Drugs Affecting the Gastointestinal System Pharmacology 49.222 Dr. Bill Diehl-Jones, RN Faculty of Nursing Agenda • Zen Review • Drugs used to treat the following disorders – Peptic ulcer – Motility dysfunction – Diarrhea – Constipation – Lactose intolerance GI Drugs • Drugs for: – Peptic ulcers – Emesis – Motility Disorders • Diarrhea • constipation Overview of GI Processes Food Digestion Secretion Absorption Motility Blood Vessels Peptic Ulcer Drugs • The Problems – Infection with H. pylori – Increased acid secretion – Inadequate mucosal defense • Solutions: – Antimicrobials (amoxicillin) – H2- histamine blockers (Ranitidine) – Prostaglandins (Misoprostol) – Proton pump inhibtors (Omeprazole) Anti-Ulcer Agents Omeprazole H+ - - K+ PARIETAL CELL In stomach Amoxicillin + Protein Kinase Ca++ + cAMP Ach-R Pirenzipine - + AC - PG-R Histamine-R - Ranitidine + Misoprostol Anti-Emesis Drugs • Why do we vomit?! • “Vomit” Centers • Chemoreceptor trigger zone – Takes chemical stimuli • Lateral reticular formation – Takes vestibular input – Controls motor mechanisms Flavours of Anti-Emetics • Phenothiazines (eg: prochlorperazine) • Dopamine blocker • Benzodiazepines (eg: ?) • 5-HT blockers (eg: ondansetron) • Corticosteroids eg: (dexamethasone) • Peppermint oil (yes, peppermint oil) Anitdiarrheals and Laxatives Diarrhea - Three Mechanisms • Osmotic – osmoticant in intestine H2O • Secretory – excessive mucosal secretion – toxins, some tumours • Motility – surgical Lactase Deficiency… One Cause of Diarrhea Enzymes • Deficiency of lactase at brush border • Increased lactose provides carbon for bacteria • Presents as bloating, crampy pain, osmotic diarrhea Microvillus Anti-Diarrheals • What causes diarrhea? So, how do antimotility agents work? First, we need to know about gut motility … • Two types of movement: – Peristaltic • moves food forward – Segmental • Mixing • Controlled by parasympathetics Effect of Parasympathetic Activity on Gut Smooth Muscle • Certain cells generate slow wave pacemaker potentials mV • This is increased by ACh Force TIME Ach controls both motility and secretion … STIMULUS STIMULUS Vagus Short Reflex ACh Long Reflex ACh Secretion Antidiarrheals • Antimotility Agents – Diphenoxylate, loperamide • Both are meperidine derivatives • Activate presynaptic opioid receptors, inhibit Ach release (see next slide) • Adsorbents – Kaolin, pectin • Agents that modify fluid/electrolyte transport – NSAIDS – Bismuth subsalicylate (Pepto Bismol) Prostaglandins and Bismuth Inhibit Secretion of Water and Electrolytes Enterocyte Na+ L H2O Na+ Cl- U PG‟s Cl- K+ M - Na+ K+ K+ E Salicylate N Enterocyte Constipation • Many Causes – Neurogenic • eg: Hirschsprung‟s – Muscle weakness • eg: post-surgery – Low-residue diets Laxatives We Know and Love • A. Irritants and Stimulants – Castor oil, aloe, phenophthalein • Castor oil broken down into ricinoleic acid • B. Bulking Agents H20 – Psyllium, bran, magnesium • Stool softeners – Ducosate, mineral oil, glycerin Clinical Gems • Aspirin and GI bleed – Aspirin is an ACID (acetylsalicylic acid, remember?) – Over-use, or use by pts. with peptic ulcer contraindicated (why?) – Enteric-coated aspirin (Entrophen®) or other analgesics may be used – Why is Ibuprofen also contra-indicated in patients with GI bleed?? Clinical Gems • Laxatives and pediatric patients – MoM, other oral laxatives to be used as a last resort – Rationale: this can cause F/E imbalances • Alternatives to laxatives: – More fibre in diet (examples?) – Increase hydration – Abdominal massage Clinical Gems • Antidiarrheals and pediatric patients – Usually considered to be contra-indicated – They may cause retention of the causative agent • Eg: a bacterium or parasite – Clostridium difficile Clinical Gems • Over-use of laxatives – Long-term use may cause dependence or „lazy bowel‟ • What non-pharmacological alternatives can you think of?