Exam 3: NSAID analgesics Flashcards
What do COX enzymes produce?
Prostaglandins, thromboxane, prostacyclin
What is the effect of prostaglandins?
vasodilation, gastric cytoprotection, nociceptor sensitization
What is the effect of thromboxanes?
promotes platelet aggregation, inflammation
What is the effect of prostacyclins?
Inhibits platelet aggregation, vasodilation, gastric cytoprotection
T/F: COX1 enzymes are for normal physiology, COX2 enzyme is induced by acute inflammation?
True
What COX enzymes do NSAIDs target?
Both COX1 and COX2
Which irreversibly inhibits COX1 and COX2 enzymes: Aspirin or other NSAIDs
Aspirin
How do NSAIDs reverse the peripheral sensitization of nociceptors?
By blocking prostaglandin synthesis
What leads to increase in body temperature?
induction of COX2 and PGE2 synthesis in epithelial cells of brain vasculature
What causes the side effect of gastric bleeding/ulcers in patients who overuse NSAIDs?
inhibition of prostaglandins and prostacyclins, which both inhibit secretion of gastric acid and promote secretion of mucus, leads to less epithelial protection
How does aspirin lead to nephrotoxicity?
vasoconstriction by blocking COX-2 enzymes
How does aspirin lead to electrolyte disturbances?
causes respiratory alkalosis (via hyperventilation), and metabolic acidosis (uncoupling oxidative phosphorylation, leading to increased lactic acid)
What are signs of a mild aspirin toxicity?
Tinnitus (increased arachidonic acid sensitizes NMDA receptors on cochlear nerve), headache, nausea, sweating, thirst, hyperventilation
What are signs of severe overdose to aspirin?
Hyperventilation, acid-base imbalance, dehydration, agitation, hyperactivity, slurred speech, fever
What is the treatment of an aspirin overdose?
Induce vomiting, use sodium bicarb to increase systemic pH, dialysis
Is hypersensitivity to aspirin immune-mediated
no
what is the likely cause of aspirin hypersensitivity?
shifting of arachidonic acid to lipoxygenase that increases leukotriene-mediated effects (bronchial constriction, increased secretion, edema, etc)
What is the treatment for aspirin hypersensitivity?
Epinephrine, avoid NSAIDs
How does low dose of aspirin guard against heart attacks?
preferentially inhibits synthesis of thromboxanes
Describe ibuprofen
Analgesis, antipyretic, anti-inflammatory, fewer GI effects than aspirin, clotting effects are reversible
Describe indomethacin
Triple-A, most potent COX inhibitor, significant toxicity (GI distress, abdominal pains)
What can indomethacin be used to treat (congenital disorder)
Patent ductus arteriosus
Describe Ketorolac
NSAID, can be injected, can replace or reduce opioid dose if addiction is an issue
What COX enzyme does celecoxib inhibit?
selective COX2 inhibitor
Describe acetaminophen
NOT ANTI-INFLAMMATORY, but it is an analgesic, antipyrretic, could target hypothalamus, low side effects
what is the problem with acetaminophen toxicity
much lower therapeutic index, metabolism can cause free radical in the liver
How do you treat acetaminophen toxicity?
N-acetylcysteine as a scavenger drug (similar to glutathione)
