Interactions At Site Of Absorption

In the complex environment of the gut there are opportunities for drugs to interfere with each other both directly and indirectly via alteration of gut physiology. Usually the result is to impair absorption.

Direct chemical interaction in the gut is a significant cause of reduced absorption. Antacids that contain aluminium and magnesium form insoluble complexes with tetracyclines, iron and prednisolone. Milk contains sufficient calcium to warrant its avoidance as a major article of diet when tetracyclines are taken. Colestyramine interferes with absorption of levothyroxine, digoxin and some acidic drugs, e.g. warfarin. Sucralfate reduces the absorption of phenytoin. Interactions of this type depend on both drugs being in the stomach at the same time, and can be prevented if the doses are separated by at least 2 hours.

Gut motility may be altered by drugs. Slowing of gastric emptying, e.g. opioid analgesics, tricyclic antidepressants (antimuscarinic effect), may delay and reduce the absorption of other drugs. Purgatives reduce the time spent in the small intestine and give less opportunity for the absorption of poorly soluble substances such as adrenal steroids and digoxin.

Alterations in gut flora by antimicrobials may potentiate oral anticoagulant by reducing bacterial synthesis of vitamin K (usually only after antimicrobials are given orally in high dose, e.g. to treat Helicobacter pylori).

Interactions other than in the gut are exemplified by the use of hyaluronidase to promote dissipation of a s.c. injection, and by the addition of vasoconstrictors, e.g. adrenaline, felypressin, to local anaesthetics to delay absorption and usefully prolong local anaesthesia.

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