Antipyretics, NSAIDs Flashcards
Eicosanoids consist of what 3 things?
- Prostaglandins
- Thromboxanes
- Leukotrienes
Whats the most abundant eiconsanoids fatty acids?
Arachidonic acid
What is the name of the enzyme complex that converts arachidonic acid to prostaglandin?
Prostaglandin G/H synthetase
What is the mechanism of action of prostaglandins?
- Act locally - paracrine/autocrine
- Interact with GPCRs
- Increase/decrease adenylate cyclase
- Major effects on smooth muscle, other effects on platelets, kidney, CNS, endocrine organs and eye
What are the physiological actions of prostacyclin (PGI2)?
- Circulation: Vasodilator and inhibits platelet aggregation
- Airways: bronchodilator
- GI: inhibits gastric acid secretion; increase mucus secretion
- Renal: enhances renal excretion of sodium and water
- Reproductive: relaxes uterine muscle
- Pain: induces pain by lowering the threshold of nociceptors
What are the physiological actions of prostaglandin (PGE2)?
- Circulation: Vasodilator; low conc. enhances and high conc. inhibits aggregation
- Airways: bronchodilator
- GI: inhibits gastric acid secretion; increase mucus secretion
- Renal: enhances renal excretion of sodium and water
- Reproductive: uterine smooth muscle contraction
- Fever and inflammation: direct pyrogen in hypothalamus
What are the physiological actions of Thromboxane (TXA2)?
- Vascular: vasoconstriction
- Stimulates platelet aggregation (major product of platelet COX1)
What are the physiological actions of PGF2alpha?
- Vascular: Vasoconstrictor
- Airway: contracts smooth muscle
- Reproductive: contracts smooth muscle
- Eye: decreases intraocular pressure.
Misoprostol (cytotec)
- PGE1 analogue
- Inhibits gastric acid secretion, reduces risk of peptic ulcer in pts taking NSAID
- Contra: Pregnancy
Latanoprost (Xalatan)
- PGF2alpha analogue
- Tx: open angle glaucoma
- Increases uveoscleral outflow which lowers intraocular pressure.
Alprostadil (Prostin) PGE1
- Used to maintaing patency of ductus arteriosus during sx.
- Vasodilator
- Erectile disfunction
What is required to convert LTA4 to LTC4?
Glutathione
5-HETE
LTB4
-Chemotactic agents
LTC4
LTD4
LTE4
- Bronchoconstrictor
- Increase vascular permeability
- Components of slow reacting substance of anaphylaxis (SRS-A)
Zafirlukast (Accolate)
Montelukast (Singulair)
- Competitive LTD4 receptor antagonist
- Prophylactic tx of asthma in adults
- Allergic rhinitis
- Aspirin sensitivity induced asthma (montelukast)
- S/Es: Headache, pharyngitis
- Inhibits Cyp 2C9, Cyp 3A4 (warfarin)
Zileuton (Zyflo)
- Inhibitor of 5-lipoxygenase (all leukotriens)
- Porphylaxis for asthma in adults (12 yr and older)
- Elevated liver enzymes, must monitor ALT
- Contra: liver disease, combination with ergot alkaloids
What is the mechanism of action for NSAIDs?
Inhibition of cyclo-oxygenase
Aspirin
- Irreversible cyclo-oxygenase inhibitor
- Analgesic, antipyretic, anti-inflammatory
- Rheumatoid and osteoarthritis
- Contra: Viral infection due to risk of Reyes syndrome in children
Ibuprofen
- Reversible inhibition of Cox 1 and 2
- Antipyretic, can be used in children
- Primary dysmenorrhea, migraine, rheumatoid/osteoarthritis
Naproxen
- Reversible inhibition of Cox 1 and 2
- Antipyretic, can be used in children
- Primary dysmenorrhea, migraine, rheumatoid/osteoarthritis
- Acute gout
Ketorolac
- Ophthalmic: allergy, cataract removal
- IV, IM, PO
- Greater analgesic activity than anti-inflammatory
- S/Es: Bleeding, Hepatic
- Must stop prior to surgery
Diclofenac
- Rheumatoid, osteoarthritis, ankylosing spondylitis
- Ophthalmic: pain, cataract sx
- Primary dysmenorrhea
- Arthotec contra during pregnancy
Indomethacin
- Oral: Rheumatoid/osteoarthritis, ankylosing spondylitis, gout, tendinitis
- IV: Closure of patent ductus arteriosus
- Take w/ food
- Must monitor urinary output
Celecoxib
- Selective COX-2 competitive reversible inhibitor
- Increased risk of cardiovasular and stroke event with high dose for prolonged time.
