Pharmacology for Anaesthesia and Intensive Care

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9780521704632c19 CUFX213A/Peck 9780521618168 December 28, 2007 14:1

19 Drugs acting on the gut

activation. Gastrin and ACh also stimulate the adjacent paracrine cells to produce

and release histamine, which acts on the parietal cell, increasing cAMP and therefore

acid secretion.

H 2 receptor antagonists

Cimetidine

Cimetidine is the only H 2 receptor antagonist with an imidazole structure.

Uses

Itis used in peptic ulcer disease, reflux oesophagitis, Zollinger–Ellison syndrome and

pre-operatively in those at risk of aspiration. It has not been shown to be of benefit in

active haematemesis, although it does have a prophylactic role in those with critical

illness.

Mechanism of action

Cimetidine is a competitive and specific antagonist of H 2 receptors at parietal cells.

Effects


Gut–the gastric pH is raised and the volume of secretions reduced, while there is

no change in gastric emptying time or lower oesophageal sphincter tone.


Cardiovascular – bradycardia and hypotension follow rapid intravenous adminis-

tration.


Central nervous system – confusion, hallucinations and seizures are usually only

seen when impaired renal function leads to high plasma levels.


Respiratory system – low-grade aspiration of gastric content that has been stripped

of its acidic, antibacterial environment will result in increased nosocomial pul-

monary infections in critically ill ventilated patients.


Endocrine – gynaecomastia, impotence and a fall in sperm count is seen in men

due to its anti-androgenic effects.


Metabolic – it inhibits hepatic cytochrome P450 and will slow the metabolism of

the following drugs: lidocaine, propranolol, diazepam, phenytoin, tricyclic antide-

pressants, warfarin and aminophylline.

Kinetics

Cimetidine is well absorbed from the small bowel (oral bioavailability approximately

60%), poorly plasma protein bound (20%), partially metabolized (up to 60% if admin-

istered orally) in the liver by cytochrome P450 and approximately 50% excreted

unchanged in the urine.

Ranitidine

Ranitidine is more potent than cimetidine.