treatment of peptic ulcer
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ANTACIDSANTACIDS Systemic ANC
Sodium bicarbonate- 1-12 mEq HCl
sodium citrate- 1- 10 mEq HCl
Non-Systemic ANC
Magnesium Hydroxide 1- 30 mEq HCl
Magnesium trisilicate 1- 10 mEq HCl
Aluminium Hydroxide gel 1- 2.5 mEq HCl
Magaldrate 1- 28 mEq HCl
Calcium carbonate 1- 20 mEq HCl
Treatment of Peptic UlcerTreatment of Peptic Ulcer
ACh
PGE2
Histamine Gastrin
Adenyl cyclase
_+
ATP cAMP
Protein Kinase (Activated)
Ca++
+
Ca++
Proton pump
KK+ H+
Gastric acid
Parietal cell
Lumen of stomach
AntacidOmeprazole
H2M
_
__
_
+
PGE receptor
+
+
Gastrin receptor+
+
+ Proglumide
Misoprostol RanitidinePirenzepine
_
Reversible competitive inhibitors of H2 receptor
Highly selective, No action on H1 or H3 receptors
Very effective in inhibiting nocturnal acid secretion ( as it depends largely on Histamine )
Modest impact on meal stimulated acid secretion (As it depends on gastrin, acetyl choline and histamine)
Histamine H2 Receptor Antagonist
Bioavailability 80 50 40 >90
Relative Potency 1 5 -10 32 5 -10
Half life (hrs) 1.5 - 2.3 1.6 - 2.4 2.5 - 4 1.1 -1.6
Duration of 6 8 12 8
action (hrs)
Inhibition of 1 0.1 0 0 CYP 450
Dose mg(bd) 400 150 20 150
Cimetidine Ranitidine Famotidine Nizatidine
HH2 2 Blockers- UsesBlockers- Uses
1. Duodenal ulcer
2. Gastric ulcer
3. Stress ulcers and gastritis
4. Zollinger-Ellison syndrome
5. Gastroesophageal reflux disease (GERD)
H2 Blockers–Side effects & Interactions
Extremely safe drugs
Cimetidine causes gynecomastia, galactorrhea
(as it is antiandrogenic & increases orolactin level)
Cimetidine inhibits CYP450 & increases conc. of Warfarin, Theophylline, Phenytoin, Ethanol.
Proton Pump Inhibitors (PPIs)
Most effective drugs in antiulcer therapy
Irreversible inhibitor of H+ K+ ATPase
Prodrugs requiring activation in acid environment
Weakly basic drugs & so accumulate in canaliculi of parietal cell
Activated in canaliculi & binds covalently to extracellular domain of H+ K+ ATPase
Acid secretion resumes only after synthesis of new molecules
DrugsOmeprazole 20 mg o.d.
Esomeprazole 20 - 40 mg o.d.
Lansoprazole 30 mg o.d.
Pantoprazole 40 mg o.d.
Rabeprazole 20 mg o.d.
Proton Pump Inhibitors – Kinetics
Given as enteric coated granules in capsule or enteric coated tablets
Pantoprazole also given intravenously
Half life – 1.5 hrs
Since it requires acid for activation - given 1 hr before meals
Other acid suppressing agents not coadministered
UsesUses
1. Gastric ulcer
2. Zollinger-Ellison syndrome
3. Gastroesophageal reflux disease (GERD)
Note: drug of choice for NSAID induced gastric/duodenal ulcer
P.P.I. – Side effects & Interactions
Extremely safe drugs
Causes hypergastrinemia which leads to carcinod tumor in rats
But no evidence of such tumors in man
Inhibit CYP 450 & hence metabolism of warfarin, phenytoin, etc
Pantoprazole & Rabeprazole have no significant interactions
Prostaglandin AnaloguesProstaglandin Analogues
Misoprostil, Enprostil, Rioprostil.
Inhibit acid secretion
↑ mucus and HCO3- secretion
Short duration of action
Misoprostol
PGE1 analogue
Modest acid inhibition
Stimulate mucus & bicarbonate secretion
Enhance mucusal blood flow
Approved for prevention of NSAID induced ulcer
Diarrhoea & cramping abd. pain – 20 %
Not so popular as P.P.I are more effective & better tolerated
UsesUses
1. NSAID associated GI disease
2. Patients not responding to H2 blocker
3. Ulcer Patients who continue to smoke
Side effects
Diarrhoea
Abdominal cramps
Abortion
AnticholinergicsAnticholinergics
Pirenzipine - M1 selective
Propantheline
Oxyphenonium
Atropine
↓ volume of gastric juice
Mucosal Protective Agents/Ulcer protectives
Sucralfate
Colloidal Bismuth compounds
Sucralfate
Salt of sucrose complexed to sulfated aluminium hydroxide
In acidic pH polymerises to viscous gel that adheres to ulcer crater
Taken on empty stomach 1 hr. before meals
Concurrent antacids, H2 antagonist avoided
( as it needs acid for activation )
Colloidal Bismuth CompoundsCoats ulcer, stimulates mucus & bicarbonate
secretion
Direct antimicrobial activity against H.pylori
May cause blackening of stools & tongue
Not used for long periods – bismuth toxicity
Available compounds :
Bismuth subsalicylate – in USA
Bismuth sobcitrate – in Europe
Bismuth dinitrate
Ulcer Healing DrugsUlcer Healing Drugs Carbenoxolone sodium
Steroid
Derivative of glycyrrhetinic acid
Augmentation of mucus production
Prolongation of lifespan of gastric epithelial cells
Prevention of bile reflux
Slowing of PG degradation in gastric mucosa
Side effect
Mineralocorticoid action
Eradication of H.pylori (Anti-H.Pylori Drugs)
Triple Therapy
Omeprazole / Lansoprazole - 20 / 30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin / Metronidazole - 1gm / 500 mg bd
Given for 14 days followed by P.P.I for 4 – 6 weeks
Short regimens for 7 – 10 days not very effective
Some other Triple Therapy Regimens are
Bismuth subsalicylate – 2 tab qid
Metronidazole - 250 mg qid
Tetracycline - 500 mg qid
Ranitidine Bismuth citrate - 400 mg bd
Tetracycline - 500 mg bd
Clarithromycin / Metronidazole - 500 mg bd
Quadruple Therapy
Given when Triple Therapy fails
Omeprazole / Lansoprazole - 20 / 30 mg bd
Bismuth subsalycilate - 2 tabs qid
Metronidazole - 250 mg qid
Tetracycline - 500 mg qid
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