Interactions Directly On Receptors Or On Body Systems

This category of pharmacodynamic interactions comprises specific interactions between drugs on the same receptor, and includes less precise interactions involving the same body organ or system; whatever the precise location, the result is altered drug action.

Action on receptors provides numerous examples. Beneficial interactions are sought in overdose, as with the use of naloxone for morphine overdose (opioid receptor), of atropine for anticholinesterase, i.e. insecticide poisoning (acetylcholine receptor), of isoproterelol (isoprenaline) for overdose with a ß-adrenoceptor blocker (ß-adrenoceptor), of phentolamine for the monoamine oxidase inhibitor-sympathomimetic interaction (oc-adrenoceptor).

Unwanted interactions include the loss of the antihypertensive effect of ß-blockers when common cold remedies containing ephedrine, phenylpropanolamine or phenylephrine are taken, usually unknown to the doctor; their a-adrenoceptor agonist action is unrestrained in the ß-blocked patient.

Actions on body systems provide scope for a variety of interactions. The following list shows something of the range of possibilities; others may be found under accounts of individual drugs:

ß-adrenoceptor blockers lose some antihypertensive efficacy when nonsteroidal anti-inflammatory drugs (NSAIDs), especially indomethacin, are coadministered; the effect involves inhibition of production of vasodilator prostaglandins by the kidney leading to sodium retention.

Diuretics, especially of the loop variety, lose efficacy if administered with NSAIDs; the mechanism may involve inhibition of prostaglandin synthesis, as above.

Potassium supplements, given with potassium-retaining diuretics, e.g. amiloride, spironolactone, or with ACE-inhibitors may cause dangerous hyperkalemia.

Digoxin is more effective, but also more toxic in the presence of hypokalemia, which may be caused by thiazide or loop diuretics.

Verapamil given i.v. with a ß-blocker, e.g. atenolol, for supraventricular tachycardia may cause dangerous bradycardia since both drugs delay atrioventricular conduction.

Theophylline potentiates p-adrenergic effects, e.g. of salbutamol, and cardiac arrhythmia may result during treatment of asthma.

Lithium toxicity may result if a thiazide diuretic is co-administered; when there is sodium depletion, resorption of lithium by the proximal renal tubule is increased and plasma concentrations rise.

Central nervous system depressant drugs including benzodiazepines, several Hj-receptor antihistamines, alcohol, phenothiazines, antiepilepsy drugs interact to augment their sedative effects.

Loop diuretics and a?ninoglycoside antibiotics are both ototoxic in high dose; the chance of an adverse event is greater if they are administered together.

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