Non-steroidal%20Anti-inflammatory%20Drugs

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Non-steroidal Anti-inflammatory Drugs

• Dr.B.V.Venkataraman
• Professor in Pharmacology
• International Medical School
• Faculti Perubatan, New BEL Rd
• Bangalore - 560054
• Venkataraman_bv_at_yahoo.com

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COX
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Physiological stimulus Inflammatory
stimulus
Macrophages/other cells
COX-1 Constitutive
Cox-2 Induced
Other inflammatory mediators
Proteases
PGs
TXA2 Platelets
PGI2, endothelium Stomach mucosa etc
PGE2, Kidney etc
INFLAMMATION
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Classification of NSAID

• COX-1 and COX-2 inhibitors
• Salicylates Aspirin
• Para-aminophenols Phenacetin, Paracetamol.
• Pyrazolons Phenylbutazone
• Indoles Indomethacin, Sulindac, Tolmetin,
  Ketorolac.
• Phenylacetates Diclofenac
• Propionates Ibuprofen, Ketoprofen,
• Fenamates Flufenamic acid and Mefenamic acid.
• Oxicams Piroxicam

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Classification of NSADs (contd)

• COX-2 inhibitors (Coxibs)
• Valdecoxib, etorocoxib
• COX-3 inhibitors
• Paracetamol
• Miscellaneous COX Inhibitors
• Nimesulide, Meloxicam, Etodolac etc
• Drugs do not inhibit PGs
• Nefopam

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SALYCILATES

• Source bark of willow (used in malaria)
• Now it is commercially synthesised.
• Salicylic acid
• Sodium salicylate
• Acetyl salicylic acid (aspirin)
• Methyl salicylic acid (oil of winter green)
• Diflunisal is a derivative of aspirin.

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SALICYLATES

• LOCAL ACTIONS
• Irritants
• Salicylic acid Keratolytic, used in ring worm
  infection
• Methyl salicylate counter irritant in relieving
  joints and muscular pain

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Aspirin systemic effects

• Analgesic

Aspirin
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Types of Analgesis

• Two types
• Narcotic analgesics
• Relieve pain and produce sedative/hypnotic
  effect e.g. morlphine, pethidine
• 2. Non-narcotic analgesics
• Relieve pain with out affecting the
  consciousness e.g. aspirin, paracetamol

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Systemic actions of aspirin

• Antipyretic action Inhibition of central PG
• Antiplatelet action

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(Anti inflammatory action)
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Systemic actions of aspirin

• TxA2 is present in platelets
• At any dose anti-platelet aggregation (inhibiting
  TXA2)
• At low dose PGI2 not inhibited
• At high dose PGI2 is inhibited.
• PGI2 vasodilator and anti-platelet aggregation.
  
• Action is irreversible.
• Duration 8-10 days (life of platelet)

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Systemic actions of Salicylates

• Renal effect PGE2 (vasodilator) coordinate with
  angiotensin-II. Chronic NSAIDs leads to
  inhibition of PGE2 and vasoconstriction.
• Respiration directly and indirectly. O2 leads to
  CO2 which stimulates respiratory centre. These
  events leads to hyper ventilation.
• Low dose decrease the uric acid level. High dose
  uricosuric effect.

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Pharmacokinetics

• Well absorbed from stomach and small intestine
• Empty stomach and acid medium helps absorption
• Deacetylation in gut wall, liver, plasma other
  tissues after absorption.
• Protein binding 80
• Conjugated with glycine.
• 1/10 is excreted in active form which can be
  enhanced with alkalinisation.

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Side effects of aspirin

• Intolerance (rare) rashes, urticaria, asthma
  etc.
• Gastric irritation
• Hypoprothrombinemia Vit K is antidote
• Reyes syndrome Children prescribed for viral
  fever. Syndrome consists of liver dysfunction
  (fatal)
• Salicylism headache, dizziness, vertigo,
  difficulty in hearing and dimness of vision. The
  symptoms are reversible once the drug is
  withdrawn.

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Treatment of acute salicylate poisoning

• Symptomatic treatment
• Patent airway
• Hyperthermia reduced by external cooling.
• Dehydration should be corrected.
• Vitamin K should be administered.
• Metabolic acidosis is corrected by NaHCO3 which
  also promotes renal excretion of salicylates.
• Forced diuresis is done by administration of
  furosemide (40 mg) in the infusion fluid.
• Dialysis is done in renal failure.

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Clinical uses of Salicylates

• Keratolytic and antifungal salicylic acid
• Counter irritant Methyl salicylic acid
• Acute rheumatic fever Streptococcal infection
  induces antibodies reacting with lymphocytes.
  These antibodies react with heart valves and
  myocardium.
• Treatment
• a. Penicillin for the streptococcal infection.
• b. Aspirin (5-8 g in divided doses) for the
  inflammation.
• c.corticosteroids can also be given.

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Clinical uses of aspirin

• Arthritis and fibromyositis In rheumatoid
  arthritis, aspirin at 5-6 g in divided doses is
  advised.
• Ischaemic heart disease In low doses (100 mg
  daily) aspirin is given to prevent platelet
  aggregation.
• Pain headache, fever, dysmenorrhoea etc.
• For closure of patent ductus arteriosus.

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Drug interaction

• Aspirin displaces oral anticoagulants, oral
  antidiabetics etc.
• Interfers with uric acid excretion (analgesic
  dose inhibit)
• Decreases the diuretic actions (thiazides and
  furosemide)
• Reduces the K sparing action of spiranolactone.