level, every pain treatment is pharmacologic or nonpharmacologic. Both have the power to help the patient, but any number of minutiae about the patient and condition dictates which therapy or combination of therapies is best.

Pharmacologic Pain Management

Numerous factors including etiology, coexisting conditions (e.g., pregnancy, disease), and pain type (e.g., neuropathic, pleuritic, visceral) steer analgesic selection. This activity primarily categorizes pharmacologic therapies by classifying pain as acute or chronic. You will understand the reason for this delineation when you read about nursing diagnoses.

Considerations for cancer pain and the geriatric and pediatric populations close the section.

Acute Pain

The Centers for Disease Control and Prevention (CDC) classifies pain lasting three months or less as acute.⁹ Today’s analgesic guidance for acute pain centers around multimodal strategies, due in part to the opioid crisis. These strategies’ end goal is effective pain relief with minimal adverse effects.^9,10 “Balanced analgesia” is the term for this concept. Its underlying principle is to reduce opioid and non-opioid dosages by attacking pain from multiple angles.¹⁰

One such approach is channels-enzymes-receptors targeted analgesia, or CERTA. This approach boils down to pathways and progression. Namely, practitioners can achieve balanced regimens by deploying interventions that act on different pathways and progressing to more potent therapies as needed.¹⁰

A balanced and stepwise approach to acute pain therapies comes to life in Table 1. As with all matters in healthcare, patient-specific care is paramount. For instance, although opioids are not necessarily first-line therapies, a non-opioid trial is not required before initiating opioid therapy.⁹

 

Table 1. Pharmacologic Medications for Acute Pain^10,11

Topical
·       Diclofenac or ibuprofen for musculoskeletal injuries ·       Camphor, menthol, and clove oil for headache or muscle pain
Mild to moderate acute pain
Medication	Example indications	What to know
Acetaminophen	Headache, sprain	·     Combine with NSAIDs for postoperative pain ·     Limit 75 mg/kg/day or 4,000 mg/day (2,000 mg/day in hepatic disease and alcohol use disorder)
NSAIDs (ibuprofen, naproxen, diclofenac, ketorolac, meloxicam, celecoxib)	Migraine, postoperative pain, low back pain	·     Patient might need a PPI ·     Combinations with acetaminophen improve analgesia
Moderate to severe acute pain
Medication	Example indications	What to know
[Opioid] + [acetaminophen or NSAID] (HYDROcodone/acetaminophen, HYDROcodone/ibuprofen, oxyCODONE/acetaminophen)	Fracture, postoperative pain	Combinations reduce the opioid dosage needed
Dual-action opioids (traMADol, tapentadol)	Therapeutic failure of other agents	·     Risk for opioid use disorder and serotonin syndrome ·     TraMADol reduces seizure threshold
Full-agonist opioids (oxyCODONE, morphine, HYDROmorphone, fentanyl)		·     Risk for sedation, respiratory depression, and opioid use disorder ·     3-day limit

 

NSAID = nonsteroidal anti-inflammatory drug

PPI = proton pump inhibitor

Nonsteroidal anti-inflammatory drugs (NSAIDs) enter virtually every discussion about acute pain. Note that this drug class may cause complications in patients with cardiovascular or renal impairment or a history of gastrointestinal (GI) bleed.^9,12

Adverse GI effects of NSAIDs are less likely to occur with a selective COX-2 inhibitor such as celecoxib. In turn, the patient is less likely to need a PPI (proton pump inhibitor) than with other NSAIDs. Eliminating a PPI lowers costs and helps inhibit polypharmacy’s adverse effects.¹¹

Is the first column of Table 1 reminiscent of alphabet soup? Drug names that resemble one another—aptly named “look-alike and sound-alike” (LASA) drugs—present an opportunity for unfortunate drug mix-ups. The LASA Drugs SIDEBAR has more information about these drug name pairings.

SIDEBAR

LASA Drugs^13,14

Nurses learn about and watch out for look-alike and sound-alike (LASA) drugs. However, the pharmacy team—the pharmacy technician, in particular—is the first line of defense in preventing related errors.

Mix-ups between HYDROmorphone and morphine constitute an example of a common and serious LASA-related problem. Some ways to help prevent med errors involving these two drugs include

1. Placing each agent and strength in its own bin or drawer.
2. Looking for tall man lettering: HYDROmorphone.
3. Stating the name of the drug before providing it to a patient for confirmation.
4. Using brand names for additional confirmation.

The LASA list is a living document. How can you keep up to date on changes and additions? The ISMP (Institute for Safe Medication Practices) maintains this table—find it here.

 

Drug name	Confused drug name
acetaminophen	acetaZOLAMIDE
buprenorphine	HYDROmorphone
carBAMazepine	OXcarbazepine
codeine	Lodine
DULoxetine	Dexilant, FLUoxetine, PARoxetine
EPINEPHrine	ePHEDrine
fentaNYL	ALfentanil, SUFentanil
gabapentin	gemfibrozil
HYDROcodone	oxyCODONE
HYDROmorphone	buprenorphine, hydrALAZINE, hydrOXYzine, morphine, oxyMORphone
ketamine	ketorolac
ketorolac	Ketalar, ketamine, methadone
methadone	dexmethylphenidate, ketorolac, memantine, Mephyton, Metadate, Metadate ER, methylphenidate, metOLazone
morphine*	HYDROmorphone
oxyCODONE	HYDROcodone, oxybutynin, OxyCONTIN, oxyMORphone
traMADol	traZODone

*Morphine has a non-concentrated oral liquid form and a concentrated oral liquid form.

Note: Names with first letter capital letters indicate trade names.

PAUSE AND PONDER: Where can you refer patients if you suspect drug abuse, or if a patient requests such a resource for himself or a loved one?

Chronic Pain

Per the CDC, pain lasting longer than three months is chronic. Following are select chronic pain management recommendations from the CDC Clinical Practice Guideline for Prescribing Opioids for Pain.⁹ Practitioners who prescribe opioids should read this comprehensive guideline in full—click here to access this free document.

1. Use nonopioid therapies to the greatest extent possible.
2. Discuss the risks and benefits of opioids with the patient.
3. Prescribe immediate-release formulations at the start of opioid therapy.
4. Start with the lowest dosage possible for opioid-naïve patients.
5. Evaluate the risk/benefit balance before increasing dosages.
6. Do not discontinue or rapidly decrease dosages in the absence of a life-threatening condition.
7. Evaluate risks and benefits 1-4 weeks after starting therapy and periodically thereafter.
8. Use a prescription drug monitoring program to help evaluate the risk of overdose.
9. Evaluate the risk/benefit balance of concurrent benzodiazepines.

Extensive news coverage of the opioid crisis means that even individuals far removed from healthcare are wary of opioids. Serious adverse effects and associations include respiratory depression, overdose, opioid use disorder, falls, and death from all causes. All healthcare providers must inform patients that benzodiazepines, alcohol, and some illicit drugs increase the risk for respiratory depression.^9,15

Common adverse effects of opioids include constipation, nausea/vomiting, and drowsiness. These effects might cause patients to discontinue therapy. Practitioners should warn against abrupt opioid discontinuation, explaining that withdrawal syndrome could result. They should inform patients that certain behaviors can mitigate adverse effects, such as hydration, fiber intake, and exercise for constipation.^9,15

What alternatives to opioids exist? Other drug classes for chronic pain include NSAIDs, anticonvulsants (pregabalin, gabapentin), and serotonin and norepinephrine reuptake inhibitors (SNRIs; DULoxetine, milnacipran).⁹ These are associated with their own risks to consider when planning a patient’s drug regimen.

Cancer Pain: The WHO Analgesic Ladder

The World Health Organization (WHO) released an algorithm in the mid-1980s to steer pain management planning in cancer, as this condition warrants unique considerations.¹⁶

The WHO analgesic ladder, replicated in Figure 1, is a major element of the algorithm. It provides visual guidance for prescribing and deprescribing adjuvant, non-opioid, and opioid analgesics for varying pain severities. Following are select examples^16,17:

• Adjuvants: antidepressants (amitriptyline, DULoxetine), anticonvulsants (gabapentin, carBAMazepine), corticosteroids, cannabinoids
• Non-opioid analgesics: NSAIDs (ibuprofen, ketorolac), acetaminophen
• Weak opioids: HYDROcodone, codeine, traMADol
• Potent opioids: morphine, HYDROmorphone, methadone, fentaNYL, oxyCODONE, buprenorphine

Figure 1. WHO Analgesic Ladder¹⁷

Reproduced from WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents, World Health Organization, Annex 1: Evaluation of Pain, P. 70, 2018.

 

Note that the model has criticisms. For instance, it can lead to the erroneous inference that NSAIDs are safe since they are the ladder’s entry point. Furthermore, the WHO designed the ladder for simplicity, causing clinicians to reference it outside the bounds of cancer pain. However, research findings point to abandoning the algorithm in chronic non-cancer pain (CNCP). Pharmacologic and nonpharmacologic strategies that better control CNCP while limiting opioid usage exist.^16,18,19

The WHO analgesic ladder is just one constituent of the extensive WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents (click here to access). Reference this manual for further guidance in cancer pain management, such as the following principles that should accompany the ladder¹⁷:

• By mouth: Use the oral route of administration when possible.
• By the clock: Administer pain medication at set intervals rather than pro re nata (PRN).
• For the individual: Tailor pain management to the individual; the ladder is only a guideline.
• With attention to detail: Base first and last doses on sleep/wake times. Write down drug and administration regimen information for caretakers. Inform patients of potential side and adverse effects.

Geriatric Considerations

Common origins of pain in the geriatric population are arthritis, postherpetic neuralgia, and cancer. And although more common as we age, pain is not a normal element of the aging process.²⁰ However, practitioners must consider certain essential physiological changes when prescribing for older patients. These include increased body fat and decreased rates of GI absorption and renal and hepatic clearance.²¹

Also notable is that older adults often experience insufficient pain relief, such as when they cannot communicate the presence or degree of pain.²¹

Drugs from several classes indicated for pain appear in the AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults (AGS: American Geriatric Society). These classes include benzodiazepines, certain antidepressants, skeletal muscle relaxants, and NSAIDs.²² Healthcare providers should check this publicly accessible document (click here to access) when prescribing or reviewing an older adult’s medications.

Consider acetaminophen to be the first-line analgesic for pain in the older adult. Hospitalized older patients with oral intake restrictions might require intravenous (IV) acetaminophen. If acetaminophen is insufficient, NSAIDs follow. They are relatively safe for short-term use such as during an emergency room visit, although the provider should consider including a PPI. In terms of safety and timelines, NSAID use increases the risk for cardiac events after just one week of regular use. Topical formulations can be an effective alternative in the face of GI or cardiovascular contraindications to NSAIDs.^21,23

Prescribers should also start opioids at a lower dosage in geriatric patients. Morphine and HYDROmorphone can be initial analgesics, but note that their metabolites are excreted by the kidneys. Therefore, fentaNYL might be a better option for the older patient with renal impairment.^21,24

Pediatric Considerations

Pain control is especially important for pediatric patients since unmanaged pain can develop into hyperalgesia (excessive response to pain).^25,26

Unlike with other populations, the first-line pain therapy for pediatric patients isn’t part of the formulary—it’s nonpharmacologic intervention. Methods range from breastfeeding for the youngest to distraction with video games for the teens.²⁷

If nonpharmacologic techniques are insufficient, the clinical team needs to make route of administration a top consideration in drug therapy. They should start with the least invasive route, considering non-parenteral routes first (inhaled, intranasal, oral, rectal, topical).²⁷ Table 2 lists common medications by route.

Table 2. Pharmacologic Medications for Pediatric Patients²⁷

Route of administration	Common medications
Topical	·    Lidocaine ·    Lidocaine and prilocaine ·    Lidocaine, EPINEPHrine, and tetracaine ·    Ethyl chloride ·    Pentafluoropropane and tetrafluoroethane
Oral	Acetaminophen, ibuprofen, naproxen, sucrose (infants)
Intranasal	Ketamine, fentaNYL, HYDROmorphone
Inhaled	Ketamine, nitrous oxide
Intravenous	Ketorolac, acetaminophen, ketamine, morphine, HYDROmorphone, fentaNYL

 

Here’s a PRO TIP: Children are not simply “small humans.” They are physiologically different from adults, necessitating special considerations in pharmacology even within sub-stages of the broad category of pediatrics. In other words, treatment for a 4-year-old cannot be the same as for her 15-year-old sister.^27,28

Moreover, when prescribing for the pediatric population—which often involves weight-based dosing—clinicians must consult prescribing guidelines specific to the pediatric population. Calculating the pediatric dosage by extrapolating the adult dosage-to-weight ratio could yield a subtherapeutic or supratherapeutic dosage.^27,28

PAUSE AND PONDER: Patients with painful conditions generally fear or dread this aspect of their affliction. What are some ways you can respond when patients communicate these feelings, such as when expressing worry that their analgesic prescriptions will be insufficient?

Nonpharmacologic Pain Management

Nonpharmacologic pain control is so important that the Joint Commission stipulates its availability in hospitals.²⁹ Supplementing drug therapy with nonpharmacologic interventions further reduces pain and does not present significant risk.⁹

Inpatient nurses are generally with patients for a short period (average length of acute care stay is approximately 6.5 days), so they might use the same techniques for acute and chronic pain.³⁰ Hence, this section doesn’t focus on such a distinction, but Table 3 lists statistics-based guidance regarding nonpharmacologic therapy specifically for chronic pain.

 

Table 3. Nonpharmacologic Strategies for Chronic Pain³¹

Pain type	Term	Successful modality(ies)
Chronic low back pain	Short	Psychological therapy, massage, stress reduction, acupuncture
	Intermediate	Psychological therapy, spinal manipulation, yoga
	Long	Psychological therapy
Chronic neck pain	Short	Low-level laser therapy
Osteoarthritis pain	Short	Exercise
Fibromyalgia	Short	Exercise
	Intermediate	Exercise

 

Short term: 1 to < 6 months

Intermediate term: ≥ 6 to < 12 months

Long term: ≥ 12 months

Note 1: “Term” is the length of time between intervention and assessment.

Note 2: This table only includes data with moderate strength of evidence.

Note 3: The research did not find high-quality evidence for nonpharmacologic pain relief for chronic tension headaches.

Because this continuing education activity centers around collaborating with the RN, the nonpharmacologic techniques detailed omit those outside the RN’s scope of practice. Interested learners can seek other literature for information about the following examples of such modalities^32,33:

• Ablation
• Acupuncture
• Cognitive behavioral therapy
• Counseling
• Electrical nerve stimulation
• Physical and occupational therapy

The coming subsections cover some techniques the RN can apply. But any healthcare provider can employ these strategies, wherever the patient is, and without preparation. Plus, you can suggest these ideas to the RN during rounds or team meetings.

Journaling

Patients can journal about their pain to reduce its intensity and its interference in their daily life. Researchers who conducted a study in CNCP had 72 patients journal quantitative information each day. Included were a body pain map, pain intensity, and ratings for disturbance to activities and quality of life. Patients recorded qualitative data at the end of each week, including pain management methods and communication with others about pain.³⁴

How did journaling help?

1. Patients understood their pain better.
2. Providers supported and communicated with patients more effectively.
3. Journals served as an outlet for negative emotions.

Here’s another PRO TIP: The study found that journaling was effective only in patients with adaptive coping mechanisms—healthy stress management techniques, such as exercise or religious practices. Consider other nonpharmacologic modalities for patients who use avoidance or other maladaptive strategies.³⁴

Mind-Body Interventions

When advising patients, it is as important to know what works as it is to know what doesn’t work. Claims regarding mind-body techniques for pain relief abound, but are any effective?

A study on mind-body interventions divided 244 participants into three parallel arms. Of 159 participants undergoing a mind-body intervention, researchers led 86 in mindfulness training and 73 in hypnotic suggestion. The control group of 85 received training regarding pain management strategies.

The mind-body interventions provided significantly more pain relief than the education session. Specifically, 15-minute sessions of the following techniques reduced pain immediately³⁵:

• Mindfulness training (23% pain reduction): patients listened to a script guiding them to focus on sensations and breathing and to accept pain and negative thoughts
• Hypnotic suggestion (29% pain reduction): patients listened to a script guiding them to visualize floating in a peaceful location and to manifest temperature or tingling in place of pain

The control group experienced a pain reduction of just 9%.

These methods do not require specially credentialed personnel—study interventionists received training from a professional certified in clinical hypnosis. Hence, the healthcare team does not need to consult a hypnotherapist to apply the hypnotic suggestion technique with each patient.³⁵

Mind-body exercise is on the table, too. Osteoarthritis Research Society International guidelines (OARSI) now name tai chi and yoga as Core Treatments for knee osteoarthritis.¹²

Distraction

Ever plop down in front of the TV to take your mind off a troubling issue? There’s science behind that! Multiple hypotheses attempt to pin down the psychology and physiology behind distraction and pain relief. Many postulate that the mind has the capacity to focus on or process only so much at a time. When people make their brains focus on something else, suddenly the pain can’t demand so much attention.^36,37,38

Unfortunately, many studies evaluating these hypotheses and methodologies are inconclusive or poorly designed. Nevertheless, one can accept several useful findings relatively confidently, summarized next.³⁶

Pain perception occurs differently in chronic pain than in acute pain. Research findings do not support distraction as an effective pain management strategy in chronic pain.³⁶

Conversely, distraction can mitigate acute pain. For instance, visual distraction—particularly if the medium is interactive—is effective in children and adults. Participants in various studies reported improved pain characteristics during activities such as playing simplistic computer games or using a virtual reality (VR) headset.^36,39,40

One study measured how long 79 children could keep a hand submerged in cold water (painful stimulus) while playing a VR video game. Each child underwent the test while watching a recording of that same game and, as a control, while simply wearing the headset. Urn randomization counterbalanced the order of the two distraction conditions. Passive visual distraction (watching the game) increased pain tolerance significantly, and active distraction (playing the game) increased it further.³⁹

In a similar study (N = 107), adults played a simple, slow computer game while a heating pad provided a painful stimulus. Participants’ pain perception variables improved during gameplay (higher pain threshold and tolerance, lower intensity).⁴⁰

Some research reveals no correlation between pain and auditory stimuli such as a recorded description of a scene or audible tones study participants were to react to.³⁶ But what happens with auditory input the listener actually enjoys? Investigating the relationship between music and pain in adults corroborates its analgesic effect, particularly when the patient chooses or approves the genre.^41,42 In fact, some investigations found pain relief to be so significant that patients required less opioids and other analgesics.^42,43,44

One such study evaluated the pain levels and morphine requirements of patients undergoing the same procedure by the same surgeon and analgesic protocol. The researchers randomized 75 patients into blocks of 25. All patients wore headphones connected to a CD player intraoperatively and postoperatively. One block’s headphones were connected to CD players playing soft music intraoperatively and sham CD players postoperatively. Sham CD players displayed track numbers on their indicators but played no audio. The second block received sham CD players intraoperatively and heard music postoperatively. The control group had sham CD players during both phases.⁴⁴

Both blocks receiving the intervention reported lower pain ratings in the post-anesthesia care unit (PACU) compared with the control group. Furthermore, total morphine required in the PACU was lower for the intervention blocks—1.2 mg for postoperative listeners, 2.3 mg for intraoperative listeners, 3.6 mg for the control group.⁴⁴

Research does not support sweeping generalizations regarding music for pain management in pediatrics. A substantial proportion of pertinent studies report inconclusive results or have insufficient sample sizes. However, two meta-analyses (429 and 5601 participants) found music therapy to reduce pain in pediatric cancer and in needlestick, procedural, and postoperative pain.^45,46

Additional methods

The nurse’s toolbelt contains an array of nonpharmacologic pain control tools, all appropriate in different contexts. A 9-year-old might enjoy a large-piece puzzle, which is unlikely to satisfy a teen. A patient with mild to moderate pain who has been resting in bed for several days might like to attempt guided imagery or meditation. That’s probably not the case for a patient wheeled into the ER following traumatic amputation of a limb.

