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24 Cards in this Set

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NSAIDS
Non-Steroidal Anti-inflammatory Drugs, aka COX inhibitors
Pharmacological Effects/Mechanism of Action
most of the actions of NSAIDS can be attributed to inhibition of the enzyme cyclo-oxygenase (COX). This enzyme metabolizes arachidonic acid to the endoperoxide intermediates and ultimately to the formation of the prostaglandins
COX-1
A constitutive enzyme found in a variety of tissues including stomach and colon, kidney, vascular smooth muscle, and platelets (involved in many “housekeeping” functions of prostaglandins).
COX-2
Involved in inflammatory responses, fever, and algesia (typically induced). Also expressed in blood vessels, kidney, heart, and brain.
Actions of Prostaglandins
PGE2, PGI2 (Prostacyclin), PGF2, PGD2, TXA2 (Thromboxane)
Vasodilation, Vasoconstriction, Increase capillary permeability
Contracts other smooth muscle (uterine, GI, bronchial)/relax bronchial smooth muscle
Promote or inhibit platelet aggregation
Inhibit mast cell secretion
Decrease intestinal secretion of gastric acid
Stimulate Na and water excretion from kidney (increase Na retention)
Stimulate mucus secretion and cytoprotection
Pyrogenic
Sensitize nerve endings to other analgesic mediators
Actions of Leukotrienes
LATB4, LTC4, LTD4
Chemoattractant for polymorphonuclear leukocytes
Long-lasting bronchial constriction
Increase capillary permeability
NSAIDS
reduce vasodilation, edema and pain assoc. with inflammation (acute phase, as compared to corticosteroids that inhibit all stages of inflamamtion)
Anti-inflammatory effects of NSAIDS
require significantly higher doses (4-6g of aspirin per day)
Analgesia
Inhibition of COX-2 prevents formation of prostaglandins at peripheral sites. Prostaglandins sensitize nociceptive receptors to algesic mediators such as bradykinin
Mild analgesics
treat chronic post-op pain, pain from inflammation, integumental pain, PMS headaches, myalgia. Ordinary doses of NSAIDS (650 aspirin, or 400mg ibuprofen)
Anti-pyresis
Centrally mediated effect via resetting of the tep control center in hypothalmus. NSAIDS inhibit COX-2 and ultimate production of prostaglandins in brain.
NSAIDS effectively reduce elevated body temp (fever). This effect is achieved with ordinary doses.
Aspirin (acetylsalicylic acid)
covalently modifies and irreversibly inhibits platelet cyclo-oxygenase. Enzyme is inhibited for the lifetime of the platelet (8-11 days). Low dose.
Cardiovascular: Platelets
inhibition of platelet COX-1 derived TxA2 with the net effect of increasing bleeding time (inhibition of platelet aggregation)
Atherosclerosis
inhibition of COX-2 can destabilize atherosclerotic plaques
Blood vessels/smooth muscle
COX-2 derived PGI2 can antagonize catecholamine and Angiotensin II-induced vasoconstriction (NSAIDS can elevate blood pressure)
Renal
COX-1 and COX-2 generated prostaglandins can both increase and decrease sodium retention.
NSAIDS tend to promote sodium retention and can therefore increase BP. Can counteract effects of many anti-hypertensives (diuretics, ACE inhibitors and beta-AR antagonists).
Patients (elderly and volume depleted) are at risk of renal ischemia with NSAIDS
GI
NSAIDS with COX-1 inhibitory activity will produce gastric distress, gastric bleeding, and sudden acute hemorrhage
Acetylsalicylic Acid (Aspirin)
prototype NSAID.
Irreversible inhibition of COX
aspirin binds to pocket that leaves behind the acetyl group on serine and that’s how the enzyme inhibits
Salicylic Acid
reversible inhibition of COX
Salicylates
non-selective COX inhibitors
absorption is rapid
Distribution is widely, bound to plasma protein
Ibuprofen, Naproxen (Aleve)
like salicylates, non-selective COX inhibitors
longer half-life than aspirin, only need 1-2 aleves per day to relieve pain
Celecoxib (Celebrex)
COX-2 selective inhibitor
Virtually without COX-1 side effects (GI, platelet)
Cardiovascular risk of COX-2 inhibitors
inhibition of anti-thrombogenic prostaglandins (PGI2)
Increased BP
destabilization of atherosclerotic plaques
COX-2 helps to stabilize the plaques, so an inhibitor will make plaque less stable and it could burst
Acetaminophen (Tylenol)
1. Anti-pyretic and Analgesic
2. Does not have anti-inflammatory effects
3. Does not cause GI distress and does not affect platelet function
4. High doses cause hepatotoxicity
5. Overdose can be treated with sulfhydryl reagent such as Acetylcysteine.