Nonsteroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the COX enzymes responsible for prostaglandin biosynthesis. NSAIDs are classified as non-selective or selective COX-2 inhibitors. Non-selective NSAIDs like aspirin and ibuprofen inhibit both COX-1 and COX-2, which can cause side effects like gastrointestinal irritation. NSAIDs provide analgesic, antipyretic, and anti-inflammatory effects through inhibition of prostaglandin production. While effective for relieving pain and inflammation, long-term NSAID use increases risk of ulcers and gastrointestinal bleeding.

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
, nefopam
Mechanism 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
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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
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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
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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 inhibitors
Hypersensitivity
 Skin rashes, urticaria, broncheospasm, anaphylactic reaction
Rey's syndrome
Pregnancy
Analgesic 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
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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 urine
Uses:
 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 children
Adverse effects:
 Skin rashes, Nausea, Hepatotoxicity, Nephrotoxicity
• Acute Paracetamol Poisoning
 Hepatotoxicity: Nausea, vomiting, diarrhea, abdominal pain, hypotension,
hypoprothrombinemia coma, death
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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
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