Drugs for the treatment of peptic ulcer disease

Question 1

Classification?

Answer 1

1. Antacids.
2. Antisecretory drugs
   Proton pump inhibitors (PPI)
   H2 – histamine receptor blockers
3. Mucosal protective agents.
4. Antimuscarinic agents.
5. Antimicrobial agents for eradication of Hellicobacter pylori

Question 2

Explain pharmacokinetics of these drugs.

Answer 2

1. Antacids : Can have systemic or non systemic variants.
2. Anti-secretory drugs :
   PPI: Delayed release formulations with enteric coating as it has actions in the intestines, food reduces rate of absorption. High distribution, BBB and BPB penetration, urinary and stool excretion.

H2 Blockers: Good oral absorption, high distribution (breast milk/placenta), hepatic metabolism and urinary excretion.

3. Mucosal protective agents : Sucralfate administered orally but has no absorption, intended for mucosal protection.
4. Anti-muscarinic agents “Atropine” for example have Topical administration on cornea, crosses BBB to exert CNS effects, hepatic metabolism and urinary excretion.

Question 3

Pharmacodynamics of these agents?

Answer 3

1. Antacids : Interact with gastric acid, increasing its PH to form salt and water (reducing acidity). Pepsin becomes inactive as it functions best in acidic PH.
2. Anti secretory drugs : PPI’s function to pass through stomach acid using enteric coating, then absorbed by parietal cells, converted to active metabolite in the parietal cells, interaction with H+/K+ ATPase channel, reducing stimulation of gastric acid secretion.

H2 blocker: Competitive antagonist of histamine at the H2 receptors of the stomach and blood vessels.

3. Mucosal protective agents: Enhance mucosal protection by healing of active ulcers, preventing inflammation. There are 2 drugs SUCRALFATE and COLLOIDAL BISMUTH SUBCITRATE.

SUCRALFATE functions to stimulate PGE2 and bicarbonate synthesis in the stomach wall.

COLLOIDAL BISMUTH SUBCITRATE functions to bind to glucoproteins, to form a protective barrier against acidity. Also causes increased Prostaglandins and bicarbonates.

Question 4

Therapeutic uses of the Antacids and the anti-secretory drugs?

Answer 4

1. Antacids: Only used for the relief of peptic ulcer and GERD symptoms (NOT FOR HEALING OF ULCER).
2. Anti secretory drugs: (PPI) - Reduce the risk of perforation/bleeding that is caused by ASPIRIN and NSAIDS. Used in active duodenal ulcers, erosive oesophagitis and GERD.

(H2 Blockers) - Peptic ulcers and GERD.