10AIMS OF ULCER TREATMENT Promotion of ulcer healing.Symptomatic relief of pain.Prevention of recurrence (relapse).Prevention of complications
11I. Gastric hyposecretory drugs. DRUG TREATMENT OF PEPTIC ULCERI. Gastric hyposecretory drugs.H2 receptor blockersMuscarinic receptor blockersProton pump inhibitorsII. Eradication of H. pylori infectionsTo prevent relapse
12DRUG TREATMENT OF PEPTIC ULCER III. Mucosal cytoprotective agents.SucralfateColloidal bismuthProstaglandin analoguesIV. Neutralizing agents (antacids).
13Gastric hyposecretory drugs H2 receptor blockersMuscarinic receptor blockersProton pump inhibitorsDecreasing gastric acidity can reduce absorption of ketoconazole & iron preparation, digoxin.
14Proton Pump Inhibitors Mechanism of actionIrreversible inhibition of proton pump (H+/ K+ ATPase) that is responsible for final step in gastric acid secretion from the parietal cell.PP inhibitors include:OmperazoleLansoprazolePantoprazole
15Illustration of Gastric secretion by parietal cells
16Pharmacokinetics: They are prodrugs – taken orally. are given as enteric coated capsulesThey are rapidly absorbed from the intestine.They are activated in the acidic medium of the secretory parietal cell canaliculus.They are inactivated if (combined with H2 receptor blockers).
17Have long duration of action (> 12 h-24 h). Once daily dose is sufficientBioavailability is reduced by food.Given 1 h before meal.Are metabolized in the liver by CytP450.They are more potent than H2 receptor blockersInhibits basal and stimulated-acid secretion.Dose reduction is required in severe liver failure.
18USES1. Zollinger Ellison syndrome (First choice).2. Resistant severe peptic ulcer ( 4-8 weeks).3. Reflux esophagitis.4. Eradication of H. pylori.
20H2 receptor blockers Mechanism of action They competitively and reversibly block to H2 receptors on the parietal cells thus reduce gastric secretion. They include:CimetidineRanitidineFamotidineNizatidine
21Pharmacokinetics Good oral absorption Plasma half life (1-3 h). Duration (4-12 h).First pass metabolism (50% Except Nizatidine 100 % bioavailability).Given before meals.Metabolized by liver.Excreted mainly in urine.Cross placenta & excreted in milk
25Adverse Effects of H2 blockers: GIT disturbances: nausea, vomitingCNS effects:Headache, dizziness, confusion (elderly – renal or hepatic dysfunction).CVS effectsBradycardia and hypotension (rapid I.V.)
26Cimetidine has other adverse effects: Endocrine effectsAntiandrogenic actions (gynecomasteia – impotence)Galactorrhea in women.Cytochrome P450 inhibitor: decrease metabolism of oral anticoagulant, phenytoin, benzodiazepines.
27Precautions Maintenance dose (Relapse may occur). Dose reduction in severe renal or hepatic failure and elderly.
28ANTICHOLINERGIC DRUGS Oxyphenonium, dicyclomine 1. Non selective muscarinic blockers:Oxyphenonium, dicyclomineDecreased gastric motilityDelayed gastric emptying- Heart burn- Atropine like side effects.
29Pirenzepine - Telenzepine 2. Selective muscarinic blockers:Pirenzepine - TelenzepineBlocks M1 receptors on the parietal cells.Selectively inhibit gastric acid secretionNo effect on gastric motilityLess side effects of cholinergic blockade.No effect on CNS.Dose : 50 mg bid for 4-6 weeksUses1.Adjuvants to H2 receptor blockers.2. decrease nocturnal pain in peptic ulcer.
30Eradication Of H Pylori Is a bacteria that causes chronic inflammation of the inner lining of the stomach.Produce enzymes (tissue damage), inflammation – ulcer.Duodenal ulcer - Gastric ulcerRisk factor for esophagus and stomach cancers.Eradication is important to prevent recurrenceof ulcer.
31Helicobacter pylori in association with gastric mucosa
32Treatment Combined therapy is usually used. Clarithromycin, tetracycline, amoxicillinProton pump inhibitors or H2 receptor blockers.Bismuth compoundsMetronidazole.Resistance may develop to antibiotics.Better eradication is obtained using proton pump inhibitors & clarithromycin.
33TreatmentThe standard first-line therapy is "triple therapy" consisting of proton pump inhibitors as omeprazole and the antibiotics clarithromycin and amoxicillin.
36Sucrose octaphosphate + aluminium hydroxide SucralfateSucrose octaphosphate + aluminium hydroxideMechanism of actionIn acidic pH, sucralfate dissociates into its components.The negatively charged sucrose octaphosphate binds with positively charged protein molecules found in damaged mucosa (Coat over the ulcer).Promote ulcer healing.Inhibition of pepsin.
37Stimulation of mucosal protective mechanisms (mucous and bicarbonates secretion). KineticsOrally, poor systemic absorption.Duration (6 h).Excreted in feces.Avoid co-administration of antacid or H2 blocker.Bette taken on empty stomach.
38Therapeutic UsesBenign gastric and duodenal ulcer.Chronic gastritis.Adverse effectsConstipation and dry mouth.Interferes with absorption of some drugs tetracycline, theophyline, Tricyclic antidepressant.
392. MisoprostolProstaglandin Analogues (PGE1 ) HCL secretion.Promote tight junction of gastric cells prevent back diffusion of HCL. mucous and bicarbonate secretion.blood flow of mucosa improve healing of ulcer.KineticsOrally, 30 min.is converted into active metabolite.Excreted in urine- must be taken 3-4 times/day.
413. Colloidal Bismuth compounds Bismuth subcitrateTripotassium dicitrato bismuthate.Mechanism of ActionIt forms a precipitate with mucous cover the ulcer with a protective coat that prevent effect of HCl.Promote healing of ulcer.Bactericidal effect against campylobacter pylori .Decrease activity of pepsin Mucous & bicarbonate secretion.
42Adverse EffectsBlack stool.Teeth discoloration.Encephalopathy (in renal dysfunction).USESTriple therapy for eradication of H. pylori.Benign gastric & duodenal ulcer.Traveller’s diarrhea
43Drugs That Neutralize HCL (Antacids) Drugs used to relief gastric pain associated with hypersecretion of HCL.Mechanism of ActionNeutralization of HCL.Inhibition of pepsin (inactive at PH 5).Therapeutic Usesrelief pain of peptic ulcer.Dyspepsia.
44I - Systemic AntacidsSodium bicarbonateNaHCO3 + HCL NaCL + CO2.Disadvantages1. Rebound hyperacidity.Stomach distension due to CO2 liberation pain sensation.3. Sodium load salt and water retention( # in cardiac patients).4. Systemic alkalosis.
45Calcium CarbonateCaCO3+HCL CaCl2 + H2O + CO2Disadvantages1. Liberation of CO2 stomach distension2. 10% is absorbed hypercalcemia.3. Rebound hyperacidity.4. Milk alkali syndrome (hypercalcemia, renal failure).
46II – Non Systemic Antacids 1. Aluminum Hydroxide Gel2. Magnesium TrisilicateAl (OH)3 + HCL HCL3 + H2O.AdvantagesLonger duration of action.Gradual neutralization of HCL No rebound hyperacidity.Adsorbs pepsin.Minimal change in acid base balance.No stomach distention