drugs for peptic ulcer and reflux

1. Drugs for peptic ulcer, emesis
and reflux disorders
Dr. Rishi Pal
Assistant Professor

2. Physiology of gastric secretion
 Stomach secretes 2-3 liters of gastric juice
/day.
 Chief/peptic cells secrete pepsinogen.
 Parietal or oxyntic cells secrete acid and IF.
 Superficial epithelial cells secrete alkaline
mucus and bicarbonates.

5. Regulation of gastric acid secretion
 Ach
 Histamine
 Gastrin
 prostaglandin-E2
Phases of gastric acid secretion
 Basal, cephalic and hormonal
 Membrane bound proton pump (H+)
 K+ ATPase

6. Peptic ulcer
 Damage to the mucosa and deeper tissue
exposed to acid and pepsin is known as
peptic ulcer.
 Causes of peptic ulcer :-
1. H. pylori infection
2. Use of NSAIDS
3. Stress

7. Classification of the drugs used in peptic ulcer
 Drugs that inhibit gastric acid secretion
1. Proton pump inhibitors: omeprazole, esomeprazole,
lansoprazole, pantoprazole, rabeprazole.
2. H2-receptor antagonists: cimetidine, ranitidine,
3. famotidine, roxatidine,nizatidine
4. Antimuscarinic agents (anticholinergics): pirenzepine,
telenzepine
5. Prostaglandin analogs: misoprostol, enprostil.

8. Anti-peptic ulcer drugs
 Ulcer protective
sucralfate, and bismuth subcitrate (CBS)
Drugs that neutralize gastric acid (antacids)
a) Systemic antacids: sodium bicarbonate and sodium citrate.
b) Non systemic antacids: magnesium hydroxide, magnesium
trisilicate, aluminum hydroxide, and calcium carbonate.

9. Anti-peptic ulcer drug
 Anti- H. pylori drugs
 Amoxicillin, tetracycline, clarithromycin,
metronidazole, tinidazole, bismuth
subsalicylate, H2-antagonists and PPIs.

10. Proton pump inhibitors
 Proton pump, K+-ATPase membrane bound enzyme play an
important role in the final step of gastric acid secretion (basal
and stimulated).
 Omeprazole is the prototype drug: these are prodrugs and
activated to sulfenamide at acidic pH. Activated form binds
covalently with SH group of H+ pump and irreversibly
inactivates it.
 PPIs administered orally 30 min. before meal. Half life short
(1.5 hr), acid secretion suppressed for upto 24 hr.

11.  Enteric coated form or powder containing
sodium bicarbonate.
 i.v. formulations available for esomeprazole,
lansoprazole, pantoprazole and rabiprazole.
 They are highly bound to plasma proteins;
extensively metabolized in liver and
metabolites secreted in urine.

12. Therapeutic uses of PPIs
1. Peptic ulcer disease
 Duodenal ulcer disease
 Gastric ulcer
 Acute bleeding ulcer
 H. pylori-associated ulcer
 Stress ulcers (curling ulcers)
 NSAIDs induced ulcers
2. Gastroesophegial reflux disease (GERD)
3. Zollinger’-Ellison syndrome.

13. Adverse effects of PPIs
 Headache, diarrhoea and abdominal pain.
 Skin rashes and arthralgia.
 May decrease vit B12 absorption
 Increase rate of infection and fracture of bones.
 Drug interactions: omeprazole can inhibit
metabolism of phenytoin, warfarin, diazepam. PPIs
decreases bioavailability of itraconazole, iron salts,
etc

14. H2-Receptor antagonists
 Mechanism of action:
 Competitively block H2 receptors on parietal
cells.
 Suppress all phases of acid secretion.
 Most effective in suppressing nocturnal acid
secretion.
 Less potent than PPIs.

16.  Administered orally and well absorbed.
 Metabolized in liver.
 Cimetidine, ranitidine and famotidine
available for i.v. administration
 Nizatidine has high bioavailability (100%)

17. Therapeutic uses of H2 blockers
Peptic ulcer disease
 Duodenal ulcer disease
 Gastric ulcer
 Acute bleeding ulcer
 H. pylori -associated ulcer
 Stress ulcers (curling ulcers)
 NSAIDs induced ulcers
2. Gastroesophegial reflux disease (GERD)
3. Zollinger’-Ellison syndrome.

18. Anticholinergic agents
 Pirenzepine
 Telenzepine
 Selective M1-receptor blocker
 Inhibit acid secretion
 Not commonly used because of their low
efficacy and anticholinergic effects.

19. Prostaglandin analogues
 Misoprostol effective orally for prevention
and treatment of NSAID-induced duodenal
ulcers.
 Inhibit gastric acid secretion.
 Increase bicarbonate and mucus secretion.
 Common side effects:
 Diarrhoea and abdominal cramps.
 Containdicated in pregnancy

20. Ulcer protective
 Sucralfate : it is complex aluminum hydroxide
and sulphated sucrose.
 Polymerized to form sticky gel that adheres
to the ulcer base and protects it.
 Form barrier against acid-pepsin.

