Pharmacological Basis Of Drug Interactions

Some knowledge of the pharmacological basis of how one drug may change the action of another is useful in obtaining those interactions that are wanted, as well as in recognising and preventing those that are not.

Drug interactions are of two principal kinds:

1. Pharmacodynamic interaction: both drugs act on the target site of clinical effect, exerting synergism (below) or antagonism. The drugs may act on the same or different receptors or processes, mediating similar biological consequences. Examples include: alcohol + benzodiazepine (to produce sedation), morphine + naloxone (to reverse opioid overdose), rifampicin + isoniazid (effective antituberculosis combination).

2. Pharmacokinetic interaction: the drugs interact remotely from the target site to alter plasma (and other tissue) concentrations so that the amount of the drug at the target site of clinical effect is altered, e.g. enzyme induction by rifampicin will reduce the plasma concentration of warfarin; enzyme inhibition by ciprofloxacin will elevate the concentration of theophylline.

Interaction may result in antagonism or synergism.

Antagonism occurs when the action of one drug opposes the action of another. The two drugs simply have opposite pharmacodynamic effects, e.g. histamine and adrenaline on the bronchi exhibit physiological or functional antagonism; or they compete reversibly for the same drug receptor, e.g. flumazenil and benzodiazepines exhibit competitive antagonism.

Synergism37 is of two sorts:

1. Summation or addition occurs when the effects of two drugs having the same action are additive, i.e. 2 + 2 = 4 (a p-adrenoceptor blocker plus a thiazide diuretic have an additive antihypertensive effect).

2. Potentiation (to make more powerful) occurs when one drug increases the action of another,

37 Greek: syn, together; ergos, work.

i.e. 2 + 2 = 5. Sometimes the two drugs both have the action concerned (trimethoprim plus sulphonamide) and sometimes one drug lacks the action concerned (benserazide plus levodopa), i.e. 0 + 2 = 5.

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