Eicosanoids and NSAID Flashcards
Prostacyclin (PGI2)
Inhibit platelet aggregation Powerful bronchodialator Inhibits gastric acid secretion/promotes mucus Increase Renal GFR Relax uterine muscle Induces pain
Prostaglandin (PGE2)
Vasodialator
Low conc enhances/high conc inhibits platelet agg.
Bronchodialator
Inhibit gastric acid secretion/ promote mucus
Increase GFR
Contracts uterine sooth muscle (low conc.)
Induces Pain and Fever
Thromboxane (TXA2)
potent vasoconstrictor enhance platelet aggregation product of platelet COX-1 Bronchoconstrictor decreased renal function (vasoconstriction) Uterine muscle contraction
Prostaglandin F2a (PGF2a)
Vasoconstrictor
Bronchoconstrictor
Contracts uterine smooth muscle
Decreases intra-ocular pressure
Misoprostol
PGE1 analog
Inhibits gastric acid secretion
Adjunct to NSAID therapy (reduce ulcer)
Contraindicated in pregnancy (uterine contraction)
Alprostadil
PGE1
maintains patent ductus arteriosus
vasodialator (increases lung perfusion = inc. O2)
Latanoprost
PGF2a analog
used to treat open angle glaucoma
LTB4
Chemotactic for PMN leukocytes/eosinophils/monocyte
hyperalgesia
Elevated in IBD
Cysteinyl Luekotrienes (LTC4, LTD4, LTE4)
Chemotactic for eosinophils
Bronchoconstrictors
Increase vascular permeability
Components of slow acting substance of anaphylaxis
Leukotriene Receptors
BLT1 - LTB4 - none - some suppression of inflammation
BLT2- LTB4 - HPETE - ?
CysLT1 -LTD4 - C4,E4 - Pulm inflam. and fibrosis respon.
CysLT2 -LTD4,C4 - E4- Pulm inflam and fibrosis respon.
Zafirlukast
Competitive, reversible LTD4 receptor antagonist
decrease airway constriction & vascular perm.
Uses: prophylactic for asthma, allergic rhinitis
Adverse: headache, pharyngitis, increase LFTs (rare)
Drug interax: inhibits CYP3A4 and 2C9
Montelukast
Competitive, reversible LTD4 receptor antagonist
decrease airway constriction & vascular perm.
Uses: prophylactic for asthma, allergic rhinitis, aspirin sensitivity induced asthma
Adverse: headache
Zileuton
Inhibitor of 5-lipoxygenase
Uses: Asthma prophylaxis
Adverse: 4-5% elevated hepatic transaminase must monitor hepatic function, Contraindicated with liver disease and ergot alkaloids
Drug interax: Decreased clearance of Theophylline, Warfarin, and Propranolol
Aspirin
Irreversible inhibitor of cyclooxygenase
Uses: Antipyretic, antiinflammitory, analgesic (limited to brain/no effect on opioid receptor)
Low dose aspirin for MI, thrombosis, transient ischeic attacks, ect. Preecclampsia
Adverse: GI pain/bleeding/ulcers, Reye’s syndrome, salycylism - characterized by tinnitis
Aspirin Dosing
Antipyretic/analgesic - 350-625mg
Anti-inflammatory - 4-6g
Lethal - 10-30g
Aspirin - Platelets
Irreversibly inhibit platelet COX
Low doses inhibit platelet TXA2 production
Prolonged bleeding time (stop 2 weeks before surgery)
Ibuprofen
Competitive, reversible COX-1 & 2 inhibitor
Use: mild to moderate pain, antipyretic, symptoms of rheumatoid and osteoarthritis, dysmenorrhea, acute migraines
Drug Interax: decrease effectiveness of ACE inhibitors
Naproxen
Competitive, reversible COX-1 & 2 Inhibitor
Better anti-inflammatory than Ibuprofen
Use: mild to moderate pain, antipyretic, symptoms of rheumatoid and osteoarthritis, dysmenorrhea, ankylosing spondylitis, acute gout
Adverse: Increased risk of stroke/MI with extended use
Drug interax: decrease effectiveness of ACE inhibitors, antacids and sucralfate (divalent cations) decrease naproxen absorption
Ketorolac (Topical)
Opthalmic prep.
Allergic conjunctivitis or recovery from cataract surgery
Ketorolac
Analgesic (comparable to morphine)
Use: Post operative pain (Moderate to severe)
IM, IV, and Oral admin. options
Inhibits platelet aggregation
Adverse: GI bleeding, Gen. bleeding, Hepatic,
Lower dose in elderly or
Diclofenac
Analgesic
Use: rheumatoid/osteoarthritis, ankylosing spondylitis, primary dymenorrhea
Opthalmic prep for post cataract surgery
Arthrotec: Diclofenac+Misoprostol - used when risk of ulcers; contraindicated in pregnancy
Zorvolex: low dose diclofenac (mild to moderate acute pain);
Adverse: elevation of AST (monitor transaminases first 8 weeks)
Metabolized by CYP2C9
Indomethacin
Oral: Acute gouty/rhematoid/osteo-arthritis, tendonitis, ankylosing spondylitis,
IV: nonsurgical closure PDA (limited by renal toxicity)
Adverse: GI pain (take w/ food), displace bilirubin from albumin, decreased urine output
Contraindicated: hyperbilirubinemia, renal failure
Celecoxib
Selective COX-2 inhibitor
Rheumatoid and osteoarthritis
Adverse: Low incidence GI pain, increased risk stroke/MI
Drug interax: metabolized by CYP2C9, watch dose w/ 2C9 inhibitors (Fluconazole)
Selecting NSAID
Same mechanism, different potency
Aspirin sensitivity cross to other NSAIDs
GI ulcers
Pregnancy - bleeding, premature closure ductus arteriosus, inhibit uterine motility
DO NOT COMBINE NSAIDs
Renal function
