Non-steroidal Anti-inflammatory
Drugs (NSAIDs)
Dr. Nishant B. Bhansali
Introduction
• These are a class of drugs having analgesic, antipyretic
and anti-inflammatory effect
• They do not depress the CNS and act peripherally for
reducing pain
• They do not produce physical dependence or have abuse
liability and are effective in inflammatory pain
• They are known as “Aspirin like analgesics”
Classification
1. Non-selective COX inhibitors
– Salicylates – Aspirin, diflunisal
– Propionic acid derivatives – Ibuprofen, Naproxen
– Acetic acid derivatives – Diclofenac, aceclofenac
– Fenamic acid derivatives – Mefenamic acid
– Pyrrolo-pyrole derivatives – Ketorolac, etodolac
– Oxicam derivatives – Piroxicam, tenoxicam
– Indole derivatives – Indomethacin
2. Preferential COX-2 inhibitors – Nimesulide,
meloxicam, nabumetone
3. Highly selective COX-2 inhibitors – Etoricoxib,
rofecoxib, lumiracoxib
4. Analgesic and antipyretics with weak anti-
inflammatory effect – Paracetamol, nefopam
Aspirin
• Mechanism of action
– COX is the enzyme responsible for the biosynthesis
of PGs
– Two types of COX (COX1 & COX2)
– Aspirin and all NSAIDs inhibit COX enzyme and
thus inhibit the generation of PGs
Pharmacological actions
• Analgesic effect
– NSAIDs are mainly used for relieving
musculoskeletal pain, dysmenorrhoea and pain
associated with inflammation or tissue damage
– Analgesic effect is mainly due to peripheral
inhibition of PG production
– Increase pain threshold by acting at cortical site
– No tolerance, sedation or dependence
• Antipyretic effect
– Thermoregulatory centre is in hypothalamus
– Fever is due to disturbance of hypothalamic thermostat
– NSAIDs resets this hypothalamic thermostat
– Antipyretic effect is due to inhibition of PG synthesis in
hypothalamus
• Anti-inflammatory effect
– By this effect produce symptomatic relief
– Do not affect the progression of the disease
– Mainly decrease inflammation by decreasing PGs
biosynthesis
– Suppress signs and symptoms of inflammation
• Antiplatelet effect
– Aspirin in low doses (75-325 mg/day) irreversibly inhibits
platelet TXA2 synthesis producing antiplatelet effect
– At high doses biosynthesis of both PGI2 and TXA2 is lost
and thus its antiplatelet effect is also lost
• Acid-base and electrolyte balance
– In therapeutic doses salicylates cause
• Respiratory alkalosis
• Compensated by excretion of alkaline urine (Compensated
respiratory alkalosis)
• Followed by respiratory acidosis
• Later there is uncompensated metabolic acidosis
• CVS
– Prolonged use of NSAIDs cause sodium and water
retention.
– May precipitate CCF in patients with low cardiac reserve
– Decrease the effect of antihypertensive drugs
• GIT
– NSAIDs irritate the gastric mucosa and produce nausea,
vomiting and dyspepsia.
Adverse drug reactions
• GIT
– Nausea, vomiting, dyspepsia, epigastric pain, acute
gastritis, ulceration and GI bleeding
– Ulcerogenic effect is the main drawback of NSAIDs
• Hypersensitivity
– Relatively more common with aspirin
– Skin rashes, urticaria, rhinitis, bronchospasm,
angioneurotic oedema and rarely anaphylactoid reaction
• In people with G6PD deficiency causes hemolytic
anaemia
• Analgesic nephropathy – prolonged uses damages
the kidney even causing renal failure
• Reye’s syndrome – children with viral infections
aspirin used as antipyretic produces liver fatty
infiltration and encephalopathy
• Pregnancy – delays onset of labour and premature
closure of ductus arteriosus
• Salicylism
– At high doses 2-3 gm/day symptoms like headache,
tinnitus, vertigo, confusion, nausea, vomiting, diarrhea,
sweating etc. occur
– Reversible on stoppage of drug
• Acute salicylate poisoning
– Common in children
– Manifestations include – vomiting, dehydration, acid-
base and electrolyte imbalance, hyperpnoea,
restlessness, confusion, coma, convulsions,
cardiovascular collapse and death
– No specific antidote, supportive and symptomatic
treatment
Clinical Uses of NSAIDs
• As an analgesic
• As an antipyretic
• Rheumatoid arthritis
• Osteoarthritis
• Gout
• Acute rheumatic fever
• Thromboembolic disorders
– Low dose aspirin is used for prophylaxis of MI and stroke
• Other uses of aspirin
– Medical closure of PDA
– Colon and rectal cancer prevention
– Radiation induced diarrhoea
– Control pruritus and flushing associated with the use of
Nicotinic acid
– Low dose aspirin can be used for pre-eclampsia
Selective COX2 inhibitors
Paracetamol
• It is effective by oral and parenteral route
• Well absorbed, widely distributed all over the body
• Metabolized in liver by sulphate and glucuronide
conjugation
• Metabolites are excreted in urine
Uses
• As an antipyretic
– Antipyretic of choice for fever due to any cause
and any age
– Very well tolerated and very few side effects
• As an analgesic
– To relieve pain due to tootache, headache, etc.
Adverse effects
• Side effects are rare, occasionally causes skin
rashes and nausea
• Hepatotoxicity with acute overdose
• Nephrotoxicity with long term use
Acute paracetamol poisoning
• Acute overdosage mainly causes hepatotoxicity
• Symptoms
– Nausea, vomiting
– Diarrhea
– Abdominal pain
– Hypoglycemia
– Hypotension
– Hypoprothrombinemia
– Death due to hepatic necrosis
Mechanism of liver toxicity
• High doses of paracetamol causes depletion of
glutathione level
• In the absence of glutathione, toxic metabolite
binds covalently with proteins in liver and kidneys
• Causes necrosis
• N-acetylcysteine replinishes liver glutathione and is
the antidote for paracetamol poisoning
Summary
• To summaries all NSAIDs
– Inhibit COX enzyme and thus inhibit PG synthesis
– Have analgesic, antipyretic and anti-inflammatory
properties
– Act peripherally and have no CNS effects as well as
side effects
– Produce GI toxicity and nephrotoxcity
– Are one of the most commonly used drugs for
relieving pain
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