Drug interactions and adverse reactions

Abstract

Drugs administered by the intravenous route can produce both therapeutic and untoward (or adverse) side-effects. The co-administration of two or more drugs may lead to either pharmacokinetic and/or dynamic drug-drug interactions. Most intravenous (i.v.) drugs produce untoward side-effects, such as pain on injection, venous sequelae, cardiovascular or respiratory depression. Other important adverse effects include specific actions of i.v. drugs on various tissues of the body (e.g. effects of etomidate and midazolam on the neuroendocrine axis), the effects of drugs or their solvents on blood coagulation or fibrinolysis, and the potential for hepatic and renal toxicity. Intravenous drugs are usually metabolized before elimination from the body, and alterations in global haemodynamics and hence in regional blood flow to the liver or kidney may result in increased efficacy and a prolongation of drug effect. Blood flow changes may be due to physiological, pharmacological or pathological factors. Intercurrent drug therapy and disease states may also affect the function of the microsomal mixed function oxidase enzymes responsible for drug metabolism. Finally, a less predictable but more serious type of adverse reaction is that of anaphylaxis or an anaphylactoid response. The incidence of such events is low, ranging from 1/7000 to 1/24000 for the barbiturates, to 1/300000 for etomidate, to 1/100000–200000 for propofol, and is even less frequent for ketamine and the opioids.