BDS 2nd year theory class

1. Drugs Used to treat Peptic
Ulcer Disease
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Assistant Professor, Maharajgunj MedicalCampus
2 March 2020 (19 Falgun 2076), Monday

2. By the end of this class, BDS 2nd year students
will be able to:
• Classify drugs used in Peptic Ulcer Disease (PUD)
• Explain the pharmacological basis of use of
different drugs for the treatment of PUD
• List the specific adverse drug reactions of
different drugs for the treatment of PUD
• Apply the gained knowledge to solve the clinical
situations related to PUD

3. Relevant Physiology: Gastric acid secretion

4. Drugs Used in PUD: Classification
Reduction of gastric
acid secretion
Neutralization of
gastric acids
Ulcer
protectives
Anti H pylori
drugs

5. Drugs Used in PUD: Classification
Reduction of gastric
acid secretion
Neutralization of
gastric acids
Ulcer
protectives
Anti H pylori
drugs
1. H2 anti histamines: Cimetidine, Ranitidine, Famotidine
2. Proton pump inhibitors: Omeprazole, Esomeprazole, Lansoprazole,
Pantoprazole
3. Anticholinergic drugs: Pirenzepine, propantheline
4. Prostaglandin analogues: Misoprostol

6. Drugs Used in PUD: Classification
Reduction of gastric
acid secretion
Neutralization of
gastric acids
Ulcer
protectives
Anti H pylori
drugs
1. Systemic: Sodium bicarbonate, sodium citrate
2. Non Systemic: Calcium carbonate, Magnesium hydroxide,
Magnesium trisilicate, Aluminium hydroxide gel,
Magaldrate

7. Drugs Used in PUD: Classification
Reduction of gastric
acid secretion
Neutralization of
gastric acids
Ulcer
protectives
Anti H pylori
drugs
• Sucralfate
• Colloidal bismuth subcitrate

8. Drugs Used in PUD: Classification
Reduction of gastric
acid secretion
Neutralization of
gastric acids
Ulcer
protectives
Anti H pylori
drugs
• Amoxicillin
• Clarithromycin
• Metronidazole, Tinidazole
• Tetracycline

9. Anticholinergics for PUD
• Nonselective: Atropine,
Propantheline,
Oxyphenonium
• Selective: Pirenzepine (M1)
• Cholinergic receptors:
• Muscuranic
• Nicotinic
• Muscuarnic receptors:
• M1 receptors:
• Stimulatory
• Gastric glands:
increased secretion

10. Anticholinergics for PUD
• Acts by reducing the gastric secretion volume
• Nonselective anticholinergics:
• High doses required
• Intolerable side effects
• Not used these days
• Selective anticholinergics:
• Reduces gastric secretion by 40-50%
• Less side effects at effective doses
• Not commonly used

11. Antihistamines in PUD
• H2 antihistamines are used:
• Competitive blockers: Cimetidine, Ranitidine, Roxatidine
• Non-competitive blockers: Famotidine
• H2 receptors:
• Gs coupled
• Increases gastric acid secretion
• Blocked by H2 antihistamines
• Acts by decreasing gastric acid secretion
• Basal, psychic, neurogenic, gastric phases decreased
• 60-70% inhibition of acid output

12. Antihistamines in PUD
• Uses
• Promote healing of gastric and duodenal ulcers
• Heal uncomplicated GERD
• Prevent occurrence of stress ulcers
• Gastrinoma
• Famotidine: Zollinger Ellison syndrome, prevention of aspiration
pneumonia
• PPIs preferred due to higher efficacy and equally good tolerability

13. Antihistamines in PUD
• Adverse Drug Reactions
• Well tolerated, low incidence of side effects
• Diarrhoea, headache, drowsiness, fatigue, muscular pain,
constipation
• CNS side effets (confusion, delirium, hallucinations, slurred
speech)
• Cimetidine:
• Galactorrhoea in females and gynaecomastia
• Reduced sperm count and impotence in males- rare

14. Drugs Used to treat Peptic
Ulcer Disease-II
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Assistant Professor, Maharajgunj MedicalCampus
5 March 2020 (22 Falgun 2076), Thursday

15. By the end of this discussion, BDS 1st year
students will be able to:
• Explain the pharmacological basis of use of
different drugs for the treatment of PUD
• List the specific adverse drug reactions of
different drugs for the treatment of PUD
• Apply the gained knowledge to solve the clinical
situations related to PUD

