Describe the mechanism of Paracetamol hepatotoxicity?

  • In normal doses, Paracetamol undergoes glucuronidation and sulphation to the corresponding conjugates, making up 95% of total excreted metabolites.
  • The alternative P450 dependant GSH conjugation pathway accounts for 5%.
  • When intake far exceeds therapeutic intake, glucuronidation and sulphation pathways are saturated, so P450 dependent pathway becomes impt. So long as there is hepatic GSH available for conjugation, no hepatotoxicity occurs.
  • Once hepatic GSH is depleted faster than its regeneration, a reactive toxic metabolite-N-acetylbenzoiminoquinone is produced. This reacts with the nucleophilic groups of cellular proteins to produce hepatotoxicity

Pass Criteria:

  • Concept of 2 paths with saturation
  • Glutathione key word

What is the antidote and how does it work?

  • NAC glutathione substitute, binding to the toxic metabolite
  • Anti oxidant

Pass Criteria:

  • NAC + donor/substitute (GSH)



In a poisoned patient what modalities are available for decontamination?

  • Skin – remove clothes, wash contaminated skin
  • GIT – emesis, gastric lavage, activated charcoal & cathartics / whole-bowel irrigation

Pass Criteria:

  • 3 of 5 to pass

How does activated charcoal work?

  • Adsorption due to its large surface area

Name some drugs or agents that activated charcoal is NOT effective in adsorbing?

  • Ions: Fe, Li, K
  • Alcohols, cyanide
  • Corrosives (acids and alkalis)

Pass Criteria:

  • 2 examples

Name a drug where repeated doses of activated charcoal may assist in elimination of the drug?

  • Carbamazepine
  • Dapsone,
  • Theophylline

Pass Criteria:

  • One Drug



What are the therapeutic uses of Penicillamine?

  • Wilsons disease
  • Copper poisoning
  • Severe rheumatoid arthritis (occasionally)

List the adverse effects of D-Penicillamine (occur in up to 1/3 of patients).


•             Nausea and Vomiting

•             Nephrotic Syndrome

•             Hypersensitivity (avoid if history of penicillin allergy)

•             Pancytopaenia

•             Pemphigus

•             Myasthenia

•             Optic atrophy

•             Arthropathy



Describe the pharmacokinetic mechanisms for drug interaction with oral anticoagulants?

Enzyme induction or enzyme inhibition -reduced plasma protein binding (all 3)

NOTES: Pharmacokinetic: amiodarone, metronidazole, trimethoprim


Describe a pharmacodynamic interaction with warfarin?

-competitive antagonism Vit K

Pharmacodynamic: aspirin, heparin, 3’d gen cephalosporin

-altered physiologic control loop – hereditary resistance

-clotting factor conc-spironolactone


At least 2 examples

Prompt “what happens to a patient on warfarin who is given Vit K”

“why does the TAIR alter?”



Outline the clinical features of salicylate toxicity?

Prompt if required: What are the acid base disturbances in salicylate toxicity?
Salicylism: hearing/tinnitus

Any CNS: coma

GIT disturbance


Respiratory Alkalosis

Metabolic Acidosis


Renal failure
Uncoupling Oxidative Phosphorylation

Describe the enhanced elimination strategies employed in managing a patient with salicylate overdose.

pH Manipulation /urinary alkalinisation

Forced Diuresis


Prompt for both



Dialysis procedures

1.            Peritoneal dialysis

2.            Hemodialysis

3.            Hemoperfusion



Describe the metabolism of methanol.


What specific modalities of treatment are available for the treatment of severe methanol poisoning?

  • Talk about alcohol dehydrogenase substrate, ETOH.
  • Mention fomepizole as an ADH antagonist.
  • Correcting acid/base status should be a priority because serious metabolic acidosis is common and a pH less than 7 is associated with poor prognosis.
  • Need to add adjuncts to minimise accumulation of formic acid – folic acid The elimination of methanol may be enhanced by administering folic acid, a cofactor in the conversion of formic acid to carbon dioxide
  • dialysis

Pass: Alcohol + 1



Describe the pharmacologic effects of glucagon.

