| Class | NSAID |
|---|---|
| Chemistry |
A vast and diverse group that defy chemical taxonomy
|
| Routes of administration |
Oral, PR, IV is available in some places. |
| Absorption |
Most are rapidly absorbed and have good oral bioavailability
|
| Solubility |
pKa 4.9 (ibuprofen) 11.9 (celecoxib); quite lipid soluble and poorly water soluble
|
| Distribution |
Volumes of distribution are fairly diverse, ranging from 0.1L/kg for ibuprofen to 5-6L/kg for celecoxib.
|
| Metabolism |
Metabolism is largely hepatic for all of these agents; notably parecoxib is an inactive pro-drug, hydrolised rapidly into valdecoxib, and diclofenac which has enterohepatic recirculation.
|
| Elimination |
All products of metabolism are renally excreted
|
| Time course of action |
Old drugs like ibuprofen diclofenac and paracetamol have very short half lives (with a much longer duration of effect due to their COX-inhibiting effects). Newer agents like celecoxib and valdecoxib have longer elimination half-lives
|
| 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 | |
| CICM details of understanding | Level 3 |
| Mentioned around Deranged Physiology | |
| Related SAQs |
Question 1 from the second paper of 2017 (ibuprofen vs. paracetamol) Question 3(p.2) from the second paper of 2007 (ibuprofen vs tramadol) |