analgesics · therapeutic uses •local •systemic ... selective-incidence of adrs less...
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Analgesics
• Analgesics-Selectively relieves pain
Two Types:
• Narcotics /Opioid analgesics: Act on CNS &
cause drowsiness
• Non narcotics/NSAIDs: Act peripherally
Non steroidal anti-inflammatory Drugs
Non Selective Cox Inhibitor
• Salicylates
• Paracetamol
• Diclofenac
• Ibuprofen
• Mephenamic acid
• Indomethacin
• Piroxicam
• Preferential COX-2 inhibitors
• Nimesulide, Meloxicam
Selective COX-2 inhibitors
• Selecoxib, Etoricoxib
• Parecoxib( Valdecoxib)
COX= Cyclo-oxygenase (enzyme)
Mechanism of ActionPhospholipids (Cell Membrane)
Phospholipase A2
(Inhibited by Lipocortin-1)
Arachidonic Acid
Prostaglandin G/H Synthase Lipoxygenase
(Cyclo-oxygenase) Inhibited by NSAIDs
Hydroperoxy acids
Prostaglandins
Prostocyclin Thromboxane A2 Others PGS
PGI2 TXA2 PGE2
PGF2α Leukotrienes
Aspirin Mechanism of Action
• Inhibit cyclooxygenase - Enzyme
responsible for synthesis of:
Prostaglandins
–Pain response
–Suppression of gastric acid secretion
–Promote secretion of gastric mucus
and bicarbonate
–Mediation of inflammatory response
–Production of fever
–Promote renal vasodilation ( blood flow)
–Promote uterine contraction
Thromboxane A2
–Involved in platelet
–aggregation
• Cyclo-oxygenase (Cox) - 2 types
Cox 1 – Non inducible – present in
stomach, Kidney, blood vessels and
platelets
Cox 2 – inducible in activated
leucocytes and other inflammatory
cells
Acetyl salicylic acid (Aspirin)
• Pharmacological action
Local
salicylic acid and methyl salicylate –
irritant
salicylic acid – keratolytic, antiseptic
and antifungal
Analgesia
• Inhibits Cox irreversible
• Others NSAIDs – reversible inhibition
• Antipyretic – salicylate reset thermostatic
mechanism at the normal level – bring down
the temperature to the normal (does not
reduce heat production)
Action on GIT
• Dyspepsia, nausea, vomiting – gastric irritation
• Peptic ulceration which upper GI bleeding –haematemesis / melaena
• Anti-inflammatory and antirheumatic
-Inhibiting PG synthesis
-reducing capillary permeability
-inhibition of neutrophil aggregation and activation
Anti Platelet Activity
• Suppress thromboxane A2 (TX-A2) –
inhibits platelet aggregation
Pharmacokinetics
• Absorbed orally from stomach and intestine
• Poor water solubility – limiting factor
• Particle size, pH of GIT, presence of food –
affect of absorption
• Metabolism and excretion
Adverse effects
• Intolerance – skin rashes, urticaria, angioedema and bronchospasm
• GIT – nausea, vomiting and ulceration
• Reye’s syndrome – in viral infection in children below 12 yrs of age (serious and fatal)
• Pregnancy and infants – delay labour at term and cause blood loss at delivery
• Cause closure of the ductus arteriosis – serious pulmonary HTN in new born
Therapeutic Uses
• Local
• Systemic
–Analgesic, antipyretic,
antiinflammatory (4 to 6 gm / day)
–Antiplatelet in IHD
Other NSAIDs
• Diclofenac, aceclofenac- More cox-2
selective-incidence of ADRs less
Ketorolac-potent as morphine
Dose-10-30mg 6hrly p o/im/ iv
Nimesulide-
Selective Cox 2 Inhibitors
• Selectivity varies 6 to 375 folds
• Gastrointestinal mucosa not affected
• Platelet aggregation not affected (TX – A2) not reduced
Celecoxib
Pharmacokinetic
–Absorption po., slowly
–Metabolism and excretion
Adverse Drug Reaction
• Dyspepsia and mild diarrhoea
Uses
–Osteoarthritis and rheumatoid arthritis
(100 – 200 mg BD)
Etoricoxib
Highest cox-2 selectivity
60-120mg/day-once daily