Hot and cold therapy are yet another option, but they require training. Practitioners must know when heat versus ice is appropriate, how to apply different equipment and media, and how to assess for effectiveness and warning signs. As such, facility policy may stipulate provider prescription before applying heating pads, ice packs, and other such therapies.

THE ADPIE FRAMEWORK

Take a slow, deep breath. Smell that blueberry filling inside its flaky, buttery home? Or that warm layer of pecans awaiting a cool scoop of vanilla? It’s time for pie…

Overarching Concept

ADPIE is an acronym describing the five elements of the nursing process: assess, diagnose, plan, implement, evaluate. It’s the framework that shapes everything the RN does.^4,8

PAUSE AND PONDER: The Joint Commission once endorsed pain as the fifth vital sign. The organization rescinded the statement following substantial backlash.⁴⁷ Does pain’s inclusion as a fundamental component of assessment increase the likelihood of treatment or result in overzealous prescribing of analgesics?

ADPIE Letter by Letter

A: Assess

Assessment is the core of nursing and the foundation of the nursing process. It involves collecting objective and subjective data about a patient’s physical and non-physical status (emotional, spiritual, economic, etc.).^8,48,49 Lab values, comorbidities, the patient’s and family’s statements, diagnostic imaging results, past medical history, physical assessment findings, and much more all coalesce into a comprehensive assessment.

Assessment sometimes lacks sharp boundaries. Take this example: A nurse passes an LPN pushing a newly admitted patient onto the unit in a wheelchair. The patient has a furrowed brow and is clutching her hip. The patient is not yet under the nurse’s care, nor did the nurse step in front of the wheelchair and proclaim, “I am now assessing you.” Yet the nurse has already assessed through passing observation that this patient might have pain in her hip, which requires further investigation.

Put simply, the adept nurse is constantly observing for key insights into the patient’s overall condition!

D: Diagnose

Recall that the nurse’s role is not to resolve an affliction, but rather to manage how it affects the patient. Just like the pharmacy team, nurses cannot diagnose medical conditions. ADPIE diagnoses are nursing diagnoses, not medical diagnoses. Entire books are dedicated to nursing diagnoses, and while in-depth coverage is outside the scope of this continuing education activity, the Nursing Diagnoses SIDEBAR contains more information.

NANDA International, Inc. is an industry-standard organization that defines nursing diagnoses.* Their taxonomy is called “NANDA-I”; however, this is not the only taxonomy, and many healthcare facilities develop their own. When it comes to pain as a nursing diagnosis, these taxonomies often list acute pain and chronic pain as the primary pain-related categories.^8,50,51

*Before 2002, “NANDA” stood for “North American Nursing Diagnosis Association.” It is no longer an acronym.⁵²

SIDEBAR

Nursing Diagnoses^4,8,48,53

Nursing diagnoses have multiple components, starting with the diagnosis itself. This can come from taxonomies such as NANDA International, Inc., the ICNP (International Classification for Nursing Practice), or the facility where the RN practices.

Take pneumonia as an example to illustrate nursing diagnoses and how they differ from medical diagnoses. The medical diagnosis is simply “pneumonia,” potentially with a qualifier such as “bacterial.” This is what the provider treats.

When selecting diagnoses, the RN considers how the illness affects the specific patient. Virtually all patients with pneumonia will have a nursing diagnosis of ineffective airway clearance.

This is a valid nursing diagnosis because the nurse can “do something for it” (and it’s in the NANDA-I taxonomy). The nurse can teach the patient turn, cough, and deep breath (TCDB) exercises to alleviate this. If the patient has impaired mobility (another nursing diagnosis), the RN can also turn the patient in bed periodically to help different areas of the lung inflate.

Say the patient is a star athlete and single father of three. The RN has additional diagnoses to consider now: anxiety, caregiver role strain, and insomnia. These issues reflect how pneumonia affects this patient, and the RN can take several steps to alleviate the problems. Potential steps include teaching anxiety management techniques, helping source childcare resources, and collaborating with the provider and pharmacist for pharmacologic sleep aids.

The other parts of a nursing diagnosis’ anatomy vary based on complex considerations, but they generally include

1. Related factors, or etiology—in the case of pneumonia, the offending species
2. Defining characteristics—objective and subjective data collected upon assessment that supports the nursing diagnosis

Having a strong handle on nursing diagnoses is a fundamental skill for an RN, as these short statements guide the outcomes and interventions.

Back to our new arrival on the unit, who the RN has learned is an 85-year-old woman named Sheila. Upon further assessment, Sheila shows signs of infection at the incision of her recent total hip replacement (THR). Sheila reports a pain level of 5 on a scale of 1 to 10 as part of the admission assessment. Multiple nursing diagnoses apply (to these and any number of other assessment findings), but the nurse notes acute pain in particular.

P: Plan

Now that the nurse has assessed the patient and made the relevant diagnoses, planning begins. Nurses plan outcomes, or goals, that are SMART: specific, measurable, achievable, realistic, and timed. They also plan interventions—ways to accomplish each outcome—that are evidence based wherever possible.^4,8,48

A simple way to look at these two components of the Plan stage is that the outcomes are what the patient will do, and the interventions are what the nurse will do.

Let’s zoom in on outcomes first. Every nursing diagnosis needs one outcome statement. Relevant data from the entire picture—Sheila’s comprehensive assessment findings—feeds into each goal.⁴⁸ We’ll define Sheila’s outcome statement for the diagnosis of acute pain as follows: Report pain of 0 to 3 on a 10-point scale by discharge. Where does the “realistic” criterion fit? Sheila’s condition is acute, and her reported pain level was 5. A rating of 0 to 3 is probably realistic for her, although it likely wouldn’t be for a patient with stage IV bone cancer.

Now for those interventions. What can or should the nurse do? Well, she must perform at least one action that supports meeting the outcome. And she’ll need to assess metrics relevant to the outcome (in this case, pain level).

All other interventions come from a complex web influenced by the nurse’s training and clinical experience. Patient teaching, collaborating, recommending and evaluating labs, and supporting nutrition and hydration are other facets of virtually all care plans. In any case, every intervention should support achievement of the respective outcome statement.

Here’s a small sample of what the RN might plan as the actions she will take (i.e., interventions) for Sheila:

1. Administer pain medication as prescribed; collaborate with provider and pharmacist to determine appropriate therapy.
2. Encourage distraction as nonpharmacologic pain management.
3. Perform wound care.
4. Teach hand and wound hygiene techniques.
5. Assess pain every four hours.

Science drives the nursing process. Each intervention supports achievement of the outcome. The outcome represents a resolution to the nursing diagnosis. The diagnosis comes from assessment data. Here’s how it all comes together: Every step of the nursing process flows into the next.⁸ The nurse’s actions are not haphazard.

I: Implement

The implementation stage involves conducting the plan: doing, delegating, and documenting.⁸ The RN acts independently for certain actions, such as performing wound care and administering medications.⁴⁸

However, no one in healthcare acts alone. The implementation stage is where collaboration happens!⁴ That’s right, this is when the RN is thinking about you, the pharmacy team. Does the RN need the pharmacist’s help teaching a patient about self-administration of a new prescription? Maybe she needs some help from the pharmacy technician for a patient who needs a special drawer in the drug dispensing cabinet. In Sheila’s case, the RN collaborates with the provider and pharmacist to discuss pharmacologic analgesia.

E: Evaluate

How do we know we’ve made a positive difference for the patient? We go back and evaluate. The RN reassesses Sheila to determine whether her situation improved. If Sheila rates her pain as 3 or lower, the goal was met, and the RN can focus on other diagnoses. If Sheila says her pain is 4 or higher, the goal is unmet, and the RN must modify the care plan.⁸ Maybe she could try another nonpharmacologic strategy. Perhaps the pharmacist and provider need to increase dosages, consider a drug with a different method of action, or change the route of administration.

NOTES ABOUT ADPIE

Like the Song that Doesn’t End

The nursing process is an endless loop. After classifying each goal as met or unmet, the RN may continue, modify, or discontinue that part of the care plan.^4,8

If a goal is unmet, the RN must revise something. Often, he must add or modify an intervention. Perhaps, though, the goal was unrealistic. Or could the assessment have been incorrect? If a patient was admitted while comatose, certain assessment data could be erroneous if his next of kin provided an inaccurate past medical history.

IE-PIE-PIE

You were promised PIE, yet collaboration with the pharmacy team wasn’t mentioned until implementation (I). What gives?

The RN is headed your way during the first round of implementation, but once you’re roped in, you can be involved in each iterative loop, particularly in the P-I-E.

Remember that assessment (A) is a key function of the nurse. Pharmacists should certainly feel free to assess patients, but for the purpose of effective collaboration, they need to recognize that a team member is performing continuous assessment. Diagnosis (D) is solely the responsibility of the nurse. Therefore, each round of PIE is when other members of the healthcare team should proactively check in. The nurse has to deal with the ads, and you just get the pie!

Too Cool for Nursing School

The acronym ADPIE is seldom mentioned outside the context of nursing school. If after this continuing education activity, you ask a nurse to collaborate on ADPIE, you might receive a less-than-friendly response. Nurses in the wild rarely plan care by literally defining each element of ADPIE. Rather, ADPIE is a cognitive process in the background of the nurse’s mind. As such, many nurses believe ADPIE to be the busy work of nursing school and inapplicable to nursing practice.

However, while some nurses assert that ADPIE is not used in the profession, it is. In fact, these elements are part of the American Nurses Association’s Scope of Nursing Practice. Even if a nurse doesn’t conscientiously analyze each letter of the formula when providing patient care, the principles remain the framework of nursing practice.^4,8

THE PHARMACY TEAM’S SLICE OF PIE: HOW TO COLLABORATE

RNs are trained to view patients holistically, connecting the dots between multiple aspects of a patient’s status and medical history.^4,8 Every dot is an input to the care plan and a piece of the puzzle the pharmacy team might need to know.

Furthermore, RNs work to establish an environment where patients feel open to sharing.⁴ Hence, the RN might have information that’s valuable to the rest of the team.

A patient who reveals he is unhoused might not have a safe place to store prescribed narcotics. If a patient shares that she suffers from bulimia nervosa, the provider and pharmacist will need to reconsider certain therapies. These include QT-prolonging tricyclic antidepressants, drugs that increase weight or appetite (some antidepressants), and bupropion, which lowers the seizure threshold.⁵⁴

What a nurse can learn from assessment that might be valuable to the pharmacy team is practically limitless. Following are some examples:

• Comorbidities—gastroesophageal reflux disease is a contraindication for many drugs.
• Dietary habits—if the patient practices fasting, this affects drugs he must take with food.
• Acute changes—the sudden onset of severe nausea calls for a change in route of administration for oral prescriptions.
• Sleep cycles—some therapies affect or are administered based on sleep/wake cycles, which the RN observes.
• Adverse effects and side effects—the nurse can keep an eye open for signs and a listening ear open for symptoms.

This list paints the picture that the RN has loads of useful information. Consider this PRO TIP: Talk to the nurses! They are the constant set of eyes on the patient. They are the patient’s interviewer, day and night.

If you know of a common issue with a drug, such as its tendency to affect appetite, ask the RN if the patient’s eating habits have changed. Maybe you attended a seminar and learned about a potential drug-drug interaction recently uncovered. If this is relevant to your patient, share this information with the nurse, and ask him to observe for the interaction. Attend the nurse’s rounds if you can. ADPIE presents multiple ways to get involved!

If you’re not sure where to start or aren’t comfortable bringing up ADPIE as a springboard, there’s a simpler way in. Introduce yourself to the RN (in person if possible) and state your objective plainly: “I’d like to collaborate!” This fulfills multiple purposes:

1. The RN receives the clear message that you want to collaborate—she won’t need to infer your objective from your actions.
2. The RN understands your goal as intended. Otherwise, the RN might mistake your sudden interest for mistrust in his competence.
3. Owing to the previous point, an RN who understands your wish to collaborate will realize that you welcome her data and opinions.

If you’re stuck on starting this conversation, be even more direct: “I did a continuing education activity last week that was all about collaborating with RNs. I want to give it a try. Can we discuss what you and I can learn from each other about our patients and how to incorporate that in our day to day?”

Still looking for another nudge? Consider setting yourself a SMART goal! Example: Introduce myself to the day-shift RNs and explain my intention to collaborate by the end of next week.

By the way, if you work with facilities with multiple shifts, make sure to visit each shift if possible. Evening and night shift personnel frequently feel neglected and forgotten, so meeting them personally shows that you acknowledge and value their work. And if you really want to win the nurse team over, maybe even show up with pie!

Further Opportunities for Collaboration

The previous section focuses on partnering with the RN organically within ADPIE, but you’re not limited to this sphere. Keep your antenna up for situations pointing to more complex issues that warrant combining forces.

Community pharmacists can detect misuse by monitoring prescription activity. Teamwork is in order if the nature of the facility where a given patient receives care involves repeated or long-term visits. In other words, if the RN will see the patient again—such as at a family physician’s office—he will establish a database of assessment data over time on this patient.

Subsequent communication with the RN is a two-way street. The pharmacist can advise the RN to be cognizant of potential misuse, or she can ask the RN about assessment findings. For instance, the pharmacist could learn through the RN that a family member might be stealing the patient’s prescriptions.

Pharmacy technicians can capture medication history when patients transfer facilities. A geriatric patient transferring between long-term care and critical care, for example, is likely to have an abundant list of prescriptions at both facilities. This implicates a high likelihood of polypharmacy, interactions, and toxic levels of components such as aspirin and acetaminophen. Plus, polypharmacy is a nursing diagnosis, which means by definition that the nurse can intervene.⁵¹ It’s a multidisciplinary problem—time to collaborate!

Does your patient need assistance communicating due to factors such as age, sensory deficit, or cognitive impairment? Work with the nurse to ensure the right pain scale is being used and that the patient has a means of communicating adverse effects.

CONCLUSION

Every member of the healthcare team has a distinct role. Nurses are no exception—they continuously assess patients by physical and verbal means and establish and continually revise care plans accordingly. Knowing each team member’s function is crucial to maximally effective collaboration. In the face of the opioid crisis, healthcare providers should capture every opportunity for better patient care, particularly in pain management. This includes incorporating nonpharmacologic pain control strategies and intelligently selecting pharmacologic methods. Regardless of the modalities chosen, abundant opportunity for coordination between the nurse and pharmacy teams exists. This is especially true when the pharmacist and pharmacy technician understand the principles behind the nursing practice and care planning, summarized by the acronym ADPIE. Marrying the concepts of pharmacologic and nonpharmacologic pain control therapies with nursing care plans enables the pharmacy team to collaborate effectively for patients’ pain relief.

 

 

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INTRODUCTION

Dotty is an 84-year-old widow suffering from osteoarthritis of the knees. Most days, she manages her pain with acetaminophen and has remained active in her community. Some days however, her painful knees make her unsteady on her feet and she has come close to falling, especially during the long walk from the parking lot through the senior center to get to BINGO.

Managing chronic pain—pain lasting three months or more—in older community dwellers is a challenge due to the link between pain and increased risk of falls. Over-the-counter (OTC) and prescribed pain medication further compound fall risk through adverse effects. More than 100 million adults in the United States (U.S.) suffer from chronic pain.¹ Common types of chronic pain include neuropathic, musculoskeletal, inflammatory, and mechanical pain. Between 30% and 40% of community-dwelling people older than 65 and 50% older than 80 fall each year.²

Despite the use of fall prevention programs, the rate of falls resulting in injury has not declined. Researchers conducted a pragmatic, cluster-randomized trial (N = 5451) at 86 primary care practices across 10 U.S. health care systems. The trial evaluated the effectiveness of a multifactorial intervention including fall risk assessment and individual fall reduction plans compared to a control group receiving usual care. The results of the study found intervention did not significantly lower fall rates.³

Many factors contribute to falls, but compelling evidence suggests that chronic musculoskeletal pain increases fall risk and people living with chronic pain show poorer executive function (mental skills that include working memory, flexible thinking, and self-control). Signs of poor executive function such as impaired impulse control, reduced ability to pay attention or focus, and problems starting, organizing or planning tasks can all contribute to fall risk. Treatment options for chronic pain include physical and behavioral medicine, neuromodulation, and surgical intervention. Despite a variety of treatment options, providers most frequently use pharmacologic approaches.

Integrated, patient-centric, multi-disciplinary management of chronic pain offers a practical solution to reducing pain, over-medication, and risk of falls. Practitioners from several disciplines can help:

• Pharmacists understand how medications work individually and in combination and provide medication management that is more informed than other professionals’ medication management.
• Pharmacists and pharmacy technicians interact routinely with the community and can provide risk screening, patient education, and referrals to other HCPs.
• Primary care physicians provide medication management including medication review and reconciliation and oversight for changes from multiple providers. Providers correctly prescribe but may not evaluate medications regularly for appropriateness.
• Physical therapists can reduce pain and improve functional mobility through exercise, modalities (i.e., ultrasound, electric stimulation, iontophoresis), manual techniques, and prescription and training on assistive and adaptive devices.
• Physical or occupational therapists may provide in-home safety evaluation and recommend modifications and equipment to reduce the risk of falls.
• Collaborative relationships between community rehabilitation therapists and local pharmacies can support patient decisions and pathways for obtaining needed devices and aids to reduce pain and fall risk.

THE CLINICAL PROBLEM

Scope of Chronic Pain and Fall Risk

Falls are the leading cause of death and injury in people 65 years of age and older. Pain often contributes to fall-risk. According to a recent Helsinki Aging Study, 61% of community-dwelling people 74 years and older reported they suffer from musculoskeletal pain that interferes with activities of daily living.⁴

Because pain contributes to falls that result in further painful injuries, a cyclical pattern occurs. More than 50% of older Americans report pain at multiple sites.⁵ The most prevalent painful conditions affecting older adults include arthritis, chronic disease complications (i.e., diabetes, cancer) and post-stroke pain).⁶

In Dotty’s case, her painfully arthritic knees prompted her to purchase a three-wheeled folding walker with a seat from an infomercial she saw on daytime television. Unfortunately, it folded while in use, collapsing to the ground along with Dotty. She ended up with a severely bruised and painful hip as a result of the fall.

While environmental accidents and age-related changes can contribute to falls, chronic pain with medication use is a significant fall risk factor. In addition to polypharmacy, studies have shown both opioid use and exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) contribute to fall risk. A retrospective, observational, multicenter cohort study of registry data in Canada (N = 67,929) concluded that recent opioid use is associated with an increased risk of falls in older adults and an increased likelihood of death from fall-related injuries.⁷ A systematic review also found an increased risk of falls is probable when elderly individuals are exposed to NSAIDs.⁸

A pharmacologic approach to pain may be necessary when pain is significant, unremitting, and affects physical function or quality of life. However, health care professionals should not overlook the importance of nonpharmacologic pain management. Non-pharmacologic pain management and the reduction of falls is an important health topic for consideration by pharmacists and pharmacy technicians.⁹

Economic and Socioeconomic Burden of Pain Related Falls

Serious injuries from falls can lead to permanent injury, functional and cognitive decline, reduced quality of life and the need for institutional care resulting in significant cost.¹⁰ The American College of Rheumatology, a leading authority and partner of rheumatology professionals, considers pain chronic when it lasts more than three months, the normal time for tissue healing. Chronic pain is a major cause of disability and linked to mental health deterioration including depression and anxiety.¹¹

Professionals use many evidence-based fall prevention programs, such as those listed on the National Council on Aging website (Evidence-Based Falls Prevention for Older Adults (ncoa.org) to reduce falls in the community. These interventions vary in length such as 2-hour workshops, in-home interviews, or 8 week to 5-month programs that focus on aging in place, exercise, balance, removal of home hazards, adaptive equipment, task modification, education, and self-management.

