Question 1

Compare and contrast the pharmacology of ibuprofen and paracetamol.

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College Answer

This was a standard compare and contrast question of common analgesic pharmacology and it was generally well answered. The use of a table ensured all areas were covered including class, indications, pharmaceutics, mode of action, pharmacodynamics, pharmacokinetics and adverse effects. The uncertain nature (and possibilities) of the mechanism of action of paracetamol was alluded to in better responses.

Details of the comparative pharmacokinetics were often lacking. Answers should have included a comment on first-pass effect, the significance of the difference in protein binding and the details of metabolism, particularly paracetamol. Metabolism limited to "hepatic metabolism and renal excretion” gained no marks as better responses were more detailed and clearer about the differences between the two drugs. Knowledge of metabolism at therapeutic doses and the effect of overdose were expected. Better answers included potential interactions with other drugs (e.g. warfarin) and contraindications to the use of these drugs.


Name Ibuprofen Paracetamol
Chemistry Aryl-propionic acid Para-aminophen derivative
Routes of administration Oral, PR, IV is available in some places oral, IV, PR
Absorption Rapidly absorbed; oral bioavailability is close to 100% Rapidly absorbed; oral bioavailability ~ 80%
Solubility pKa 4.9; quite lipid soluble and poorly water soluble pKa 9.5; moderately soluble (equally badly in water and lipid)
Distribution VOD = 0.1L/kg; 99% protein bound (to albumin) VOD = 0.9L/kg; 15-20% protein bound
Target receptor COX-1 and COX-2 isoforms of the cycloxygenase enzyme Molecular targets are uncertain
Metabolism Almost 100% of the dose is metabolised in the liver: oxidation into water-soluble inactive metabolites Hepatic metabolism: major pathway is glucouronidation and sulfation;
minor pathway involves the formation of a toxic metabolite (NAPQUI) which needs to be detoxified by conjugation with gluathione
Elimination All products of metabolism are renally excreted All products of metabolism are renally excreted
Time course of action Half-life is 1.8 to two hours (duration of COX inhibition is much longer) Half life of paracetamol is only about 2 hours
Mechanism of action Inhibition of cyclooxygenase enzymes leads to decreased synthesis of prostaglandins, which decreases the vascular regional response to inflammation, and decreases the sensitivity of peripheral nociceptors. COX-1 inhibition also leads to the dysregulation of vascular antihrombotic effects of PGI2 and to the decreased secretion of bicarbonate and mucus in the gastric mucosa Mechanism of analgesic effect of paracetamol is unclear, and is likely a combination of "effects on prostaglandin production, and on serotonergic, opioid, nitric oxide (NO), and cannabinoid pathways". (Sharma & Mehta, 2014)
Clinical effects COX-1 inhibitor and nonselective NSAID side effects:
GI ulceration (decreased gastric mucosal pH and mucus synthesis)
Acute kidney injury (microvascular renal dysfunction)
COX-2 inhibitor side effects:
Anti-inflammatory activity is mainly due to COX-2 inhibition
Prothrombotic side effects are due to COX-2 inhibition
CCF exacerbation and hypertnesion
Analgesia; co-anagesic effect with other agents; vasodilation when given IV; antipyrexial effect
Single best reference for further information TGA PI document TGA PI document


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