Pharmacology - Gastrointestinal

Question 1

Name some classes of antiemetics and their mechanism of action

Answer 1

• serotonin 5-HT3 antagonists: ondansetron (serotonin antagonist)
• corticosteroids: dexamethasone (unknown)
• phenothiazines: stemetil (D2 blocker), largactil (D2+ blocker), phenergen (H1+ blocker)
• substituted benzamides: metoclopramide (D2 blocker)
• butyrophenones: droperidol (D2 blocker)

Question 2

What is the mechanism of action and adverse effects of Metoclopramide

Answer 2

Mechanism: dopamine (D2) antagonist at the chemoreceptor trigger zone (CTZ), centrally acts as antiemetic, peripherally acts as a prokinetic

Side effects:
- CNS: neuropsychiatric, restlessness, drowsiness, insomnia, anxiety, agitation
- EPSE: parkinsonian features, dystonia, akathisia, tardive dyskinesia
- NMS
- Endocrine: hyperprolactinaemia, galactorrhoea

Question 3

What is the mechanism of action, routes of administration and side effects of Ondansetron

Answer 3

• mechanism: 5-HT3 receptor antagonist (mostly peripheral)
• administration: 4-8mg PO/IV/SC/IM
• uses: chemotherapy, post-operation nausea
• side effects: headache, dizziness, constipation, diarrhoea, prolonged QT
• modify dosing in hepatic failure (not renal failure)

Question 4

What are the adverse effects of Prochlorperazine (stemetil)

Answer 4

EPSE
sedation
anticholinergic effects
allergy

Question 5

What are the classes and mechanism of action of laxatives

Answer 5

-bulk forming laxatives: psyllium
colloids that absorb water and forms bulky gel that promotes peristalsis
-stool softener: docusate
softens stool to permit water and lipids to penetrate
-osmotic laxatives: lactulose
soluble but non-absorbable compounds that increase stool liquidity
-stimulant laxatives: senna
direct stimulation of enteric nervous system
-opioid receptor antagonist: methylnaltrexone
blocks intestinal mu opioid receptor

Question 6

What is polyethylene glycol

Answer 6

• laxative used as preparation for endoscopic procedures
• balanced isotonic solution so that no significant intravascular fluid shift occurs
• osmotically active sugar, not absorbed

Question 7

What is the mechanism of action of PPI

Answer 7

• mechanism: forms covalent disulfide bond with H+/K+ATPase causing irreversible inhibition of the proton pump
• IV infusion is preferred because PPI only inactivates actively secreting pumps

Question 8

How do you increase bioavailability of oral PPI

Answer 8

• lipophilic weak bases so best absorbed in basic environment (small bowel)
• taken as inactive prodrugs
• acid resistant enteric coat prevents gastric elimination
• take on empty stomach because food decreases bioavailability (take 1 hour prior to meal)