A Case-Based Approach to Integrating Opioid Pharmacokinetic and Pharmacodynamic Concepts in Cancer Pain Management

Abstract

Opioids are prescribed for cancer pain. Over the past decade, the annual increase in opioid prescriptions has been accompanied by an increase in opioid-associated deaths. Health care professionals must be proficient in proper dosing, titrating, and monitoring of opioid medications. With the numerous opioid medications and formulations available, an understanding of pharmacokinetic (PK) and pharmacodynamic (PD) concepts is necessary to appropriately individualize opioid-based cancer pain regimens. The purpose of this review is to highlight PK/PD concepts that are clinically relevant to the use of opioids. By way of a cancer pain patient case scenario, PK/PD concepts that are relevant in the initiation, titration, and rotation of an opioid regimen are discussed.

Opioid Therapy in Acute and Chronic Pain

“…Pharmacodynamic effects include not only the primary desired outcome of analgesia but adverse effects of sedation, euphoria, dysphoria, nausea, vomiting, hypotension, gastrointestinal hypomotility (ie, constipation), QTc prolongation (eg, methadone), respiratory depression, pruritus, and urinary retention, among others . Often, the prescriber must titrate the dose to balance the desired pharmacodynamic response of pain control with undesirable side effects.…”

“…Pharmacodynamic effects include not only the primary desired outcome of analgesia but adverse effects of sedation, euphoria, dysphoria, nausea, vomiting, hypotension, gastrointestinal hypomotility (ie, constipation), QTc prolongation (eg, methadone), respiratory depression, pruritus, and urinary retention, among others. 16 Often, the prescriber must titrate the dose to balance the desired pharmacodynamic response of pain control with undesirable side effects. The mixed agonistantagonist opioids (eg, butorphanol) have "ceiling effects" on analgesia (higher doses do not result in greater analgesia), whereas buprenorphine has a "ceiling effect" on respiratory depression that makes it safer for use in opioid use disorder.…”

Cancer Pain Management: Opioid Analgesics, Part 2

“…Opioids activate the endogenous pain-modulating system of opioid peptides (e.g., enkephalins, endorphins, and dynorphins) and spinal cord and brain receptors (μ, kappa [κ], and delta [δ]) to alter pain perception (Branford, Droney, & Ross, 2012;Lam, Pirrello, & Ma, 2016;Pasternak, 2014). The μ agonists also indirectly modify descending spinal cord inhibitory pathways (Pathan & Williams, 2012).…”

“…po = oral; IR = immediate release; SR = sustained release; ER = extended release; SNRI = serotonin and norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant; MAOI = monoamine oxidase inhibitor; conc = concentrate; IV = intravenous; SC = subcutaneous; M3G = morphine-3-glucuronide; H3G = hydromorphone-3-glucuronide, hERG = human ether-a-go-go-related gene; QTc = corrected QT; pr = rectal; NMDA = N-methyl-Daspartate; TD = transdermal; TM = transmucosal; IM = intramuscular. Information from Andresen et al (2010); Branford et al (2012); Davis & Walsh (2001);DePriest et al (2015); Enggaard et al (2006); Gudin (2012); Kalso (2005); Lam et al (2016); Mercadante (2015); Portenoy & Ahmed (2014); Prommer (2015); Smith (2011).…”