1. Metabolic —

•             Binds with receptors on liver cells (G protein-linked l’ adenylyl cyclase & cAMP)

•             Catabolism of stored glycogen, raising blood glucose level

•             No effect on skeletal muscle

•             Also cause release of insulin from B-cells, catecholamines from Pheo and calcitonin from medullary carcinoma cells


2. Cardiac effects

•             Potent inotropic & chronotropic effect on heart via cAMP without requiring functioning beta-receptor


3. Large doses of glucagon produce relaxation of smooth muscle (not via cAMP)

2 of 3 to pass

What are the indications for using glucagon clinically?

1.            Severe hypoglycaemia

2.            Overdose on Betablockers (5-10mg IV will reverse hypotensionlbradycardia)

3.            Relaxation of intestine during radiology of bowel

4.            Diagnosing endocrine disorder-

•             Type I Diabetes (no C-peptide response to glucagen)

•             Suspected tumours, eg Insulinoma, Pheo, medullary carcinoma (cause rise in hormone)

2 of 3 to pass

What are the adverse reactions produced by glucagon?

•             Transient nausea & vomiting

•             Relatively free from severe adverse reaction

•             hyperglycaemia



What is an antivenom?

Immunoglobulin or antibody (specifically IgG FAB) produced by another animal in response to a venom. Used in humans IV or IM to neutralise venom after an envenomation.

Pass: Must get Ab or Ig produced by animal

What antivenoms are used in Australasia?

Snake –polyvalent and monovalent (black, brown, death adder, tiger, taipan, sea snake); stonefish, redback spider, box jellyfish, funnelweb spider

Pass: Must get Snake – polyvalent & monovalent & 2 others

What are the side effects of antivenom?

Allergy, anaphylaxis, serum sickness

Pass: Bold

What animals are used in the production of different antivenoms?

Horse –snake, stonefish, redback; Sheep –box jellyfish; Rabbit –funnel web

Pass: Must get horse/snake and 1 other



Name some drugs that are used in the treatment of opiate addiction.

Methadone, N acetylmethadol, buprenorphine clonidine, lofexidine, Naltrexone, naloxone

Pass: Must get methadone and 1 other

Outline the principles of how these agents work.

Methadone –longer acting, opiate angonist, orally active –patient can

be stabilised and gradually withdrawn but addictive also. N acetylmethadol –an even longer acting methadone analogue. Buprenorphine –partial opiod antagonist that can be given once daily, low doses for detoxification and higher doses for maintenance.

Clonidine –central acting sympatholytic agent that mitigates signs of withdrawal sympathetic


Lofexidine –clonidine analogue with less hypotensive effects

Naltrexone-long acting orally active pure opiod antagonist, patients must be detoxified first

Naloxone – rapid onset pure antagonist, short half-life, precipitate withdrawal

Pass: Must get methadone principles and state that overall agents must be orally active and long acting. 1 other agents PD also.



What is an antagonist?

  • Receptor antagonists bind to receptors but do not activate them. The primary action of antagonists is to prevent agonists from activating receptors.

Pass Criteria:

  • Bold to pass

What is the difference between a competitive and non-competitive antagonist?

  • Competitive antagonist
    • In the presence of increasing concentration of antagonist, higher concentrations of agonist will produce a given effect e.g. propanolol and noradrenaline/adrenaline
  • Irreversible or non-competitive antagonist
    • Bind via covalent bonds or just binding so tightly to receptor so receptor unavailable for agonist
    • Duration of action of antagonist depend on rate of turnover of receptor-antagonist molecules

Pass Criteria:

  • Bold to pass

What type of antagonist is naloxone?

  • Competitive

What effect does a competitive antagonist have on the concentration-effect curve?

  • Shift agonist vs effect curve to right. Higher concentrations of agonist can overcome competitive antagonist.