1. GASTRO-INTESTINAL DRUGS

2. GI Drugs Drugs for: Peptic ulcers GERD Emesis Motility Disorders
Diarrhea
constipation

3. Peptic Ulcer Drugs The Problems Solutions: Infection with H. pylori
Increased HCl secretion
Inadequate mucosal defense
Solutions:
Antimicrobials (amoxicillin)
H2- histamine blockers(Cimetidine)
Prostaglandins (Misoprostol)
Proton pump inhibitors (Omeprazole)

4. ANTIMICROBIAL Amoxicillin Metronidazole Tetracycline Clarithromycin
Triple therapy: PPI + Metronidazole or amoxicillin + clarithromycin
Quadruple therapy: Bismuth sub + metronidazole + tetracycline + PPI or H₂-receptor antagonist

5. ADJUNCT MANAGEMENT REST, RELIEVE STRESS STOP/REDUCE SMOKING/DRINKING
Inclination of the bed head at 45 degrees
DIET
NON-IRRITATING
FREQUENT

6. Regulation of gastric acid secretion
Gastric acid secretion by parietal cells of the gastric mucosa is stimulated by acetylcholine, histamine and gastrin.
The binding of AcH, gastrin and histamine to their various receptors results in the activation of protein kinases which in turn stimulates the H⁺/K⁺-ATPase proton pump to secrete hydrogen ions in exchange for K⁺ into the lumen of the stomach
Gastrin and AcH act by inducing an ↑ in calcium level
While receptor binding of prostaglandin E₂ and somatostatin inhibits adenylyl cyclase

8. H2 RECEPTOR BLOCKERS
Cimetidine
Ranitidine
Famotidine
Nizatidine

9. Mech Of Action:H2 receptor antagonists competitively inhibits the binding of histamine on H2 receptors located on gastric parietal cell, thereby preventing acid secretion into the stomach lumen.
It also inhibits gastric acid secretion induced by gastrin.

10. THERAPEUTIC USES
Peptic ulcers
Acute Stress ulcer
GERD

11. Side effects:
Headache, diarrhea, Mental confusion, muscular pain, dizziness
( ALSO GYNACOMASTIA ,GALACTORRHEA and REDUCED SPERM COUNT WITH CIMETIDINE)

12. Drug interaction:↓ absorption of drugs that require acidic medium for absorption e.g., ketoconazole, vit B12
Cimetidine is a P450 inhibitor and ↑es activity of drugs that are metabolized via P450

13. PROTON-PUMP INHIBITORS
OMEPRAZOLE
LANSOPRAZOLE
PANTOPRAZOLE
ESMOPRAZOLE
RAMIPRAZOLE
SIDE EFFECTS:
ACHLORHYDRIA
GASTRITIS

14. Action
Blocks the H⁺/K⁺ATPase pump, thereby preventing the secretion of H⁺ for K⁺ into the stomach lumen.

15. USES Erosive esophagitis Peptic ulcer GERD
Gastric acid hypersecretory states, including Zollinger -Ellison syndrome
A GASTRIN PROUCING TUMOR

16. PROSTAGLANDINS MISOPROSTOL(PGE1)
These inhibit the secretion of Hcl by stimulate production of mucus and bicarbonate ( Cytoprotective effect).
Only used for NSAID induced ulcers.
Not used commonly for others.
CI: DURING PREGNANCY

17. ANTIMUSCARINIC DRUGS Dicylomine Propantheline Pirenzepine Hyoscyamine
Mepenzolate

18. Uses: Muscarinic receptor stimulation increases secretory activity.
Mech of Action: prevents gastric acid secretion.
Not as effective as H2 receptor blockers
Uses:
Zollinger – Ellison Syndrome
Peptic ulcer disease

19. SE Dryness of mouth Blurred vision Urinary retention
Cardiac arrhythmias

20. MUCOSAL PROTECTIVES SUCRALFATE COLLOID BISMUTH SALTS
Prevents mucosal injury, reduce inflammation and heal existing ulcers.

