1. H2 Blockers and Proton Pump Inhibitors
Dr. : Asmaa Fady
MD., MSC, M.B, B.Ch
اسم ورقم المقرر – Course Name and No.
4/27/2019

2. Learning objectives: By the end of the lecture, the student should,
Understand the key points of pathophysiology of the peptic ulcer disease
Enumerate various classes of drugs used in peptic ulcer disease
Define the characteristic pharmacokinetics, pharmacodynamics and side effects of H2 receptor blockers and PPI drugs used in peptic ulcer disease.
Know the cytoprotective drugs mainly misoprostol and its use in NSAIDs-induced peptic ulcer.
اسم ورقم المقرر – Course Name and No.
4/27/2019

3. Pathogenesis of peptic ulcer:
Peptic ulcer is a break in the gastric or duodenal mucosa that arises when the normal mucosal defensive factors are impaired or overwhelmed by aggressive luminal factors. This imbalance results in any degree of gastrointestinal mucosal irritation, inflammation or ulceration.
اسم ورقم المقرر – Course Name and No.
4/27/2019

4. Pathogenesis of peptic ulcer:
Aggressive factors
Defense factors
a- HCl.
a- Prostaglandins (E & I)
b- Pepsin.
b- Mucus.
c- Helicobacter Pylori.
c- Bicarbonates
d- Bile salts.
d- Blood supply
e- Mucosal regeneration
اسم ورقم المقرر – Course Name and No.
4/27/2019

5. Clinical Features of peptic ulcers
1. Symptoms & signs:
Epigastric pain & tenderness.
Anorexia, Nausea & Vomiting.
Hemorrhage
2. Investigations
Endoscopy
Presence of H. pylori: Endoscopic biopsy, serological test & Urea breath test.
Associated Complications:
1- Upper gastrointestinal bleeding (patients may present with hematemesis, melena, fatigue caused by anemia, or syncope).
2- Perforation.
3- Obstruction. Patients with recurrent duodenal or pyloric channel ulcers may develop pyloric stenosis
4-Silent ulcers and complications are more common in older patients and in patients taking NSAIDs.
4/27/2019

6. Goals of Therapy: 1- Relief of pain. 2- Promotion of healing.
3- Prevention of recurrence.
4- Preventing ulcer complications
اسم ورقم المقرر – Course Name and No.
4/27/2019

7. Drug therapy used in Ttt of peptic ulcer
A) Antacids (Neutralization of secreted HCl) B) Anti-secretory Drugs (Reduction or inhibition of Acid Secretion) C) Mucosal Protectives (Enhancement of Mucosal Resistance) D) Eradication of H. pylori. E) Other adjuvant Drugs.

8. اسم ورقم المقرر – Course Name and No.
4/27/2019

9. Drug therapy used in Ttt of peptic ulcer
1) Antacids (Neutralization of secreted HCl):
- Aluminum Hydroxide + Magnesium hydroxide
2) Antisecretory Drugs (Reduction of Acid Secretion):
I- H2-Receptor Blockers.
II- Proton Pump Inhibitor (H+/K+ ATPase Inhibitors).
III- Antimuscarinic Drugs (M3 receptors)
IV- Gastrin Antagonists.
V- Prostaglandins (E &I)
3) Mucosal Protectives (Enhancement of Mucosal Resistance):
1- Sucralfate.
2- Prostaglandins
4) Eradication of H. pylori:
1- Metronidazole Bismuth compounds. 3- Amoxicillin Tetracycline. 5- Clarithromycin.
5) Other adjuvant Drugs:
1- Sedatives or Tranquillizers e.g. Diazepam (# Psychic effect on acid secretion)
2- Tricyclic Antidepressants.

10. 1. Antacids: very weak agents
They Produce:
1- Chemical Neutralization of HCl Relief of Pain.
2- Elevation of pH Activity of Pepsin.
3- Some PGs & Eradication of H. pylori.
Useful in treatment of:
1- Peptic Ulcer Rapid relief Supplement other drugs during initiation of treatment.
2- Gastro-Esophageal Reflux Disease (GERD) & Heart burn.
3- Gastritis
Classification: 1- Chemical Anti-Acids Physical Anti-Acids.
Multiple side effects.
4/27/2019

11. 2. Anti-secretory Drugs (Reduction of Acid Secretion):
H2-Receptor Blockers: Cimetidine- ranitidine- famotidine- Nizatidine
Anti-muscarinic Drugs (M3): Pirenzepine.
Gastrin Antagonists: Gastrin receptor blockers: Proglumide. N.B.: Gastrin is a hormone secreted by cells in the pyloric glands and increases HCL and pepsin secretion
Prostaglandins: Misoprostol.
Proton Pump Inhibitor (irreversible H+/K+ ATPase Inhibitors): Omeprazole- pantoprazole- lansoprazole- rapeprazole- esomeprazole.
اسم ورقم المقرر – Course Name and No.
4/27/2019

