Exam 1 NSAIDS Flashcards
Which NSAID has the longest history?
aspirin
What is inflammation?
- occurs upon infections or noxious stimuli
- eliminates harmful agents and necrotic cells
- initiates the healing process
- may injure normal tissues → too strong response, prolonged response, inappropriate response
- signs → heat, redness, swelling, pain, loss of function
What are the chemical mediators of inflammation?
- vasoactive amines → histamine and serotonin
- eicosanoids → prostaglandins, leukotrienes, and lipoxins
- platelet activating factor (PAF)
- cytokines → TNF, interleukin (IL), chemokines → acute inflammation and chronic inflammation is interferon gamma
- complement components → C3a and C5a
- coagulation and kinin systems → bradykinin, thrombin, fibrinopeptides
What are eicosanoids?
- short lived mediators (seconds to minutes)
- autocrine and paracrine signaling
- bind to GPCRs in target cells → generation of cAMP is dilation and release of calcium is constriction
What does PGE2 do?
dilate blood vessels and bronchi and has oxytocic dilation of uterus
What does PGF2alpha do?
constricts blood vessels and bronchi and oxytocic constriction of uterus
What does PGI2 do?
dilates blood vessels and inhibits platelet aggregation
What does PGI2 do?
dilates blood vessels and inhibits platelet aggregation
What does TXA2 do?
constricts blood vessels and aggregates platelets
What is arachidonic acid?
- 20 carbon polyunsaturated fatty acids that are essential → get it from food
- most abundant and important precursor of eicosanoids
- released from membrane phospholipids by phospholipase A2
- corticosteroids suppress the production of phospholipase A2 → will shut down the production of eicosanoids
What are the 4 different pathways of the oxygenation of arachidonic acid?
- PGH synthase COX pathway → prostaglandins, thromboxanes
- lipoxygenase pathway → leukotrienes
- epoxygenase (cytochrome P450) pathway
- isoprostane pathway (free radical reaction)
What is PGH synthase?
- PGH synthase has both cyclooxygenase and hydroperoxidase activities
- COX reaction → radical mediated
- hydroperoxidase reaction → conversion of hydroperoxyl group (OOH) to hydroxyl group (OH)
What are the isoforms of PGH synthase?
- PGH synthase 1 → COX 1 which is constitutively expressed in various tissues and have housekeeping functions like gastric cytoprotection
- PGH synthase 2 → COX 2 which is expressed upon stimulus in inflammatory and immune cells and stimulated by growth factors, tumor promoters and cytokines
- inhibited by NSAIDS
What is the precursor to make the different prostaglandins?
PGH2
What is the difference between prostaglandins and thromboxanes?
prostaglandins → in vascular endothelia, PGI2 is vasodilator and inhibits platelet aggregation → if too much bleeding may occur
thromboxanes → in platelets, TXA2 is vasoconstrictor and induces platelet aggregation → if too much can increase heart attack or stroke
What is alprostadil?
- PGE1
- relaxes smooth muscles and expand blood vessels
- used for erectile dysfunction by injection or as a suppository
What is misoprostol?
- PGE1 derivative
- cytoprotective to prevent peptic ulcer
- terminates early pregnancy in combination with mifepristone (RU-486)
What is latanoprost?
- topically active PGF2a derivative (prodrug)
- contricts blood vessels
- used in ophthalmology to treat high pressure inside the eye (glaucoma)
What is prostacyclin (epoprostenol)?
- PGI2
- powerful vasodilator and inhibitor of platelet aggregation
- used to treat pulmonary arterial hypertension by IV injection or inhalation
- should not be used with anticoagulants which can induce bleeding disorder
What are the activities of NSAIDS?
- anti-inflammatory
- analgesic
- antipyretic
What are the uses of NSAIDS?
- treatment of moderate pain, fever, and inflammation from acute inflammation
- treatment of early stage RA and OA
- cancer prevention by preventing unnecessary inflammation
What is the mechanism of action for NSAIDS?
- inhibition of PGHS or COX which catalyzes the formation of prostaglandins
- many NSAIDS inhibit both COX 1 and COX 2
What are the classes of NSAIDS?
- salicylates → aspirin
- arylacetic acids → indomethacin
- arylpropionic acids → ibuprofen
- non-carboxylate NSAIDS → meloxicam
- COX 2 selective NSAIDs → celecoxib
What are side effects of NSAIDs?
- GI
- blood coagulation
- renal
- hypersensitivity
- Reye’s syndrome
- CNS