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GASTROINTESTINAL VIVAS 2009-1, 2006-2 What is the mechanism of action of ondansetron - Selective 5-HT3 receptor antagonists both peripheral in intestinal vagal afferents and central in chemoreceptor trigger zone and vomiting center in lateral medulla What are the clinical uses of ondansetron - Chemotherapy-induced nausea and vomiting e.g. 8 mg every 8 -12 hours - Postoperative and post radiation nausea and vomiting - Other indications: acute or chronic medical conditions or gastroenteritis (not well evaluated) Name some side-effects of ondansetron - Headache, dizziness and constipation - Small prolongation of QT interval What are the routes of administration and dose of ondansetron? - Similar doses, 4-8mg, oral tablet or wafer, IV 2008-2 Describe the mechanism of action of metoclopramide? - Dopamine antagonist (D2 receptors) - Central w/ anti-nausea/emetic effect on the Chemoreceptor Trigger Zone (area postrema) Peripheral blockade of GI dopamine receptors allowing cholinergic smooth muscle stimulation w/ increased oesophageal peristaltic amplitude, increases lower oesophageal sphincter pressure and enhanced gastric emptying List the adverse effects of metoclopramide? - Relate to central dopamine antagonist action - Restlessness, drowsiness, insomnia, anxiety, agitation - Extrapyrimadal effects: dystonias, akathisia, parkinsonian features - Risk of tardive dyskinesia with chronic use - Hyperprolactinemia (galactorrhoea, gynecomastia, impotence, menstrual disorders) 2008-1, 2005-1 What classes of drug can be used as antiemetics? 1. Serotonin 5-HT3 antagonists: the “trons” 2. Phenothiazines: prochlorperazine, promethazine 3. Butyrophenones: haloperidol 4. Substituted benzamides: metoclopramide, a D2 antagonist 5. H1 antihistamines: diphenhydramine, cyclizine 6. Anticholinergics: hyoscine 7. Others: Benzos, Cannabinoids, Corticosteroids List and explain the adverse effects of prochlorperazine ? - Acute dystonia (dopamine blockade) - Sedation (antihistamine effects) - Anticholinergic effects (antimuscarine effects) - Allergy 2008-2, 2005-2 Using examples, outline the mechanism of action of the various types of laxative? Bulking Hydrophyllic colloids, agar, psyllium seed, bran, kiwifruit (high in fibre) (reflex contaction) Softening Permit water and lipids to penetrate: Docusate, glycerine Osmotic Lactulose, Magnesium citrate and magnesium hydroxide, polyethylene glycol, sorbitol Stimulant (act early) castor oil -(act late) cascara, senna, aloes (contain emodin alkaloids which are liberated after absorption from the intestine and excreted in the colon) -(prolonged action by enterohepatic circulation) phenolphthalein & biscodyl Cl- channel activator Lubiprostone Opioid receptor Methylnaltrexone antagonist 5HT-3 agonist Tegaserod Polyethylene glycol is used as a prep for endoscopic procedures. What features make it safe for all patients? 2005-2 - Balanced - Osmotically active sugar (PEG) with NaCl, NaHC03, KCl - No significant osmotic shifts. Best ingested rapidly for bowel cleansing 2008-1 Explain the rationale for the use of octreotide in upper gastrointestinal bleeding - Octreotide reduces splanchnic blood flow, (?By glucagon release inhibition) therefore reduces portal venous pressure - This reduces blood loss from bleeding oesophageal varices and in some cases of severe duodenal ulcer related bleeding What are the pharmacokinetic differences between octreotide and somatostatin? - Octreotide is a somatostatin analogue that has a longer half life than somatostatin (1.5hrs vs 3 min) so can be given as an IV infusion or subcutaneously (Supp Question – What other agents may be useful in the prevention and treatment of upper GI bleeding) - PPIs – omeprazole - H2 anatagonists – cimetidine, ranitidine - Vit K, prothrombinex, FFP - Tranexamic acid .