12. 2. Anti-secretory drugs: I) H2 receptor blockers: * Cimetidine
Pharmacokinetics:
Well Absorbed Orally & Parentally.
Distributed ALL over the body. (Passes BB & Placental barrier).
1/3 Metabolized in liver. It is a hepatic microsomal enzyme inhibitor.
2/3 Excreted Unchanged in Urine & Milk.
Pharmacodynamics:
1- Selective Competitive Blocker of Histamine H2-receptors. No action on H1 or H3. ( 70%) of HCl secretion.
2- Reduces gastric acidity:
a- Both volume & Hydrogen ion concentration.
b- Formation of pepsin.
3- Does Not affect gut motility.
اسم ورقم المقرر – Course Name and No.
4/27/2019

13. 2. Anti-secretory drugs: I) H2 receptor blockers:* Cimetidine
Therapeutic Uses of Cimetidine:
1- Peptic Ulcer (Gastric & Duodenal):
*Promotes the healing of the ulcers & prevent their recurrence.
**Decrease the dose in Renal & hepatic patients.
2- Ulcers due to Stress and Iatrogenic ulcers.
3- I.M. or I.V. in Upper G.I.T. bleeding after burn, trauma or acute renal failure
4- Pre-anesthetic in emergency operation & labor to prevent aspiration of gastric HCl.
اسم ورقم المقرر – Course Name and No.
4/27/2019

14. 2. Anti-secretory drugs: I) H2 receptor blockers:* Cimetidine
Side Effects & Drug Interactions of Cimetidine: 1- Sudden stop : Recurrence of the ulcer & Bleeding. 2- GIT Upsets : Constipation or diarrhea. 3- Hypersensitivity reactions e.g. Skin rash & Itching. 4- Affect liver & kidney (increases Serum creatinine). 5- Hepatic Microsomal Enzyme Inhibitor ( decreases Cytochrome P450): decrease Metabolism of Warfarin, Theophylline & Phenytoin.
اسم ورقم المقرر – Course Name and No.
4/27/2019

15. 2. Anti-secretory drugs: I) H2 receptor blockers:* Cimetidine
Side Effects & Drug Interactions of Cimetidine: 7- In Males (Anti-Androgen) : Gynecomastia & Spermatic count. 8- In Females (Increases Prolactin) : Galactorrhea & Infertility. 9- Confusion and delirium in old age (pass BBB) 10- Blood Dyscrasias : Agranulocytosis, Aplastic Anemia & Thrombocytopenia. 11- Muscle pain.
اسم ورقم المقرر – Course Name and No.
4/27/2019

16. 2. Anti-secretory drugs: I) H2 receptor blockers:
2. Anti-secretory drugs: I) H2 receptor blockers: * Ranitidine, Nizatidine and Famotidine
1-Pharmacokinetics similar to Cimetidine BUT LONGER & Not pass BBB.
2- Pharmacodynamics Similar to Cimetidine BUT STRONGER (5-10 Times).
3- Side Effects similar to Cimetidine BUT SAFER :
a- NO Hepatic Microsomal Enzyme Inhibition.
b- NO effect on males or females.
d- NO BBB (NO CNS effects in Elderly).
Famotidine (Pepcid): the strongest one.
Extremely safe drugs
اسم ورقم المقرر – Course Name and No.
4/27/2019

17. 2. Anti-secretory drugs: II) Proton Pump Inhibitors (PPIs)
1- Omeprazole (Losec)
2- Esomeprazole (Nexium)
3- Lansoprazole (Lanzor)
4- Pantoprazole (Controloc)
5- Rabeprazole
Weak basic drugs.
Acid sensitive drugs (destructed by HCL): use enteric coated tablets.
Prodrugs.
اسم ورقم المقرر – Course Name and No.
4/27/2019

18. 2. Anti-secretory drugs: II) Proton Pump Inhibitors (PPIs)
Pharmacokinetics
Well absorbed orally. Affected by gastric acidity. Given as enteric coated preparation. Should be given on empty stomach. Pantoprazole also given intravenously.
Pass BBB & pass Placental barrier
Concentrated in acid canaliculi of gastric parietal cells (weak bases)
Hepatic metabolism.
Metabolites are excreted in urine.
اسم ورقم المقرر – Course Name and No.
4/27/2019

