Drug Interactions

It is usual for patients to receive a number of drugs at the same time.
It is a phenomenon which occurs when the effects of one drug are modified by the prior or concurrent administration of another drug(s). A drug interaction may result in beneficial or harmful effects and may be classified into:

Pharmaceutical drug interactions:

Serious loss of potency can occur from incompatibility between an infusion fluid and a drug that is added to it.
For example diazepam if added to infusion fluid there will be a precipitate formation → loss of therapeutic effect.

Pharmacokinetic drug interactions:

1) Interaction during absorption: Drugs may interact in the gastrointestinal tract resulting in either decreased or increased absorption.
e.g. Tetracycline + Calcium → Decreased absorption of tetracycline.
2) Interaction during distribution: A drug which is extensively bound to plasma protein can be displaced from its binding sites by another drug or displacement from other tissue binding sites. e.g.

(i) Sulfonamide can be displaced by salicylates from plasma proteins and it leads to sulfonamide toxicity.
(ii) Quinidine displaces digoxin from binding sites in tissues and plasma and leads to digoxin toxicity.
3) Interactions during biotransformation: This can be explained by two mechanisms:
(i) Enzyme induction.
(ii) Enzyme inhibition.
(i) Enzyme induction: By this the biotransformation of drugs is accelerated and is a cause of therapeutic failure. If the drug A is metabolized by the microsomal enzymes, then concurrent administration with a microsomal inducer (drug B) will result in enhanced metabolism of drug A. e.g. Warfarin (anticoagulant) + Barbiturate (enzyme inducer) → decreased anticoagulation. Enzyme inducers: Rifampicine, phenytoin, sulfonamides, etc.
(ii) Enzyme inhibition: By this the biotransformation of drugs is delayed and is a cause of increased intensity, duration of action and some times toxicity.
e.g. Warfarin + Metronidazole (enzyme inhibitor) → Haemorrhage.
Enzyme inhibitors: Disulfiram, isoniazid, allopurinol, cimetidine, etc.
e) Interactions during excretion: Some drugs interacts with others at the site of excretion i.e. in kidneys. e.g. Penicillin (antibiotic) + Probenecid (antigout drug) → Increases the duration of action of penicillin (Both drugs excreted through tubular secretion).