Even with fall prevention programs, the number of falls among older community dwellers is increasing. The reason for the rising number of elderly falls is multifaceted^12,13:

• The population of older adults is growing with more people living longer and remaining in their homes.
• Access to and participation in fall prevention programs varies among community elderly.
• In an aging population, musculoskeletal disability and resulting pain increases.
• As musculoskeletal disability increases, the number of invasive joint surgeries such as hip and knee replacements rises. The projected volume of primary total knee replacements alone will increase by more than 400% over the next 20 years.
• 7% to 23% of patients after hip and 10% to 34% after knee replacement have long-term post-operative pain.

When surgeries such as joint replacement result in chronic pain, providers primarily use medication to address pain due to limited treatment options. The combination of aging, more joint replacement surgeries, and concomitant medication use requires more attention to pharmaceutical services in the role of fall prevention. Furthermore, age-related changes in pharmacokinetics and pharmacodynamics may increase the risk and incidence of adverse drug events related to falls.⁶

IMPACT OF PAIN MEDICATION ON FALLS

Risk of Opioid Use in the Elderly

After her fall, an ambulance whisked Dotty to the hospital. Luckily, she did not sustain any fractures and the emergency department physician sent her home with a prescription for opioids, advised follow up with her primary care doctor, and gave her a flyer for a local fall prevention program.

The use of opioids for pain management is a significant public health concern particularly among older community dwellers at risk for falls. Prescribed opioid use among middle-aged and older adults is more prevalent than among younger adults.¹⁴ Moreover, one-fourth (25.4%) of adults aged 65 years and older who take opioids report being long-time opioid users for a period of 90 days or longer (see Figure 1).¹⁵

An average of 8.6 million non-institutionalized older adults filled at least one opioid prescription between 2018 and 2019, while 2.7 million older people filled five or more opioid prescriptions or refills. Older women were more likely than men to fill one or more opioid prescriptions.¹⁶ In addition to age, socioeconomic factors and patient demographics impact opioid use. According to the statistical brief published by the Agency for Healthcare Research and Quality (AHRQ), elderly adults who were poor filled five or more opioid prescriptions compared to low- and middle-income adults (see Figure 2).¹⁶

A large retrospective, observational, multicenter cohort study of registry data of 67,929 Canadian patients with a mean age of 80.9 (±8.0) evaluated the link between recent opioid use and fall-related injuries. The study identified patients who had filled an opioid prescription in the two weeks preceding an injury were 2.4 times more likely to have a fall than any other type of injury. Patients who had a fall-related injury who used opioids were also at increased risk of in-hospital death.⁷

A systematic review and meta-analysis of 30 studies evaluated the impact of opioid use on falls, fall injuries, and factures among adults at least 65 years old. The study found that opioid use was associated with falls, fall injuries, and fractures.¹⁷

Sedation is a common adverse effect of opioids. Medication with sedative effects can lead to daytime drowsiness, reduced alertness, and impaired motor function. Older adults experience these adverse effects more frequently, particularly during the first few days of taking a new pain medication.¹⁸ Anticholinergic burden is one of the opioids’, such as oxycodone, lesser-known effects. Anticholinergic drugs impact central nervous system functions and can result in cognitive impairment, confusion, and blurred vision compounding the risks of sedation.¹⁹

Because opioids cause drowsiness, orthostatic hypotension (dizziness or lightheadedness when standing up or otherwise changing position), and hyponatremia (low sodium levels leading to nausea, vomiting, loss of energy and confusion), they can increase fall risk. Risk is more prominent in older adults already prone to falls. Active drug half-life and metabolites are prolonged in older adults with renal impairment because most drugs, particularly water-soluble drugs, are eliminated by the kidneys.²⁰ Understanding renal function is therefore important when assessing dosing risks in the older population. Reviewing for combination opioid use is also important in all patients, and particularly older patients. For example, physicians and pharmacists must take caution with patients using codeine and oxycodone together.²¹

Risk of OTC Pain Medication

Physicians often prescribe acetaminophen as a first-line or preferred OTC pain medication for older adults with nociceptive pain, which is pain caused by physical trauma, burns or surgery, because of potential adverse effects of NSAID (diclofenac, etodolac, fenoprofen, ibuprofen, ketorolac, meloxicam , naproxen) use. Long-term NSAID use is associated with adverse gastrointestinal, renal, and cardiovascular effects. An observed decrease in prescription NSAID and acetaminophen use may be due in part to the increased availability and variety of OTC NSAIDs over time, a phenomenon reported for other medications after becoming available OTC.²²

NSAIDs are among the 5% to 10% most commonly prescribed medications for pain and inflammation. The prevalence of NSAID use in the over-65 population is as high as 96%.²³ Physicians and other healthcare providers often prescribe NSAIDs for acute or chronic arthritic pain because of their anti-inflammatory results over just the analgesic effect of acetaminophen.²²

Problems may arise related to NSAID-related toxicity in the elderly. Similar to opioids, age-related changes in pharmacokinetics may affect how the elderly metabolize NSAIDs. Dose reduction is appropriate for naproxen, ketoprofen, and salicylates in healthy older patients. Additionally, prescribers may need to reduce the dosage of diflunisal, indomethacin, sulindac, and mefenamic acid for the elderly in the presence of renal disease.²⁴

Table 1 lists the adverse effects of long-term use of NSAIDs that can impact fall risk.

Table 1. NSAIDs Adverse Effects²³

System	Adverse Effects
Kidney	Increased risk of nephrotoxicity Promotes renal vasoconstriction and reduced renal perfusion Electrolyte imbalance such as hyperkalemia Reduced glomerular filtration rate Nephrotic syndrome Chronic kidney disease Acute interstitial nephritis Sodium retention Edema Renal papillary necrosis
Gastrointestinal	Increased risk of GI bleeding
Cardiovascular	Edema Myocardial infarction Thrombotic events Stroke Hypertension

 

Study data has been inconsistent but overall trends support an association of falls with NSAIDs use in the elderly. A systematic review of 13 studies published between 1966 and 2008 specifically reviewed fall risk associated with NSAIDs in the elderly population. The overall mean age of study participants was high, preventing generalizability to a larger population. However, all studies showed an increased risk of falling associated with NSAIDs.⁸ A similar systematic review identified 22 studies that enrolled patients older than 60 years to assess the association between medication use and falling. These analysts reviewed nine different drug classes (antidepressants, antihypertensives, benzodiazepines, beta-blockers, diuretics, narcotics, neuroleptics and antipsychotics, NSAIDs, and sedatives and hypnotics) encompassing 79,081 participants. The use of sedatives and hypnotics, neuroleptics and antipsychotics, antidepressants, benzodiazepines and NSAIDS resulted in an increased likelihood of falling. The unadjusted odds ratio estimate for likelihood of falls related to NSAIDs was 1.21 (95% CI, 1.01-1.44) compared to 0.96 (95%CI, 0.78-1.18) for narcotics.²⁵

The Case for Non-Pharmacologic Pain Management

The evidence supporting the need for nonpharmacologic pain management treatment is compelling. The population is aging, the prevalence and incidence of musculoskeletal disability is on the rise, and use of pain medication is associated with known risks. While all adverse effects of taking pain medication are important, falls can be among the most debilitating and costly for the elderly.

 

Pharmacists and pharmacy technicians are front line community healthcare providers in pivotal positions to positively impact fall reduction. By moving beyond medication management, pharmacists and pharmacy technicians can proactively participate in a multi-disciplinary approach to reduce reliance on pain medication and facilitate non-pharmacologic treatment including physical therapy.

DEVELOPING AN INTEGRATED PATIENT-CENTRIC TEAM-BASED APPROACH TO FALL PREVENTION

Pharmacists’ Role in Medication Management

Pharmacists play a key role in fall prevention by recognizing “fall risk-increasing drugs” (FRIDs), identifying at-risk patients, and collaborating with other healthcare professionals including physicians, home care nurses, and physical therapists by making appropriate referrals.

 

A traditional first step for pharmacists and pharmacy technicians is medication management. Knowing FRIDs is important (see Table 2).

Table 2. FRIDs at-a-glance

Classes of Fall Risk-Increasing Drug
Antidepressants	Antihypertensives	Opioids	NSAIDs
Anticonvulsants	Antipsychotics	Sedative hypnotics	Antispasmodics
Anticholinergics	Benzodiazepines	Antihistamines	Antispastics

 

Polypharmacy, exposure to FRIDs, or the combination of polypharmacy including FRIDs can be associated with fall risk. Pharmacists should also consider exposure to potentially inappropriate medications (PIMs) as described in prescribing guidance tools such as the American Geriatric Society (AGS) Beers Criteria.²⁶

The Beers Criteria considers five broad categories of potentially inappropriate medications used in the elderly²⁷:

1. Medications considered potentially inappropriate
2. Medications potentially inappropriate in patients with certain diseases or syndromes
3. Medications to be used with caution
4. Potentially inappropriate drug-drug interactions
5. Medications whose dosages should be adjusted based on renal function.

Additionally, the National Council on Aging (NCOA) advocates for a thorough medication review for older adults at risk of falling, noting that OTC medications can cause harmful interactions and increase falls.

The five important problem areas identified by pharmacists in conjunction with the program’s algorithms include²⁸

1. Unnecessary therapeutic duplication
2. Use of medications that can cause falls and confusion
3. Use of medications that can cause cardiovascular problems
4. Inappropriate use of non-steroidal anti-inflammatory drugs
5. Review for effectiveness of opioid prescriptions and alternate options

An example of unnecessary therapeutic duplication occurs when patients take a muscle relaxer such as meloxicam with an OTC for inflammation like naproxen. Many patients are also unaware of medications that can cause falls and confusion such as OTC antihistamines. Patient education directly from pharmacists or pharmacy technicians can be beneficial in preventing falls related to these types of OTC drugs.

After her fall, Dotty filled her opioid prescription and continued taking acetaminophen due to the pain in her knees and hip from the fall. Since her providers or pharmacist had not “prescribed” acetaminophen, they were unaware of the unnecessary analgesic duplication.

While medication management and identification of FRIDs is important to reducing risk of falls, it is not a substitute for a comprehensive multi-disciplinary approach. A recently published systematic review of the use of fall risk-increasing drugs looked at 14 observational or intervention studies that assessed FRID use in participants 60 years or older. Participants had experienced a fall resulting in a hospitalization or emergency department (ED) visit. The studies reported the prevalence of FRID use was 65% to 93% at the time of hospitalization or ED admission among older adults with a fall-related injury. Further, studies within the review found FRID use did not decrease at one and six months following a fall. Intervention trials included in the review demonstrated that interventions to reduce FRIDs did not result in a significant reduction in falls. The authors conclude that medication review with suggestions to the primary care provider as a stand-alone intervention was ineffective in preventing falls. Interventions to reduce FRID use are only one part of a more comprehensive strategy.²⁹

Dosing and Deprescribing to Reduce Falls

When making decisions to deprescribe opioids, prescribers and pharmacists should consider whether the opioid use matches an appropriate indication. Since opioids are strong analgesics, their indications should be for moderate to severe acute pain, post-operative pain, or palliative care. Prescribers and pharmacists should always consider deprescribing when there are no indications for prescribing an opioid and safer alternatives are available.⁶

Opioid dosing should always be specific to the individual with lower doses for older adults. Reducing the dose or switching to a less potent analgesic to maintain effective pain management is a viable strategy while implementing other nonpharmacologic techniques such as physical therapy.⁶

Pharmacists are skilled in identifying medications for discontinuation based on known risks. A careful plan for tapering and discontinuing drugs at an appropriate pace is critical to avoid increasing patients’ pain, stress, and discouragement. Various tools are available to pharmacists to collaborate with patients to create a deprescribing plan.³⁰ Examples of resources to assist healthcare providers optimize medications while minimizing adverse events include the Medication Appropriateness Index Calculator ( https://globalrph.com/medcalcs/medication-appropriateness-index-calculator/) and the AGS Beers Criteria available from the American Geriatrics Society (https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/jgs.18372). No one tool is the gold standard and inconsistencies exist among the various resources.³¹

For example, the STOPPFall tool provides deprescribing in a stepwise manner.¹⁸ STOPPFall recommends reducing the opioid dose by 5% to 25% of the daily dose every one to four weeks. If adverse effects occur during deprescribing, prescribers can reduce the dose more slowly. If the patient dose is high or he or she has been using the opioid for a longer period, deprescribing should proceed very slowly.

Conversely another tool, MedStopper, indicates when a patient has been taking an opioid daily for more than four weeks, prescribers should reduce the dose by 25% every three to four days. Upon any symptoms of withdrawal, they should increase the dose back to 75% of the previous tolerated dose. Once at 25% of the original dose with no withdrawal symptoms, they can discontinue the drug.³² Prescribers and pharmacists should monitor patients during and after deprescribing for symptoms of withdrawal such as musculoskeletal or gastrointestinal symptoms, restlessness, anxiety, insomnia, diaphoresis (excessive sweating), anger, and chills.

Pharmacy Fall Risk Prevention Service

To be an integral part of a more comprehensive fall prevention intervention, pharmacies should consider offering a fall prevention service. Establishing a community fall prevention service consists of fall risk screening, consultation to assess modifiable fall risk factors with referral to appropriate non-pharmacological intervention, medication check, and comprehensive medication review and adjustment by the pharmacy and primary prescriber.

Use of an appropriate screening tool by pharmacists or pharmacy technicians is a major step to reducing risk of falls. To assist healthcare professionals in reducing fall risk, the Centers for Disease Control and Prevention (CDC) developed the STEADI (Stopping Elderly Accidents, Deaths, and Injuries) initiative. This initiative includes three steps for providers to address their patient’s fall risk.^31,33

• Screening for fall risk by asking patients if they have experienced past falls, feel unsteady, or are afraid of falling
• Reviewing and managing their medications to determine if they impact fall risk and stopping, switching, or reducing them
• Studies shows recommending vitamin D supplements to improve bone, muscle, and nerve can reduce risk of falls in the elderly

The CDC and the University of North Carolina Eshelman School of Pharmacy and School of Medicine developed an algorithm called STEADI-R_X to improve collaboration between healthcare providers and pharmacists based on the CDC’s STEADI initiative. STEADI-R_X incorporates the Joint Commission of Pharmacy Practitioners (JCPP) Pharmacists’ Patient Care Process and an algorithm for integrating fall screening and prevention into pharmaceutical care. It also includes a tool kit for use by healthcare providers to help reduce risk of falls.³⁴ Figure 3 shows the STEADI-Rx’s key steps.

                                                                     

The STEADI-RX Community Fall Risk Checklist³⁵ (https://www.cdc.gov/steadi/pdf/provider/steadi-rx/STEADIRx_pharmacy_fallrisk_checklist-508.pdf) is available to help the pharmacy staff quickly identify risk factors including fall history, postural hypotension episodes, and review medication classes associated with fall risk.

Getting Started with A Fall Risk Service

The STEADI-Rx Older Adult Fall Prevention Guide for Community Pharmacists, available from the CDC at https://www.cdc.gov/steadi/steadi-rx.html,³⁶ provides a framework for how to start a fall prevention service, identifies best practices, and provides tools and references for implementing a successful program.

To start an in-pharmacy fall reduction program, a key recommendation is to first identify a program champion. This is either a pharmacist or trained pharmacy technician who will serve as the lead role and ensure proper design and implementation of the program. Next, an environmental scan may help identify the patient population that will benefit from the service and how it fits into existing workflow. A fundamental aspect of conducting an environmental scan may include an analysis of strengths, weaknesses, opportunities, and threats (SWOT) to identify any internal or external obstacles to implementation, described in Sample Fall Prevention SWOT Analysis.

 

SIDEBAR: SAMPLE FALL PREVENTION SERVICE SWOT ANALYSIS

STRENGTHS - Internal factors include available resources and staff

WEAKNESSES - Internal obstacles may be poor workflow or documentation procedures

OPPORTUNITIES - External factors to support a successful service include an age-appropriate population, supportive providers, and state physical therapy direct access provisions to facilitate referrals

THREATS - External factors that may hinder a successful service such as nearby pharmacies with strong prevention services, reimbursement or other financial factors inhibiting patient participation

 

The guide also recommends conducting a readiness assessment to determine the steps needed to implement the service and to develop an action plan. The readiness assessment addresses staffing, resources, and training needed and assure there is appropriate support from leadership before moving forward. Depending upon existing pharmacy workflow, a pharmacy technician can lead a fall prevention service with pharmacist support when they need clinical judgement and expertise.

 

Coordinating Care: Physical Therapy and Physician Support

Dotty eventually came into the pharmacy looking for a “better” assistive device. She seemed confused about what device to choose and reported she recently had a fall. With her permission, a fall risk screening revealed she was taking both NSAIDs and opioids and had not been referred to physical therapy. She stated the ED gave her a flyer for a fall prevention program, but she didn’t go because it conflicted with BINGO at the senior center.

 

Pharmacists and prescribers should consider practice guideline recommendations to determine when to make referrals to physical therapy for the nonpharmacologic treatment of pain. It is important to consider reducing reliance on opioids and inappropriate use of NSAIDs.

 

Data from the National Ambulatory Medical Care Survey identified 11,994 visits representing a cross-section of all age patients between 2007-2015 where ICD-9 (diagnosis) codes indicated new chronic musculoskeletal pain. The survey found that healthcare providers prescribed patients opioids 21.5% of the time when they presented with new symptoms of chronic musculoskeletal pain but prescribed physical therapy just 10% of the time.³⁷

Numerous studies have examined the relationship between early physical therapy and opioid use for chronic musculoskeletal pain including back neck, shoulder, and knee. Due to its incidence, prevalence and associated costs, a preponderance of studies focused on low back pain (LBP). A retrospective analysis using commercial health insurance claims data from 2009-2013 observed 148,866 patients aged 18 to 64 years with a new primary diagnosis of LBP over a 1-year period. Compared to patients who received late or no physical therapy, patients who saw a PT first had an 89.4% lower probability of obtaining an opioid prescription.³⁸

Another cross-sectional observational study using the National Ambulatory and National Hospital Ambulatory Medical Care Surveys between 1997 and 2010 also identified lower PT referral rates among LBP patients aged 16 to 90 years old insured by Medicare and Medicaid. The study estimated 170 million visits for LBP led to 17.1 million PT visits. Further, visits not associated with PT referrals were more likely to be associated with opioid prescriptions.³⁹

Healthcare providers do not always prescribe nor do patients use physical therapy as a frontline treatment for chronic pain. Patients may use physical therapy along with other nonpharmacologic treatments, such as behavior health interventions or medication. Physical therapy is an integral part of multidisciplinary care, particularly to support success with opioid taper or cessation. Physical therapy treatments to reduce pain include exercise, manual therapy, electrical nerve stimulation, and other physical agents.

When conducting a pharmacy fall risk service, pharmacy staff may encounter patients with chronic pain who have not received physical therapy prior to treatment with pain medication. The screening process will be the first step in assessing true risk.

Pharmacy staff can use the STEADI-RX Provider Consult Form(s) for Medication or Fall Screening to share medication therapy problems with the patient’s provider or to refer the patient to a physical therapist for a full fall risk assessment.^40,41 A physical therapist’s formal fall risk assessment is more in-depth than the screening tool used at the pharmacy and includes an evaluation of gait, balance, and strength. When using these forms or any other type of communication, states have different physical therapy direct access provisions and limitations. Pharmacies can verify the levels of patient access to physical therapist services in the U.S. through the American Physical Therapy Association (https://www.apta.org/contentassets/4daf765978464a948505c2f115c90f55/direct-access-by-state-map.pdf). After referral, physical therapists should respond within seven days. If they don’t, the patients or pharmacy should contact the PT again.

Pharmacists and pharmacy technicians identifying at-risk patients during an initial fall risk screening performed at the pharmacy should refer patients to physical therapy for a full fall risk assessment. Physical therapists use a variety of objective assessment tools to address gait and balance such as the Tinetti Balance and Gait Assessment, Berg Balance Scale, or Timed Up and Go test to determine fall risk and areas for intervention. Therefore, when implementing a pharmacy fall reduction service, it is important for pharmacists to develop relationships with local outpatient physical therapy clinics able to accept referrals for fall risk evaluations.