16. Proton pump inhibitors in PUD
• Inhibits common final steps in gastric secretion
• Dose-dependent action
• Can totally abolish HCl secretion
• Mechanism of action:
• Gets activated at pH < 5 (gastric pH)
• Reacts co-valently with H+ K+ ATPase pump (proton pump) and
inhibits irreversibly: Hit and Run Drugs
• Acid secretion resumes only after synthesis of new pump
molecules (~ 18 hrs)

17. Proton pump inhibitors in PUD
• Pharmacokinetics
• Administered orally in enteric coated (e.c.) form
• Do not be break or crush the tablets
• Oral bioavailability (omeprazole): ~50%
• Bioavailability reduced by food: should be taken in empty stomach, followed 1 hour later by a meal
• Omeprazole is highly plasma protein bound
• Rapidly metabolised in liver by CYP2C19 and CYP3A4 (plasma t½ ~1 hr)
• Excreted in urine
• Inhibition of HCl secretion occurs within 1 hr, reaches maximum at 2 hrs, is still half
maximal at 24 hrs and lasts for 2–3 days
• At steady state all PPIs produce 80–98% suppression of 24 hour acid output with
conventional doses
• Secretion resumes gradually over 3–5 days of stopping the drug

18. Proton pump inhibitors in PUD
• Uses
• Promote healing of gastric and duodenal ulcer
• Bleeding peptic ulcer
• Stress ulcers
• Gastro-esophageal reflex disorder
• Erosive esophagitis
• Zollinger Ellison Syndrome
• Prevention of recurrence of NSAIDs induced ulcer

19. Proton pump inhibitors in PUD
• Adverse effects:
• Rare, well tolerated
• Nausea, loose stools, headache, abdominal pain, muscle and joint pain,
dizziness (3-5%)
• Rashes, leucopenia, hepatic dysfunction
• Atrophic gastritis on prolonged use
• Accelerated osteoporosis among elderly patients: high dose and long term
use
• Omeprazole (prolonged use): gynecomastia, erectile dysfunction
• Subacute myopathy, arthralgias, headache and skin rashes have been
reported

20. Ulcer Protectives: Sucralfate
• Basic aluminum salt of sulfated sucrose
• Mechanism of action:
• Polymerizes at pH < 4 by cross linking of molecules,
assuming a sticky gel-like consistency
• Preferentially and strongly adheres to ulcer base,
especially duodenal ulcer
• Surface proteins at ulcer base are precipitated
• Acts as a physical barrier
• Dietary proteins get deposited on this coat

21. Ulcer protectives: Sucralfate
• Minimally absorbed after oral administration
• Should not be given with antacids
• Infrequently used now because of need for 4 large well-timed
daily doses and the availability of simpler and more effective
H2 blockers/PPIs.
• Indications:
• Ulcer healing (duodenal, gastric)
• Bile reflux
• Gastritis
• Prophylaxis of stress ulcers
• Topical: burns, bedsores, diabetic/ radiation ulcers, excoriated skin

22. Ulcer Protectives: Sucralfate
• Adverse drug reaction
• Constipation
• Hypophosphatemia
• Dry mouth and nausea

23. Ulcer Protectives: Colloidal Bismuth
Subcitrate
• It is a colloidal bismuth compound; water soluble but precipitates at
pH < 5
• Mechanism of action (possibilities):
• May increase gastric mucosal PGE2, mucus and HCO3 ¯ production
• May precipitate mucus glycoproteins and coat the ulcer base
• May detach and inhibit H.pylori directly
• Milk and antacids should not be taken concomitantly

24. Ulcer Protectives: Colloidal Bismuth
Subcitrate
• Majority eliminated unchanged in faeces
• Small amounts absorbed are excreted in urine
• Adverse drug reactions:
• Diarrhoea, headache and dizziness
• Poor patient acceptance of CBS
• Blackening of tongue, dentures and stools
• Inconvenient dosing schedule
• Indication: Add on drug for triple drug Anti- H. pylori therapy

25. Anti- H. pylori regimes

26. Clinical scenario 1
• You attend a patient of dental pain that was not managed adequately
by local measures
• The patient also gives a history of frequent dyspepsia
• You decide to start one of the NSAIDs drugs.
• Which NSAIDs would you choose?
• How will your new drug have effect on the dyspepsia of the patient? What
can you do to prevent aggravating the dyspepsia of the patient?

27. Clinical Scenario 2
• A patient came to you in ED with complains of pain abdomen and
sour brash for 30 mins.
• He had spicy food in quantities more that he usually consumes for his
dinner.
• You decide to prescribe one of the gastric acid lowering agent.
• Which drug would you prescribe?
• How is your option better that other gastric lowering agents?