Peptic ulcer disease is an imbalance of between acid+pepsin and mucus+bicarbonate to result in deterioration of the epithelial barrier. o Gastric Acid Secretion: ACh, gastrin, histamine, PgE - stim adenylate cyclase o Helicobacter pylori is the most common cause of gastric/duodenal ulcers
**Cisapride is also used when nothing else works but has fatal cardiac arrhythmias possible
Mechanism of action and adverse effects of proton pump inhibitors, histamine H2 antagonists, cytoprotective agents and antacids.
Proton Pump Inhibitors Omeprazole o Irreversibly blocks the H+/K+ ATPase (proton pump) o Inactive prodrug (protonated at acid pH to active derivative) o Side effects: Diarrhoea, flatulence, nausea o Treats: Peptic ulcer, gastroesophageal reflux, prophylaxis against ulcer development by NSAIDS (Single daily dose gives long-lasting inhibition) H2 Receptor Antagonist - Cimetidine and Ranitidine o Competitively block histamine-induced acid released by parietal cells. o Less acid suppression than PPI o Cimetidine - inhibits cytochrome P450 enzymes Drug interacts with phenytoin and warfarin (inactivates them) Antiandrogenic - gynaecomastia (swelling of breasts) Prolactin Confusion, drowsiness, headache, rash, diarrhoae o Ranitidine - little to no inhibition of cytochrome P450 enzymes and antiadrogenic activity and fewer side effects Cytoprotective Agents - Misoprostol, Sucralfate, Bismuth o Analogue of PgE1 (cytoprotective PG) o Side effects: Diarrhoea, uterine contraction, contraindicated in pregnancy o Sucralfate - binds to ulcer base (mucosal protecting action, stimulates PG and bicarbonate production) o Bismuth - binds to ulcer base (inhibits H. pylori), precipitates at acid pH to protect mucosa and stimulates PG and bicarbonate production. Antacids - AlOH, MgOH, NaHCO3 (used in combinations) o Weak bases acting to neutralize gastric acid o Symptom relief (not usually used in ulcer healing) o NaHCO3 - Can cause alkalosis (not intended for long-term use)
Mechanism of action and adverse effects of muscarinic anticholinergics, histamine H1 antagonists, dopamine D2 antagonists, serotonin 5-HT3 antagonists and cannabinoids.
Anticholinergics Muscarinic Antagonists Hyoscine o Motion sickness (Short duration) o Little antiemetic effect in other situations o Side effects: Anticholinergic side effects Antihistamines H1 Antagonists - Cyclizine o Motion sickness o Little antiemetic effect in other situations o Side effects: Sedation Dopamine receptor antagonists (D2) o Decrease vomiting caused by drugs (Chemotherapy) o Phenothiazines (Ex: prochlorperazine), Butyrophenones (Ex: haloperidol) o Side effects: Extrapyramidal, increased prolactin secretion Serotonin receptor antagonists (5-HT3) Ondansetron o Decrease vomiting caused by drugs (especially chemotherapy) o Side effects: constipation, headache Cannabinoids THC analogues acting on CB receptor Nabilone o Decrease vomiting due to drugs stimulating CTZ (chem-receptive trigger zone) o Side effects: drowsiness, psychological effects (incl. psychosis) o Steroids can be used as a refractory emesis.
Mechanism of action and adverse effects of aminosalicylates, corticosteroids, immunosuppressive agents, antimicrobials and TNFa inhibitors.
5-Aminosalicylates Sulfasalazine [Mesalamine] o Inhibit leukotriene/prostaglandin formation o Adverse effects: GIT disturbance, hypersensitivity reactions Corticosteroids - Hydrocortisone, prednisolone (topical), Budesonide (low bioavail.) o Inhibit of cytokine production to induce remission Immunosuppressive Agents Azathioprine [Mercaptopurine] o Purine analogues which inhibit nucleic acid synthesis Antimicrobials - Metronidazole o Interrupt bacterial role in inflammatory process TNF- inhibitors - Infliximab o Antibodies to inflammatory effects of TNF- in the gut for refractory Crohns
Mechanism of action and adverse effects of dietary fibre/bulk-forming laxatives, osmotic laxatives and contact/stimulant laxatives.
Dietary Fibre/ Bulk-forming laxatives o Increasing stool mass via component polysaccharides (transit over 1-7 days) o Bran; methylcellylose; ispaghula o Adverse effects: Drug absorption, intestinal/oesophageal obstruction, +water Osmotic Laxatives MgSO4, MgOH, NaPO4, Lactulose o Engaged in bowel and hold water in lumen via osmotic properties o Increased transit over 1-3 hours o Adverse effects: Little absorbed but care in children and w/ renal impairment Contact/Stimulant Laxatives o Direct stimulation of myenteric plexus/mucosa o Decreased permeability of mucosal surface o Increased transit over 6-8 hours
Mechanism of action and adverse effects of oral rehydration/electrolyte balance, anti-infective agents, absorbent agents and opioid derivatives.
Constipating Agents Absorbent compounds o Absorb fluids and toxins Opiates o Muscle tone and propulsive movements o Sensory stimulation for defaecation reflex Opiate derivatives without CNS effects and dependence of morphine o Diphenoxylate and Loperamide