21. SUCRALFATE
Mech Of Action: Complex of polyaluminum hydroxide and sulfated sucrose sulfate which binds proteins in normal and ulcerated mucosa forming a gel that acts as a physical barrier that impairs diffusion of HCl and degradation of mucus by acid and pepsin.
USES: Duodenal ulcer

22. COLLOID BISMUTH SALTS May inhibit pepsin activity
Increase secretion of mucus
Forms a gel that coats and protects the ulcer crater by preventing the diffusion of acid.

23. ANTACIDS SIDE EFFECT CONSTIPATION DIARRHOEA
DRUGS
Al(OH)3
Mg (OH )2
NaHCO3
COMMON SIDE EFFECT
– MAY AFFECT ABSORPTION OF MANY OTHER DRUGS
Azoles, floroquinolones, tetracyclines, warfarin, quinidine
SIDE EFFECT
CONSTIPATION
DIARRHOEA
SYSTEMIC ALKALOSIS, belching & flatulence
AL(OH)3: CONSTIPATION, hypophosphatemia, osteodystrophy

24. Anti-Emesis Drugs Why do we vomit?!
Stimulation of the “Vomiting Centers” , “chemoreceptor trigger zone” and vestibular system (which functions mainly in motion sickness).

25. EMESIS/VOMITING RECEPTORS INVOLVED DOPAMINE – DA2 SEROTONIN- 5 HT3
Histamine- H1-receptor via the vestibular system
Muscarinic: via the vestibular system

26. Anti-emetic MEDICATIONS used for chemotherapy induced emesis
DOPAMINE ANTAGONISTS- Prochlorperazine, Metoclopramide, Haloperidol
CANABINOIDS: DRONABINOL
CORTICOSTEROIDS – Dexamethasone
5-HT3 ANTAGONISTS
ONDANSETRON
GRANISETRON

27. Antiemetic agents for motion sickness
Anti histamines: diphenhydramine, dimenhydrinate, meclizine
Anti muscarinic:
Works via blockade of the vestibular system which gives afferent input to the vomiting center e.g., scopolamine

28. **ONDANSETRON** POWERFUL CENTRAL ACTING ANTIEMETIC COSTLY
CONTROLS VOMITING POSTOP AND IN PT’S UNDERGOING CANCER CHEM..
SE;
HEADACHE
DIARRHEA

29. Diarrhea - Three Mechanisms
Osmotic
osmoticant in intestine
Secretory
excessive mucosal secretion
toxins, Infections
Inflammatory
H2O

30. Lactase Deficiency… One Cause of Diarrhea
Enzymes
Deficiency of lactase at brush border
Presents as bloating, crampy pain, osmotic diarrhea
Microvillus

31. Antidiarrheals Antimotility Agents
Diphenoxylate, Loperamide
Both are meperidine derivatives
Activate presynaptic opioid receptors, inhibit Ach release → ↓ peristalsis
Adsorbents: by adsorping intestinal toxins
Kaolin, pectin
Agents that modify fluid/electrolyte transport
NSAIDS ( Inhibit prostaglandins)
Bismuth subsalicylate (Pepto Bismol)
Bismuth : decreases fluid secretion in the bowel

32. Bismuth subsalicylate (Pepto Bismol)
Decreases fluid secretion in the bowel.
Used for Traveler’s Diarrhea

33. Constipation Many Causes Neurogenic eg: Hirschsprung’s Muscle weakness
eg: post-surgery
Low-residue diets

34. LAXATIVES B. Bulking Agents: A. Irritants and Stimulants
Castor oil, aloe, Bisacodyl
Castor oil broken down into ricinoleic acid (irritant)
B. Bulking Agents:
Psyllium, bran, lactulose magnesium (form gels)
C. Stool softeners
Ducosate sodium, mineral oil, glycerin suppositories,.
H20
Bulking agent: forms gel causing water retention → ↑ peristaltic activity