Question 22

Compare and contrast the pharmacology of drugs that alter the pH of gastric
fluid.

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College Answer

Moderately well answered overall, however many candidates lacked a systematic
approach to their comparison of the pharmacology of drugs that alter the pH of
gastric fluid. Few candidates discussed pharmacokinetics in sufficient detail, with
only a very limited discussion comparing the absorption, metabolism and elimination
of even common drugs. Relevant information such as bioavailability, duration of
effect, and available formulations with dosing was often lacking. Similarly, little
attention was given to important drug interactions. Many candidates included drugs
which are used for gastric problems or mucosal protection, but do not specifically
influence gastric pH e.g. sucrulfate. Some candidates gave unnecessarily detailed
accounts of the physiology of gastric fluid production and the acid-base mechanisms
involved. All candidates provided details of H2 blockers and PPIs, but often did not
list representative examples or compare the effects on basal versus stimulated acid
secretion. Many candidates also discussed antacids, but did not indicate their
mechanisms of action properly and did not outline potential adverse effects. Some
candidates included prostaglandin analogues and anticholinergic drugs for
completeness and were able to indicate their roles in affecting gastric acid secretion.
Syllabus: Q2a 2b,c
Recommended sources: Basic and Clinical Pharmacology, Katzung, Chp 62

Discussion

It would be important to point out that sucralfate in fact does affect gastric pH, as it is a complex salt of aluminium hydroxide and sulfated sucrose. When it disperses in stomach acid, it releases a surprising amount of aluminium hydroxide, which then goes on to do some good antacid work.

Drug classes	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
Administration	All of these drugs can be administered as oral or IV formulations, except for sucralfate and antacids
Absorption	Apart from antacids and sucralfate, all are are well absorbed by the oral route. Antacids and sucralfate are minimally absorbed
Distribution	Atropine, H2As and PPIs have small volumes of distribution (0.2-2.0 L/kg) Misoprostol is widely distributed
Elimination	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
Side effects	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

References

Aihara, Takeshi, et al. "Pharmacological control of gastric acid secretion for the treatment of acid-related peptic disease: past, present, and future." Pharmacology & therapeutics 98.1 (2003): 109-127.

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