Lecture presentation for BSc Nursing

1. DRUGS USED TO TREAT
PEPTIC ULCER DISEASE
DR. PRAVIN PRASAD
M.B.B.S., MD CLINICAL PHARMACOLOGY
ASSISTANT PROFESSOR, MAHARAJGUNJ
MEDICALCAMPUS
21 JUNE 2020 (7 ASAR 2077), SUNDAY

2. BY THE END OF THIS CLASS, BSN 1ST 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
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3. RELEVANT PHYSIOLOGY: GASTRIC ACID SECRETION
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4. DRUGS USED IN PUD: CLASSIFICATION
Reduction of
gastric acid
secretion
Neutralization of
gastric acids
Ulcer
protectives
Anti H
pylori
drugs
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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 5

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
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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
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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
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9. ANTICHOLINERGICS FOR PUD
• Nonselective: Atropine,
Propantheline,
Oxyphenonium
• Selective: Pirenzepine
(M1)
• Cholinergic receptors:
• Muscuranic
• Nicotinic
• Muscuarnic receptors:
• M1 receptors:
• Stimulatory
• Gastric glands:
increased
secretion
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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
50%
• Less side effects at effective
doses
• Not commonly used
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11. ANTIHISTAMINES IN PUD
• H2 antihistamines are used:
• Competitive blockers: Cimetidine, Ranitidine, Roxatidine
• Non-competitive blockers: Famotidine
• Acts by decreasing gastric acid secretion
• Basal, psychic, neurogenic, gastric phases decreased
• 60-70% inhibition of acid output
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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
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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
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14. 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)
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15. 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 metabolized 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
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16. 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
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17. 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
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18. 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
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19. 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
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20. ULCER PROTECTIVES: SUCRALFATE
• Adverse drug reaction
• Constipation
• Hypophosphatemia
• Dry mouth and nausea
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21. 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
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22. 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
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23. INTRODUCTION
• Basic substances which neutralize gastric acid and raise pH of gastric
contents
• Includes:
• Aluminum Hydroxide, Magnesium Carbonate, And Magnesium
Trisilicate
• Are Available As Tablets And Liquids
• May be combined with:
• Simethicone: reduces flatulence
• Alginates: protects the lining of the esophagus (gullet) from stomach
acid
• Sodium Alginate And Alginic Acid
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24. ANTACIDS: MECHANISM OF ACTION
• Neutralises the gastric acid
• Acid Neutralising Capacity: number of mEq of 1N HCl that are brought to pH 3.5 in 15
min (or 60 min in some tests) by a unit dose of the antacid preparation
• Leads to:
• Decrease in pain
• Allow the ulcers to heal
• Decreases the activity of pepsin
• Secreted as an inactive form, gets activated in pH < 4
• May lead to rebound acidity
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25. NON SYSTEMIC ANTACIDS
• Insoluble and poorly absorbed basic compounds react in stomach to form the
corresponding chloride salt
• Chloride salt again reacts with the intestinal bicarbonate so that HCO3¯ is not
spared for absorption—no acid-base disturbance occurs
• However, small amounts that are absorbed have the same alkalinizing effect as
NaHCO3
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26. NON SYSTEMIC ANTACIDS
• Magaldrate
• hydrated complex of hydroxymagnesium aluminate that initially reacts rapidly with
acid and releases alum. hydrox. which then reacts more slowly
• The freshly released alum. hydrox. is in the unpolymerized more reactive
form
• Thus, magaldrate cannot be equated to a physical mixture of mag. and alum.
Hydroxides
• It is a good antacid with prompt and sustained neutralizing action. Its ANC is
estimated to be 28 mEq HCl/g
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27. ANTACID COMBINATIONS
• Fast (Mag. hydrox.) and slow (Alum. hydrox.) acting components yield prompt as well
as sustained effect
• Mag. salts are laxative, while alum. salts are constipating: combination may annul each
other’s action and bowel movement may be least affected
• Gastric emptying is least affected; while alum. salts tend to delay it, mag./cal. salts
tend to hasten it
• Dose of individual components is reduced; systemic toxicity (dependent on fractional
absorption) is minimized.
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28. ANTI- H. PYLORI REGIMES
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29. CONCLUSION
• Drugs used for PUD is classified in 4 main groups
• Proton pump inhibitor is most commonly used in Acid-Peptic
Disease
• Highly effective
• Less side effects
• Anticholinergic drugs exert their therapeutic as well as adverse
effect due to blockade on muscarinic receptors
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