Teori Obat-obatan dispepsia

Agents that inhibit gastric acid production

and antiulcer drugs
DRUGS EXAMPLES
1. Agents that neutralize acids NaHCO3, Al(OH)3,
Mg(OH)2
2. Agents that reduce gastric acid
secretion Cimetidine,ranitidine,
a) H2 receptor blockers famotidine, nizatidine

Omeprazole,
b) Proton pump inhibitor Esomeprazole,
Focus on Lanzoprazole,
Pantoprazole, Rabeprazole

c) M1 selective antagonist Pirenzepine

3. Agents enhancing mucosal defense Sucralfate, misoprostol,
mechanism (cytoprotective Factors) bismuthsubsallicylate
 Proton Pump Inhibitor
• Definition
PPI is inhibitors of the gastric H+,K+-ATPase (proton pump)

• Basic Structure

Side Chain

Benzimidazole

Pyridine
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Diferences in Structure

Esomeprazole

4
Li et al, 2004
 PPI ACTIVATED
MECHANISM
Pka2 Shows Why PPI Become Activated
On The Proton Pump In Canaliculus
pKa2

Second protonation nucleophylity

electrophylity
First protonation

pKA1

pKa1 shows why PPI is selectivity

Accumulated in parietal cell
 Mechanism of PPI
Prodrugs

Acid catalyzed conversion

Tetracyclic planar
sulphenamide
Active Form

The sulphenamide binds covalently to key cysteine groups on

the proton pump to cause prolonged inhibition of gastric
acid secretion
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Stedman & Barclay, 2000
 pKa Values of Marketed PPI

• Onset Of Action Depends On Coversion Rate PPI

• Conversion Rate Of PPI Depends On Pka2 (Majority)
• Activation Rate :
Omeprazol & Esomeprazole > Rabeprazole > Lansoprazole >
Pantoprazole

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 PPI AVAILABLE IN INDONESIA
PPI Tablet Capsule Dry
(enteric (microgranule) Injection
coated)
Omeprazol - 20mg 40mg/vial

Lansoprazol 30mg, 15mg 30mg 30mg/vial

Pantoprazol 20mg, 40mg - 40mg/vial

Rabeprazol 10mg, 20mg - -

Esomeprazol 20mg. 40mg - 40mg/vial

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 ABSORBTION

Omeprazole Lansoprazol Pantoprazol Rabeprazol esomeprazol

BA 30-40% 80-85% 77% 52% 64%
Food effect Minimal Delayed Minimal Minimal -
absorbtion

• The Implication Food intake  Bioavailibility of

PPI approximately 50% decreased by food
• PPI should be given ½ h – 1 h before meal
because taking a meal can activated proton
pump

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ABSORBTION

Oral Dosage Form

PPI is acid labile  so PPI formulated as enteric
coated capsule  pass through the stomach intact
to be absorbed in the Proximal Small Intestine

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DISTRIBUTION

Omeprazole Lansoprazol Pantoprazol Rabeprazol esomeprazol

Protein binding 95 97 98 96.3 97

Entered breast milk No No Yes No No

Label C B B B B

• Distribution cross placenta

Based on RCT, Exposure to PPI during the first trimester of
pregnancy was not associated with a significantly increased of
major birth defect

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 METABOLISM

Omeprazole Lansoprazol Pantoprazol Rabeprazol esomeprazol

Metabolism hepatic hepatic hepatic hepatic hepatic
CYP 2C19, 3A4 2C19, 3A4 2C19 2C19, 3A4 2C19, 3A4
Hepatic Dosage Severe  Dosage Dosage Dosage
impairment Adjustmet decreased Adjustmet Adjustmet adjustment is
is needed dose is needed is needed needed
(prolonged t½)  For patients
with
severe liver
impairment (Child
Pugh class C), do
not
exceed a dose of 20
mg.

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ELIMINATION

Omeprazole Lansoprazol Pantoprazol Rabeprazol esomeprazol

Urin 77% 33% 71% 90% 80% inactive
metabolit mentabolit 1% active
Feces Very small 67% 18% 10% 20% feces
unchanged
drug
Renal No dosage adjustment is needed (no significant changes)
impairment

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