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