antiulcer and prokinetic agents Flashcards
what are agents that neutralize acid?
antacids
- examples NaHCO3, Al(OH)3, Mg(OH)2
What are agents that decrease gastric secretions and how do they do that?
Agents that decrease Gastric Acid Secretion -
H2 Receptor Blockers: H2 Antagonists: - Cimetidine – First H2 Blocker not used. RANITIDINE, Famotidine, Nizatidine
Proton Pump Inhibitor: PPI - OMEPRAZOLE, Lansaprazole
M1 selective Muscarinic antagonist - PIREZIPINE
Agents enhancing mucosal defence mechanism (cytoprotective factors), what are these drugs?
Sucralfate, Misoprostol, Bismuth Subsalicylate
For eradication of helicobacter pylori (antimicrobial agnets) 7 or 14 days: H. Pylori combo pack/Day, what is the triple or quadruple combinations?
i)A PPI + Antibacterial Combination
ii) Amoxicillin + Clarithromycin;
iii) Bismuth subsalicylate
iv) Metronidazole / Tetracycline
If resistance exists add the fourth one (iv)
Triple / Quadrple combination:
i) Include a PPI - a must to elevate pH
i) ) Amoxicillin/Clarithromycin
iii) Bismuth compound
iv) Metronidazole / Tetracycline
what’s the physiology of gastric acid secretion?
Gastric Acid Secretion is Regulated by Neural (ACh Cholinergic - Muscarinic) Endocrine (Gastrin) and Paracrine (Histamine) secretory factors - Stomach.
Secretory Products: HCl, Pepsin, Mucus, HCO3
Aggressive Factors: HCl, Pepsin, Helicobactor Pylori infection, Oxidative Stress, Free Radicals, NSAIDs, Corticosteroids, Smoking.
Defensive/ Cyto-protective factors:
Mucus, HCO3 Secretion and PGEs (PGE1 and PGE2)
what are the antacids? what do they do? and what are their advantages and disadvantages?
1) Agents that Neutralize acid: Antacids: (NaHCO3, Al(OH)3, Ca(CO)3.
These are weak bases that form salts with HCl causing Chemical NEUTRALIZATION to buffer acid in the stomach. Antacids are thought to heal ulcer by protective effect particularly aluminum compounds.
Advantages: Immediate Pain Relief, Less expensive.
Disadvantages: i) Short Duration of Effect
ii) Rebound Gastric Acid Secretion.
for the antacids NaHCO3, CaCo3, Al(OH)3, and Mg(OH)2, what are their properties?
NaHCO3 - high capacity neturalize, NaCl is salt formed in stomach, the solubity of that is high, and the adverse effects are systemic alkalosis, and food retention.
CaCo3 - moderate capacity neturalize, CaCl2 is salt formed in stomach, the solubity of that is moderate, and the adverse effects are hypercalcemia and nephrolithiasis.
Al(OH)3 - high capacity neturalize, AlCl3 is salt formed in stomach, the solubity of that is low, and the adverse effects are constipation (most important), and hypophosphatemia, drug adsorption reduces drug bioavailability.
Mg(OH)2 - high capacity neturalize, MgCl2 is salt formed in stomach, the solubity of that is low, and the adverse effects are Diarrhea, hypermagnesmia (in patient with renal insufficiency).
for agents that reduce gastric acid secretion, what do H2 receptor antagonists do and what are they?
2) Agents that reduce Gastric acid secretion:
a) H2 Receptor Antagonists: (Cimetidine,RANITIDINE, Famotidine, Nizatidine). They inhibit 90% acid secretion in basal food-induced as well as nocturnal acid production states. Thus, they are helpful in healing gastric and duodenal ulcers and prevent their recurrence. Have benefits in preventing increased gastric acid secretion in Zollinger-Ellison syndrome.
Cimetidine First H2 Blocker that was once popular. Has several adverse effects, not a choice now – drugs come and go!- Ranitidine is now an OTC drug !
what were the problems with cimetidine?
