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Preferential and selective COX-2 inhibitors.pptx
- 1. BY- MADHUMITA DIXIT JR-3 PHARMACOLOGY DEPARTMENT MOTILAL NEHRU MEDICAL COLLEGE ,PRAYAGRAJ
- 2. Cyclo-oxygenase inhibitors -These drugs have three major therapeutic actions 1)Anti-inflammatory action: The decrease in prostaglandin E2 and prostacyclin reduces vasodilatation and, indirectly, oedema. Accumulation of inflammatory cells is not directly reduced. 2) Analgesic effect: Decreased prostaglandin generation means less sensitization of nociceptive nerve endings to inflammatory mediators such as Bradykinin and 5- hydroxytryptamine. Relief of headache is probably a result of decreased prostaglandin-mediated vasodilatation. 3) Antipyretic effect: Interleukin-1 releases prostaglandins in the central nervous system, where they elevate the hypothalamic set point for temperature control, thus causing fever, NSAIDs prevent this.
- 3. NIMESULIDE-This NSAID decreases synthesis of Prostaglandins due to selective inhibition of COX-2 Enzyme and minimal inhibition of COX 1 As well as- 1)Reduces generation of superoxide by neutrophils 2) inhibits PAF synthesis and TNF-alfa release 3)Free radical scavenging 4) Inhibits metalloproteinase activity in cartilage Uses- 1)Acute pain 2)Primary dys-menorrhoea
- 4. Nimesulide is not recommended for long duration due to its association with an increased risk of Fulminant hepatic failure. Despite its risk of hepatotoxicity, a 2012 evaluation by the European Medicines Agency (EMA) concluded that the overall benefit/risk profile of nimesulide is favourable and in line with that of the other NSAIDs such as diclofenac, ibuprofen, and naproxen provided that the duration of use is limited to 15 days and the dose does not exceed 200 mg/day. Contraindications-1)Children under 12 years 2)Hepatic impairement 3)Chronic kidney disease 4)Pregnancy and Lactation 5)Active gastrointestinal ulcers
- 5. DICLOFENAC SODIUM- Reversibly inhibits COX-1 and COX-2,hence decreases formation of Prostaglandins. Uses- 1)Ankylosing spondylitis 2)Rheumatoid arthritis 3)Osteoarthritis 4)Primary dysmenorrhoea 5)Migraine 6)Pain 7)Gout It has good tissue penetrability and concentration in synovial fluid is maintained for 3 times longer period than in plasma, exerting extended therapeutic action in joints.
- 6. Pregnancy –Category C(1st and 2nd Trimester) Category D(3rd Trimester) Lactation- Excreted in breastmilk,maternal use of NSAIDS should be avoided if breastfeeding infant has platelet dysfunction, thrombocytopenia or ductal- dependent cardiac lesion. Side effects->10%- Cardiovascuar-Edema Hepatic-Increased serum level of transaminases
- 7. BOXED WARNING- 1)Serious cardiovascular thrombotic events- NSAIDS may cause Myocardial infarction and Stroke. Risk may occur early in treatment and may increase with duration of use. Diclofenac is contraindicated in the setting of Coronary Artery Bypass Graft (CABG) surgery. 2)Serious GI bleeding, ulceration and perforation- Elderly patients and patients with prior history of peptic ulcer disease and/or GI bleeding are at greater risk of serious GI events.
- 8. ETODOLAC- Etodolac is used for the management of mild to moderate pain, fever, and inflammation. •Etodolac is used with caution in patients taking anticoagulants, such as Warfarin, because it increases the risk of bleeding. • Patients taking both Lithium and Etodolac may develop toxic blood lithium levels. •Etodolac has been found to interact with certain anti- depressant medications, such as Sertraline or Fluoxetine, which can increase risks of stroke, heart attack, and other cardiovascular conditions.
- 9. Parameters Nimesulide Diclofenac Meloxicam Etodolac F(%) 68% 60% 89% 80% PPB >97.5% >99% 99.4% 100% Metabolism Hepatic Hepatic Hepatic Hepatic Plasma t1/2 1.8-4.7hrs 1.2-2hrs 20hrs 7.3 ± 4.0hrs Excretion Renal(50%) Fecal(29%) Bile(40%) Urine(60%) Urine(50%) Feces(50%) Renal Onset of action 15 minutes 30 minutes - 45-60 min
- 10. SELECTIVE COX-2 INHIBITORS(COXIBS)- Currently, 3 selective COX-2 inhibitors Celecoxib, Etoricoxib and Parecoxib are available in India. USES-1)Osteoarthritis 2)Rheumatoid Arthritis 3)musculoskeletal pain 4) primary dysmenorrhoea 5)Ankylosing spondylitis 6)Dental pain
- 11. Side effects-Cardiovascular events: NSAIDs are associated with an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including myocardial infarction and stroke. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease Gastrointestinal events: NSAIDs may increase risk of serious gastrointestinal (GI) ulceration, bleeding, and perforation
- 12. Parameter Celecoxib Etoricoxib Parecoxib F(%) - 100% 100% PPB 97 92 98 Metabolism Liver(CYP2C9) Liver(CYP3A4) Liver(CYP2C9, CYP3A4) Plasma t1/2 7.8hrs 22hrs 22min Excretion Feces(57%) Urine(27%) Renal(70%) Feces(20%) Renal(70%)
- 13. THANK-YOU