الفهرس | Only 14 pages are availabe for public view |
Abstract SUMMARY AND CONCLUSION NSAIDs are among the most widely used medicines in the world. The mechanism of action of NSAIDs is attributed to the inhibition of COX enzyme which exists in two isoforms(COX-1 and COX-2). The anti inflammatory and analgesic efficacies are thought to be mainly due to inhibition of theinducible COX-2, whereas the adverse effects seem to be caused by inhibition of the constitutional COX-1. This suggested the development of selective COX-2 inhibitors asanalgesic and anti-inflammatory drugs. COX inhibitors are used in treatment of many diseases as rheumatological diseases which include osteoarthritis (treatpain and inflammation as well as disease-modifying effects), gout (FDA has approved naproxen, indomethacin, and sulindac for the treatment of acute gout), rheumatoid arthritis and systemic lupus erythematosus (treat inflammatory symptoms), ankylosing spondylitis, vasculitis (as prophylaxis against cardiovascular and cerebrovascular events).They are also used in treatment of neurological disorders which include alzheimer’s disease (delay in the onset of the disease so they act as prevention not treatment), depression (enhance efficacy of antidepressants and decrease in depressive symptoms), epilepsy (improve antiepileptic drug efficacy),tension-type headache (first-line therapy), schizophrenia (adjuvant therapy), cerebrovascular disease (cornerstone of primary and secondary stroke prevention) parkinson disease (neuro-protective effects) and neuropathy (diabetic peripheral neuropathy). COX inhibitors are used in treatment and prevention of different types of cancer including GIT (esophagus, stomach, duodenum, small intestine and large intestine), lung, urinary bladder and hematological malignancies. COX inhibitors are used to treat major symptoms of cancer cachexia. Other Uses of COX inhibitors include treatment of pain, cardiovascular disease and NSAIDs are the cornerstone of musculoskeletal pain management. COX inhibitors have many side effects on GIT as esophageal injury, gastric injury, increase gastric motility, gastro-duodenal damage and risk of GI bleeding, NSAIDinduced enteropathy with obscure GI bleeding, primary macroscopic colitis, collagenous colitis, increased risk of complicated diverticular disease, and exacerbations of preexisting inflammatory bowel disease. COX inhibitors have side effects on liver including hepatitis, ductopenia and others. Increased risk of adverse cardiovascular events was reported with COX inhibitors. A five-fold increase in thromboembolic events (primarily acute myocardial infarction, AMI) was observed in the rofecoxib group which was withdrawn from the market. The nephrotoxic effects of NSAIDs are documented and accounts for around 15.5% of all cases of drug induced renal failure. The concept of classic analgesic nephropathy has now been largely attributed to abuse of phenacetin-containing analgesic mixtures. Number of studies has shown that the coxibs exert renal side effects similar to those of classical NSAIDs. The drug Interactions of both celecoxib and non-selective NSAIDs include diminishing of the antihypertensive effect of angiotensin-converting enzyme inhibitors, reduction of the natriuretic effect of diuretics. Also among drug interaction, Celecoxib inhibits the metabolism of metoprolol and increases lithium level while rifampicin increases the clearance of celecoxib. |