PHARMACOKINETIC CONSIDERATIONS
Section snippets
PHARMACOKINETICS AND PHARMACODYNAMICS
Pharmacokinetics is the study of drug disposition in the body over time including absorption, distribution, metabolism, and elimination of drug molecules.3, 12, 39, 44, 46, 72 Pharmacodynamics describes the relationship between the concentration of the drug at the site of action and the physiological response.3, 29, 46, 59 The relationship between pharmacokinetics and pharmacodynamics is illustrated in Figure 1. The pharmacologic effect of a drug can be described by the interaction of the drug
PHYSIOLOGIC CHANGES AFFECTING PHARMACOKINETICS IN THE CRITICALLY ILL PATIENT
Unfortunately, very few studies have evaluated the pharmacokinetic and pharmacodynamic properties of drugs in critically ill patients. Most pharmacokinetic studies are performed using healthy volunteers or patients who are only minimally ill, with these data extrapolated to critically ill patients. Unstable patients often present significant hemodynamic alterations and organ dysfunction, which may significantly alter drug transport throughout the body and movement into tissue. The alterations
OPIOID NARCOTIC ANALGESICS
Opioid narcotic analgesics such as morphine, fentanyl, meperidine, and hydromorphone are extensively used in the ICU for providing both analgesia and sedation.40, 68, 75 The partial agonists and mixed agonist-antagonist opioids such as pentazocine, butorphanol, and buprenorphine are associated with a ceiling effect for analgesia, have a high incidence of psychotomimetic effects, and may induce acute opioid withdrawal in opioid-dependent patients; as a result they are not usually useful agents
Oral
Narcotic analgesic drugs may be administered orally in the ICU only to those patients with functioning GI tracts. Many ICU patients will not tolerate enteral therapy and should initially receive parenteral analgesia. Patients who have altered absorptive surface of the intestines may have decreased absorption due to decreased microvilli, but they may also have a higher percentage of drug reaching the blood if metabolic enzymes in the microvilli cells are decreased in amount or activity. The oral
Patients at Risk
Opioid analgesics are commonly administered in the ICU to control pain or to reduce anxiety. The means of administration may be bolus injection, continuous infusion, or patient-controlled analgesia. The primary risks of sedation and respiratory depression are compounded by additive/synergistic effects of tissue injury, concomitant drugs, and accumulation of metabolic waste products. While it is advantageous for the caregiver to administer a constant infusion of narcotic analgesic, drug
SUMMARY
Limited studies of the pharmacokinetics of pain medication suggest altered serum elimination when the liver is hypoperfused or affected by severe cirrhosis. Drugs that are eliminated by Phase I oxidation reactions are sensitive to changes in hepatic blood flow, while drugs eliminated by Phase II glucuronidation are more affected by diseased hepatocytes. Additionally, alterations in renal function decrease elimination of both parent drugs and metabolites, resulting in toxicity for selected
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Cited by (31)
Pharmacokinetics and Pharmacology of Drugs Used in Children
2019, A Practice of Anesthesia for Infants and ChildrenPharmacokinetics and Pharmacology of Drugs Used in Children
2018, A Practice of Anesthesia for Infants and ChildrenSedation Analgesia and Neuromuscular Blockade in Pediatric Critical Care: Overview and Current Landscape
2017, Pediatric Clinics of North AmericaCitation Excerpt :Fentanyl is more lipid soluble than morphine and has a more rapid onset of action because of quicker penetration of the central nervous system. Fentanyl may be administered by the intravenous, intramuscular, epidural, transdermal, intranasal, and intrathecal routes.15,17 Long-term continuous infusions of fentanyl may result in a prolonged elimination half-life and duration of action as a result of drug accumulation in peripheral tissues.
Pharmacokinetics and Pharmacodynamics in the Critically Ill Child
2008, Pediatric Clinics of North AmericaCitation Excerpt :Fentanyl is more lipid soluble than morphine and has a more rapid onset of action because of quicker penetration of the central nervous system. Fentanyl may be administered by the intravenous, intramuscular, epidural, transdermal, intranasal, or intrathecal routes [26,28]. Long-term continuous infusions of fentanyl may result in a prolonged elimination half-life and duration of action as a result of drug accumulation in peripheral tissues.
Pharmacology and pharmacokinetics of sedatives and analgesics
2004, Gastrointestinal Endoscopy Clinics of North America
Address reprint requests to David F. Volles, PharmD, BCPS, University of Virginia Health System, Department of Pharmacy Services, P.O. Box 10002, Charlottesville, VA 22906–0002