Académique Documents
Professionnel Documents
Culture Documents
Limiting tissue damage The need of anti-inammatory drugs arises antiwhen the inammatory response is inappropriate, aberrant, sustained, or causes destruction of tissue
Among many mediators, more important mediators are : Eicosanoids Biological oxidants, Cytokines, Adhesion factors, Digestive enzymes (proteases, hyaluronidase, collagenase, and elastase)
Only the first three of these are therapeutic targets for anti-inflammatory drugs
Eicosanoids
Derivation from a 20-carbon unsaturated fatty acid, arachidonic acid (eicosatetraenoic acid) Arachidonic acid obtained from membrane phospholipid & synthesized de novo at the time of cellular stimulation Arachidonic acid may also be derived from sequential actions of phospholipase C and diacylglyceryl lipase Arachidonic acid
COX-1 constitutive isoform, responsible for the basal production of prostaglandins, prostacyclins, and thromboxanes COX 2, inducible COX, expression & activity increase by stimuli of inflammatory cytokines & other inflammatory stimuli The final product of the COX pathway is tissue specific The production of inflammatory eicosanoids is an important target of many anti-inflammatory antidrugs. The side effects of these drugs frequently result from their inhibition of eicosanoid
Carboprost ,PGF2 analogue, can be used to terminate pregnancy or to control refractory postpartum bleeding by stimulating uterine contraction Epoprostenol, synthetic prostacyclin, use to treat Epoprostenol primary pulmonary hypertension Zafirlukast, Zafirlukast leucotrien receptor antagonist, use to treat asthma Zileuton, inhibit enzyme in lipooxygenase pathway, Zileuton can be used to treat asthma
NSAIDs
Prostaglandins of the E and F series evoke some of the local and systemic manifestations of inflammation :
vasodilation,
hyperemia, increased vascular permeability, swelling, pain, and increased leukocyte migration
Intensify
NSAIDs non selectictive COX inhibitors The degree of inhibition vary from drugs to drugs The spectrum of toxicity produced by each NSAID is related to its inhibition of specific COX isoforms
Drugs plotted below the line are more potent inhibitors of COX-2 than drugs plotted above the line. The COXdistance to the line is a measure of selectivity