Because musculoskeletal pain is highly prevalent and a leading cause of disability, physical therapists are crucial members of the interdisciplinary pain management team. Physical therapists work effectively by providing nonpharmacologic treatment of pain incorporating various pain-relieving modalities such as transcutaneous electrical stimulation, heat or cold therapy, joint or soft tissue mobilizations or the use of braces or splints. In addition to physical therapy treatment to address pain, physical therapists also recommend various assistive and adaptive devices. Patients may use these devices to reduce pain through off-loading a painful limb or making mobility including ambulation and transfers (i.e., moving from one position to another such as from sitting to standing, or getting in or out of bed) easier and safer.

Improperly selected or poorly fitted devices can result in further injury, pain or falls. Receiving instructions and training on proper use of assistive devices and compliance with instructions has not been strongly correlated. A small (N=17) observational cross-sectional study and focus group investigated older adults’ use of walkers in the home setting compared to current guidance in an attempt to identify circumstances leading to deviation from instructions for use. This study observed incorrect use of walkers 16% to 29% of the time associated with reduced stability.⁴² Another study found comparable results from a questionnaire of 94 patients using a cane for hip pathology.;47% of these patients were using the aid in the incorrect hand and of this group, 64% used their dominant hand. Furthermore, 66% of respondents reported they never received instruction on the correct hand to use. The study concluded that a significant percentage of patients are using canes incorrectly which may be due to lack of education.⁴³

A patient-appropriate assistive device, when fitted and used correctly, can reduce pain and increase physical activity in patients with chronic pain, painful or impaired gait and other mobility issues. Selection and fitting of an assistive device should always be conducted through a PT evaluation. PTs use a multi-factorial assessment of the patient’s physical and cognitive abilities of and consider the environment in which the patient will use the device (see 5 Factors of Device Prescription). PTs will also ensure devices match a patient’s height, weight, and size when selecting the best assistive device.

 

SIDEBAR: 5 FACTORS OF DEVICE PRESCRIPTION

1. Cognitive Function
2. Coordination
3. Upper-body, hand and grip strength
4. Physical endurance
5. Walking environment

 

Upon competition of their evaluation, it is important for the therapists to know what types of OTC assistive and adaptive devices are available for purchase at local pharmacies to support patient needs. Although assistive devices are often available at physical therapy clinics, a patient’s health insurance plan may not include reimbursement for devices. Often OTC devices and aids are priced lower at retail locations and purchased directly by patients or family members.

Rather than have Dotty guess and purchase a “better” assistive device, the pharmacy referred her to a physical therapist who determined that at least initially, a 4-point walker with front wheels would provide her the most stability and allow her to walk safely in both her home and the community.

Table 3 describes items often recommended by therapists to reduce pain, fall risk, and improve home safety. See Fun Facts to learn about the history of walkers.

Table 3. Assistive & Adaptive Devices

Item	Description	Purpose
Bed Rails	Railing inserted between mattress and box spring or physically attached to bedframe	Assist with transfer out of bed by allowing people to pull their body to change position using arms/upper body
Cane, Walker	Ambulation assist devices. Canes can be single point, multi point (quad) and walkers with or without wheels	Provides additional point of contact to improve balance, alleviate weakness, or offload a painful joint
Commode, Raised Toilet Seat, Toilet Seat Rails	Portable toilet, elevated seat or arm rails	Assist with safe transfer on and off toilet
Grab Bars	Bars and railings permanently affixed to walls near showers, toilets, entry ways, steps, stairs	Promotes safe transfers from sit to stand, up and down stairs, in and out of shower
Grabbers or Reachers	Reaching aid with grab assist	Allows items to be safely grabbed if out of reach or if mobility, pain, or strength impairs reaching and grabbing
Neoprene braces and wraps	Supportive and compressive wraps and braces for ankles, knees, wrists	Provide joint protection, stability, and pain relief
Shoe wedges or inserts	Partial or full inserts used inside of shoes	Cushion or improve postural alignment to offload painful foot
Shower Chairs	Waterproof, quick dry, slip resistant stool or chair	Allows safe seating in shower to reduce slipping or falling and fatigue with standing

 

 

SIDEBAR: FUN FACTS^43,44,45,46

A walker, walking frame, or rollator is a mobility device used by people suffering from leg or back pain, weakness, impaired balance, amputation, or poor stamina.

• Walkers first appeared in the 1950s.
• The first US Patent was awarded in 1953 to William Cribbes Robb of the United Kingdom for device called a “walking aid” filed with the British patent office in 1949.
• Two US patents in 1957 are for variants with wheels.
• The first non-wheeled designed walker was patented in 1965 by Elmer F. Ries of Ohio. In 1970, Alfred Smith of California patented the first walker resembling modern day walkers.

 

Establishing Effective Team Communications

Communication between pharmacists, prescribers, and therapists is important to monitor progress and avoid symptoms of medication withdrawal. As patients progress with their therapy plan of care, medication dosing may be easier to adjust. Ongoing patient education from pharmacists and pharmacy technicians can help avoid unnecessary patient self-medication with OTC pain relievers during the transition period.

 

The physician or primary care provider receives regular updates from the physical therapy team and can provide the pharmacy with necessary progress to help coordinate dose reduction or deprescribing. When designing the workflow for a pharmacy fall prevention service, the program champion should be sure to include a schedule for giving and receiving team updates.

 

With ongoing treatment, the physical therapist reported Dotty was making progress toward her therapy plan of care goals. Upon completion of therapy Dotty would be stronger, have less pain, and reduce or eliminate pain medication, and graduate to using a single point cane as needed. Since Dotty’s Medicare insurance plan only covered the cost of the 4-point wheeled walker, she would have to purchase the cane out-of-pocket and would be returning to the pharmacy with the PT’s recommendation so that the PT could fit and train Dotty on its proper use during her therapy sessions.

Closing the Treatment Gap

The benefits of a pharmacy fall reduction service are multi-fold. Moving beyond medication management closes the current treatment gap in the delivery of consistent and effective fall prevention. By working collaboratively with other HCPs, pharmacists help achieve better fall prevention outcomes by reducing or eliminating pain medications while facilitating non-pharmacologic pain management and improved functional mobility improvement.

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INTRODUCTION

The opioid epidemic has gripped the United States (U.S.) for more than two decades.¹ Opioid overdose is the number one cause of death for adults aged 25 to 64 years old, which significantly contributes to the decline in the average lifespan.¹ The rise of synthetic opioids (primarily fentanyl) augments the uptick in overdoses, referred to as the “3^rd wave” of the opioid epidemic.^1,2 In fact, 8 in 10 fatal opioid overdoses in the U.S. now involve synthetics.¹ Non-fatal overdose is also significant; for every opioid-induced fatality, up to 8.4 non-fatal overdoses occur.¹

 

Prescription opioids are also a noteworthy contributor to the rise in opioid overdose deaths.² Healthcare providers started prescribing opioids for chronic, non-cancer pain (e.g., arthritis, back pain) in the 1990s.³ In the decades since, patients started receiving increasingly higher doses of prescription opioids for long-term chronic pain management.^2,3 In 2015, the amount of opioids prescribed per person was three times higher than it was in 1999.³ Even when patients take opioids as prescribed, they are still at risk of accidental overdose and drug-drug (e.g., benzodiazepines) or drug-alcohol interactions.² Their household contacts are also at risk.

 

Naloxone—an opioid antagonist—is the only approved treatment to reverse opioid overdose.⁴ The drug competes for the same receptor sites opioids use, effectively and rapidly reversing their effects (i.e., respiratory depression, sedation, and hypotension).⁴ Naloxone is available in intranasal, subcutaneous, and intramuscular formulations for outpatient use and intravenous formulations for inpatient use.^5,6 Naloxone is a safe antidote for suspected overdose, and its use has caused the number of opioid overdose deaths to decrease in communities where it is readily available.²

 

The U.S. Food and Drug Administration (FDA) has undertaken a series of measures to increase accessibility to this lifesaving medication.⁷ Until recently, naloxone was only available via prescription. In March 2023, the FDA approved the first naloxone product for over-the-counter (OTC), nonprescription use.^6,7 This aims to improve access to naloxone, increase the number of locations where it is available (e.g., drug stores, convenience stores, grocery stores, the Internet), and help reduce opioid overdose deaths across the country.

 

INCREASED ACCESSIBILITY

The FDA first approved naloxone in 1971 as a prescription drug.⁶ It wasn’t until 2014 that the agency approved the first naloxone auto-injector for use outside of a healthcare setting, followed by a nasal spray formulation in 2015.⁸ Its status as a prescription-only medication made initial access difficult and inconsistent across the country and various high-risk groups.

 

In the mid-1990s, community-based programs implemented efforts to increase distribution to high-risk individuals.⁶ Consequently, naloxone dispensing from retail pharmacies increased substantially from 2010 to 2015, with a 1170% increase between 2013 and 2015.⁶ Naloxone dispensing remains inadequate, however, with only one naloxone prescription dispensed for every 70 high-dose opioid prescriptions.

 

Pharmacist Naloxone Prescribing

It’s common knowledge that pharmacists are highly accessible, trusted healthcare professionals, so their role in naloxone distribution is not surprising. Their accessibility, medication expertise, access to patients’ medical records, and regular patient interaction are valuable tools for increasing naloxone availability.⁶

 

Many states across the U.S. have enacted naloxone access laws (NALs) to expand pharmacists’ scope of practice through standing orders or collaborative practice agreements, allowing them to distribute naloxone without a patient-specific prescription.⁶ Studies show that NALs significantly increased naloxone prescribing, but not enough.⁶ Despite NALs, many pharmacists remain uncomfortable dispensing the drug without a patient-specific order given limited training, lack of understanding state laws, and lack of reimbursement for patient education. Some evidence also exists that pharmacists are afraid of potential legal ramifications.⁶

 

Shifting to the Other Side of the Counter

The FDA has a specific process for shifting from prescription to OTC approval.⁹ Prescription products can undergo a full switch or partial switch. A full switch converts the drug product covered under a New Drug Application (NDA) to nonprescription marketing status entirely. A partial switch only converts some of the conditions of use (e.g., indications) to nonprescription status and retains others within prescription status. A full switch requires a sponsor to submit an efficacy supplement to an approved NDA or a 505(b)(2) application, but a partial switch requires an entirely new NDA.⁹ Ultimately, approval of a prescription-to-OTC switch application depends on the FDA deciding that prescription status is “not necessary for the protection of the public health by reason of the drug’s toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, and…the drug is safe and effective for use in self-medication as directed in proposed labeling.”⁹

 

The FDA has been working to authorize an OTC version of naloxone since 2019 by prioritizing applications and assisting manufacturers pursuing OTC naloxone approval.⁸ The agency announced in January 2019 that preliminary assessment showed that consumers understood a model drug facts label well for OTC naloxone nasal spray and manufacturers found the label acceptable, a slow but steady step in the right direction.⁸ In late 2022, the FDA issued a Federal Register notice indicating that certain naloxone products—up to 4 mg nasal spray and up to 2 mg intramuscular or subcutaneous autoinjector—may be approvable for nonprescription use.¹⁰ This did not immediately approve naloxone products for safe and effective OTC use, but it did provide the framework for manufacturers to pursue approval.

 

The FDA granted priority review status to the application to approve branded naloxone nasal spray (Narcan) for OTC use.¹¹ It was then the subject of an advisory committee meeting in February 2023 where the committee voted unanimously to approve naloxone for nonprescription marketing.¹¹

 

What’s Next?

It’s important to note that the prescription to OTC switch does not automatically apply to all forms of naloxone. Only branded Narcan 4 mg nasal spray is now granted OTC status, not its generic counterparts.⁷ Manufacturers of generic products with Narcan listed as their reference listed drug product will need to submit a supplemental application to switch their products to OTC status. Other brand name naloxone nasal spray products of 4 mg or less must also update labeling and apply individually for a switch to OTC status.⁷

 

Pharmacy teams should also be aware that the drug will not be available on drug store shelves immediately.¹² The manufacturer will need to implement manufacturing and supply chain changes to support nonprescription packaging requirements. According to the drug’s manufacturer, pharmacies can expect the OTC formulation to be available in late summer 2023. Until then, the prescription product will be readily available through current access channels.¹²

 

Cost is also important to consider. The drug’s manufacturer has yet to reveal pricing plans for the OTC version, but it plans to work with public interest groups who are now charging about $47.50 per box.¹³ Health economists predict that the price of OTC Narcan could land somewhere between $35 and $65, plus a retailer’s markup.¹³ Unfortunately, this price could be prohibitive for many individuals, especially those who misuse opioids. Some also fear that this could encourage individuals to shoplift the drug, forcing locations to move the product behind the pharmacy counter or behind glass and creating a barrier to those who can afford it but are uncomfortable asking for it.¹³

 

As for accessing the drug outside of a pharmacy setting (e.g., convenience stores, gas stations), additional barriers may exist. Some states require a special license for non-pharmacy businesses to sell OTC medications, which can effectively create “naloxone deserts” where the drug is not available for purchase. In the state of Connecticut, for example, 28 towns currently do not have stores with permits to sell OTC medications, causing residents to travel to obtain the lifesaving antidote.¹⁴ Pharmacy teams should check their state’s law regarding OTC sales to direct interested individuals on where to obtain the drug.

 

NEW OPPORTUNITIES FOR THE PHARMACY TEAM

Naloxone shift to OTC availability may seem to take the load off pharmacy teams when it comes to collaborative practice agreements and NALs, but the pharmacy team should remain heavily involved in naloxone distribution. OTC medications are often not covered by insurance, so pharmacists should stay vigilant about active NALs and collaborative practice agreements to prescribe the drug for people with cost concerns.

 

Assessing Overdose Risk

Prescription or not, a crucial role for pharmacy staff is identifying patients for whom naloxone is appropriate. Anyone exposed to opioids, regardless of the source, is at risk of overdose and should be considered for naloxone.¹⁵ This applies to people taking opioids for pain with or without other medications and those who misuse opioids. As the drug is bystander-administered, caregivers of individuals at risk of overdose may also request naloxone and should be educated about its use.¹⁵

 

Paying attention to opioid dosing is important when considering patients for naloxone. A dose of 50 morphine milligram equivalents (MME) per day doubles the risk of fatal opioid overdose compared to 20 MME or less.³ Patients taking 90 MME or more daily are 10-times more likely to die from an overdose.³ Other overdose risk factors include¹⁵

• concurrent benzodiazepine and/or alcohol use
• history of substance use disorder, including opioid addiction
• comorbid mental illness (e.g., depression, anxiety)
• filling prescriptions at multiple pharmacies and/or from multiple prescribers
• receiving a methadone prescription
• recent emergent medical care for opioid poisoning, intoxication, or overdose
• recent period of abstinence (e.g., release from incarceration, discharge from an opioid detox or abstinence-based program)
• renal or hepatic dysfunction
• comorbid respiratory conditions (e.g., smoking, chronic obstructive pulmonary disease, emphysema, asthma, sleep apnea)

 

Counseling on Naloxone Nasal Spray Use

The FDA deemed naloxone nasal spray safe enough for OTC use, but that doesn’t preclude the need to counsel individuals on its safe and appropriate use. Pharmacists should counsel all patients buying OTC naloxone nasal spray about signs of an opioid overdose, how to administer naloxone, and other important clinical pearls. Signs of an opioid overdose include¹⁵

• pale and/or clammy skin
• limp body
• pinpoint pupils
• blue or purple lips, nose, and/or fingernails
• vomiting or making gurgling noises
• unconscious or unarousable
• breathing very slow or not at all

 

Pharmacists should advise individuals to administer naloxone in the event of suspected overdose even if they are not 100% sure the victim is in fact suffering from an overdose.¹⁶ Administering naloxone to someone who is not actually suffering from opioid overdose is better than withholding care from an overdose victim based on uncertainty. See Sidebar: Saving a Life is Scary for additional information to ease concerns regarding naloxone administration.

 

SIDEBAR: Saving a Life Is Scary^15,17

Often, individuals are trained and ready to perform lifesaving first-aid procedures like CPR or the Heimlich maneuver, but they are afraid of the implications if things take a turn for the worse. Naloxone administration is subject to these same liability concerns. Individuals may also be concerned about legal repercussions when calling for help at the scene of an overdose. Ensure that individuals know about supporting laws and regulations that protect them to increase comfort and confidence with administering the drug:

• Good Samaritan*: Protects people who call for emergency medical assistance at the scene of an overdose from being arrested for drug possession.
• Liability protection/third party administration: Protects naloxone prescribers and bystanders who administer the drug and allows bystanders to obtain naloxone for use on opioid overdose victims.

 

*Some states have Good Samaritan laws that differ from general ones. For example, Ohio places limits on the number of times someone can be granted Good Samaritan immunity and requires that overdose victims seek referral for addiction treatment within 30 days. Pharmacy teams should stay current with state-specific Good Samaritan laws regarding naloxone.

 

Naloxone nasal spray is available in a two-pack of single-use, prefilled devices that cannot be reused.^4,5 The device should not be primed. Pharmacists should advise people buying OTC naloxone nasal spray about the following administration steps^4,16:

• Check for a suspected overdose (i.e., yell “wake up,” shake the person gently)
• If the individual does not wake up, lay them on their back
• Hold the nasal spray device with a thumb on the bottom of the plunger
• Insert the nozzle into one nostril and press firmly to administer the dose
• Call 911 immediately
• Stay until medical assistance arrives, even if the person wakes up
• Give another dose if the person does not wake up after 2 to 3 minutes or they become very sleepy again initial arousal
• Continue giving doses every 2 to 3 minutes until the person wakes up or medical assistance arrives (it is safe to keep giving doses)

 

Naloxone is a relatively safe drug, but it still comes with risks and clinical pearls that cannot be ignored. Abrupt opioid reversal in physically dependent individuals can cause acute withdrawal.^4,7 Signs and symptoms include body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, and tachycardia.⁴ Patients may also become aggressive upon sudden reversal of opioids. Naloxone is only effective in reversing opioid overdoses, not in treating other types of overdoses, so it is crucial that individuals seek emergency medical attention following naloxone administration.

 

CONCLUSION

Naloxone is a vital tool for preventing fatal opioid overdose. Pharmacists should be prepared to identify people at risk of overdose and assess their need for this lifesaving drug, make all individuals aware of its OTC availability, and counsel on its safe and appropriate use.

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Introduction

 

Consider this: It’s 10:30 PM on a Friday night, 30 minutes before you leave for the weekend. Suddenly, from across the emergency department you hear, “Get OFF me! No, I have not t-t-taken anything! If you come ANY CLOSER, things are going to get physical!” Not a moment later, an order pops up for ketamine hydrochloride 500 mg intramuscularly (IM) for severe agitation. Concerned, a colleague asks you, “Is this safe? Is this effective? I have never seen a dose this high before. Isn’t this just for horses?”

 

Ketamine made its debut in human clinical practice in the 1960s when several chemists at Parke Davis Company were searching for an anesthetic with similar effects to phencyclidine (PCP). PCP, ketamine’s notorious kissing cousin, was a promising new anesthetic in the 1950s because of its dissociative effects. However, the chemists quickly became unimpressed with its adverse effect profile (i.e., long-lasting psychoactive effects after anesthesia). Humans experienced intense prolonged emergence delirium following PCP anesthesia, relegating its use to veterinary practice.¹ Chemists searched for a better anesthetic and found ketamine, which has similar dissociative effects without PCP’s negative consequences. Ketamine is a more desirable anesthetic because it has a shorter half-life (2.5 hours) compared to PCP (21 hours) and it causes less delirium.^1,2

 

Prescribers have begun using ketamine for several off-label uses and patients have also started using the drug or structural analogs in a variety of formulations illicitly. Pharmacists and technicians can ensure ketamine’s safe use by keeping current with new formulations and indications, both approved and unapproved. This continuing education activity will dive into the clinical and social consequences of ketamine use.

