Rx of p ulcer

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Treatment of PepticUlcer 

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ProglumideACh

PGE2

HistamineGastrin

 Adenyl

cyclase

 _+

ATP cAMP

Protein Kinase(Activated)

Ca++

+

Ca++

Proton pump

KK+ H+

Gastric acid

Parietal cell

Lumen of stomach

 Antacid Omeprazole

Ranitidine

H2M3

Misoprostol 

 _

 _

 _

 _

+

PGEreceptor 

+

+

Gastrin

receptor +

+

+

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 Action of Anti Action of Anti--Ulcer drug groupsUlcer drug groups

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 Antacids

Weak bases that neutralise acid Also inhibit formation of pepsin

(As pepsinogen converted to pepsin at acidic pH)

Present day antacids : Aluminium Hydroxide

Magnesium Hydroxide

Not part of Physician prescribed regimen

OTC drug for symptomatic relief of dyspepsia

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 Antacids ² cont«

Duration of action :

30 min when taken in empty stomach2 hrs when taken after a meal

Side effects : Al3+ antacids ± constipation ( As they relax gastric

smooth muscle & delay gastric emptying)

Mg2+ antacids ± Osmotic diarrhoea .In renal failure Al3+ antacid ± Aluminium toxicity

&

Encephalopathy

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 Antacids ² Common additives

Simethicone ± Decrease surface tension ,therebreduce bubble formation

 Added to prevent reflux .

  Alginates - Form a layer of foam on top of gastric contents & reduce reflux

Oxethazaine ± Surface anaesthetic

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 Antacid - Interactions

 Adsorb drugs and form insoluble complexes

that are not absorbed .

Clinical importance :

Interactions can be avoided by taking

antacids 2 hrs before or after ingestion of other drugs .

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Now answer this question

Is it rational to combine aluminium hydroxide

and magnesium hydroxide in antacidpreparations ?

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 Answer 

Combination provides a relatively fast and

sustained neutralising capacity .

(Magnesium Hydroxide ± Rapidly acting

  Aluminium Hydroxide - Slowly acting )

Combination preserves normal bowel function.

(Aluminium Hydroxide ± constipation

Magnesium hydroxide ± diarrhoea )

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H istamine H 2R eceptor  Antagonist

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, acetylcholine and histamine)

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H 2 Blockers²Side 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.

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Now answer this question

Your friend wants to take a H2 antagonist before

he takes alcohol to avoid gastric irritation .Heconsults you .Which H2 antagonist will you ask

him to take ?

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 Answer :

Famotidine

Ex planation :

 All H2 antagonist except famotidine inhibit

gastric first pass metabolism of ethanol andincrease its bioavailability .

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Proton Pump Inhibitors

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

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Proton Pump Inhibitors

Omeprazole 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.

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Now answer this question

It is given in the previous slides that the half life of 

proton pump inhibitors is 1.5 hours only and

these drugs are generally given once daily. How

this can be justified ?

 Answer :

P.P.I - Irreversible inhibitors of H+

K+

 ATPase

(Hit and run drugs)

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P.P.I. ² 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 metabolsim of 

warfarin, phenytoin, etc

Pantoprazole & Rabeprazole have no significant

interactions

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Now  Answer this Question

 A patient comes to your clinic at midnightcomplaining of heart burn. You want to relieve his

pain immediately. What drug will you choose?

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Mucosal Protective  Agents

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Mucosal Protective  Agents

Sucralfate

Misoprostol

Colloidal Bismuth compounds

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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 )

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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

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Colloidal  Bismuth Compounds

Coats 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

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Now answer this question

 A pregnant lady (first trimester) comes to you

with peptic ulcer disease. Which drug will youprescribe for her ?

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 Answer :

 Antacids or Sucralfate

Ex planation ;

H2 antagonists cross placenta and are also

secreted in breast milk. Safety of Proton pump

inhibitors not established in pregnancy.Misoprostol causes abortion .

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Can you identify these people ? 

Nobel prize

Medicine ±

2005

Barry J Marshall J. Robin Warren

Discovery

of H.pylori &

its role in

ulcer 

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Eradication of H .pylori

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Triple Therapy

The BEST among all the Triple therapy regimen is

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

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Triple Therapy ² cont «

Bismuth subsalicylate ± 2 tab qid

Metronidazole - 250 mg qid

Tetracycline - 500 mg qid

Some other Triple Therapy Regimens are

Ranitidine Bismuth citrate - 400 mg bd

Tetracycline - 500 mg bd

Clarithromycin / Metronidazole - 500 mg bd

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Quadruple Therapy

Given when Triple Therapy fails

Omeprazole / Lansoprazole - 20 / 30 mg bd

Bismuth subsalycilate - 2 tabs qid

Metronidazole - 250 mg qidTetracycline - 500 mg qid

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N  ow you have learnt about drugs used for treating 

 peptic ulcer ? Are there any drugs that can cause peptic ulcer ? 

Drugs causing peptic ulcer  Non Steroidal Anti Inflammatory Drugs

(NSAIDs)

Glucocorticoids Cytotoxic agents

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Stress induced ulceration after head trauma

Cushing¶s ulcer 

Stress induced ulceration after severe burns

Curling¶s ulcer 

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