Compare and contrast the pharmacology of drugs that change the pH of gastric fluid.
The main points candidates were expected to mention were the major drug groups (antacids,
H2 antagonists, proton pump blockers), describe their mechanism of action; briefly mention
relevant pharmacokinetics and then briefly discuss the potential problems and interactions
when using them. Additional credit was given for answers providing more detail.
Many answers did not mention antacids or prostaglandin analogues, choosing only to discuss
H2 receptor blockers and proton pump blockers. Even then, many answers included incorrect
pharmacokinetic data. Drug interactions were rarely mentioned. A discussion of normal
gastric acid secretion was not asked for and was not rewarded with marks
Available classes are:
- antacids such as aluminium hydroxide,
- anticholinergic drugs such as atropine,
- H2 antagonists such as ranitidine
- Proton pump inhibitors such as pantoprazole
- PGE2 agonists such as misoprostol
- All of these drugs can be administered as oral or IV formulations, except for sucralfate and antacids
- Apart from antacids and sucralfate, all are are well absorbed by the oral route.
- Antacids and sucralfate are minimally absorbed
- Atropine, H2As and PPIs have small volumes of distribution (0.2-2.0 L/kg)
- Misoprostol is widely distributed
- H2 antagonists are mainly renally cleared
- PPIs and misoprostol are mainly metabolised by the liver
- Atropine is 50% metabolised and 50% excreted unchanged
|Mechanism of action
- Antacids combine with hydrochloric acid to produce a chloride salt and water, neutralising the acid.
- Sucralfate converts into a polymer anionic gel which coats the mucosa as a protective barrier, and also releases aluminium hydroxide (an antacid)
- Anticholinergic drugs, H2 antagonists and misoprostol all decrease cAMP, which results in decreased apical availability of proton pumps (H+/K+ ATPase proteins). These are all reversible competitive inhibitor effects.
- PPIs bind covalently and irreversibly to H+/K+ ATPase proteins, disabling them
- Antacids can cause constipation, alkalosis, and occasionally contain toxic ingredients (aluminium, bismuth). They can also bind other drugs, decreasing their availability.
- Anticholinergic drugs cause tachycardia, mydriasis, urinary retention, and constipation
- Sucralfate can cause constipation
- H2 antagonists can interfere with CYP450 enzymes
- PPIs cause hypomagnesemia, interstitial nephritis, and increase the risk of hospital-acquired pneumonia and C.difficile infection
- Misoprostol causes diarrhoea and uterine contractions