 

What’s Ketamine?

Ketamine is a schedule III-controlled substance approved by the U.S. Food and Drug Administration (FDA) for use as a general anesthetic for diagnostic and surgical procedures.² Ketamine is commercially available in the United States as a solution/injection under its brand (Ketalar) and as generic ketamine.² Healthcare providers most often use intravenous (IV) ketamine, but it may be used IM or compounded into an oral solution. 

 

Healthcare providers also use ketamine off-label for analgesia, agitation, and major depressive disorder. These indications emanate from ketamine’s mechanism of action: it acts specifically on the N-methyl-D-Aspartate (NMDA) receptor as a non-competitive antagonist to block glutamate binding.³ Glutamate, a major excitatory neurotransmitter, binds to receptors throughout the nervous system. The NMDA receptor is an ionotropic receptor responsible for the brain’s neuroplasticity, memory, learning, and recovery.^4-6 Blocking this receptor with high ketamine doses (ranging from 0.5 to 2 mg/kg) results in dissociation, decreases in spinal reflexes, and produces a cataleptic state (loss of voluntary movements and reduced consciousness) that is applicable to its current clinical use in anesthesia.² However, at low doses, ketamine can produce analgesia and stimulate new pathways within the brain that reduce depressive symptoms and improve mood.

 

Although ketamine has useful applications in medicine, prescribers must be aware of the adverse effects and risk factors associated with use and should consider how these effects apply to their patients before initiating the medication. Ketamine adversely impacts multiple organ systems (see Table 1), including but not limited to the cardiovascular system. Increases in blood pressure and heart rate are important cardiovascular effects associated with ketamine therapy.² These cardiovascular effects make it a drug of choice for anesthesia induction in patients with cardiovascular shock, where it anesthetizes patients while improving blood pressure and improving organ perfusion. However, clinicians must avoid ketamine use in patients with preexisting hypertensive conditions or other patients who have limited baroreceptor buffering capacity (baroreceptor buffering is the body’s ability to sense blood pressure) because of those same effects mentioned above.⁶

 

Table 1. General Adverse Effects of Ketamine^2,6

System	Adverse effects
Cardiovascular	Cardiac arrhythmias, increased blood pressure,* increased heart rate
Central nervous system	Prolonged emergence from anesthesia,* psychosis,* dissociation,* drug dependence, increased intracranial pressure
Dermatologic	Injection site irritation
Gastrointestinal	Nausea,* vomiting, anorexia
Genitourinary	Lower urinary tract dysfunction, bladder dysfunction
Respiratory	Laryngospasm,* respiratory depression,* apnea
Immunologic	Anaphylaxis
Other	Hypersalivation, diplopia (double vision), nystagmus (uncontrollable rapid eye movement)

*Common or serious adverse effects of ketamine use

 

Further contraindications include hypersensitivity to ketamine or its components.⁷ The American College of Emergency Physicians (ACEP) does not recommend ketamine use in patients with schizophrenia or in children younger than three months of age. The ACEP also advises against solely using ketamine as an anesthetic in procedures involving the pharynx, larynx, and bronchial tree. This recommendation primarily applies to patients with airway instability because ketamine can cause laryngospasms.⁵ Table 2 lists additional considerations in special populations.

Table 2. Special Population Considerations with Ketamine^2,6-8

Special population	Concerns	Recommendation
Pregnancy	Crosses the placenta; may have potential risk to fetus	Avoid use; evaluate benefits vs risk
Breastfeeding	Compatibility and safety unknown	Avoid breastfeeding to children with respiratory risk factors
Pediatrics	Can be given with anticholinergics to minimize hypersalivation	Refer to pediatric dosing. Avoid in infants < 3 months of age
Elderly	May be sensitive to dissociative adverse effects	Refer to adult dosing
Kidney dysfunction	No additional concerns	Refer to dosing parameters
Liver dysfunction	Hepatobiliary dysfunction with recurrent use	Refer to dosing parameters; monitor LFTs with repeated ketamine use
LFTs = liver function tests

 

Healthcare providers should monitor patients' vital signs closely during treatment with ketamine. Anesthesiologists and pharmacists must continuously watch patients undergoing surgical or diagnostic procedures for proper induction and maintenance of dissociative effects.² In patients who must take repeated doses of ketamine (e.g., for chronic pain management or psychiatric disorders), healthcare providers should order liver function tests at baseline and every one to two days during treatment.^2,6,9,10

 

Ketamine’s Kissing Cousins

As shown in Figure 1, ketamine is structurally related to many compounds. The drugs in Figure 1 antagonize the NMDA receptor and exhibit a dissociative effect.¹ PCP is one of the most notoriously abused drugs. Compared with ketamine, PCP is 10 times more potent and has a longer duration of action due to its strong affinity for the NMDA receptor. Both ketamine and PCP can replicate schizophrenia’s positive, negative, and cognitive symptoms and exacerbate underlying schizophrenia. But because ketamine has lower potency and a shorter duration of action, it induces fewer severe psychiatric effects than PCP.¹

Figure 1. Molecular structure of ketamine and structurally related dissociative drugs¹¹

           

Although ketamine’s labeling includes many precautions, it is an emerging option because of its therapeutic benefits. Xi Biopharmaceuticals is developing a sublingual wafer to treat acute pain while Janssen Pharmaceuticals has developed a nasal spray formulation for treatment resistant depression.^12,13 Table 3 compares the current ketamine formulations that are FDA-approved or under investigation.

 

Table 3. Ketamine Counterparts^12-14

Cousins	Formulation	Use & Dose	Approval or Trial Phase
Ketalar (ketamine hydrochloride)	Injectable	Anesthesia 0.25 – 0.35 mg/kg followed by CIVI 1 mg/kg/hr	FDA-approved
Wafermine (ketamine)	Sublingual Wafer	Acute Pain 25 mg, 50 mg & 75 mg PRN for 12 hrs	End-of-Phase 2 Clinical Trials
Spravato (esketamine)	Nasal Spray	Treatment Resistant Depressive Disorder 28 mg, 56 mg, 84 mg twice a week	FDA-approved
ABBREVIATION: CIVI = continuous intravenous infusion

 

ABUSE, ADDICTION, DEPENDENCE

 

Why is Ketamine Dangerous?

Long-term ketamine abuse is associated with memory, attention, and judgment impairment. The actual risk of ketamine abuse in the general population is low compared to other substances of abuse, but patients with polysubstance abuse disorder tend to use it.¹⁵ A study examining polysubstance abuse conducted in New York City found that polydrug use occurred because of an unexpected opportunity to use ketamine after already consuming other drugs. Researchers also determined that polysubstance abusers purposefully used ketamine with another substance to achieve an individually desired effect. Oftentimes polydrug-using events occurred within a group and each member contributed something: ketamine, knowledge, other drugs, or space to use drugs.¹⁶

 

Currently, ketamine is only commercially available as an injectable liquid. Dealers illegally sell ketamine as a recreational injectable substance or a white powder that resembles cocaine. The Department of Justice and Drug Enforcement Administration report that illegally distributed ketamine is diverted or stolen from veterinary clinics or smuggled into the United States from Mexico.¹⁷ Dealers can then synthesize ketamine into a powder or sell it as an injectable liquid.¹⁸ Prices average from $20-$25 per dose (50 mg to 100 mg).¹⁹ Drug abusers find ketamine’s dissociative sensations and hallucinations appealing. Users can inject liquid ketamine, or snort or smoke powdered ketamine.¹⁷ Ketamine is a popular drug to facilitate physical or sexual assault because it is a colorless, tasteless, and odorless liquid making it difficult for victims to detect. Additionally, ketamine is known to cause impaired coordination, confusion, and memory loss.²⁰

 

Ketamine’s IV administration started in the early 1990s. Injection events occur most frequently in large cities with high rates of homelessness, like New York City and Los Angeles.¹⁸ Researchers conducted a study with 213 people who abused IV ketamine.¹⁸ Among these users, 84% admitted to abusing ‘harder’ drugs first, with heroin predominating. Users reported their first ketamine injection happening among a group of people. This group often included people well known to them who provided knowledge and the materials for injecting.¹⁸

 

What attracts people to a dissociative drug with unknown psychoactive effects? Exactly that: the unknown. With most abused drugs, the user understands the effects they will experience. When someone takes ketamine, the reaction to each dose is unknown. Some users seek variety. Ketamine users have described an out of body experience that expands internal and external realms and realities.¹⁸ On the other hand, abusers also describe a “K-Hole”—an experience that they describe as near-death that results when they ingest too much ketamine.¹⁷

 

Timothy Wyllie, a spiritualist, describes ketamine doses as a curve over time through realms. He describes the domains abusers experience as they dose ketamine²¹:

• The realm “I,” for internal reality, occurs at doses 30 to 75 mg roughly 10 minutes after injection.
• The extraterrestrial reality realm, “They,” occurs at doses 75 to 150 mg approximately 15 minutes after injection.
• The realm “We,” for network creation realm, occurs at doses from 150 to 300 mg mg approximately 15 minutes after injection.
• An unknown realm exists at doses of more than 300 mg.

The doses studied for depression fall in the realm of internal reality. At these doses, users can see areas needing self-improvement that they were unaware they had the ability to fix. Drug users prefer subanesthetic doses but those that are higher than doses studied for treating depression. As the dose increases, users become so far removed from reality that “extraterrestrial” experiences begin.²¹

 

 

KETAMINE USES

 

Anesthesia

Patients unable to maintain and protect their airways require endotracheal intubation. Healthcare providers use ketamine as a sedative to facilitate rapid sequence induction and intubation (RSII), by inducing an anesthetized state, prior to paralyzing the patient. The decision to intubate is based on the patient’s Glasgow Coma Score.^22,23 A score of 8 or less qualifies a patient to receive endotracheal intubation.²³ Healthcare providers follow a RSII strict algorithm, shown in Table 4, detailing the order in which medications should be administered based upon the onset and duration of action.

Table 4. Algorithm of Rapid Sequence Induction & Intubation^22,23

Step of RSII	What and Why	Medications Used
Premedication*	Airway manipulation causes a sympathetic activation due to a pressor response. This sympathetic response leads to an increase in intracranial pressure and mean arterial pressure.	alfentanil, fentanyl, lidocaine, sufentanil
Sedation	Used to induce an anesthetic state before a paralytic is used and the airway manipulated. Crucial that a patient is properly sedated before paralyzed.	Also known as induction agents: etomidate, ketamine, midazolam, propofol
Paralytics±	Neuromuscular blocking agents are given to relax pharyngeal and diaphragmatic muscles allowing for an endotracheal tube to be placed.	rocuronium, succinylcholine, vecuronium

*: Based upon time constraints/needs this step may be omitted

±: It is imperative to confirm a patient is properly sedated before beginning paralysis because if the patient is awake, they may feel the tube insertion

 

The drugs used in RSII possess unique characteristics, including IV use, quick onset, and short duration of action.²³ Traditionally, etomidate has been the gold standard for RSII, but ketamine is quickly becoming a commonly used alternative.²³ Table 5 highlights the differences between etomidate and ketamine.

 

Table 5. Comparison of Etomidate and Ketamine^22,23

	Etomidate	Ketamine
Dose for Induction	0.3 mg/kg	1.5 mg/kg or 0.1-0.5 mg/kg/min with 10% given as induction bolus
Onset of Action	10-15 seconds	< 30 seconds
Duration of Action	4-10 minutes	10-15 minutes
Benefits	Stable hemodynamic profile, decreases metabolic rate, decreases cerebral blood flow, increases generalized seizure threshold	Sedative and analgesic properties,* cardiovascular and respiratory stimulation, and smooth muscle relaxation (beneficial in reactive airway disease, hypotensive, volume depleted, and septic patients)
Risks	Adrenal suppression, do not use in septic shock, lowers focal seizure threshold, increased incidence of ARDS	Potentiates effect of epinephrine, increases cardiac oxygen demand, may increase ICP,** emergent reactions, infusion related respiratory depression, hypersalivation
ABBREVIATIONS: ARDS = acute respiratory distress syndrome, ICP = intracranial pressure   * Ketamine can be used as a combined premedication and induction step ** Data is conflicting, however, may not be suitable for patients with head trauma

 

The differences between etomidate and ketamine create a significant role in RSII for both drugs, but for different presenting conditions. Ketamine is gaining popularity for its use in septic patients, hypotensive patients, and those with reactive airway diseases. Choosing etomidate is preferable for patients with a hemodynamically stable profile and patients with traumatic brain injury where it could be cerebroprotective.

 

Analgesia (pain)

 

Ketamine’s use in pain management is controversial due to limited data, but this dataset is growing.^15,24 Before considering subanesthetic ketamine doses, prescribers should collaborate with patients and other clinical team members to try other approved pain regimens.²⁵ Using ketamine for its analgesic properties should be based on patient-specific criteria. The prescriber must assess the patient’s treatment goals, current medical conditions, pain types, and available protocols.

 

Ketamine is not discussed in available pain guidelines. Some literature recommends its use after unsuccessful trials of at least two opioids. Data supporting ketamine’s use in both acute and chronic pain management is mixed in its findings.^26,27 Most trials conclude ketamine can reduce acute pain exacerbations but note that prescribers must be cautious of its adverse effects.¹⁵ Data from small trials indicate using ketamine to overcome opioid withdrawal and opioid-induced-hyperalgesia (neuropathic pain) may be possible. Ketamine has a unique ability to counteract the unfavorable responses patients might experience on chronic high-dose opioids by its mechanism of action.^24,28 Overstimulated opioid receptors from high dose opioid use causes more hyperalgesia. Several small case reports describe patients on high-dose chronic opioid therapy who reduced their opioid doses after low-dose ketamine administration.²⁹

 

An open labeled audit determined that IV ‘burst’ ketamine therapy improved analgesia in neuropathic pain and painful bone metastases. Researchers enrolled 39 cancer patients who were refractory to opioid therapy. Patients received bursts of low-dose ketamine (100 to 500 mg/day) over three to five days and reported somatic and neuropathic pain relief for up to eight weeks.¹⁵

 

Limited evidence supports oral ketamine’s effect in chronic pain and most studies that examine its use are case reports or non-comparative trials. Compared to IV administration, lower oral ketamine concentrations are associated with analgesic effects. Oral ketamine has been associated with higher serum levels of its metabolite, norketamine. This metabolite seems to contribute to oral ketamine’s analgesic effects due to its shorter half-life and ability to reach much higher peak plasma concentrations than after IV administration. However, researchers have not extensively explored this in current literature.²⁹

 

Healthcare providers and patients face many hurdles when using ketamine for pain relief. Prescribers should avoid high ketamine doses that may cause a range of serious adverse effects. Unlike opioids, ketamine has a ceiling effect and maximum dose. Oral ketamine administration has a low bioavailability and is directly linked with a high rate of adverse effects.^15,27

 

Agitation

Due to ketamine’s dissociative properties, clinicians are increasingly using ketamine for treating pre-hospital and in-hospital agitation. Lacking a uniform definition for agitation, healthcare providers, institutions, and organizations may use different criteria to choose medication intervention in an agitated patient. Although the picture of agitation may change depending on the situation, validated scales like the Altered Mental Status Scale (AMSS) can define agitation’s severity.³⁰ The AMSS translates agitation into a quantifiable, real concept. The line between agitation and delirium is often unclear but has major ramifications for a patient’s treatment and outcome.³⁰ For example, excited delirium, an agitation subtype, classifies a patient’s agitation past the emotional component and includes psychomotor, metabolic, and contributing disease states as possible reasons for agitation.³⁰

 

As with most psychiatric disorders, identifying and treating agitation has been suboptimal. Since the 1980s, a popular cocktail of medications, known among emergency department physicians as the “B-52” order, has been the mainstay of agitation treatment in psychiatric facilities and emergency departments.³¹ When examining the B-52 order’s components, it is easy to see the correlation between the regimen and the American jet-powered strategic bomber from which it derives its name: Benadryl 50 mg IM, haloperidol 5 mg IM, lorazepam 2 mg IM.³¹ The B-52 order serves as a reminder of the suboptimal approach traditionally taken when confronted with an agitated patient.

 

Ketamine’s different routes of administration have benefits and disadvantages. Although less invasive, oral ketamine takes a longer time to reach the therapeutic range, something that is undesirable in an overly aggressive patient. Intravenous administration has the quickest onset but is the most invasive. Securing IV access may not always be possible. The IM route is the most often used method for agitation control for its quick “on/off” onset and duration of action, and its applicable dosage form.

 

A review explains ketamine’s uses and benefits in comparison to other, more traditional agitation treatments.³⁰ In terms of agitation efficacy, ketamine provides the same, if not better, response when compared to its more traditional counterparts.³⁰ Ketamine has a significantly faster onset of action when compared to haloperidol (5 minutes versus 17 minutes) and requires less redosing (5% of patients re-dosed versus 20% of patients re-dosed, respectively).³⁰ However, ketamine continues to show a higher incidence of adverse effects when compared to its anti-psychotic counterpart (percent incidence calculated from six studies where adverse events were recorded as a secondary outcome):³⁰

• emergence reaction 12.3% (8/65 patients)
  • An “emergence reaction” is an often hostile, psychiatric episode brought about by ketamine use
• hypersalivation 31.8% (22/69 patients)
• nausea and vomiting 8.5% (7/82 patients)
• respiratory complications 7.6% (9/118 patients)

 

Although studies report a higher incidence of adverse reactions when using ketamine for agitation, it is important to consider study limitations: small patient populations, co-administration of drugs, and lack of adverse event reporting (only half of 12 studies included adverse reactions).³⁰ If used properly, ketamine can be a safe, quick-acting drug to stop agitation when compared to traditional treatments.

 

Some law enforcement agencies use ketamine. However, when they use ketamine improperly, or when adverse effects arise, ketamine can have dangerous consequences. Over a four-day period during late August of 2020 in Colorado, police gave 23-year-old Elijah McClain and 25-year-old Elijah McKnight excessive ketamine doses for agitation.³² McClain died from cardiac arrest and McKnight survived but required life support in the hospital.³² It is inappropriate to allow untrained police officers to inject ketamine as a law enforcement tool. However, police defend using ketamine saying suspects with mental health issues or suspects taking drugs can be belligerent and dangerous. A Minnesota whistleblower lawsuit filed by a former emergency medical services worker claims police pressured them to allow ketamine use uneccessarily.³² In Minneapolis, ketamine used by police rose from four incidents per year in 2015 to 62 in 2017.³² This marked increase in ketamine use is upsetting many healthcare professionals. Dr. Mary Dale Peterson, president of the American Society of Anesthesiologists, says that ketamine can have “dangerous complications,” just like any other anesthetic. Dr. Peterson points out that justifiably using ketamine occurs very rarely.³²

 

Whistleblowers cite complications from unwarranted ketamine use are associated with emergence reactions, and improper dosages.³² McClain died when he was given a ketamine dose for a 200-pound man but only weighed 143 pounds.³² Pharmacists can play a role in educating other healthcare professionals about proper dosing and management of ketamine’s serious adverse effects.

 

Major Depressive Disorders

Generally, major depressive disorder’s (MDD) treatment focuses on pathophysiology and regulates serotonin, norepinephrine, and dopamine.³² Medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibits (SNRIs), tricyclics, tetracyclics, and serotonin modulators all target an increase in synaptic neurotransmitter levels.³² Unfortunately, these drugs are not consistently effective for all patients, require an 8-week trial period, and have unfavorable adverse effects. For many providers and their patients, MDD treatment can feel like an awful waiting game—one that they sometimes lose.

 

Ketamine is becoming increasingly popular for its use in treating refractory depression. However, it requires healthcare providers to understand how it works to avoid putting patients into a “K-hole.” It offers a different approach to the current FDA-approved drugs for MDD. Ketamine prevents glutamate reuptake; excess glutamate produces an antidepressant effect. Ketamine, at subanesthetic doses, produces euphoria, and improves symptoms within 24 hours after infusion.^4,14,32,33 Depressive symptoms improve rapidly, but the effects last only a few days to weeks. As a result, ketamine is most useful as an adjunctive treatment option. Patients feel better for a brief period, giving their antidepressants a chance to start working.

