| Class | NSAID |
|---|---|
| Chemistry |
Aryl-propionic acid
|
| Routes of administration |
Oral, PR, IV is available in some places |
| Absorption |
Rapidly absorbed; oral bioavailability is close to 100%
|
| Solubility |
pKa 4.9; quite lipid soluble and poorly water soluble
|
| Distribution |
VOD-0.1L/kg; 99% protein bound (to albumin)
|
| Metabolism |
Almost 100% of the dose is metabolised in the liver: oxidation into water-soluble inactive metabolites
|
| Elimination |
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)
|
| Target receptor |
COX-1 and COX-2 isoforms of the cycloxygenase enzyme |
| 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 |
| 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 |
| Literature reference |
TGA PI document |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |