Q1

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)

Pass Criteria:

  • 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

Q2

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

Pass Criteria:

  • 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

Q3

Name some antiemetics used in the Emergency Department.

Ondansetron (or Granisetron or Tropisetron)

Metoclopramide

Prochlorperazine

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


Q4

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

 


Q5

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)

Pass Criteria:

  • 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.

Pass Criteria:

  • 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.

Pass Criteria:

  • 2 concepts

Q6

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

Pass Criteria:

  • Bold, plus 1 receptor location

What are the doses and routes of administration of Ondansetron?

  • 4-8 mg
  • SL
  • PO
  • IV
  • SC
  • IM

Pass Criteria:

  • Bold, plus 3 of 5

What are the adverse effects of Ondansetron?

  • Constipation
  • Headache
  • Dizziness
  • QT prolongation

Pass Criteria:

  • 1 of 4 to pass

In which disease states would you need to modify the dosing?

  • Hepatic failure
  • Not with renal failure or age

Pass Criteria:

  • Bold to pass

What are some other classes of antiemetic drugs?

  • Phenothiazines
  • Antihistamines
  • Cannabinoids
  • Benzodiazepines
  • Butryophenones (Droperidol)
  • Benzamides (ie: Metoclopramide)
  • Neurokinin receptor antagonists
  • Corticosteroids

Pass Criteria:

  • 3 of 8 to pass

Q7

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.

Pass Criteria:

  • 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%)

Pass Criteria:

  • 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

Pass Criteria:

  • Bold plus 1 to pass.

Bonus: What are some of its adverse effects?

  • Nausea
  • Vomiting
  • Abdominal cramps
  • Flatulence
  • Steatorrhoea

Pass Criteria:

  • 1 to pass.