19. 2. Anti-secretory drugs: II) Proton Pump Inhibitors (PPIs)
Pharmacodynamics
1- Prodrugs: Activated in the acid environment of the secretory canaliculi of the parietal cells of the stomach. Since it requires acid for activation. 2- Irreversible inhibitor of H+/K+ ATPase enzyme. Their effect is prolonged until synthesis of new H+/K+ ATPase enzyme. 3- decrease gastric acidity up to 100%. BUT NO effect on gastric motility. 5- increase Gastrin secretion (unimportant)
اسم ورقم المقرر – Course Name and No.
4/27/2019

20. 2. Anti-secretory drugs: II) Proton Pump Inhibitors (PPIs) Therapeutic uses:
1- peptic ulcer.
2- GERD (gastro-esophageal reflux disease).
Extremely safe drugs
اسم ورقم المقرر – Course Name and No.
4/27/2019

21. 2. Anti-secretory drugs: II) Proton Pump Inhibitors (PPIs) Side effects and drug interactions:
1- CNS : Headache, Dizziness & Drowsiness.
2- GIT : Nausea, Diarrhea & Abdominal colic.
3- Omeprazole (HME I) decreases Metabolism of Warfarin, Theophylline & Phenytoin.
4- Prolonged use (years):
decrease Ca absorption : ppt. osteoporosis and bone fractures.
Decreased Vit. B Vit. B 12 deficiency anemia.
Increase the risk of (bacterial colonization): respiratory & enteric infections due to the loss of the antibacterial properties of an acidic environment.
اسم ورقم المقرر – Course Name and No.
4/27/2019

22. 2. Anti-secretory drugs: III- Anti-Muscarinic Drugs
Pirenzepine & Telenzepine (atropine substitutes)
Selective M1-blockers Acidity.
Selective blockade of M1 receptors on vagal ganglia innervating the stomach motility
More effective when used with other drugs e.g. H2- blockers.
Adverse effects (atropine like reactions).
Contraindications: glaucoma & prostatic hypertrophy.
اسم ورقم المقرر – Course Name and No.
4/27/2019

23. 3. Mucosal Protective Agents
They act by Enhancement of Mucosal Resistance via increasing protective PG level.
PG E2 & I2 (Misoprostol)
Sucralfate.
Colloidal Bismuth compounds.
اسم ورقم المقرر – Course Name and No.
4/27/2019

24. 3. Mucosal Protective Agents: a. Misoprostol: PG E1 analogue.
Mechanism:
1- decrease H Cl secretion (Anti-Secretory).
2- increase Mucus secretion
3- increase Blood supply to the mucosa.
4- increase HCO3 secretion.
5- Promotes healing of ulcer (vasodilators, promote healing)
6- Prevent gastric ulcer induced by corticosteroids or NSAID (iatrogenic ulcer)
Side Effects:
a- Oxytocic: ppt. uterine contractions: (Abortion). Contraindicated in pregnancy.
b- Diarrhea, Nausea & abdominal pain
اسم ورقم المقرر – Course Name and No.
4/27/2019

25. 3. Mucosal Protective Agents: b. Sucralfate : sucrose - AL++ - sulfate
Mechanism:
in the presence of HCl, it dissociates into sulfate sucrose and AL hydroxide:
Sulfate sucrose part Attach to proteins present in mucous and convert it into gel which cannot be destructed by pepsin.
The negative charge of sulfate allows demulcent action on ulcer base.
Adsorb destructive bile and pepsin.
↑ PGs secretion
Side Effects: due to AL
1- Constipation
2- ↓ Absorption of food & drugs (cimetidine – digoxin – phosphate – tetracycline – quinolone – ketoconazole- iron)
اسم ورقم المقرر – Course Name and No.
4/27/2019

26. 3. Mucosal Protective Agents: c. Colloidal Bismuth compounds
Increase PGs, Coats ulcer, stimulates mucus & bicarbonate secretion
Direct antimicrobial activity against H. pylori.
Weak Antacid action.
May cause blackening of stools & tongue
Not used for long periods – bismuth toxicity.
اسم ورقم المقرر – Course Name and No.
4/27/2019

27. 4. Eradication of Helicobacter pylori
Triple Therapy
Quadruple therapy
اسم ورقم المقرر – Course Name and No.
4/27/2019

28. Triple Therapy The BEST among all the Triple therapy regimen is:
Omeprazole /or Lansoprazole / 30 mg bd
Clarithromycin mg bd
Amoxycillin /or Metronidazole gm / 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
اسم ورقم المقرر – Course Name and No.
4/27/2019

29. Quadruple Therapy Given when Triple Therapy fails
Omeprazole or / Lansoprazole / 30 mg bd
Bismuth subsalycilate tabs qid
Metronidazole mg qid
Tetracycline mg qid
اسم ورقم المقرر – Course Name and No.
4/27/2019

30. اسم ورقم المقرر – Course Name and No.
4/27/2019