 

In addition, prescribers have few options for patients with MDD who have suicidal behaviors and ideation. Ketamine seems promising for patients at an elevated risk for self-harm. The Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression trial examined ketamine’s potential benefits for 80 suicidal patients with MDD. The results of this randomized controlled study showed that ketamine was superior to midazolam in improving the Scale for Suicidal Ideation (SCI). Patients’ SCI scores improved 4.96 points within 24 hours after a ketamine infusion of 0.5 mg/kg over 40 minutes.³² This suggests clinical use of ketamine as an adjuvant agent for acute episodes of suicide ideation in patients maintained on guideline recommended therapy for MDD may be appropriate. However, patient safety remains a concern (e.g., dissociative effects, abuse potential, respiratory, and cardiovascular effects).

 

As mentioned earlier, esketamine (Spravato) is ketamine’s S-enantiomer and FDA-approved for treatment-resistant depression.³³ In the TRANSFORM-1 randomized controlled trial, the antidepressant/esketamine groups did not have a statistically significant change in Montgomery-Asberg Depression Rating Scale (MADRS) total score (from baseline to study day 28) when compared to the antidepressant placebo group.^34,35 However, the changes based on the MADRS were clinically meaningful and showed that esketamine has a beneficial role in treatment-resistant depression when used as an adjuvant agent.^36,37 The combination of esketamine with an antidepressant produced desirable outcomes while minimizing adverse effects. Although adverse effects were low, several adverse effects are possible: vertigo, nausea, vomiting, anxiety, sedation, abuse potential, increased blood pressure, dissociation, and suicidal thoughts/behaviors.³³

 

CONCLUSION

To paraphrase the father of toxicology, Paracelsus, it’s all about the dose. Ketamine is the poster child drug for this statement. Ketamine has the potential to be an important adjuvant therapy for the treatment of a range of conditions. Those listed in this CE—anesthesia, analgesia, and major depressive disorder—are currently the most studied disorders where ketamine and its derivatives may be useful. Due to ketamine’s dissociative and analgesic effects through NMDA antagonism, there may be additional future potential uses for ketamine in pain control and psychiatric disorders. Simply, ketamine treats not only the physical manifestations of these conditions but the emotional component that providers can easily overlook. However, the current data sets are small, many use rating scales instead of final health outcomes, and a larger and longer term series of trials are required to fully determine the place of ketamine in the treatment armamentarium for patients.

 

Pharmacists and other healthcare providers will need to distinguish between therapeutic use and addiction. Often, these lines are muddled. Providing education is a first step to preventing abuse. Usually, addiction is a manifestation of an untreated, or undertreated, medical condition. Pharmacist intervention helps patients and healthcare providers to make the safest, most informed decisions possible to ensure the best possible outcomes.

 

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Introduction

Substance Use Disorders (SUDs), continue to be a major concern in the United States. In 2017, nearly 20 million people reported an SUD because of alcohol or illicit drug use.¹ Costs associated with substance abuse are approximately $249 billion dollars for alcohol and $193 billion dollars for illicit drugs.^2-4

 

Alcohol use is second to nicotine for substance use among all substances misused.¹ In 2017, 140 million persons aged 12 and older reported alcohol use. A total of 16.7 million reported heavy alcohol use of five or more days over a 30-day timespan. Heavy alcohol use is defined as drinking four or more drinks on one occasion for females and five or more drinks in males. Heavy alcohol use can result in several health-related concerns, to include cirrhosis, depression, cancer, neuropathy, and pancreatitis to name a few.⁵

 

Typically, clinicians often treat people who have SUDs after they have developed the condition.^6,7 Other approaches include inpatient or outpatient treatment programs for those with SUDs and prevention programs to educate and inform the public of the dangers associated with substance use.

An alternative approach to these methods is to identify persons with at-risk behaviors for substance misuse and provide interventions to reduce long-term use and harm. This approach is called SBIRT. SBIRT stands for Screening, Brief Intervention, and Referral to Treatment.⁷ This evidence-based approach addresses harmful behaviors BEFORE they escalate to a full-blown SUD.

Who can perform SBIRT? 

Many healthcare professionals can perform SBIRT, including doctors, nurses, pharmacists, pharmacy technicians, and behavioral health specialists. SBIRT is also adaptable to a team-based approach. Pharmacists and pharmacy technicians are in a particularly good position to perform SBIRT, as they are accessible, especially in community pharmacy settings.⁸ SBIRT can also be applied in several clinical settings, such as hospitals and ambulatory care clinics.

SBIRT’s first step involves the screening process. Using a universal screening approach is an important point of the screening process. A universal approach means screening everyone, regardless of who they are, or how they look or act. This makes sense because clinicians cannot determine if someone is using alcohol or other substances based on appearance and behavior. Pharmacists and pharmacy technicians can screen patients in any pharmacy setting to include community, hospital, and ambulatory care. In busy community settings, a targeted approach may be necessary. With targeted approaches, pharmacy teams might screen individuals who are on opioids, benzodiazepines, and other medications that have the potential for abuse. Ideally, however, the universal approach is better. If we focus only on certain populations, we may target individuals who don’t have an SUD and overlook someone who has an SUD but takes no prescription medications. The initial screening question is simple: a single yes/no question that determines if further screening is necessary.

PAUSE AND PONDER: When and where would you use SBIRT in your pharmacy practice?

 

How to Perform SBIRT in a Community Pharmacy Setting

Many pharmacy team members think that they cannot or should not perform SBIRT in their settings. With pharmacy teams expanding their responsibilities, it’s entirely possible to add SBIRT to the community pharmacy tool kit.

Community pharmacy teams need to note that they do not need to perform SBIRT in its entirety. In some cases, pharmacists and technicians may only perform the screening and then refer the patient to a provider for treatment. Pharmacists can perform a brief intervention if opioid misuse is a concern. For example, the pharmacist may access the prescription drug-monitoring program and recognize the patient is seeing multiple providers and using several pharmacies to fill opioid prescriptions. In this case, the pharmacist can perform a screening and brief intervention with the patient to discuss safe opioid use and possible referral to treatment.

Roberta is a 27-year-old female who presents to the pharmacy with a prescription for oxycodone. The pharmacy technician enters the prescription information and notices that Roberta picked up a 30-day supply two weeks ago. The technician informs the pharmacist about the early refill. The pharmacist refers to the prescription drug-monitoring program and notices that Roberta filled two other opioid prescriptions from different doctors at two different pharmacies. The pharmacist screens Roberta and provides a brief intervention.

Pharmacists can refer a patient to treatment or provide information on treatment centers based on the discussion. For example, while engaging with the patient the pharmacist may recognize that the patient is purchasing needles/syringes for illicit drug use. This is a perfect opportunity for the pharmacist to provide a referral to treatment.

 

When screening for alcohol and drugs, healthcare providers use pre-screening questions developed by the National Institute of Alcohol Abuse and Alcoholism for alcohol and the National Institute of Drug Abuse for drugs. Pre-screening questions determine whether additional screenings are necessary.

For alcohol the pre-screening question is, “Do you sometimes drink beer, wine, or other alcoholic beverages?” If the individual answers no, no further screening is necessary. If the individual answers in the affirmative or screens positive for alcohol, the screener would perform additional screening based on the Alcohol Use Disorders Identification Test (AUDIT) to evaluate alcohol use further.⁹

The same holds true for pre-screening for drug use. If an individual answers in the affirmative to the pre-screening question, “How many times in the past year have you used an illegal drug or a prescription medication for nonmedical reasons?” then the screener would use the Drug Abuse Screening Test (DAST-10) questionnaire to evaluate drug use further.¹⁰ (See Figure 1)

Figure 1. DAST-10 Questionnaire¹⁰

 

Let’s start with the AUDIT questionnaire. This 10-question screening tool addresses recent alcohol use, dependence symptoms, and harmful behaviors. (See Figure 2) Once the screening is complete, the scoring will determine next steps.

Figure 2. AUDIT Questionnaire⁹

 

Some key points to consider when using the AUDIT are the recommended drinking limits and size of the beverage. Did you know that the serving size of a glass of wine is five ounces, and that one bottle of wine typically contains five glasses? A serving of beer is 12 ounces, and a serving of spirits (hard liquor) is one and one-half ounces. The screener should explain serving sizes to the patient to ensure an accurate account of alcohol consumption and score of the AUDIT.

Recommended drinking limits for men are two drinks/day and no more than 14 drinks/week and for women one drink/day and no more than seven drinks/week. For those 65 or older, the recommended limits are similar to women: one drink/day and no more than seven drinks/week.¹¹ Consuming more than the recommended limits can result in binge drinking which is associated with greater harm and dependence. Binge drinking is five or more drinks for men or four or more drinks for women, and people who are 65 or older.¹²

The AUDIT score determines the severity and next steps that may include a brief intervention or referral to treatment. Individuals scoring between 0 and 7 are low risk and individuals scoring 20 or greater are considered dependent use and would benefit from a referral to treatment.

Pharmacy teams who are familiar with other screening methods may recall that a positive binge drinking finding would require an intervention using those methods. Using the AUDIT, binge drinking alone may not require an intervention. The intervention or referral to treatment would depend on the overall score of the AUDIT.

Scoring the AUDIT

Dependent Use (20+)

Harmful Use (16‒19)

At-Risk Use (8‒15)

Low Risk (0‒7)

 

The screening process for drugs is like that used for alcohol. The DAST-10 questionnaire assesses drug use in the past 12 months. (See Figure 1) Interpretation of the results determines the suggested action. Figure 3 describes screening results and suggested intervention. For example, a score of between 3 and 5 using the DAST-10 suggests harmful use and moderate degree of problems related to drug use.

Scoring the DAST-10

High Risk (6+)

Harmful Use (3‒5)

Hazardous Use (1‒2)

Abstainers (0)

 

Once the screener completes the screening, the score determines next steps for the patient. Next steps could include feedback, brief intervention, and or a referral to treatment. (See Figure 3.) For example, in persons with a low risk, feedback can include discussing the results of screening and risk of harm. A brief intervention is recommended in persons with risky or harmful behavior based on screening results.

 

Perform a screening for alcohol and drug use using a patient case

Joe is a 32-year-old man who hurt his back three years ago in a car accident. He has used opioids since the accident, but he still complains of pain. He supplements his medications by purchasing additional opioids online and on the street. Joe also has a history of alcohol use. He consumes three to four beers on most days. His family is concerned with his alcohol and drug use and recommends he seek help.

Below are his responses to the AUDIT and DAST-10 questionnaires. Based on his responses to the questions calculate his risk level for alcohol and drug use. See Tables 1 and 2.

Table 1. AUDIT Screening for Joe

Question	Answer	Score
How often do you have a drink containing alcohol?	Daily	4
How many drinks containing alcohol do you have on a typical day when you are drinking?	4	1
How often do you have six or more drinks on one occasion?	Once in  awhile	1
How often during the last year have you found that you were not able to stop drinking once you had started?	Never	0
How often during the last year have you failed to do what was normally expected of you because of drinking?	Monthly	2
How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session?	Never	0
How often during the last year have you had a feeling of guilt or remorse after drinking?	Never	0
How often during the last year have you been unable to remember what happened the night before because of your drinking?	Never	0
Have you or someone else been injured because of your drinking?	No	0
Has a relative, friend, doctor, or other health care worker been concerned about your drinking or suggested you cut down?	Yes	4
Total Score		12

 

Based on Joe’s responses to the AUDIT what is his score and risk level?

Based on his responses to the questions Joe scored 12 on the AUDIT, which puts him as at-risk-use.

 

 

Table 2. DAST-10 Screening for Joe

 

Question	Answer	Score
Have you used drugs other than those required for medical reasons?	Yes	1
Do you abuse more than one drug at a time?	No	0
Are you unable to stop using drugs when you want to?	Yes– The pain gets too great	1
Have you ever had blackouts or flashbacks as a result of drug use?	No	0
Do you ever feel bad or guilty about your drug use?	No	0
Does your spouse (or parents) ever complain about your involvement with drugs?	Yes	1
Have you neglected your family because of your use of drugs?	No	0
Have you engaged in illegal activities in order to obtain drugs?	Yes	1
Have you ever experienced withdrawal symptoms (felt sick) when you stopped taking drugs?	Yes	1
Have you had medical problems as a result of your drug use (e.g., memory loss, hepatitis, convulsions, bleeding)?	No	0
Total Score		5

 

Based on Joe’s responses to the DAST-10 what is his score and risk level?

Based on his responses to the questions Joe scored a five, which indicates harmful use. We will come back to Joe and determine next steps for him.

Summary of screening

• Screening is an important first step to determine the severity and risk level of substance use
• Use a universal screening approach
• Determine the level of risk and intervention based on screening results
• Pharmacists and pharmacy technicians can successfully perform screenings

Brief Intervention (BI)

Following the screening process and based on the results, a BI may be necessary. A brief intervention, also referred to as a brief negotiated interview (BNI), can be performed by a healthcare professional such as a pharmacist, doctor, nurse, or behavioral specialist. Addiction experts recommend using a BNI for those with “at risk” or harmful level of risk based on screening results. During the BNI, the healthcare professional uses motivational interviewing (MI) to have a conversation with the patient and evoke the patient’s personal motivation for change.¹³ Before we talk more about BNIs, let’s talk about the five stages of change.¹⁴ Change happens gradually, and individuals can move through the different stages depending on the situation and can move in and out of the different stages. In pre-contemplation, individuals may not be ready to make a change. Figure 4 depicts the five stages of change.

Figure 4. Stages of Change¹⁴

MI has several components, which can be overwhelming and confusing. Here is a brief outline of the components.

Components of MI

• Key qualities of MI
• Basic Principles of MI
• BNI Process
• OARS Framework

What is a brief intervention’s purpose and how do we use MI to evoke change? Motivational interviewing is an evidence-based approach to changing behaviors.^13,15

Key qualities of MI include¹³

• Facilitate communication between the healthcare professional and patient, where information and guidance is given
• Empower individuals to change based on what’s important to them
• Respect patient’s autonomy to facilitate change

Healthcare professionals can use MI to engage the patient as an equal partner. Although the name motivational interviewing suggests the healthcare professional is motivating the patient, that isn’t the case. MI is not a way to change individuals, make demands of patient, or instruct them what to do or not do. MI is a way to help examine situations and options for patients. MI is not easy to learn and takes practice. Pharmacists may find MI difficult to apply because counseling and instructing patients is part of everyday practice. MI is different and recognizes that patients are responsible for their actions and taking action to make changes.

MI can be very useful when people

• Have mixed feelings or are ambivalent about change
• Have low confidence about making changes
• May be uncertain about whether they want to make changes, creating low desire
• Are not clear about the benefits of change and concerns related to the current situation, so do not deem change important

MI is based on four basic principles^15,16:

• Express empathy
• Develop discrepancy
• Roll with resistance
• Support self-efficacy

Expressing empathy is an important first step of the MI process. You do this by seeking to understand how the person feels without judgement. (See Side Bar-tips to express empathy)

 

Side Bar: Tips to Express Empathy

• Maintain eye contact but avoid staring
• Use reflective listening to hear and understand and repeat back the information
• Avoid sympathy, “I’m sorry this happened to you”
• Ask clarifying questions
• Avoid passing judgement

 

Developing discrepancy

Using this principle, the provider discusses the discrepancy between the patient’s values and behavior. This involves discussing the good and the bad related to the behavior. Most patients are aware of the dangers related to substance misuse but are ambivalent about making a change. Discrepancy between the patient’s goals and current behavior motivates change.

Roll with resistance

During the BNI, patients may become defensive when talking about their substance use. This resistance is often because of a fear to change. To decrease resistance, the healthcare professional can redirect the discussion for the patient to understand the harm associated with the behavior. Last, the provider can explore the pros and cons of the patient’s behaviors. For example, a patient may enjoy the euphoria of heroin use (pro) but conversely contracts a cellulitis infection (con).

Support self-efficacy

This guiding principle focuses on supporting patient goals. Patients may feel that they cannot meet goals or expectations. It is important that the provider believe in the patient and promote confidence to support change.

Here is an example of a brief intervention.

Cynthia is at the pharmacy having a discussion with the pharmacist. She is concerned about her alcohol use. The pharmacy technician performs the AUDIT screening and provides the results to the pharmacist for discussion. AUDIT Score: 15 “At-risk use”

Cynthia: “I have been drinking more often over the last few months.”

Pharmacist: “Tell me more about that, Cynthia.” (Reflective listening)

Cynthia: “Work has been very stressful, and alcohol helps me relax. I used to drink only socially on the weekends with friends but now I drink almost every day. My teenage daughter sees me drink every night and she tells me I should stop because it’s not good for me. I don’t want to be a bad role model for her.”

Pharmacist: “So you are saying that you drink alcohol almost every day so that you can cope with the stress at work?” (Reflective listening)

Cynthia: “Yes. I am using alcohol to cope with stress at work.”

As you can see by the conversation above, the pharmacist reflects on Cynthia’s concerns regarding stress and work, which cause her to drink alcohol to cope. The pharmacist makes no judgement on whether the behavior is bad or that she should stop drinking. The pharmacist applies reflective listening and expresses empathy.

Developing discrepancy looks at current behaviors versus future goals. Let’s continue the conversation with Cynthia and apply this principle.

Pharmacist: “It sounds like you are having a hard time at work. But you also love your daughter and want to be a good role model for her. Is that right?” (Developing discrepancy)

Here the pharmacist emphasizes Cynthia’s concerns with her alcohol use and how that affects her daughter. This is the discrepancy. This allows Cynthia to recognize the pros and cons of her alcohol use so that she may change her behavior.

In roll with resistance, patients may pushback stating that they don’t have a problem, or their drinking or drug use is not a problem. In this case, it may require further discussion of current behavior and negative effects related to that behavior. The correlation of cause and effect can motivate the patient to change.

Last, support self-efficacy, where patients are responsible for deciding on actions they will make to support change. This is important because patients take the responsibility of making changes.

Regardless of the stage, MI encourages the patient to express the desire to change or what is referred to as “change talk.” In change talk, look at the following: desire, ability, reasons and need or acronym DARN. See the example below based on the conversation with Cynthia earlier.

Desire: “I need to drink less alcohol.”

Ability: “I could find healthier ways of coping with the stress at work, like yoga or meditation.”

Reasons: “I want my daughter to be proud of me.”

Need: “I might lose my daughter.”

 

This “change talk” can prepare the individual to make changes and act on those changes. As mentioned earlier, MI is a collaborative approach between the patient and healthcare professional providing the brief negotiated interview and involves four fundamental processes. Let’s talk about each of the processes.

1. Engage
2. Focus
3. Evoke
4. Plan

 

Engage

Having an honest and open conversation that engages the patient is the first step in the process. Listening without passing judgement or trying to fix the problem is important. The OARS framework includes interactive techniques to engage the patient. OARS stands for open questions, affirmations, reflections, and summaries. Table 3 describes each element of the framework and purpose.

Table 3. OARS framework¹⁵

Interview Skill	Description	Purpose
Open-ended questions	Ask the patient open-ended question vs. yes or no	Builds trust Gathers information
Affirmations	Show empathy for the patient Acknowledge the patient’s ability to make a change in their life Emphasize key points that are important to the patient.	Discuss/encourage patient’s abilities and healthy behaviors Build the patient’s confidence and self-efficacy
Reflections	Listen and understand what the patient is saying and repeating back to the patient	Repeat back what was said Incorporate unspoken feelings thoughts or behaviors
Summaries	Review key points of the conversation Use reflective listening	Help the patient see the big picture Create an action plan Emphasize key points of the conversation

 

 

Focus

During the conversation, focus on guiding patients to identify behaviors they struggle with or ambivalent to make a change. During the conversation, understand the patient’s dilemma or ambivalence. Asking what is important to them can help to identify the target and behavior that may inhibit them from reaching their goals.

