INTRODUCTION NSAIDs are non-steroidal anti- inflammatory drugs, also known as NAIDs, non-steroidal anti-inflammatory agents/analgesics (NSAIAs) or non-steroidal anti-inflammatory medicines(NSAIMs).
medications with analgesic (pain reducing), antipyretic (fever reducing) effects. In higher doses they also have anti- inflammatory effects - they reduce inflammation (swelling). Non-steroidal distinguishes NSAIDs from other drugs which contain steroids, which are also anti-inflammatory. NSAIDs are non-narcotic (they do not induce stupor).
GENERAL MECHANISM OF ACTION OF NSAID Agents that suppress inflammatory response to mechanical, thermal, ischemic, immunological and infection-induced injury. Aspirin (the prototype of NSAIDs) irreversibly inhibits cyclooxygenase enzyme to arrest prostaglandin synthesis (i) Cyclooxygenase-1 (COX-1) (ii) Cyclooxygenase-2 (COX-2) Anti-inflammatory Action NSAIDs provide analgesia secondary to their effects of inflammatory. Referred as ‘non-opioid analgesics’ - effectively relieve mild-moderate pain Aspirin reduce generation of mediators of pain at the site of tissue damage. Bradykinin exacerbates pain sensation. Analgesic Action to control fever Block the synthesis of endogenous pyrogens Increase heat dissipation, balance heat production and heat loss in body Modulate temperature control at hypothalamic level Antipyretic Action
ASPIRIN Pharmacological Actions produces actions on many systems Central Actions Causes stimulation of CNS At high doses, leads to convulsions then depression Increases labyrinthine pressure and produces tinnitus and reversible high tone deafness Respiratory System A dose-dependent direct and indirect effects of aspirin on respiratory system contributes to serious acid-base disturbance Gastrointestinal System A gastric irritant and ulcerogenic agent Blood A cardioprotective drug Metabolism Produces multiple actions on metabolism
Drug Interactions Aspirin gastrointestinal toxicity ◦ Reduced by co-administration antacids or H2 receptor blockers (ranitidine) or proton pump inhibitors (omeprazole) or sucralfate or misoprostol. Aspirin+ alcohol ◦ Increased gastrotoxicity of aspirin – high risk of ulceration Aspirin+warfarin ◦ Aspirin displaces warfarin fromplasma protein ◦ Increases toxicities of warfarin by reducing prothrombin level. Aspirin+ACEI, Aspirin+ß blockers, Aspirin+Diuretics ◦ Reduction in the efficacy of antihypertensive effects Aspirin+fluoroquinolones ◦ Increased incidence of convulsions Aspirin+aminoglycoside antibiotics ◦ Increased ototoxicity Aspirin+probenecid ◦ Antagonism of uricosuric action Aspirin+cyclosporine ◦ Increased nephrotoxicity
PARACETAMOL An analgesic and antipyretic over-the counter drug. Not an anti-inflammatory drug A household analgesic and fever reducing agent. For pt who cannot take aspirin and children.
Mechanism of Action A prostaglandin synthesis inhibitor, inflammatory lesions are rich in peroxides aracetamol fails to inhibit the synthesis of prostaglandins if peroxides present Paracetamol is given orally Metabolized in liver and a liberated metabolite ‘N- acetyl-para-benzoquinone- imine (NAPQI) is toxic. A choice of analgesic in bronchiol, asthmatic, and peptic ulcer patients (325-500 mg every 4-6 hours up to a maximum of 3 g / day.
Adverse Effects of Paracetamol Rare and if appear, usually mild. Higher dose – can produce methaemoglobinemia and renal toxicity Mixed analgesic preparation on chronic administration may cause interstitial analgesic nephropathy. Ingestion of 10-15 g causes severe hepatocellular necrosis, renal tubular necrosis with nausea, vomitting, sweating and abdominal pain N-acetyl-cysteine or methionine as antidote for acute paracetamol poisoning