NSAIDs Flashcards
Difference between TXA2 and TXA3
TXA2 is a vasoconstrictor, TXA3 is not
Cycloxygenases convert Arachidonic Acid into what? (2 names)
PGG2 (Cyclic Endoperoxidases)
Peroxidase converts what to what?
PGG2 to PGH2
What is Prostaglandin synthetase:
enzyme complex of cyclo-oxygenase and
peroxidase
COX-1 vs COX 2
COX-1 constitutive form - found in blood vessels, stomach & kidney
COX-2 inducible form
Involved in inflammation
Levels elevated by inflammation & cytokines
Decreased by administration of glucocorticoids
What kind of receptor are Prostaglandin receptors?
GPCR
Where is prostacyclin (PGI2) synthesized?
vascular smooth muscle cells and endothelial cells
Prostacyclin actions on: vasculature platelets airways GI renal reproductive pain
Tone - Vasodilator
platelets - inhibits platelet aggregation
Airways - bronchodilator
GI- Inhibits gastric acid secretion; increase mucus secretion Renal - Enhances renal excretion of sodium & water Reproductive - relaxes uterine muscle
Pain - Induces pain by lowering the threshold of nociceptors
Prostaglandin (PGE2) actions on: vasculature platelets airways GI renal reproductive pain fever
Vascular - vasodilator
Platelets: low conc enhances and high conc inhibits platelet aggregation
Airway - bronchodilator
GI - Inhibits gastric acid secretion & stimulates gastric mucus secretion
Renal - Promotes renal salt and water excretion
Reproductive - Uterine smooth muscle, increases contraction
pain - Induces hyperalgesia at localized area
Fever - PGE2 IS A DIRECT PYROGEN IN HYPOTHALAMUS
Where is TXA2 synthesized?
platelets, lung, kidney
Effects of TXA2 (2)
Vasoconstriction
Stimulates platelet aggregation
PGF2α actions on: vasculature airway reproductive eye
Vascular - Vasoconstrictor
Airway - contracts airway smooth muscle cells
Reproductive - Contracts uterine smooth muscle/dysmenorrhea
eye - decreases intraocular pressure
Misoprostol is what kind of drug?
PGE1 analog
Misoprostol clinical use
Inhibits gastric acid secretion, reduces risk of peptic ulcer in patients taking NSAID
Misoprostol contraindication
pregnancy, women of childbearing age must use contraceptive measures
Latanoprost is what kind of drug?
PGF2α analog
Latanoprost clinical use
ophthalmic preparation for open angle glaucoma
Latanoprost mechanism
increases outflow of aqueous humor, reduces ocular pressure
Alprostadil is what kind of drug?
PGE1 analog
Alprostadil clinical use and form given
maintain patency of the ductus arteriosus via IV infusion
Which Arachidonic Acid metabolites are chemotactic?
LTB4 and 5-HETE
LTC4, LTD4, and LTE4 actions (3)
Bronchoconstrictor
increase vascular permeability
Components of slow reacting substance of anaphylaxis
Zafirlukast and Montelukast mechanism
competitive leukotriene LTD4 (CysLT1) receptor antagonist
Zafirlukast and Montelukast
Prophylactic agent in treatment of asthma in adults
Montelukast - Especially good for aspirin-induced asthma.
Zafirlukast and Montelukast interactions
Zafirlukast inhibits P450 isozyme CYP2C9 and CYP3A4 Warfarin
Food reduces bioavailability
Zileuton mechanism
inhibitor of 5-lipoxygenase
Blocks conversion of arachidonic acid to leukotrienes
Zileuton use
Prophylaxis for asthma in adults and children (12 yr and older)
Zileuton toxicity
hepatotoxic
Zileuton decreases clearance of what 3 drugs?
Theophylline
Warfarin
Propranolol
NSAIDs mechanism (and exceptions)
competitive, reversible inhibitors COX1/COX2
aspirin is irreversible
Celecoxib is COX2 inhibitor
NSAIDs clinical use (3)
Antipyretic
Analgesics for mild to moderate pain
Anti-inflammatory
NSAIDs side effects (4)
GI irritation and ulcers
Bleeding, Inhibits platelet aggregation
Inhibit uterine motility
Fluid retention
NSAIDs contraindications
pregnancy - last trimester
Cross sensitivity with aspirin (contraindication)
Aspirin mechanism
irreversible COX inhibitor
acetylates enzyme
Aspirin actions (3)
analgesic (mild to moderate pain)
antipyretic
anti-inflammatory
Aspirin clinical use
arthritis initial therapy
low dose prevents MI
How does Aspirin prevent MI?
irreversibly inhibits TXA2 production in platelets
Aspirin side effects
GI pain, hemorrhage & ulcers
Aspirin contraindication
viral infection due to Reye’s Syndrome
Ibuprofen (Advil), Naproxen (Aleve) mechanism
reversible inhibition of COX
Ibuprofen (Advil) clinical use (4)
antipyretic, can be used in children
Arthritis
acute migraine attacks
primary dysmenorrhea
Naproxen (Aleve) clinical use (3)
arthritis
ankylosing spondylitits
acute gout
Benefit of Ibuprofen and Naproxen over Aspirin?
less GI ulcers
Naproxen contraindications
Naproxen clearance reduced in liver cirrhosis
increased risk of stroke/cardiovascular event
Ketorolac mechanism of action
inhibits COX
Ketorolac clinical use
Ophthalmic allergy and inflammation following cataract surgery
Post-operative pain
Only NSAID approved for moderate to severe pain
Ketorolac side effects
Bleeding
hepatotoxicity
Lower dose in patients under 110 lbs or elderly or elevated creatinine
Ketorolac contraindications
During labor/delivery or during lactation
DICLOFENAC clinical use
arthritis and ankylosing spondylitits
Ophthalmic preparation for post-cataract surgery
Arthotec contraindication?
Contraindicated during pregnancy
Arthotec is a combination of what drugs and is used in what patients?
Diclofenac and Misoprostol
patients at high risk for GI ulcer
Indomethacin IV clinical use?
non-surgical closure of patent ductus arteriosus
Indomethacin contraindications
renal and hyperbilirubinemia
Celecoxib mechanism
selective COX-2 competitive reversible inhibitor
Celecoxib clinical use
arthritis
Celecoxib side effects
GI pain
increased risk of cardiovascular and stroke event with high dose for prolonged time
Celecoxib drug interaction
-monitor dose carefully when given with fluconazole inhibits Cyp 2C9
Acetaminophen mechanism
Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally.
Acetaminophen clinical use
Antipyretic
Analgesic for mild to moderate pain, osteoarthritis
poor anti-inflammatory
Acetaminophen side effects
Hepatotoxicity (acute)
2. Renal toxicity with chronic use
Auranofin (oral) and Gold Sodium Thiomalate (given IM) mechanism
Inhibit maturation and function of phagocytes and T cells
Decrease levels of rheumatoid factor
Auranofin side effects and Gold Sodium Thiomalate side effects (4)
Can occur months after discontinuation of therapy
Gray color to skin
Nephrotic Syndrome
Thrombocytopenia