Evoke

During the evoke process, we want patients to discuss their reasons for change and incorporate “change talk” during the conversation. Let’s go back to the conversation with Cynthia. Cynthia recognizes that she drinks alcohol to cope with the stress at work. She is also concerned that her drinking upsets her daughter and Cynthia wants to be a good role model. Her reason for change is that she wants to be a good role model for her daughter. Changing her behavior for her daughter is important to her.

Plan

The patient would commit to a plan of action that is simple, realistic, specific, and attainable. The patient should also set a timeline for the plan.

The incorporation of core skills is fundamental to MI. The acronym OARS, involves four interviewing skills to enhance motivation for change.¹⁵

Asking open-ended questions allows patients to provide more information and can provide insight to their feelings and thoughts. Close-ended questions only elicit a yes or no response with no further details. Here is an example of an open-ended versus close-ended question.

• Close-ended question: Do you drink alcohol often?
• Open-ended question: How much alcohol do you drink per week?

Affirmations

Statements of affirmation acknowledge the patient’s ability to make a change. Statements by the provider emphasize key points most important to the patient and support the patient to make changes.

Reflections

Reflections involve listening and understanding what the patient is saying. This can be as simple as repeating back the patient’s statements and incorporating the patient’s unspoken feelings or intent. Furthermore, reflections confirm with the patient that what you are repeating back is accurate. An example might be saying, “I heard you say that you have tried to stop drinking in the past and you have not been able to do it and I sense you are frustrated. Is that correct?” The latter statement incorporates the patient’s unspoken feelings and confirms an accurate account of the reflection.

PAUSE AND PONDER: Along the substance use continuum, with whom would you negotiate a reduction in use to lower risk levels?

Performing a BNI

A BNI uses MI to raise awareness in patients with risky or harmful substance use. Here are four important steps to follow when conducting a BNI.

Build rapport-raise the subject

Open the conversation by beginning with a general conversation and ask permission to discuss the topic of substance use. For example, you could say: “Thank you for meeting with me today. Would you mind speaking with me? Could I ask you some questions about your substance use?”

This engages the patient in the conversation. The conversation could highlight the patient’s substance use and explore the pros and cons of the situation. For example, with Cynthia, her alcohol use allows her to cope with stress at work. Conversely, her alcohol use makes her daughter upset and she wants to be a good role model for her. During the BNI, the provider should use open-ended questions to allow the patient to provide more information and further explore the patient’s substance use. Incorporating reflective listening, summarizing what the patient says, and weighing the pros and cons allows for decisional balance.

Provide feedback

After listening to the patient ask permission again to offer feedback based on the conversation. Review the screening results with the patient and connect consequences to substance use. Here is an example.

Karla is a 32-year-old mother of three children. She and her children are in the emergency department because of a car accident. Karla’s alcohol level is 0.09.  (Blood alcohol levels ≥ 0.08% = legally impaired)

You perform a screening on Karla using the AUDIT. Her score reveals harmful use and when asked about her alcohol use causing injury, she states in the affirmative that she was under the influence of alcohol while driving with her children and feels extremely guilty and upset. During the conversation you ask permission to speak to Karla about her alcohol use and how this may be a direct cause of the accident. Karla may recognize the impact of her alcohol use and change her behavior.

Build readiness to change

Here we ask if they may be willing to make some changes. When doing so we can ask how willing they are or how ready they are to make a change. The provider can use a visual tool to assess willingness to change. This visual tool is a readiness ruler. (See Figure 5.) When approaching the patient, clinicians can use the readiness ruler in a way similar to that of a pain scale. For example, “On scale of 1 to 10, where 1 means you are not at all ready to change to 10 meaning you are very or completely ready to change. How ready are you to make a change about your substance use?”

Figure 5. Readiness Ruler¹⁵

PAUSE AND PONDER: What would be your response to a patient that states they are a 3 on the readiness ruler?

Negotiate a plan for change

Based on the screening results, the plan can vary. It may involve reducing risky use of substances and or a referral to treatment. The plan should be simple, realistic, specific, and attainable. Following up with patients to discuss changes and reinforcing the plan for change will promote long-term success.

Referral to Treatment

Patients diagnosed with an SUD by a provider or who have behaviors that are substance dependent (e.g., substance related injuries or inability to stop) or high-risk, such as increased frequency of substance use, require treatment. Healthcare professionals can easily refer the patient to treatment. Initiating the referral process by calling a trained treatment specialist on behalf of the patient to schedule an appointment can better assist the patient. Many resources are available to find treatment centers for patients. SAMHSA’s National Treatment Facility Locator is a helpful resource to locate a treatment center:¹⁷ http://findtreatment.samhsa.gov. Treatment options include counseling, medication assisted treatment, complimentary wellness, and support groups. The level of care is individualized and based on the severity of the substance use and comorbidities.

Key points for referral to treatment

• Make a plan with the patient
• Use a warm handoff
• Decide how you will communicate with the provider
• Confirm the plan with the patient

A warm handoff involves personally introducing the patient to the treatment provider. This helps build rapport and trust and increases the patient’s willingness to schedule an appointment. Warm handoffs are also more successful than passive referrals.

SBIRT in Practice

Healthcare professionals can utilize SBIRT in many areas of practice. Pharmacists and pharmacy technicians are one of the most accessible healthcare professionals, especially in community pharmacy settings. In this setting, pharmacists and pharmacy technicians can meet with patients to perform screenings, conduct a BNI, or refer to treatment, with the ultimate goal of reducing the risk of an SUD and patient harm.

Harm reduction is key to help to minimize adverse effects related to substance use.¹⁸ Harm reduction involves policies, programs, and practices that focus on the individual’s human rights. The goal of harm reduction is to keep people safe. Providers can reinforce positive changes in patients using MI. Examples of harm reduction include drug take back programs, access to naloxone, and syringe distribution.¹⁸ Distributing clean needles/syringes not only reduces harm for the persons using them but also contributes to community safety by reducing the spread of HIV, hepatitis, and other blood borne diseases.

Sadly, in community pharmacy settings, several barriers exist. Some include lack of privacy, lack of staffing, lack of time, and stigmas.^{19, 20}   A stigma is an inaccurate belief against individuals based on a specific characteristic, race, or nation of people.^22,23 Often, we see this in patients with a mental illness. Stigma towards individuals with SUDs also exist and are one of the most challenging barriers because of a misconception that an SUD is not a disease or medical condition and individuals with an SUD are at fault.²³ You may hear people say, “They don’t want to get better” or “I don’t want those kinds of people in my pharmacy.” Stigmas can impede care and harm the patient.

It is important to recognize that an SUD is a medical condition and requires treatment. Stigmatizing language like “addict” or “junkie” has a negative connotation and can lead to barriers in care. Avoid using stigmatizing language. For example, an addiction is an SUD. Clinicians need to replace the words “addict” or “junkie” with the words “person with an SUD.” This recognizes the disease and not the person with the SUD.

Patient case Joe and brief intervention.

Joe is a 32-year-old man who hurt his back three years ago in a car accident. He has used opioids since the accident, but he still complains of pain. He supplements his medications by purchasing additional opioids online and on the street. Joe also has a history of alcohol use. He consumes three to four beers on most days. His family is concerned with his alcohol and drug use and recommends he seek help.

AUDIT score: 12-At risk use

DAST-10 score: 5-Harmful use

What recommendations are appropriate based on the screening results?

Joe’s alcohol screening score of 12 shows that he is at risk use and his DAST-10 score of 5 shows that his use of drugs is harmful. In Joe’s case, he would benefit from a brief intervention and referral to treatment.

A brief intervention would be helpful for Joe. Here is an example of an intervention between Joe and the pharmacist at the ambulatory care clinic.

Pharmacist: “Good morning, Joe. Would it be OK if I speak with you for a few minutes about your screening results that you took earlier?”

Joe: “I guess that would okay.”

Pharmacist: “Based on your screening results, your alcohol use puts you at risk for harm and your drug use is possibly already harmful for your health and for those around you.”

Joe: “I don’t know what you are talking about. I don’t have a problem.”

Pharmacist: “Let me ask you this. From your perspective what is your relationship with alcohol and drugs?”

Joe: “Well I guess I do drink every day and I am on oxycodone for the pain. I was in an accident a few years ago and the pain won’t go away. I need the oxy. My family thinks I need help.”

Pharmacist: “Thank you for opening up to me and telling me how you feel after your accident and that you’re still in pain. Tell me some of the things that are good about your alcohol and drug use and some things that are not good?”

Joe: “Well alcohol helps me forget about my problems for little bit. The drugs help my pain, but I feel guilty sometimes because I buy it off the street because my doctor won’t give me enough.”

Pharmacist: “What is it about your drug use that makes you feel guilty?”

Joe: “My family means a lot to me, and I am afraid that my wife might leave me and take the kids.”

Pharmacist: “It sounds like you love your family. What changes do you think you could make about your alcohol and drug use?”

Joe: “Well I guess I could cut back on my drinking and find some other ways to deal with my stress. I rely too much on the oxy so I don’t think I could cut back on that right now.”

Pharmacist: “That’s great that you are willing to cut back on your alcohol use. Tell me what that would look like?”

Joe: “I think I could limit myself to three beers a day instead of four or five. I can start there and see how it goes.”

Pharmacist: “That’s a great start. On a scale of 1-10 where 1 means that you are not at all ready to make this change and 10 meaning that you are completely ready where do you think you would put yourself on this scale?”

Joe: “I guess I would rate myself as being a 7.”

Pharmacist: “Joe, that’s great. A 7 is very close to being completely ready to make this change. Can I ask you what is holding you back from you being at a 10?

Joe: “I don’t think that I am completely ready to make a change. I am also afraid of failing.”

Pharmacist: That is a valid fear. Speaking with someone about your alcohol use and treatment can really help. Would you be willing to meet Dr. Smith here at the office and set up an appointment with him?”

Joe: “Sure. I could meet him now while I am at the clinic.”

The pharmacist walks Joe down the hall to meet Dr. Smith who is a behavioral specialist focusing on SUDs. The pharmacist performs a warm handoff, introducing Joe to Dr. Smith.

The pharmacist engaged Joe in the conversation and reflected on what Joe said and felt. During the conversation, the pharmacist asked open-ended questions to gain more insight into Joe’s alcohol and drug use and discussed his readiness to make a change. Joe rated himself as a 7 on the readiness scale. Discussing where they are on the readiness ruler can determine patients’ willingness to change, possible resistance, and potential fears. Joe recognized the pros and cons of his alcohol and drug use and made a plan to decrease his alcohol use and meet with a behavioral specialist about his drug use.

Conclusion

SBIRT is a public health approach to intervene with individuals at risk of an SUD. SBIRT is effective in reducing alcohol use by 40% and illicit drug use by 76%.²⁴ Applying universal screening and promoting change to reduce high-risk behavior before it escalates to an SUD can greatly reduce patient harm and minimize healthcare costs.

Depending on the setting, time constraints, day-to-day workload, and staffing, SBIRT may be a challenge to perform.  Pharmacists and pharmacy technicians should be knowledgeable about SBIRT and treat persons with SUDs, where feasible, in a professional, caring manner. SBIRT can be a useful approach to identify those with at risk behaviors and apply early intervention methods to minimize harm and development of an SUD.

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INTRODUCTION

In 2020, The World Health Organization estimated that 40 million people need palliative care each year.¹ Palliative care is “an interdisciplinary care delivery system designed to anticipate, prevent, and manage physical, psychological, social, and spiritual suffering to optimize quality of life for patients, their families, and caregivers.”² As patients near the end of their lives, they may elect to pursue hospice care with a greater focus on maintaining their dignity and comfort.³ Such care is available in a variety of settings, including acute care hospitals, nursing homes, assisted living facilities, hospice houses, and the patient’s own home.⁴

A misconception—that palliative care is relevant only at the end of a patient’s life—is common. All patients contending with serious illnesses can benefit from palliative services.⁵ Patients with chronic diseases may choose to pursue both active treatment of their condition and palliative care for symptom management, working with a specialized, interdisciplinary team of healthcare professionals.⁴ This team collaborates with patients and their families to identify the patient’s treatment priorities and work to eliminate suffering throughout the course of the disease.⁶

Pharmacists are important members of the palliative care team and are involved with developing and implementing an individualized treatment plan for each patient.⁷ These plans “[require] specific patient goals with pharmacologic and nonpharmacologic management to improve quality of life while reducing costs and unnecessary medications.”⁷ Pharmacists provide valuable input to prescribers regarding medication selection, dosing recommendations, and nontraditional routes of administration, all of which will vary from patient to patient.^6,7

Pharmacy staff also have the opportunity to educate patients and their families directly regarding appropriate medication use and side effect management. Additionally, they may dispel myths about opioid use in palliative and hospice care and help identify allergies and adverse reactions. They are also well-placed to identify instances of medication diversion in both inpatient and outpatient settings.^6-8

Healthcare providers should feel comfortable managing patients pursuing palliative and hospice care, recognizing that medication is but one part of the care provided. The focus should be squarely on patients and their families and the goal of alleviating their suffering, no matter the stage of their disease.

PRINCIPLES OF PALLIATIVE/HOSPICE CARE

Palliative care is comprehensive in its management of the patient. According to the International Association for Hospice and Palliative Care, it⁹

• Provides relief from pain and other distressing symptoms
• Affirms life and regards dying as a normal process
• Integrates the psychological and spiritual aspects of patient care
• Offers a support system to help the family cope during the patient’s illness and in their own bereavement

Knowing that palliative care is not withdrawal or withholding of care is critical; it is simply a treatment with a different goal in mind: in this case, comfort, whether the patient is seeking cure or not. Palliative care comprises many components aside from medication; these may include varied offerings like mental health counseling, art therapy, and pastoral care, among others. All hospice care is palliative in nature, but not all palliative care is hospice care.¹¹

Table 1 compares both types of care.

Table 1. Characteristics of Palliative vs. Hospice Services12-14
	Palliative Services	Hospice Services
When is it implemented?	As early as diagnosis; at any stage of disease	6-month life expectancy or less
Is it used along with active treatment/life-prolonging measures?	Yes	No
Where is it offered?	Usually an acute care facility or outpatient clinic, but may also be offered in nursing home, hospice house, or private residence	Various settings, including an acute care facility, nursing home, hospice house, private residence
Are psychosocial/emotional support services offered?	Yes	Yes
Does it involve treatment, including medication, for symptom relief?	Yes	Yes

Opioids in End-of-Life Care: Management of Pain and/or Dyspnea

Pain and dyspnea (also known as shortness of breath or air hunger) are common symptoms at the end of life.^15,16 This holds true even for patients without a respiratory causative diagnosis such as chronic obstructive pulmonary disease; patients with cancer (70%), AIDS (11% to 62%) and other terminal illnesses also experience difficulty breathing at the end of life.¹⁷ And in one study of 988 terminally ill patients, half experienced moderate or severe pain.¹⁸ Easing these symptoms reduces patient and family distress during the active dying process.

OPIOID PHARMACOLOGY

Opioids are the mainstay of therapy for pain and dyspnea in end-of-life care due to their multimodal mechanism of action.¹⁵ In the body, they bind to three different opioid receptor subtypes, known as mu-, kappa-, and delta-receptors.^16,19

• Mu (μ) are responsible for analgesia, sedation, gastrointestinal distress, respiratory depression, euphoria, dependence
• Kappa (κ) are responsible for analgesia, sedation, dyspnea and respiratory distress, euphoria
• Delta (δ) are responsible for analgesia and spinal analgesia

These receptors are present in pain pathways in the central nervous system; by binding to them, opioids inhibit stimulatory neurotransmitters that conduct pain signals to the brain.²⁰

Dyspnea’s exact mechanism at the end of life is poorly understood; however, opioids’ ability to mitigate shortness of breath is possibly due to their secondary effects. Opioids may alter a patient’s ventilatory response to carbon dioxide, ease hypoxia, change inspiratory flow resistive loading, and improve oxygen consumption.²¹ In other words, opioids decrease respiratory drive, alter the perception of breathlessness, change peripheral opioid receptors’ activity in the lung, and decrease anxiety, all of which contribute to the sensation of dyspnea.²² Patients and caregivers perceive the shortness of breath as anxiety and often reach for the benzodiazepines to relieve this discomfort. However, opioids are the drug of first choice for dyspnea and may provide relief of the underlying cause thereby minimizing anxiety.

 

Selecting an Opioid

 

Consideration of patient-specific factors should guide the healthcare provider’s selection of opioid for pain and dyspnea.^23,24 Opioids’ pharmacokinetic profiles differ, sometimes substantially, from one medication to another. ²⁵ Additionally, patients’ unique genetic identities may influence an opioid’s bioavailability, metabolism, and the patient’s physical response to the opioid.²³ Table 2 lists some questions clinicians should ask themselves when deciding on a pain management regimen.

 

Table 2. Clinical Considerations in the Selection of Opioids for a Patient Receiving Palliative Care25
Consideration	Example
What kind of pain am I treating?	Breakthrough vs. chronic, neuropathic vs. skeletomuscular
What are the patient’s needs and goals?	Some patients may prioritize total pain relief; others may tolerate more pain in order to be less sedated
Is it practical and easy to administer the ordered dose?	Order reasonable, whole-number doses at even dosing intervals, i.e., avoid oxycodone 3 mg by mouth every 5 hours
Is the patient likely to derive meaningful relief from this regimen?	Consider renal and hepatic function, body composition, feasible routes of administration, drug interactions, etc.

Common Opioids Used in Palliative and Hospice Settings

Opioids are classified into four groups based on their chemical structure:

• Phenanthrenes
• Benzomorphans
• Phenylpiperidines
• Diphenylheptanes

The importance of these chemical structures will be discussed in the “Dispelling Common Hospice Myths” section.

Table 3 describes opioids commonly used in the palliative and hospice settings, and some of their pharmacokinetic and pharmacodynamic characteristics.

Table 3. Opioids* Commonly Used in the Palliative and Hospice Settings15,16,26
Opioid	Pharmacokinetic and Pharmacodynamic Characteristics
Morphine (Avinza, Kadian, MS Contin, Duramorph, MSIR)	Phenanthrene HydrophilicMetabolism: glucuronidation Highly protein-bound Mean elimination half-life: 2 hours
Hydrocodone (Norco, Hycet, Vicodin, Lorcet, Lortab) Note: only available in combination with non-opioid analgesics	Phenanthrene Metabolism: CYP2D6 enzyme Mean elimination half-life: 2.5-4 hours
Oxycodone (Oxycontin, OxyIR, Roxicodone, XTAMPZA, Percocet) Note: available on its own and in combination with non-opioid analgesics	Phenanthrene Metabolism: CYP2D6, CYP3A4 enzymes Mean elimination half-life: 2.5-3 hours
Hydromorphone (Dilaudid, Exalgo)	Phenanthrene HydrophilicMetabolism: glucuronidation Mean elimination half-life: 2-3 hours
Fentanyl	Piperidine Metabolism: CYP3A4 enzyme
Tramadol (Ultram, Ryzolt)	Mu-opioid agonist Metabolism: CYP2B6, CYP2D6 and CYP3A4 enzymes Mean elimination half-life: 6-8 hours

*Note: Methadone, a diphenylheptane synthetic opioid derivative, is also commonly used for palliative and hospice patients with severe pain who are not opioid-naïve. Its metabolism is non-linear and its dosing is complicated; this continuing education activity will not discuss methadone in detail.²⁶

Renal and Hepatic Dysfunction

Renal and hepatic metabolism affects multiple opioids. Table 4 discusses the use of these medications in instances of advanced kidney or liver disease and identifies drugs that should be avoided in these populations. In patients with impaired metabolism of opioids, providers should select the lowest effective dose and titrate cautiously to effect.

