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Non steroidal anti inflammatory drugs
Non steroidal anti inflammatory drugs
Non steroidal anti inflammatory drugs
Non steroidal anti inflammatory drugs
Non steroidal anti inflammatory drugs
Non steroidal anti inflammatory drugs
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Non steroidal anti inflammatory drugs

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  • 1. • NON STEROIDAL ANTI INFLAMMATORY DRUGS• Classification• Non Selective COX Inhibitors:  Salicylates : Aspirin , Diflunisal  Propionic acid derivatives: Ibuprofen, Ketoprofen, Naproxen, Flurbiprofen,  Acetic acid derivatives: Diclofenac , Aceclofenac  Fenamic acid derivatives: Mefnamic Acid  Pyrrole -pyrrole derivatives: Piroxicam , Tenoxicam  Indole derivatives: Indomethacin , Sulindac• COX 2 inhibitors: Minisulide , Meloxicam, Nebumetone• Highly selective COX 2 inhibitors: etoricoxib, parecoxib• Analgesic – antipyretics with poor anti-inflammatory effect: Paracetamol , nefopamMechanism of action COX is enzyme responsible for biosynthesis of various prostaglandins There are two well recognized iso forms COX called Cox 1 and COX 2 COX I is constitutive found in most tissues such as blood vessels, stomach and kidneys PGS have important physiological role in most tissues COX2 is induced during inflammation by cytokines and endotoxins and is responsible for the production of prostanoid mediators of inflammation Aspirin and most of non steroidal ant inflammatory drugs inhibit both COX 1 and COX 2 isoforms thereby decrease PG and thromboxane synthesis The antiinflammatory effect of NSAIDS is mainly due to inhibition of COX 2 Aspirin causes irreversible inhibition of COX activity. Rest of the NSAIDS cause reversible inhibition of enzyme 1
  • 2. Pharmacological actions of aspirin and other NSAIDS: Aspirin is prototype drug The other non selective NSAIDS vary mainly in their potency, analgesic , ant inflammatory effects and duration of action Analgesic effect NSAIDS are mainly used for relieving musculoskeletal pain , dysmenorrhea and pain associated with inflammation or tissue damage Analgesic effect is mainly due to peripheral inhibition of PGS production They also increase pain threshold by acting as sub cortical site These drugs relieves pain without causing sedation tolerance or drug dependence Antipyretic effect The thromboregulatory centre is situated in hypothalamus Fever occurs when there is disturbance in hypothalamic thermostat NSAIDS reset the hypothalamic thermostat and reduce the elevated body temperature during fever They promote heat loss by causing cutaneous vasodilatation and sweating They do not effect normal body temperature The antipyretic effect is mainly due to inhibition of PGS in hypothalamus Anti-inflammatory effect: Anti -inflammatory effect is seen at high doses(aspirin 4-6 g/day in divided doses ) These drugs produce only symptomatic relief They suppress sign and symptoms of inflammation such as pain , tenderness swelling vasodilatation and leukocyte infiltration but they do not effect the progression underlying disease The inflammatory action of NSAIDS is mainly due to inhibition of prostaglandins synthesis at the site of injury 2
  • 3.  They also affect other mediators of inflammation (bradykinin , histamine , serotonin and thus inhibit granulocyte adherence to the damaged vasculature NSAIDS also cause modulation of t cell function stabilization of lysosomal membrane and inhibition of chemo taxis Antiplatelets effect: Aspirin in low doses (50-325 mg ) irreversible inhibits TXA 2 synthesis and produces antipalatelet effect which last 8-10 days i.e. the life time of platelets Aspirin in high doses 2-3 g/day inhibits both PGI 2 and TXA 2 synthesis hence beneficial effect of PGS is lost. Acid base and electrolyte imbalance: In therapeutic doses salicylates causes respiratory alkalosis . In toxic doses the respiratory centre is depressed and can lead to respiratory alkalosis In toxic doses the respiratory centre is depressed and can lead to respiratory acidosis GIT Irritates gastric mucosa and produce nausea vomiting and dyspepsia The salicylic acid formed from aspirin also contributes to these effect Aspirin also stimulates CTZ and produce vomiting CVS Prolonged use of aspirin and other NSAIDS causes Na and water retention They may precipitate CCF in patients with low cardiac reserve They may also compromise the effect of antihypertensive drugs 3
  • 4.  Urate excretion: Salicylates in therapeutic doses inhibit urate secretion into renal tubules and increase the plasma urate levels• In high doses salicylates inhibit the reabsorption of uric acid in renal tubules and produce uricosuric acid Adverse effects Nausea , dyspepsia epigastric pain , acute gastritis , ulceration and GI bleeding Ulcerogenic effect is major drawback of NSAIDS which is minimized by taking: after food Buffered aspirin Misoprostol, H2 blockers proton pump inhibitors with NSAIDS Selective cox 2 inhibitorsHypersensitivity Skin rashes, urticaria, broncheospasm, anaphylactic reactionReys syndromePregnancyAnalgesic neuropathy• Salicylism The salicylate intoxication may be mild or severe The mild form is called as salicylism The symptoms include headache , tinnitus , vertigo confusion , nausea , vomiting , diarrhea sweating , hyperpnoea, electrolyte imbalance The symptoms are reversible on stoppage of therapy Common manifestations are vomiting , dehydration, acid base balance hyperpnoea , restlessness, confusion, coma convulsions , cardiovascular collapse pulmonary edema , hyperpyrexia and death 4
  • 5. • Treatment Hospitalization Gastric levage followed by administration of activated charcoal Fluid and electrolyte and acid base balance restoration I/V sodium bicarbonate to treat metabolic acidosis It also alkalinizes the urine and enhances renal excretion of salicylates External cooling Hemodailysis in severe cases Vit k1 and blood transfusion is given if there is bleeding• SELECTIVE COX 2 INHIBITOR• PARACETAMOL Paracetamol is effective by oral and parentral routes Well distributed all over the body Metabolized in liver by sulphate and glucuronide conjugation Metabolites are excreted in urineUses: Antipyretic: reduce body temperature during fever Analgesic: to relieve headache, toothache, myelgia, dysmenorrhoea Preferred analgesic and antipyretic in patients with peptic ulcer hemophilia, bronchial asthma and childrenAdverse effects: Skin rashes, Nausea, Hepatotoxicity, Nephrotoxicity• Acute Paracetamol Poisoning Hepatotoxicity: Nausea, vomiting, diarrhea, abdominal pain, hypotension, hypoprothrombinemia coma, death 5
  • 6. Mechanism of toxicity and treatment: Toxic metabolite is detoxified by conjugation with glutathione and gets eliminated High doses of paracetamol causes depletion of glutathione levels In absence of glutathione toxic metabolites binds with protein in liver ,kidney and cause necrosis Alcoholics and premature infants are more prone to hepatotoxicity N- acetylcysteine or oral methionine replenishes the glutathione stores of the liver and protects liver cells Activated charcoal is administered to decrease the absorption of paracetamol from gut Charcoal heamoperfusion is effective in severe liver failure Hemodialysis is required in cases with acute renal failure 6

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