About author :
Abhilash A*, Ajay kumar A, Prabhu Raj KJ, Dr. Hindustan Abdul Ahad
B. Pharmacy, Balaji College of Pharmacy, Anantapur, AP, India
Sodium salicylate was first used therapeutically for the treatment of rheumatic fever in 1875, but it wasnot until 1899 that acetylsalicylic acid was introducedinto medicine. Phenylbutazone followed in 1946,indomethacin in 1964, and together with aspirin are amongst the oldest of the non-steroidal anti-inflammatory drugs (NSAID). Over the past twodecades there has been a proliferation of newer andmore potent agents such that there are now more than 20 different NSAIDs. NSAIDs have proved to be effective anti-inflammatory and analgesic agents. However, the standardmethod of providing postoperative pain relief followin ganything but the most minor surgery is the intermittentintramuscular injection of opioid analgesics.The present system of pain control is far from satisfactoryand this has prompted both an exploration of moreeffective routes and methods of opioid administration and a renewal of interest in the use of NSAIDs for the relief of postoperative pain. A recenteditorial in the Lancet pointed out that the potentialcontribution of NSAIDs as sole analgesic after minor surgery or as adjuvants to opioid analgesics followingmajor surgery has been overlooked. Combined analgesic regimens can be expected to reduce opioidrequirement, with all of the advantages that thisentails. In addition, the longer half-lives, particularlyof some of the newer NSAIDs, means that there is less likelihood of breakthrough pain.
Key words: NSAIDs, Indomethacin, Phenylbutazone, Opioid Analgesics.
Mechanism of action:
Although NSAIDs exert a wide range of effects on cellular metabolism they all inhibit the synthesisof prostaglandins at one or more points in theendoperoxide biosynthesis pathway. This inhibitionof prostaglandin biosynthesis is believed to be thebasis of their analgesic action since the productsof arachidonic acid production promote the painassociated with inflammation (Figure 1). NSAIDinducedinhibition of prostaglandin biosynthesis isreversible, except following salicylates which result inirreversible acetylation of the enzyme cyclooxygenase.Prostaglandins inhibit gastric acid secretion and promote mucus production. Inhibition of prostaglandin synthesis therefore may cause gastric irritation byimpairment of the cytoprotective effects of prostacyclin on gastric mucosa. This effect is compounded by vasoconstriction.Under certain circumstances prostaglandins andprostacyclin may have an important vasodilator rolein maintaining renal blood flow and glomerularfiltration rate. Cyclooxygenase inhibitors should be used with caution postoperatively where the releaseof vasoactive substances such as angiotensin II,noradrenaline or antidiuretic hormone, may adversely affect renal blood flow.
NSAIDs can damage the gastrointestinal mucosa,impair renal function and may be associated with anincreased risk of postoperative hemorrhage. They can also provoke acute asthma in susceptible patients. In general the more potent the NSAID the greater the likelihood of adverse effects.Gastrointestinal side effects are the commonest adverse reaction to NSAIDs and constitute thegreatest risk of death (Table 2). The dosage and duration of NSAID treatment are the most importantdeterminants of the likelihood of gastric mucosal damage. Although gastrointestinal hemorrhage isgenerally rare after short term administration the risk of bleeding in the surgical patient following briefacute exposure is unclear. Dyspepsia and ulceration are much more common and may even occur followingadministration of rectal and parenteral formulations. There is endoscopic evidence that the prostaglandinE1 analogue misoprostol can prevent the NSAID induced gastric and duodenal ulcers associated with long-term treatment, whereas H2 antagonists onlyprotect against duodenal ulcers33.Anecdotal reports of NSAID-induced renal failure abound, but there is almost no data from prospectivestudies.
NSAIDs on their own can providesatisfactory analgesia immediately following minorto intermediate surgery. Immediately following majorsurgery NSAIDs can reduce opioid requirements byat least 20% and can provide adequate analgesia ontheir own in the later postoperative period. Analgesiais most effective when infusions (either intramuscularlyor intravenously) or mandatory dosing regimensare employed. NSAIDs have a low incidence of sideeffects, particularly with short-term exposure, and concern regarding adverse reactions should not beallowed to limit their usefulness. Nevertheless, NSAIDs should be used with great care, if at all, incertain specific circumstances. The preoperative administration of NSAIDs is logical but its safety is uncertain. NSAIDs should be avoided in cases where extensive surgical resection is anticipated.