 

Table 4. Opioids in Organ Impairment15,27,28,29

 

Safe	Use with Caution	Avoid
Renal Impairment
Hydromorphone Methadone Fentanyl	Hydrocodone Oxycodone Tramadol	Morphine
Hepatic Impairment
Hydromorphone Fentanyl Morphine	Hydrocodone Oxycodone Tramadol	Methadone

EQUIANALGESIC DOSE CONVERSIONS

It is common in palliative and hospice care for patients to require multiple opioids for symptom management.³⁰ As patients transition from the acute inpatient setting to outpatient care, clinicians should also consider converting parenteral opioid doses to oral forms whenever possible.^31,32 This aids patient comfort and eases administration, particularly when a caregiver, rather than a medical professional, is responsible for the patient’s medication management.

Equianalgesia refers to various opioids’ analgesic doses that are estimated to provide the same pain relief.³³ Equianalgesic dose conversion charts and calculators are widely available as tools to help clinicians determine appropriate opioid dosages for patients; however, pharmacists should be aware that all conversion charts are approximations and are only to be used as guides.^34,35 Different sources may have slight variances in their conversion factors.³⁶ Clinicians may use these charts as a way to double-check their arithmetic by comparing the doses calculated using different tables. Table 5 is one example of an equianalgesic dose conversion chart. Additionally, because of patient-specific factors, the appropriate dose for a patient may not always be the one calculated based on a standardized ratio. There is no substitute for sound clinical judgment!

 

Table 5. Equianalgesic Opioid Dose Conversions 15,37
Drug	Oral Dose	Parenteral Dose	Conversion Ratio (to oral morphine)
Morphine	30 mg	10 mg	3:1
Oxycodone	20 mg	--	2:3
Hydrocodone	20 mg	--	2:3
Hydromorphone	7 mg	1.5 mg	Oral hydromorphone: 1:4 Parenteral hydromorphone: 1:20

 

To convert from one parenteral or oral opioid dose to another, follow these steps3,33,37,38: 1.       Determine the total daily dose of current regimen in morphine equivalents a.       Add all doses of opioids the patient receives over a 24-hour period b.       Calculate equianalgesic morphine dose by multiplying the dose of the opioid you are switching from by the conversion factor*   2.       Reduce the total daily dose of the new opioid by 25%-50% for incomplete cross tolerance*   3.       Select the new dosing interval, accounting for short- and long-acting dosage forms a.       Convert the total daily dose (TDD) of the old opioid to the new opioid using a dose conversion chart b.       Determine the breakthrough/as-needed (PRN) dose of the new opioid by calculating 10-15% of the TDD for each PRN dose   Utilize short dosing intervals (every 1-3 hours) for PRN pain control in hospice/palliative care

* Incomplete Cross Tolerance On occasion, clinicians may need to switch patients from one opioid to another when a patient develops tolerance (decreased pharmacologic response pursuant to repeated or prolonged drug exposure).39 Incomplete cross tolerance occurs when patients have developed some level of tolerance to opioids with pharmacologically similar structures. However, the extent of this tolerance varies, and clinicians may unintentionally overdose patients by over-estimating their ability to handle an equianalgesic dose of a new opioid.39 To account for this phenomenon, clinicians should consider reducing the dose of the new opioid (i.e., the one you are switching to) by 25% to 50%.39,40 Many patients experience decreased analgesia from their pain regimen over time and benefit from opioid rotation. Opioid rotation is the process of switching the patient to a novel opioid not currently part of their pain management plan.33 Of note, clinicians may also consider opioid rotation if patients experience intolerable side effects from a drug within the same class.   Example 1: Converting from the parenteral to the oral form of the same drug Convert a patient on an IV morphine drip at 1 mg/hr, to an oral regimen or sustained-release morphine. Convert from IV to PO formulation using conversion factor 24 mg IV morphine TDD * [3 mg PO morphine/1 mg IV morphine] = 72 mg PO morphine in 24 hours Split total daily dose into two oral doses of the extended-release formulation 72 mg ÷ 2 = morphine sulfate ER 36 mg PO every 12 hours; but morphine sulfate ER is available in 30 mg tabs Final dose – morphine sulfate ER 30 mg PO every 12 hours Calculate 10-15% of TDD for the breakthrough dose TDD = 60 mg 10% of TDD = 6 mg 15% of TDD = 9 mg Round to 10 mg PO morphine every 4-6 hours PRN; this dose was rounded up because we had to lower the around-the-clock dose due to the available dosage form.   Example 2: Converting from the parenteral form of one drug to the oral form of another drug Convert hydromorphone 1 mg IV every 2 hours to a pain control regimen involving oxycodone extended release (ER) and oxycodone immediate release (IR) for breakthrough pain. Calculate total daily dose Hydromorphone 1 mg IV every 2 hours = 12 mg IV hydromorphone/day Convert to new opioid using conversion factor 12 mg IV hydromorphone x [20 mg oxycodone/1.5 mg IV hydromorphone] = 160 mg oxycodone/24 hours Dose reduce by 25% 25% of 160 mg = 40 mg oxycodone 160 mg – 40 mg = 120 mg oxycodone/24 hours Round to a reasonable, whole number dose and interval for long-acting formulation 120 mg oxycodone/24 hours = 60 mg oxycodone ER every 12 hours Calculate 10-15% of the TDD for breakthrough dose 120 mg oxycodone TDD x 10 to 15% = 10 mg or 15 mg every 3-4 hours Use remaining 50% of total daily dose as short-acting formulation

 

Note that healthcare providers still need to use good clinical judgment when determining the final recommendation; there is no standardized dosing interval for short-acting opioids, although long-acting opioids are not given more frequently than every eight hours.^41,42

ROUTE-SPECIFIC CONSIDERATIONS

Intensol Formulations

Oral opioids are the formulation of choice for most patients pursuing palliative and hospice care.⁴³ At the end of life, many patients become frail and lose muscle tone, resulting in decreased swallowing ability; however, many of the most common medications used in hospice, including morphine, come in a highly concentrated intensol formulation. These concentrated products deliver sizable doses in very small liquid volumes.⁴⁴

Even in cases of severe pain and advanced illness, oral morphine remains an effective and suitable option; while inpatient facilities sometimes use morphine infusions, infusions are often unnecessary for patients at the end of life.^44,45 To be most effective, clinicians should prescribe and administer morphine around the clock at consistent intervals to ensure steady pain control.⁴⁵

Concentrated morphine solution (Roxanol) is available in a 20 mg/1 mL solution, allowing effective delivery of the medication even in patients unable to swallow.⁴⁶ In this situation, the caregiver can prop the patient’s body to a 30-degree angle and instill up to 1 mL of the intensol solution into the buccal (cheek) area. This area serves as a “reservoir” for the medication as it slowly trickles down into the gastrointestinal tract where it is absorbed.⁴⁴

Transdermal Fentanyl Patches

Transdermal fentanyl patches may be a reasonable option for opioid-tolerant patients requiring around-the-clock pain control. Clinicians, however, should never employ transdermal fentanyl for immediate or intermittent pain relief as it takes approximately 24 hours (up to as much as 48 hours) for serum fentanyl concentrations to reach a constant state.⁴⁷ Package labeling also specifies that prescribers should only use fentanyl patches in patients who

• are already receiving opioid therapy
• have developed opioid tolerance, and
• are receiving a total daily dose at least equivalent to [fentanyl] 25 mcg/hr.⁴⁷

Opioid tolerance, for the purpose of using a fentanyl patch, is defined as having been on at least 60 mg of morphine or its dosage equivalent daily for at least a week.⁴⁷

Proper application of the fentanyl patch is necessary to ensure optimal pain relief and reduce the likelihood of adverse reactions. Clinicians should communicate the following to patients prescribed transdermal fentanyl patches⁴⁷:

• Each new fentanyl patch should be applied to a different skin site after removal of the previous one
• The patch need not be applied to the area of discomfort or pain
• Patients may tape the edges of the patch with first aid tape
• If the patch falls off before 72 hours, dispose of it by folding it in half and flushing down the toilet
• Fentanyl patches must never be cut
• Never place a heating pad over a fentanyl patch

Do not escalate fentanyl patch doses more frequently than every two to three days. When a patch is first applied, serum fentanyl concentrations will increase with the first few applications.⁴⁷ Following several rounds of patch applications, serum concentrations eventually reach steady state, meaning that it is difficult to measure a patient’s pain relief accurately during the initiation of a new transdermal fentanyl dose.⁴⁷ Premature dose escalation may lead to overdose.

Additionally, body composition is an important clinical consideration when using transdermal fentanyl. This drug’s absorption is related to a patient’s body fat composition as fentanyl is lipophilic. Patients who are cachectic (wasting physically with weight and muscle mass loss due to disease) or suffer from profuse sweating, as many cancer patients do, will derive minimal benefit from transdermal fentanyl patches.^44,48 Heat will increase the absorption of fentanyl from the patch, so heating pads must never be applied directly over the patch and patients with fever should have their patch removed and an alternate dosage form should be used.

It is appropriate to use fentanyl patches in conjunction with opioids given by other routes of administration. Judicious use of the patches may reduce the need for breakthrough pain doses by providing more consistent drug delivery over the 72-hour application period. Levy’s Rule (See Figure 1) provides the conversion factor to calculate equianalgesic transdermal fentanyl doses based on a patient’s total daily dose of oral morphine equivalents.⁴⁹

 

FIGURE 1

Levy’s Rule: Fentanyl patch dose (in mcg) = half of the TDD oral morphine

Managing a Pain Crisis

A pain crisis is a situation in which a patient’s pain is severe and uncontrolled, causing the patient, family, or both severe distress; the pain crisis may be sudden in onset or the result of worsening chronic pain.²⁵ Clinicians should address this rapidly-escalating, uncontrolled pain promptly and aggressively. When patients are in pain crises, members of the treatment team, including nurses, pharmacists, and physicians, must work together to monitor their responses to opioid administration closely and make adjustments accordingly.⁵⁰

Clinicians should double the dose of the immediate-acting opioid every twenty minutes until the patient’s pain is controlled and conduct a review of the pain management plan thereafter to determine if dosage or administration frequency need to be changed.²⁵ Opioids have no maximum dosage limit; particularly in the palliative care setting, doses must be titrated to an appropriate level of pain relief that ensures a satisfactory result.

PAUSE AND PONDER: A patient is in pain crisis. You recommend doubling her dose of intravenous hydromorphone every 20 minutes, but her new nurse is nervous about increasing her dose so aggressively. How do you explain the treatment plan and alleviate his concern?

DISPELLING COMMON HOSPICE MYTHS

For many patients and their families, hospice is a difficult term to face at first. Pharmacists are in a unique position, both in the inpatient and outpatient settings, to speak to them as medication experts.⁷ Patients may express hesitation around opioid use related to a variety of factors.^3,51 One study (N = 496) explored terminally-ill patients’ reasons for declining pain management; patients indicated that they feared addiction, found mental or physical side effects unwelcome, and resented the burden of medication in terms of number of doses.¹⁸ Table 6 lists some common misconceptions about opioid use in hospice care and suggests responses pharmacists can use to educate patients about these medications’ place in palliative care.

 

Table 6. Myths and Facts About Opioid Use in Hospice Care3,52-55
Myth	Fact
“Opioids will make me die faster”	When used appropriately, opioids will not hasten death and can help relieve breathing discomfort many patients experience at the end of life.
“I will get addicted to opioids”	Patients may develop a tolerance to opioids, which occurs when they experience decreased pain relief compared to when they started taking the medication. This is a result of the way the drug works in the body. Patients may need higher doses to achieve the same effect. This is different from addiction. Addiction is a disease that involves a person’s repeated use of a drug despite experiencing negative consequences. Needing higher doses of an opioid does not mean a person is addicted.
“Going on hospice care and taking opioids means giving up”	Hospice provides care tailored to a patient’s dignity, comfort, and quality of life. It is not the same as withdrawing medical treatment; in fact, a multidisciplinary team of healthcare professionals manages patients in hospice. Medications, like opioids, are only one component of the care hospice patients receive.
“I get too constipated when I take opioids”	Constipation is a common opioid side effect that does not resolve over time, so clinicians need to prescribe appropriate laxatives for patients on opioids. Constipation in itself is not a contraindication to the use of opioids in palliative/hospice care.

 

Allergy vs “Allergy”

 

Another common misconception patients have regarding opioid use relates to allergies, as many opioid side effects mimic symptoms of true allergic reactions.⁵⁶ Palliative care clinicians need to be able to differentiate between a true allergy and an adverse reaction to determine appropriate pain regimens for patients safely.

 

True drug allergies, also known as type I hypersensitivity reactions, are due to immunoglobulin E (IgE)-mediated release of antibodies against the offending agent.⁵⁷ This reaction, in its severest form presenting as anaphylaxis, occurs in less than 2% of patients.^56,57 While the gold standard for identifying a true drug allergy is drug provocation testing, achieved by exposing a patient to small doses of suspected drugs and monitoring for a reaction, clinicians rarely order drug provocation testing in practice and it is even less relevant in the hospice population.⁵⁸

 

In contrast to drug allergies, adverse reactions (see Table 7) are known or expected responses, different from the intended therapeutic effect, to a medication.⁵⁹ Such adverse reactions are commonly due to the parent opioid’s active metabolites.¹⁶

 

Table 7. Management of Common Opioid Adverse Reactions56,62
Adverse Reaction	Do patients develop tolerance to this adverse reaction?	Management
Nausea/vomiting	Yes	May recommend use of prophylactic antiemetics (i.e., ondansetron, metoclopramide)
Constipation	No	Routinely recommend concomitant use of a stool softener (i.e., psyllium or docusate) or stimulant laxative (i.e., senna, bisacodyl)
Itching	Yes	May recommend use of prophylactic H1 or H2 histamine antagonist (i.e., diphenhydramine, loratadine, famotidine)

 

 

Patients may also demonstrate pseudo-allergy to an opioid, which is an adverse reaction that appears to mimic a true allergy but is unaffected by IgE.⁵⁶ These may include mild itching, skin redness, or bronchospasm but do not necessarily indicate an allergic reaction.⁶⁰ Instead, they are more commonly due to a histamine-mediated response.⁶⁰ Histamine release is related to the opioid’s potency; the more potent the opioid, the less histamine release and the lower the likelihood of a histamine-mediated reaction.

 

If a patient demonstrates any one of these symptoms or develops several that are mild in severity, it does not necessarily signal the patient has an immune-related allergy to opioids. Similarly, histamine-meditated adverse reactions do not mean opioids as a class are contraindicated for use in the affected patient. Clinicians in this scenario can opt to pre-medicate the patient with antihistamines or steroids before administering an opioid for a few days until the effect is minimized.⁶⁰ They may also consider an alternative opioid in a different pharmacologic opioid class which may be more tolerable.⁶⁰

 

PAUSE AND PONDER: What questions would you ask patients to assess whether they are experiencing an allergy versus a side effect?

 

Cross-reactivity can occur when a chemical component of one medication is like that in another, resulting in an allergic reaction to both drugs.⁶¹ Understanding opioids’ chemical structures (see Table 8) allows clinicians to determine risk of cross-reactivity when they are concerned about a true allergy. Cross-reactivity may occur within the same class; for example, a patient with a true allergy to codeine should not take oxycodone. However, it is reasonable for a patient with an allergy to a drug in one class of opioids to take a medication from another class.⁶² The risk for cross-reactivity in this situation is low, but if the patient has a true allergic reaction, they should only take an opioid from another class under supervision of a healthcare professional until allergy to that product is ruled out.⁶²

 

Table 8. Chemical Classes of Opioids16
Phenanthrenes	Benzomorphans	Phenylpiperidines	Diphenylheptanes
Buprenorphine Butorphanol Codeine Hydromorphone Morphine Nalbuphine Oxycodone Oxymorphone	Pentazocine	Alfentanil Fentanyl Meperidine Sufentanil	Methadone

 

DIVERSION

Drug diversion is defined as “a criminal act or deviation that removes a prescription drug from its intended path from the manufacturer to the intended patient.”⁶³ The hospice setting is not immune to the risk of diversion. Given the estimate that more than 90% of hospice and palliative care patients receive a controlled pain medication, diversion is a very real concern.³⁰ One survey of 371 hospices revealed that 31% of facilities interviewed reported at least one case of confirmed diversion in the past quarter.⁶⁴

Palliative care presents unique diversion issues because it is often delivered in the patient’s home, rather than a facility. The home environment, while often the preferred site of care, is less closely monitored and controlled than in an inpatient setting, making it a susceptible site of opioid diversion.⁶⁵ Caregivers, family members, healthcare providers, and patients themselves may all divert opioids.⁶⁶

Identifying diversion

Providers should be able to identify instances of possible diversion and take reasonable steps to prevent it from happening.⁶⁷ State prescription drug monitoring programs (PDMPs) are one such way to monitor patient’s access to opioids.⁶⁸ These programs vary from state to state, but all allow authorized providers to review a patient’s controlled substance fill history.⁶⁸ Practitioners should make it a habit to review their state’s PDMP prior to filling a prescription for a controlled substance to determine whether a patient may seek out multiple prescribers or visit different pharmacies. Such behavior does not always indicate drug misuse or diversion but should prompt the pharmacist to identify any risky activity. Other common “red flags” that may signal a person is diverting medication:

□ Frequent or early refill requests from patient or caregiver

□ Inaccurate or missing record-keeping by pharmacy or hospice agency

□ Noncommunicative patients who appear to always be in severe pain/distress

□ Impaired caregivers, including both family members and home health staff

The University of Maryland, Baltimore, in conjunction with the Hospice Foundation of America, has developed 15 recommendations for preventing medication diversion and misuse in hospice care.⁶⁹ These include recommendations related to several care areas featured in Figure 2.

FIGURE 2

 

Hospice Prescriptions Transmitted by Facsimile

Federal and state laws regulate controlled substances dispensing for hospice patients. Specifically, prescribers may fax prescriptions for C-II medications to retail pharmacies without needing to subsequently furnish a hard copy as they would for a non-hospice patient.⁷⁰ The federal law regarding faxing C-II prescriptions for hospice patients states that “a prescription prepared in accordance with §1306.05 written for a Schedule II narcotic substance for a patient enrolled in a hospice care program certified and/or paid for by Medicare under Title XVIII or a hospice program which is licensed by the state may be transmitted by the practitioner or the practitioner's agent to the dispensing pharmacy by facsimile. The practitioner or the practitioner's agent will note on the prescription that the patient is a hospice patient. The facsimile serves as the original written prescription for purposes of this paragraph (g) and it shall be maintained in accordance with §1304.04(h).”⁷⁰ The faxed prescription must indicate that it is for a hospice patient in order to be filled legally—pharmacy teams should make note of this rule and ensure prescribers so annotate prescriptions. 

Conclusion

Patients in palliative and hospice care have unique needs. Clinicians should be familiar with how the two types of care differ and their common characteristics. To manage a patient’s pain and dyspnea, healthcare providers should have a solid foundational knowledge of opioid medications and an understanding of how to select and tailor patients’ pain control regimens to their specific needs. There is no treatment algorithm for pain management, just as there is no standardized equianalgesic opioid dose conversion chart. Clinicians must account for patient- and drug-specific factors and use their own judgment when transitioning patients from one opioid to another to ensure adequate pain control. Certain formulations, such as intensol and transdermal patches, also have route-specific considerations. Pharmacists particularly are well-placed to educate other healthcare professionals as well as patients and their caregivers about opioids’ place in palliative/hospice care. They can “myth-bust” common hospice misconceptions, help identify allergies and adverse reactions, and inform treatment decisions related to acute situations (like pain crises) and transitions from inpatient to outpatient settings. They can also be closely involved in monitoring, documenting, and preventing issues related to medication diversion. Drug therapy is a significant component of palliative/hospice care. It requires a thorough and sensitive understanding by medical staff so that patients derive maximum benefit from it as they approach the end of their lives. Alleviation of suffering, and the protection of a patient’s dignity, should be at the core of any medication decisions made for these patients.

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