SN7 SHORT NOTE 5M

Classify drug interactions. Describe the pharmacokinetic and pharmacodynamic interactions with examples.

Pharmacology · 2nd Professional — Para-Clinical

Definition and Classification

A drug interaction occurs when the effect of one drug is altered by the prior or concurrent administration of another drug, food, or chemical.

Type	Basis	Examples
Pharmaceutical	Physical or chemical incompatibility outside the body, in the syringe or infusion	Penicillin inactivated by mixing with an aminoglycoside; diazepam precipitates in infusion fluids; calcium with ceftriaxone
Pharmacokinetic	One drug alters the absorption, distribution, metabolism or excretion of another — the plasma concentration changes	See below
Pharmacodynamic	The drugs act on the same receptor, system or physiological process; the plasma concentration is unchanged	See below

Pharmacokinetic Interactions

Stage	Mechanism	Examples
Absorption	Chelation, adsorption, altered pH, altered motility, altered gut flora	Calcium, iron and antacids chelate tetracyclines and fluoroquinolones; cholestyramine binds digoxin and warfarin; metoclopramide speeds gastric emptying
Distribution	Displacement from plasma protein binding	Aspirin, sulphonamides and phenylbutazone displace warfarin; sulphonamides displace bilirubin in neonates, risking kernicterus
Metabolism	Enzyme induction or inhibition	Rifampicin (inducer) causes oral contraceptive failure; erythromycin (inhibitor) with a statin causes rhabdomyolysis
Excretion	Competition for tubular secretion; altered urine pH; altered renal blood flow	Probenecid blocks penicillin and methotrexate secretion; NSAIDs and diuretics raise lithium levels; bicarbonate increases aspirin excretion

Pharmacodynamic Interactions

Type	Meaning	Examples
Additive (summation)	1 + 1 = 2	Aspirin with paracetamol
Synergism (potentiation)	1 + 1 = greater than 2	Trimethoprim with sulphamethoxazole (sequential blockade); penicillin with an aminoglycoside; alcohol with benzodiazepines
Antagonism	One drug opposes the effect of another	Naloxone with morphine (competitive); vitamin K with warfarin (physiological); protamine with heparin (chemical); adrenaline with histamine (physiological)
Altered receptor sensitivity	Indirect modification	Diuretic-induced hypokalaemia increases digoxin toxicity — one of the commonest clinically significant interactions

CLINICAL PEARL

The hypokalaemia interaction is worth stating carefully because it is pharmacoDYNAMIC, not pharmacokinetic. A thiazide does not alter the digoxin level at all. It lowers potassium, and since potassium and digoxin compete for the same site on the Na+/K+ ATPase, less potassium means more digoxin binding. The patient becomes toxic at a perfectly normal plasma level — which is why the level must always be read alongside the potassium.

Drugs Especially Prone to Harmful Interaction

Those with a narrow therapeutic index — warfarin, digoxin, phenytoin, lithium, theophylline, aminoglycosides, ciclosporin, oral hypoglycaemics, cytotoxics
Those with a steep dose–response curve
Those requiring precise plasma levels — antiretrovirals, antiepileptics, immunosuppressants
Patients at particular risk — the elderly, those on polypharmacy, and those with hepatic or renal impairment

Applied Aspects

Take a complete drug history including over-the-counter, herbal and traditional medicines — patients rarely volunteer these, and in India ayurvedic and other traditional preparations are very widely used
Not all interactions are harmful — many are used deliberately: carbidopa with levodopa, clavulanic acid with amoxicillin, probenecid with penicillin, naloxone in opioid overdose
Separate the doses of interacting drugs where the interaction is one of absorption — tetracyclines and antacids by at least two hours
Monitor when starting or stopping an interacting drug; the risk is as great on withdrawal as on introduction
Prescribe as few drugs as possible — the number of potential interactions rises steeply with the number of drugs, and polypharmacy in the elderly is a major and avoidable cause of hospital admission

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