21.  Increase mucus-bicarbonate secretion.
 Given orally empty stomach.
 Reduced absorption of digoxin, tetracyclines,
ketoconazole, fluoroquinolones. etc.
 Concurrent use of PPIs, H2 blocker should be
avoided.

22. Bismuth containing preparation
 Bismuth salisylates and colloidal bismuth subcitrate.
 React with protein in the base of ulcer and protect it
from peptic digestion.
 Stimulates secretion of PGE2, mucus and
bicarbonate.
 Anti-microbial effects against H. pylori.

23. Drugs that neutralized gastric acid
Ideal antacids
1. Insoluble and neutralize acid
2. Should not liberate CO2
3. Non-absorbable
4. Should not disturb acid-base balance

24. Types of antacids
Systemic: sodium bicarbonate and sodium citrate
Non systemic: magnesium hydroxide, magnesium
trisilicate, aluminum hydroxide gel and calcium
carbonate.

25. Antifoaming agents
 Methylpolysiloxane
 Oxethazaine
 Sodium alginate

26. Anti H. pylori agents
 Gram negative, rod shaped bacteria
associated with gastritis, duodenal ulcer,
gastric ulcer and gastric carcinoma.
 Cause mucosal inflammation
 Ammonia produced by urease activity
damage cells.

27. Combination therapy
 To prevent or delay development of resistant
organism.
 Prevent relapse
 Promote rapid ulcer healing
 Eradicate H. pylori infection
 Treatment for 1 or 2 weeks required

28. Triple therapy x 14 days
Lansoprazole 30 mg BD+ clarithromycin 500 mg BD +
Amoxicillin 1 g BD
Quadruple therapy x 14 days
lansoprazole 30 mg BD + bismuth subsalicylate 525 mg QID +
tetracycline 500 mg QID + Metronidazole 500 TDS
After completion of above regimen, PPIs should be
continued for six more weeks.

29. Emetics and antiemetics pathways

30. Emetics and antiemetics
 Mechanism of vomiting
 Pregnancy, infection, drugs, radiation, painful
stimuli, motion sickness, metabolic and
emotional disturbances.
 Neurotransmitters involved Ach,
histamine,5HT and dopamine.

31. Emetics
 Mustard
 Common salt
 Ipecac
 Apomorphine
 Used for certain poisoning cases

32. Contraindications for emetics
 Emetics
 Children
 Unconscious patient
 Corrosive and caustic poisoning
 CNS Poisoning
 Kerosene poisoning

33. Antiemetics
Classification of antiemetics
 Anticholinergics: scopolamine, dicycloamine
 Antihistamines (H1-blockers): dimenhydrinate,
diphenhydramine, cyclizine,meclizine,
hydroxyzine,promethazine,doxylamine, cinnarizine
 5HT3-receptor antagonists: ondansetron,
granisetron, dolasetron, palonosetron

34. Antiemetics
 Prokinetic agents: metoclopramide,
domperidone
 Neuroleptics: chlorpromazine, fluphenazin,
prochlorperazine, haloperidol
 Cannabinoids: dronabinol
 Adjuvant antiemetics: glucocorticoids,
benzodiazepines

35. Anticholinergics as antiemetic
 Scopolamine for motion sickness, it blocks
afferent impulses from vestibular apparatus
to the vomiting center by its anticholinergic
action.
 Its sedative effects also contributes for its
antiemetic effect.
 Scopolamine not effective in other types of
vomiting.

36. Antihistamine H1 blocker as antiemetic
 Motion sickness, morning sickness, post
operative and other types of vomiting.
 Dimenhydrinate, diphenhydramine,
doxylamine, promethazine, cyclizine,
meclizine.
 Have sedative and anticholenergic action.
 Meclizine has longer duration of action.

37. 5HT3-receptor antagonist as antiemetic
 Ondensetron is prototype drug
 Granisetron, dolasetron,palanosetron.
 Blockade of 5HT3 receptor on vagal afferent in the
gut also block 5HT3 receptors in CTZ & STN.
 Used for anticancer drug-induced nausea and
vomiting, effective in hyperemesis of pregnancy,
postoperative and post radiation vomiting but not
effective in motion sickness.

38. 5HT3 receptor antagonist

39. Prokinetic drugs
 Drugs promote coordinated movements of
upper GIT and hasten gastric emptying are
called prokinetic drugs.
 Metoclopramide: D2 receptor antagonist
 Have central and peripheral action.
 Enhance release of Ach from myentric
neurons.
 Used in GERD

40. Mechanisms

41. Prokinetic effects

42. Neuroleptics
 Prochlorperazine
 Used for vomiting due to systemic infection,
drugs, uraemia.
 Cannabinoids: dronabinol used for cancer
chemotherapy
 Adjuvant antiemetics: glucocorticoids,
benzodiazepines.

43. Anti emetics