31. Gastrointestinal and Antiemetic Drugs Flashcards
What are the main two causes of peptic ulcer disease?
Infection with Helicobacter pylori and use of NSAIDs.
What are the approaches to treating peptic ulcer disease?
Eradicating H. pylori infection, reduce gastric acid secretion with PPIs or H2 antagonists, protect gastric mucosa from damage.
What antimicrobials are used in H pylori eradication in peptic ulcer disease?
Amoxicillin, clarithromycin, metronidazole, tetracycline.
What H2-histamine receptor blockers are used in peptic ulcer disease management?
Cimetidine, famotidine, nizatidine, ranitidine.
What PPIs are used in peptic ulcer disease management?
Omeprazole, lansoprazole, esomeprazole.
Name a prostaglandin used in peptic ulcer disease management.
Misoprostol.
Name an antimuscarinic agent used in peptic ulcer disease management.
Dicyclomine.
What antacids are used in peptic ulcer disease management?
Aluminium hydroxide, calcium carbonate, magnesium hydroxide, sodium bicarbonate.
Which mucosal protective agents can be used in peptic ulcer disease management?
Bismuth subslicylate, sucralfate.
How is H pylori infection diagnosed?
Endoscopic biopsy of gastric mucosa, serology, or urea breath tests.
What is the triple therapy approach to H pylori eradication?
PPI + 2 x antibiotics (depends on hospital’s guidelines - amoxicillin + clarithromycin).
Which hormones stimulate gastric acid secretion?
Acetylcholine, histamine, and gastrin.
How do ACh, histamine, and gastrin stimulate gastric acid secretion?
Receptor mediated binding activates protein kinases which stimulate the H+/K+/ATPase to secrete hydrogen ions in exchange for K+ into the lumen of the stomach.
What is the action of H2 receptor antagonists?
Competitive antagonists of histamine, this is fully reversible.
What are the uses of H2 receptor antagonists?
Peptic ulcers, acute stress ulcers, GORD.
What are the ADRs of H2 antagonists?
Endocrine effects of cimetidine - gynaechomastia, galactorrhoea. CNS effects - confusion, altered mentation. Reduce efficacy of drugs that require an acidic environment for absorption.
What is the mechanism of action of PPIs?
Binds to H+/K+/ATPase so suppresses the secretion of hydrogen ions into gastric lumen.
What is Zollinger-Ellison syndrome?
Gastrin-producing tumour causes hypersecretion of HCl.
What is another benefit of PPIs other than reducing acid production?
Reduces risk of bleeding from ulcers caused by aspirin and other NSAIDs.
What are the ADRs of PPIs?
Inhibit CYP2C19 => DDIs. Increased risk of fractures (particularly if used for >1 year), low vitamin B12 and calcium, diarrhoea, Clostridium difficile, hypomagnesaemia, increased incidence of pneumonia.
How can prostaglandins improve peptic ulcer disease?
They inhibit secretion of acid and stimulate secretion of mucus and bicarbonate. If there’s a deficiency of prostaglandins in peptic ulcers, this balance can be corrected.
What are the key ADRs of prostaglandins?
Diarrhoea and nausea.
What are antacids?
Weak bases tat react with gastric acid to form water and a salt to diminish gastric acidity. Also reduces pepsin activity.
What are antacids used for?
Symptomatic relief of peptic ulcer disease and GORD, healing of duodenal ulcers.
What are the ADRs of antacids?
Constipation or diarrhoea depending on drug, absorption problems in patients with renal problems.
What are the cytoprotective properties of antacids?
Enhance mucosal protective protection mechanisms so prevent mucosal injury, reduce inflammation, and heal existing ulcers.
What are the two brainstem sites that have key roles in the vomiting reflex pathway?
Chemoreceptor trigger zone in postrema, vomiting centre in lateral reticular formation of medulla.
What is the role of the chemoreceptor trigger zone in the postrema?
Responds to chemical stimuli in blood or CSF.
What is the role of the vomiting centre in the lateral reticular formation of the medulla?
Coordinates the motor mechanisms of vomiting and responds to afferent input from brainstem and cortical structures.
What can be used in motion sickness?
Loperamide, an antimotility drug.
What are the major factors in diarrhoea?
Increased motility in the GI tract and decreased absorption of fluid.
What are the drug classes used to treat diarrhoea?
Antimotility drugs, adsorbents, agents that modfiy fluid and electrolyte transport.
Name an antimotility agent used in diarrhoea.
Loperamide.
What is the action of loperamide on the gut in diarrhoea?
Opioid-like actions to activate presynaptic opioid receptors in enteric nervous system to inhibit ACh release and decrease peristalsis.
What are the methods for treating constipation?
Irritants and stimulants, bulk laxatives, saline and osmotic laxatives, stool softeners, lubricant laxatives, chloride channel activators.
What is the action of senna?
Stimulant laxative - causes evacuation of the bowels within 8-10 hours and causes water and electrolyte secretion into bowel.
What is the action of bulk laxatives?
They form gels in the large intestine causing water retention and intestinal distension so increase peristaltic activity.
How do osmotic laxatives work?
They hold water in the intestine by osmosis. This distends the bowel and increases intestinal activity, so produces defecation in a few hours.
Name an osmotic laxative.
Lactulose.
45yo women has persistent heartburn and an unpleasant, acid-like taste in her mouth. She is suspected to have GORD so she is advised to eat smaller meals, not eat just before bed, and to prop her head up at night. Two weeks later her symptoms are still concerning for her. What should be prescribed? A. anatacid, e.g. aluminium hydroxide. B. dicyclomine C. antianxiety agent, e.g. alprazolam. D. esomeprazole
D. esomeprazole - PPI to reduce acid production and promote healing.
A couple are celebrating their 40th wedding anniversary and go to Peru. They have had past experience while travelling that mean they'd like an agent for diarrhoea. Which should be given? A. omeprazole. B. loperamide. C. famotidine. D. lorazepam.
B. loperamide - antidiarrhoeal, unlike the rest of the list. (A is a PPI, C is an H2 antagonist, and D is a sedative and anxiolytic).
27yo woman is 34 weeks pregnant and on bed rest, she is mildly constipated. What should be recommended? A. castor oil B. docusate C. mineral oil D. loperamide
B. docusate - safe in pregnancy (castor oil isn’t as it can cause uterine contractions, mineral oil isn’t used in bedridden patients as aspiration risk and loperamide is an anti-diarrhoetic).
Which of the following can cause discolouration of the tongue? A. amoxicillin. B. omeprazole. C. bismuth compounds. D. lubiprostone.
C. bismuth compounds - black discolouration.
Which of the following is not generally well tolerated for treatment of constipation? A. castor oil B. methylcellulose C. polyethylene glycol D. docusate
A. castor oil - can cause severe cramping.
An elderly woman with recent Hx of MI has occasional heartburn. She is on aspirin, clopidogrel, simvastatin, metoprolol, and lisinopril. Which should be avoided? A. calcium citrate B. famotidine C. omeprazole D. ranitidine E. calcium carbonate
C. omeprazole - it can reduce efficacy of clopidogrel as it inhibits conversion to active form.
Which of the following GI drug is contraindicated in pregnancy? A. calcium carbonate B. famotidine C. lansoprazole D. misoprostol
D. misoprostol - stimulates uterine contractions.
