P1: PSB Printer: Yet To Come
9780521704632c19 CUFX213A/Peck 9780521618168 December 28, 2007 14:1
19 Drugs acting on the gut
Metabolic – inhibition of hepatic cytochrome P450. This is limited, and although
close monitoring is recommended with concurrent use of warfarin and phenytoin,
their effects are rarely potentiated. The effects of diazepam may be increased via a
similar mechanism.
Miscellaneous – rashes and gastrointestinal upset are rare.Kinetics
Omeprazole is degraded in gastric acid and so is prepared as a capsule with enteric-
coated granules so that absorption occurs in the small intestine. It is a prodrug,
becoming active within the parietal cell. It undergoes complete hepatic metabolism
bycytochrome P450 to inactive metabolites, which are excreted in the urine (80%)
and bile (20%).
Lansoprazolemay be considered as an alternative to omeprazole.Antimuscarinics
Pirenzipineis a selective antimuscarinic that was used in the treatment of gas-
tric ulcers. It is relatively selective on the gut and decreases acid secretion but less
effectively than H 2 blockers and the proton pump inhibitors. Its use has been dis-
continued.Drugs influencing gastric motility
Metoclopramide
Metoclopramide is a dopamine antagonist with structural similarities to pro-
cainamide although it has no local anaesthetic properties.Uses
Metoclopramide is used as a prokinetic and an antiemetic (see Chapter 18 ).Mechanism of action
Itsprokinetic actions are mediated by antagonism of peripheral dopaminergic (D 2 )
receptors and selective stimulation of gastric muscarinic receptors (which can be
blocked by atropine).Effects
Central nervous system – extrapyramidal effects, the most common manifestations
of which are akinesia and occulogyric crisis, are only seen when metoclopramide
is given in high doses, in renal impairment, and to the elderly and the young. They
can be treated with the anticholinergic agent benztropine. Metoclopramide may
cause some sedation and enhance the actions of antidepressants. The neuroleptic
malignant syndrome may also be triggered. Its central effects on the chemoreceptor
trigger zone are discussed in Chapter 18.