Gastric, PUD

Question 1

MOA of Antacid?

Answer 1

Antacids are bases

Protect gastric mucosa by neutralizing HCl to form salt and water

Inactivate pepsin that can damage mucosal protective barrier (work best in pH 1-2)

Question 2

Uses of antacid?

Answer 2

For symptomatic relief of pain and promote peptic ulcer healing but no good evidence for preventing NSAID-induced ulcer
Relief heartburn, dyspepsia and GERD
Prevent stress-induced ulcer

Question 3

ADR of Antacids?

Answer 3

1. Mixtures of Mg and AI compounds often made for this drug.
   Mg can cause - diarrhoea
   AI can cause - Constipation + phosphate excretion.
2. Sodium compounds: Na overload, alkalosis
3. Calcium compounds: Renal stones (Ca Phosphate ppt)
4. Gastric acid rebound secretion - body makes even more acid
5. Cation toxicity in renal failure
6. Caution for Heart Failure patients

DDR:
1. Bind to form complexes with oral quinolones, oral tetracycline
2. Affects absorption and GI transit of many drugs e.g. Isoniazid
3. Take antacids 2-3h before or after other medications

Question 4

Names of H2 Antagonists?

Answer 4

Famotidine
Ranitidine
Cimetidine
Nizatidine

Question 5

MOA of H2 Antagonists?

Answer 5

Competitively, reversibly block histamine stimulation of gastric acid secretion by reducing cAMP - attenuate protein kinases stimulation on H+K+ATPase proton pump

Question 6

Uses of H2 Antagonists?

Answer 6

For Reflux esophagitis
For GERD
For Zollinger-Ellison syndrome (gastrinoma) - tumour in pancreas or duodenum - gastrin
Prevent stress-induced ulcer

1. Effective for inhibiting fasting and nocturnal secretion (Histamine dependent)
2. Less effective for meal-stimulated acid secretion. Process is gastrin+Ach+Histamine dependent.

Question 7

ADR of H2 Antagonists?

Answer 7

Common:
1. Constipation
2. Headaches

Rare:
1. Agitation

Cimetidine can cause headaches, mental confusion in elderly, bowel movement disturbance, gynaecomastia

Question 8

Name of Proton Pump Inhibitors?

Answer 8

Omeprazole

Question 9

MOA of Omeprazole?

Answer 9

Block proton pump, the final step in gastric acid secretion. Only blocks active proton pumps, not quiescent ones

1. Inactive pro-drugs, enteric-coated to protect from gastric acid
2. Diffuses back from SI to stomach to convert to active drug
3. Protonated, activated and concentrated in parietal cell canaliculi
4. Reactive thiophilic sulphenamide active drug
5. Form covalent disulphide bond with cysteine residue on proton pump, inhibiting it
6. Takes 3-4 days before full inhibition of all proton pumps.
7. Takes 4-5 days after withdrawal to return to pre-treatment acid level, making new pumps.

Question 10

Uses of Omeprazole?

Answer 10

Peptic Ulcer treatment and maintenance therapy.
Prevent NSAID-induced ulcers and stress ulcers
Treat GERD
Zollinger-Ellison Syndrome and other gastrinomas

Question 11

ADR of Omeprazole?

Answer 11

GI - Nausea, diarrhoea, colic
CNS - Headache, dizziness, sleepiness
Reduced gastric acid barrier - bacterial overgrowth
Skin rashes
Transient rise in hepatic aminotransferase
Inhibit CYP450 - raise diazepam conc.

1. With long-term use:
   Inhibit acid secretion - hypergastrinemia - ECL hyperplasia

Question 12

What is Triple therapy?

Answer 12

Omeprazole + Clarithromycin + Amoxicillin OR Metronidazole
After completely, PPI is continued for 4-6 weeks to ensure complete healing

Question 13

What is second line quadruple therapy?

Answer 13

1 Bismuth + 2 antibiotics (Metronidazole+Tetracycline) + 1 PPI