Using examples, outline the mechanism of action of the various types of laxative?
- Irritants or Stimulants
- (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
- Bulking agents -hydrophyllic colloids, agar, psyllium seed, bran
- Osmotic -magnesium citrate and magnesium hydroxide, polyethylene glycol, sorbitol, lactulose
- Stool softeners: agents that emulsify with the stool and soften it (mineral oil,glycerine, detergents such as docusate (dioctyl sodium sulphosuccinate)
- 3 out of the 4 mechanisms with at least 1 correct example
- Note: anything that distends intestine leads to peristaltic activity i.e. bulking and softening agents
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
- Reduces splanchnic blood flow
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
Name some antiemetics used in the Emergency Department.
Ondansetron (or Granisetron or Tropisetron)
Diphenhydramine (or other antihistamines). Meclizine. Hyoscine. Benzodiazepines. Chlorpromazine. Droperidol
Bold to pass
Compare the mechanisms of action of ondansetron and metoclopramide.
Act at different receptors:
Ondansetron: Peripheral 5HT3 blockade (vagal and spinal afferents, Reduces sensory visceral output) + Central 5HT3 blockade (vomiting centre and CTZ)
Metoclopramide: D2 blockade (CTZ). Increases oesophageal motility. Increases LOS pressure. Increase gastric emptying
Bold to pass
Describe the potential adverse effects of metoclopramide.
CNS: Restlessness, drowsiness, insomnia, anxiety, agitation – common (20%), esp. elderly
Extrapyramidal effects: acute dystonia, akathisia, parkinsonian effects, more likely with higher doses Tardive dyskinesia with chronic dosing
Pass: Must mention acute dystonia + one other CNS effect
What different mechanisms of actions of laxatives do you know? Give examples.
1. Bulk-forming Psyllium, methylcellulose Increased bloating and flatus
2. Stool softening Permit water and lipids to penetrate. Docusate, glycerine, mineral oil
3. Osmotic 1 — nonabsorbable sugars/salts. Mg02 Sorbitol, lactulose
4. Osmotic 2 Polyethylene glycol
5. Stimulant Senna, aloe, cascara Castor oil
1-3 to pass
Polyethylene glycol is used as a prep for endoscopic procedures. What features make it safe for all patients?
1. Balanced. Osmotically active sugar (PEG) with NaCI, NaHCO3, KCI
2. No significant osmotic shifts. Best ingested rapidly for bowel cleansing
Describe the mechanism of action of PPIs.
- Irreversibly inactivates H+K+ATPase, blocking the proton pump -inhibiting >90% acid secretion, for up to 24 hours (time taken for synthesis of new enzymes)
- Bold to pass
Why is an IV infusion preferred to a single bolus dose?
- Only inactivates actively secreting acid pumps (<10% in fasting patients), hence single dose only decreases acid secretion for a few hours.
- Bold to pass
Regarding oral formulations of proton pump inhibitors, please describe strategies used to increase their bioavailability and activity.
- Taken as inactive pro-drugs
- Begin as acid resistant enteric coated to prevent gastric elimination
- Take on empty stomach as food decreases bioavailability.
- Weak bases so pass into acidified parietal cells, where concentrated 1000x, becomes activated and binds to H+K+ATPase
- Take 1 hour prior to meal so peak dose drug occurs when most pumps are active.
- 2 concepts
What is the mechanism of action of Ondansetron?
Prompt: Where are thes receptors found?
- 5-HT3 receptor antagonist
- Effect brought about at peripheral (gut) > central receptors
- Chemoreceptor trigger zone and vomiting centre
- Bold, plus 1 receptor location
What are the doses and routes of administration of Ondansetron?
- 4-8 mg
- Bold, plus 3 of 5
What are the adverse effects of Ondansetron?
- QT prolongation
- 1 of 4 to pass
In which disease states would you need to modify the dosing?
- Hepatic failure
- Not with renal failure or age
- Bold to pass
What are some other classes of antiemetic drugs?
- Butryophenones (Droperidol)
- Benzamides (ie: Metoclopramide)
- Neurokinin receptor antagonists
- 3 of 8 to pass
Explain the mechanism of action of octreotide.
A somatostatin analogue that inhibits the release of GH, TSH, glucagon, insulin and gastrin. It also reduces splanchnic blood flow and portal pressure.
- 2 bold to pass.
Describe the pharmacokinetics of octreotide.
- Plasma elimination half-life is 80 minutes
- Metabolised by the liver (30 – 40%) and excreted unchanged by the kidney (20%)
- Know half-life (range 40 – 120 minutes)
What are some of its clinical uses?
- Acute control of bleeding form oesophageal varices
- Sulphonylurea overdose
- Reduce symptoms caused by hormone secreting tumours (e.g. acromegaly, carcinoid, gastrinoma)
- Locating endocrine tumours using radiolabelled octreotide
- Bold plus 1 to pass.
Bonus: What are some of its adverse effects?
- Abdominal cramps
- 1 to pass.