Two or more drugs at the same time may exert their effects independently or may interact. The interaction may be potentiation or antagonism of one drug by another, or occasionally some other effect. Adverse drugeffect.tions should be reported to the medicine and health care products Regulatory (MHRA).
A drug interaction may be pharmacodynamic or pharmacokinetic.
●Pharmacodynamic interactions
These are interactions between drugs which have similar or antagonistic pharmacological effects or side effects. They may be due to competition at receptor sites, or occur between drugs acting on the same physiological system. They are usually predictable from a knowledge of the pharmacology of the interacting drugs; in general, those demonstrated with one drug are likely to occur with related drugs. They occur to a greater or lesser extent in most patients who receive interacting drugs.
●Pharmacokinetic interactions
These occur when one drug alters the absorption, distribution, metabolism, or excretion of another, thus increasing or reducing the amount of drug available to produce its pharmacological effect. They aren't easily predicted and many of them affect only a small proportion of patients taking the combination of drugs.
Pharmacokinetic interactions are of several types.
◆Affecting absorption.
The rate of absorption or the total amount absorbed can both be altered by drug interactions.Delayed absorption is rarely of clinical unless high Peak plasma concentrations are Required ( eg when giving an analgesic). Reduction in total amount absorbed, however, may result in ineffective therapy.
Due to changes in protein binding .. to a variable extent most drugs are loosely bound to plasma proteins. Protein binding sites are non-specific and one drug can displace another thereby increasing its proportion free to diffuse from plasma to its site of action. This only produces a detectable increase in effect if it's an extensively bound drug ( more than 90%) that isn't widely distributed throughout the body. Displacement from protein binding plays a part in the potentiation of warfarin by sulfonamides and tolbutamide but the importance of these interactions is due mainly to the fact that warfarin metabolism is also inhibited.
◆Affecting Metabolism
many drugs are metabolized in the liver. Induction of the hepatic microsomal enzymes system by one drug can gradually increase the rate of metabolism of another resulting in lower plasma concentrations. Barbiturates, Griseofulvin, many antiepileptics, and Rifampicin are the most important enzymes inducers. Drugs affected include warfarin and the oral contraceptives.
◆Affecting renal excretion
Drugs are eliminated through the kidney both by glomerular filtration and by active tubular secretion. Competition occurs between those which share active transport mechanisms in the proximal tubule. For example, Salicylates and some other NSAIDs delay the excretion of methotrexate; serious methotrexate toxicity is possible.