CNS: confusion, somnolesence, headache, dizziness
Immunological: skin rashes, myalgia, itching
Gonadal effects: Gynecomastia, loss of libido, impotence (elevates estrogens and prolactin secretion)
Inhibits CyP450: Inhibits the metabolism of various drugs that are concomitantly taken: phenytoin, warfarin, theophylinne, TCA, BDZ.
These adverse effects are relatively least with Ranitidine and none with Famotidine.
what do proton pump inhibitors do? what are they?
No Rationale in combining a PPI with a H2 Blocker for except in ZES to have rapid control of Acid secretion.
(H+K+ATPase Inhibitors: Omeprazole, Lansaprazole)
Irreversible inhibitor of proton pump; blocks 98% of acid secretion in all forms of ulcer and hypersecretory - Zollinger-Ellison Syndrome (ZES).
The drug is given in gelatin coated capsule to RESIST breakdown in stomach acid. It reaches the intestine, well absorbed, enters blood stream, reaches the parietal cell and blocks the Proton Pump irreversibly. It binds irreversibly- inhibits proton pump in Parietal Cells to decrease HCl Secretion into the lumen. Tailor made drug.
Drawbacks of PPI: Decreased Vit B12 absorption, Hip Fractures on long term use. While PPIs have a Relatively rapid onset of action than H2 Blockers takes 2 to 3 days to show changes in gastric pH [elevation in gastric pH!]
The drugs omeprazole ?
PPI are Effective in patients - refractory to H2 receptor blockers. causes prolonged inhibition of acid secretion.
Note: Omeprazole and H2 blockers are most effective in acute/chronic/prophylactic management of ulcer.
what is the pharmacology of sucralfate?
Cytoprotective Mucosal Defensive Agents:
Sucralfate: Sucrose Octasulfate Aluminium Hydroxide is a Gel that gives a protective coating over the ulcerated region and prevents further erosion. Note: It also Stimulates PGE1 production so it decreases acid production; adsorbs pepsin, gives a protective coating as a gel.
what are the disadvantages of cytoprotectives like sucralfate, misoprostol, and bismuth subsalicylate, and what do they do?
Disadvantages of Sucralfate: Gives a fine coating,decreases GIT Motility - Constipation, Dry mouth, decreases the bioavailability of other drugs because of adsorption.
b) Misoprostol: Methyl PGE1 analog. It mimics PGE1 and enhances the production of Mucus and HCO3. Mild decreases in acid production. Thus, it is cytoprotective, prevents ulceration. Particularly effective in drug induced peptic ulcer induced by NSAIDs and Corticosteroids.
Disadvantages: Diarrhea, Contraindicated in Pregnancy.
c) Bismuth subsalicylate: Gives a Protective coating. Increases Mucus and PG production, Eradicates H. Pylori.
what is the pharmacological management of H. Pylori infection?
Gram-negative rod colonizes in the gastro-duodenal area.
Causes Erosion of the protective epithelial cells.
Leading to inflammatory gastritis and severe peptic ulcer.
Treatment with a Proton Pump inhibitor (PPI) + Combo. Antibacterial Coverage is Vital for total eradication of H. pylori.
Treatment: i) PPI [note: H. pylori needs low pH to survive],
ii) Amoxicillin + Clarithromycin Combination,
iii) Metronidazole (PPI+ 2 Antimicrobials is Std. Triple pack)
Alternatively, a Quadruple combination therapy
with inclusion of iv) Bismuth compound or Tetracycline eradicates the Resistance form of H. Pylori infection.
Treat for either a course of 7 days or 14 Days and withdraw treatment after Testing a stool specimen - for H. Pylori proteins - negative. In resistant type infection give
what is Zollinger-Ellison Sydrome (ZES)? and what is the treatment?
Gastrinoma of the Duodenum - 2/3rd are Malignant
Elevated Gastrin Levels - peptic ulceration, gastric hyper
secretion presence of gastrinoma, a non beta cell tumor
of the pancreas with high level of gastrin output, a
multiple neoplasm accompanied by neoplasm of the
pituitary and parathyroid gland.
Goal: Give High dose Proton pump inhibitor (omeprazole or
lansoprazole) until resorting to surgery or
chemotherapy for removal of tumor to avoid
perforation of the stomach and peritonitis.
