GI drugs : PPIs , Antacids and Ulcer protectives

Ppt regarding ,
GI DRUGS
PPIs , Antacids and Ulcer protectives

1. GI DRUGS PPIs , Antacids and Ulcer protectives Dr Aakash Chandan Labh 1 st Year Junior Resident Department of Pharmacology & Therapeutics King George’s Medical University, U.P, India

2. CONTENTS Introduction PPIs Antacids Ulcer protectives Summary References

3. PROTON PUMP INHIBITORS

4. PROTON PUMP INHIBITORS Most potent supressors of gastric acid secretion are inhibitors of the gastric H + K + ATPase or proton pump Diminish the daily production of acid (basal and stimulated) by 80-90% Prodrugs that require activation in an acid environment.

5. PROTON PUMP INHIBITORS Omeprazole - Prototype Esomeprazole Lansoprazole Pantoprazole Rabeprazole Ilaprazole

6. Once-daily dosing – sufficient to achieve an effective level of acid inhibition Amount of H + K + ATPase increases after fasting – should be given before first meal of the day.

7. To prevent degradation of PPIs by acid in the gastric lumen and improve oral bioavailability, oral dosage forms are supplied in different formulations: Enteric-coated pellets within gelatin capsules (rabeprazole) Delayed-release tablets (lansoprazole, pantoprazole, rabeprazole) Delayed-release capsules ( dexlansoprazole , esomeprazole, omeprazole, lansoprazole) Delayed-release oral suspension (esomeprazole, omeprazole, pantoprazole)

8. PHARMACOKINETICS Administered orally - Enteric coated tablet or granules filled in capsules should not be broken or crushed before swallowing. Bioavailability of all PPIs is reduced by food - should be taken in empty stomach when only ~10% of proton pumps are active followed 1 hour later by a meal to activate the H+K+ATPase at a time when plasma concentration of the PPI is maximal.

9. PHARMACOKINETICS Rapidly absorbed Highly protein bound and Extensively metabolized by hepatic CYPs, particularly CYP2C19 and CYP3A4.

10. USES 1. Peptic ulcer Rapid pain relief Faster healing , Duodenal ulcers – 2-4 weeks, Gastric ulcers – 4-8 weeks Maintenance therapy with lower doses – prevent ulcer relapse Integral component of H-pylori therapy DOC- NSAID induce gastric/duodenal ulcers.

11. USES 2.Bleeding peptic ulcer 3.Stress ulcers 4.Gastroesophageal reflux disease - DOC 5.Zollinger-Ellison syndrome – High dose oral PPIs- DOC 6.Aspiration pneumonia

12. ADVERSE EFFECTS Minimal and are very safe drugs. Nausea, loose stools, headache, sleeplessness, muscle and joint pain, dizziness No harmful effects of PPIs during pregnancy are known. Accelerated osteoporosis among elderly patients (possibly due to reduced calcium absorption in the absence of gastric acid) has been associated with high-dose long-term use of PPIs for GERD.

13. ANTACIDS

14. ANTACIDS Basic substances - neutralize gastric acid and raise pH of gastric contents. Antacids do not decrease acid production. Systemic and Nonsystemic Antacids

15. Systemic Antacids 1.Sodium bicarbonate Water soluble, Acts instantaneously, Duration of action –short -> Quick symptom relief Potent Neutralizer Demerits – Absorbed systemically, produces CO 2 in stomach, Acid rebound, Increases Na + load Uses – Heartburn, alkalinize urine, treat acidosis 2.Sodium Citrate

16. Nonsystemic Antacids Insoluble and poorly absorbed basic compounds React in stomach to form corresponding chloride salt No acid – base disturbances Eg – Magnesium Hydroxide Magnesium Trisilicate Aluminium hydroxide gel Magaldrate Calcium Carbonate

17. Antacid combinations Combination of 2 or more antacids. Advantages Fast (Mg Hydroxide) and slow (Al Hydroxide) – acting componenets yield prompt as well as sustained effect. Mag. Salts are laxative, Al – constipating , combination – annul each other’s action, Bowel movement – least affected

18. Gastric emptying – least affected , Al salts delay, Mg/Ca salts – hasten Dose of individual components reduced, systemic toxicity – minimized Drug Interaction By raising gastric pH and by forming complexes, the non-absorbable antacids reduce the absorption of drugs – tetracyclines, Iron salts, Flurorquinolones , Ketoconazole, H2 blockers etc. Uses Intercurrent pain relief, dyspepsia, acidity

19. ULCER PROTECTIVES

20. ULCER PROTECTIVES 1.Sucralfate Basic aluminium salt of sulfated sucrose Sucralfate polymerizes at pH <4 by cross linking of molecules, assuming a sticky gel-like consistency. Preferentially and strongly adheres to the ulcer base Acts as a physical barrier - preventing acid, pepsin and bile from coming in contact with the ulcer base. Dietary proteins get deposited on this coat, forming another layer.

21. No acid neutralizing action Delays Gastric emptying Minimally absorbed after oral administration. Antacids should not be taken with Sucralfate Dose – ulcer healing dose- 1g taken in empty stomach 1 hour before the 3 major meals and at bed time for 4-8 weeks. 2. Colloidal Bismuth Subcitrate

22. SUMMARY PPIs - potent supressors of gastric acid secretion are inhibitors of the gastric H + K + ATPase or proton pump – decrease the daily production of acid. Antacids - Basic substances - neutralize gastric acid and raise pH of gastric contents. Ulcer Protectives - Preferentially and strongly adheres to the ulcer base acts as a physical barrier.

23. REFERENCES Sharkey K, MacNaughton W. Pharmacotherapy for gastric acidity, peptic ulcers and gastroesophageal reflux disease. In: Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw Hill; 2023. p. 1071-1084 Tripathi KD. Drugs for peptic ulcer and GERD. In: Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Medical Publishers; 2019. p. 695-721.

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