digestive system part 2

I. DRUGS USED IN ACID-PEPTIC DISEASES

PROTON PUMP INHIBITORS I. DRUGS USED IN ACID-PEPTIC DISEASES • available from the late 1980s • H+/K+ ATPase catalyze the final step in acid secretion 16 • PPIs block any stimuli induced secretion • any degree of inhibition • even in a single dose

PROTON PUMP INHIBITORS I. DRUGS USED IN ACID-PEPTIC DISEASES • Irreversible proton pump inhibition, resynthesis >18h • block 98% of acid secretion, need 3-4 days of daily medication • the „pro-drug” is acid sensitive (enteric-coated capsules) • lipophylic weak bases (pK a 4-5), diffuse across the cell 17 membrane > concentrated within the parietal canaliculi (>1000-fold) • protonated, converted to active, reactive sulfonamide • optimal effect: 30-60 min before meal • short half-life (0.5-2 h) • hepatic metabolism, no renal clearence S.E.: diarrhea, headache, abdominal pain, subnormal vitamin B12 levels, abnormal Ca2+ absorption, ECL-cell hyperplasia, hypergastrinemia, achlorhydria, GI infection (Salmonella, Shigella)

hypergastrinemia, achlorhydria, GI infection (Salmonella, Shigella)
I. DRUGS USED IN ACID-PEPTIC DISEASESSubstituted benzimidazolesOmeprazole LOSEC racemic mixture of R- and S-isomersavailable as i.v. Formulationhyperplasia of ECL cellsno clinical significance

PROTON PUMP INHIBITORSsustained hypergastrinaemia due to acid inhibition
hypochlorhydria bacterial overgrown nitrate to nitrozamin
Esomeprazole NEXIUM S-isomer of omeprazole
Pantoprazole binds to two cysteins, available as i.v. formulatiomust be given as a continuous infusion over 24-48 h)Lansoprazole PREVACID Rabeprazole AcipHex

I. DRUGS USED IN ACID-PEPTIC DISEASES 3. Zollinger – Ellison syndrome First choice drug 4. Gastrinoma High doses Clinical uses of PPIs 20 Side effects - nausea - vomiting - abdominal pain - headache

D, Prostaglandin analog I. DRUGS USED IN ACID-PEPTIC DISEASES (ulcer disease, GERD, acid dyspepsia) 28 acid inhibition and mucosal protective effects: reduces histamine-stimulated cAMP production stimulates mucus and bicarbonate secretion enhances mucosal blood flow increases epithelial regeneration (cytoprotective, vasodilatative, inhibits thrombocyte aggr.) S.E.: diarrhoea, cramps, abortion Strongly limited use

I. DRUGS USED IN ACID-PEPTIC DISEASES II. DRUGS STIMULATING GI MOTILITY III. LAXATIVES IV. ANTIDIARRHEAL AGENTS V. DRUGS USED FOR THE TREATMENT OF PHARMACOLOGY OF THE GI TRACT 29 IRRITABLE BOWEL SYNDROME (IBS) VI. ANTIEMETIC AGENTS VII. DRUGS USED TO TREAT INFLAMMATORY BOWEL DISEASE S VIII. PANCREATIC ENZYME SUPPLEMENTATION IX. BILE ACID THERAPY, TREATMENT OF HEPATITIS B and C, PBC, AACH X. DRUGS USED TO TREAT COMPLICATIONS OF CIRRHOSIS

H1-receptor blockers (antihistamines) also have anticholinergic effect on M1 receptors Diphenhydramine, Dimenhydranate, Cinnarazine - weak antimetics - poorly effective in vomiting caused by the kemosensitive trg. Z - seasick, emetic compounds, pregnancy S.E.: sedation, drowsiness, headace, confusion, cycloplegia, VI. ANTIEMETIC AGENTS 56 S.E.: sedation, drowsiness, headace, confusion, cycloplegia, dry mouth, urinary retention 5-HT3-receptor antagonists Ondansetron [Zofran] , Granisetron [Kytril], Dolasetron Indication: chemotherapy-, irradiation- or postoperative-induced vomiting (combined with dexamethasone or other drugs) before the cancer therapy, followed by 5 days of oral treatment S.E.: headache, dizziness, constipation, prolongation of QT interva