Drug interactions and lethal drug combinations.

Although the development of drugs of greater potency and efficacy confers on the physician increasing power to treat serious diseases, it also increases the number and seriousness of potential adverse effects and drug interactions which can occur. Most hospital patients receive more than one drug at a time, the average number often being greater than five (Smith, Seidl, and Cluff, 1966). The incidence of drug reactions rises with the number of drugs prescribed simultaneously. In patients prescribed one to five drugs the incidence of reactions is 18-6%, while in patients prescribed six or more it rises to 814% (Hurwitz and Wade, 1969). The Boston Collaborative Drug Surveillance Program (1972) surveyed the incidence of drug reactions in 9900 patients admitted to nine acute disease hospitals and one chronic disease hospital. There were 83 200 drugs administered, and 3600 adverse reactions occurred of which 6-9% were due to drug interactions. The most serious interactions included depression of the central nervous system, severe hypotension, gastrointestinal bleeding, psychotic behaviour and superinfection. Although the clinical importance of drug interactions has been exaggerated in some reports, the number which end in a fatal outcome is disproportionately high. In a survey of 6199 medical inpatients in five general hospitals and one chronic disease hospital, 744 patients died in hospital, and of these deaths 27 were considered to be due to drug treatment, of which nine were caused by drug interactions (Shapiro, Slone, Lewis, and Jick, 1971). The physician should be alert to the danger of drug interactions in a number of circumstances. 1 When the pharmacological effect of a drug is harmful in excess and when the therapeutic ratio is low. Examples are hypoglycaemic drugs, anticoagulants, digoxin, depressants of the central nervous system, cytotoxic drugs. 2 When a drug produces an altered state of receptor sensitivity in the sympathetic nerve terminals, eg, monoamine oxidase inhibitors (MA0Is), tricyclic antidepressants, hypotensive drugs. 3 When interactions occur with medicines that can be bought over the chemist's counter. For example, aspirin can displace oral anticoagulants from their plasma-protein-binding sites, and indirectly acting sympathomimetics contained in cough mixtures can cause a hypertensive crisis in patients on monoamine oxidase inhibitors. Self-medication is common, and often involves drugs obtained on prescription for a previous illness. 4 When several clinics or doctors are involved in the care of a patient, one doctor may not be aware of what another has prescribed. 5 When preparations which contain more than one ingredient are prescribed by their trade names. There are a number of ways in which drugs may interact. These will be outlined and illustrated in the remainder of this paper.