| Class | NSAID |
|---|---|
| Chemistry |
Diarylheterocyclic NSAID
|
| Routes of administration |
Oral and IV |
| Absorption |
Rapidly absorbed; oral bioavailability ~ 100%
|
| Solubility |
pKa 6.7; highly water soluble
|
| Distribution |
VOD=0.8L/kg; 98% protein-bound. Valdecoxib, the active metabolite, is 80% protein bound and has a VOD of around 8-10L/kg
|
| Metabolism |
Undergoes rapid amine hydrolysis into valdecoxib, which is slowly metabolised in the liver into inactive metabolites.
|
| Elimination |
All products of valdecoxib metabolism are renally excreted
|
| Time course of action |
Elimination half-life of valdecoxib is 8-12 hours (parecoxib the pro-drug has a half life of about 20 minutes)
|
| Target receptor |
Mainly COX-2 isoform 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 |
| 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 |