3Peptic Ulcer Drugs The Problems Solutions: Infection with H. pylori Increased HCl secretionInadequate mucosal defenseSolutions:Antimicrobials (amoxicillin)H2- histamine blockers(Cimetidine)Prostaglandins (Misoprostol)Proton pump inhibitors (Omeprazole)
4ANTIMICROBIAL Amoxicillin Metronidazole Tetracycline Clarithromycin Triple therapy: PPI + Metronidazole or amoxicillin + clarithromycinQuadruple therapy: Bismuth sub + metronidazole + tetracycline + PPI or H₂-receptor antagonist
5ADJUNCT MANAGEMENT REST, RELIEVE STRESS STOP/REDUCE SMOKING/DRINKING Inclination of the bed head at 45 degreesDIETNON-IRRITATINGFREQUENT
6Regulation 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 stomachGastrin and AcH act by inducing an ↑ in calcium levelWhile receptor binding of prostaglandin E₂ and somatostatin inhibits adenylyl cyclase
9Mech 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.
16PROSTAGLANDINS 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
21SUCRALFATEMech 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
22COLLOID BISMUTH SALTS May inhibit pepsin activity Increase secretion of mucusForms a gel that coats and protects the ulcer crater by preventing the diffusion of acid.
23ANTACIDS SIDE EFFECT CONSTIPATION DIARRHOEA DRUGSAl(OH)3Mg (OH )2NaHCO3COMMON SIDE EFFECT– MAY AFFECT ABSORPTION OF MANY OTHER DRUGSAzoles, floroquinolones, tetracyclines, warfarin, quinidineSIDE EFFECTCONSTIPATIONDIARRHOEASYSTEMIC ALKALOSIS, belching & flatulenceAL(OH)3: CONSTIPATION, hypophosphatemia, osteodystrophy
24Anti-Emesis Drugs Why do we vomit?! Stimulation of the “Vomiting Centers” , “chemoreceptor trigger zone” and vestibular system (which functions mainly in motion sickness).
25EMESIS/VOMITING RECEPTORS INVOLVED DOPAMINE – DA2 SEROTONIN- 5 HT3 Histamine- H1-receptor via the vestibular systemMuscarinic: via the vestibular system
26Anti-emetic MEDICATIONS used for chemotherapy induced emesis DOPAMINE ANTAGONISTS- Prochlorperazine, Metoclopramide, HaloperidolCANABINOIDS: DRONABINOLCORTICOSTEROIDS – Dexamethasone5-HT3 ANTAGONISTSONDANSETRONGRANISETRON
27Antiemetic agents for motion sickness Anti histamines: diphenhydramine, dimenhydrinate, meclizineAnti 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;HEADACHEDIARRHEA
29Diarrhea - Three Mechanisms Osmoticosmoticant in intestineSecretoryexcessive mucosal secretiontoxins, InfectionsInflammatoryH2O
30Lactase Deficiency… One Cause of Diarrhea EnzymesDeficiency of lactase at brush borderPresents as bloating, crampy pain, osmotic diarrheaMicrovillus
31Antidiarrheals Antimotility Agents Diphenoxylate, LoperamideBoth are meperidine derivativesActivate presynaptic opioid receptors, inhibit Ach release → ↓ peristalsisAdsorbents: by adsorping intestinal toxinsKaolin, pectinAgents that modify fluid/electrolyte transportNSAIDS ( Inhibit prostaglandins)Bismuth subsalicylate (Pepto Bismol)Bismuth : decreases fluid secretion in the bowel
32Bismuth subsalicylate (Pepto Bismol) Decreases fluid secretion in the bowel.Used for Traveler’s Diarrhea
34LAXATIVES B. Bulking Agents: A. Irritants and Stimulants Castor oil, aloe, BisacodylCastor oil broken down into ricinoleic acid (irritant)B. Bulking Agents:Psyllium, bran, lactulose magnesium (form gels)C. Stool softenersDucosate sodium, mineral oil, glycerin suppositories,.H20Bulking agent: forms gel causing water retention → ↑ peristaltic activity