Non-steroidal anti-inflammatory drugs
The non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly used class of pharmacological agents in the world. They are extremely efficacious medications for pain and the inflammatory response. Their primary mechanism occurs by inhibiting the enzyme cyclo-oxygenase, which coexists in two main isoforms, COX-1 and COX-2. They have significant side-effects, which include GI bleeding, cardiovascular toxicity, and renal impairment.
Many non-steroidal anti-inflammatory drugs exist, but trials have failed to find significant differences in their effectiveness in treating musculoskeletal symptoms . Their main differences are in side-effect profiles:
- selective COX-2 inhibitors are less likely to cause peptic ulcers but increase the risk of myocardial infarctions and other cardiovascular diseases
The main pharmacological action of non-steroidal anti-inflammatory drugs is inhibiting the synthesis of prostaglandins (PGs) by blocking the activity of the cyclo-oxygenase enzymes, COX-1 and COX-2.
COX-1 is important for the production of prostaglandins which are key to the integrity of the GI mucosa, the maintenance of renal function, platelet interlinking and other key homoeostatic actions. COX-2 is central to the synthesis of prostaglandins key to pain, fever and the inflammatory response. Thus ideally NSAIDs maximize their COX-2 inhibition, therefore blunting inflammation, but minimize their effects upon COX-1 activity, thus decreasing the risk of adverse effects.
In general, non-steroidal anti-inflammatory drugs, pass easily through the GI mucosa with good bioavailability. NSAIDs bind to carrier proteins in the bloodstream. Hepatic catabolism is the norm, with renal excretion. Effective half-lives of the agents vary widely, as low as 20 minutes for aspirin, and two days for piroxicam.
- disturbance of electrolytes, e.g. hyperkalemia
- decreased glomerular filtration rate (GFR)
- nephrotic syndrome
- renal papillary necrosis
- acute interstitial nephritis