Pharmacokinetic drug interactions in anaesthetic practice. 1991

M Wood
Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville, Tennessee.

Patients receive on average 10 different drugs while in hospital; when fewer than 6 are administered the probability of an adverse drug interaction is about 5%, but when more than 15 are given the probability increases to over 40%. Patients presenting for anaesthesia and surgery are likely to receive multiple preoperative drug therapy and also many perioperative medications as part of their anaesthetic regimen. Thus, there is a considerable potential for interactions to occur in anaesthetic practice. Pharmacokinetic interactions occur when the administration of 1 drug alters the disposition of another, and hence alters the concentration of drug at the receptor site, leading to altered drug response. These changes in drug concentration at the receptor site may be produced by alteration of (a) drug absorption and uptake into the body, (b) drug distribution, (c) drug metabolism and (d) drug elimination or excretion by nonmetabolic routes. Interactions affecting the absorption of orally administered medications are often due to the indirect effect of 1 drug on gastric motility and emptying, which leads to reduced, delayed or variable systemic drug availability. Gastric emptying time before elective surgery is normal, but premedication with morphine, pethidine (meperidine) and anticholinergics all delay gastric emptying and hence drug absorption. Inhalational anaesthesia of short duration does not appear to affect drug absorption, although halothane anaesthetic used for longer periods produces a slight delay in gastric emptying. Volatile anaesthetics have been shown to delay the intramuscular absorption of ketamine. Anaesthetic agents may affect drug distribution, and peak concentrations of propranolol, for example, are 4 times higher during halothane anaesthesia in dogs, accompanied by a marked decrease in volume of distribution. This effect has been noted for other drugs, including thiopental and verapamil. Volatile anaesthetics also affect plasma protein binding, leading to displacement interactions in some cases. Volatile anaesthetics affect the metabolism of concomitantly administered drug (a) by altering the rate of delivery to the organ of clearance (e.g. decreasing hepatic blood flow) and (b) by altering the activity of drug metabolising enzymes. It is now well recognised that all the volatile anaesthetics currently in use inhibit the metabolism of a large variety of drugs, e.g. propranolol, lidocaine (lignocaine), fentanyl and pethidine. Other examples of interactions of clinical importance to anaesthesiologists include those between cimetidine and the local anaesthetics and benzodiazepines; inhibition of plasma cholinesterase by drugs such as ecothiopate; interactions between monoamine oxidase inhibitors and sympathomimetics or pethidine and between monoamine oxidase inhibitors and sympathomimetics or pethidine and between isoniazid and enflurane.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D010599 Pharmacokinetics Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology. ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000042 Absorption The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
D000758 Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.
D000777 Anesthetics Agents capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general ANESTHESIA, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthetic,Anesthetic Agents,Anesthetic Drugs,Anesthetic Effect,Anesthetic Effects,Agents, Anesthetic,Drugs, Anesthetic,Effect, Anesthetic,Effects, Anesthetic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions

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