Anti-inflammatory Drugs: NSAIDs Flashcards
Arachidonic acid is the precursor molecule for
prostanoids and leukotrienes
Phospholipase A2 (PLA2) hydrolyzes arachidonic acid from the
cell membrane
Phospholipase A2 (PLA2) hydrolyzes
arachidonic acid from the cell membrane
Cyclooxygenase-1 (COX-1) is _________ expressed
constitutively expressed
Cyclooxygenase-2 (COX-2) expression is induced by
inflammation
Thromboxane A2 (TXA2) is synthesized by
COX-1
TXA2 (synthesized by COX-1) causes
vasoconstriction
COX-1 synthesizes
gastric cytoprotective prostaglandin
COX-2 is expressed in
vascular endothelial and smooth muscle cells
Prostacyclin (PGI2) is synthesized by
COX-2
PGI2 causes
vasodilation
PGI2 inhibits
platelet aggregation
COX-1 and COX-2 synthesize prostaglandins that
dilate the afferent arteriole
COX-2 synthesizes prostaglandins that
- Increase vascular permeability
- Increase pain sensitivity
- Induce fever
NSAIDs reversible inhibit
both COX-1 and COX-2
NSAIDs include
- Diclofenac
- Ketorolac
- Indomethacin
- Meolxicam
- Piroxicam
- Naproxen
Inhibition of COX-1 by NSAIDs can
- Prolong bleeding time
- Cause GI bleeding
- Cause gastric inflammation, erosions, and ulceration
NSAIDs can increase blood pressure due to
COX inhibition in the kidney, decreasing sodium excretion
NSAIDs can cause
- Acute interstitial nephritis
- Renal papillary necrosis (sloughing of renal papillae)
- Aplastic anemia
- Hypoaldosteronism (decreased mineralocorticoids)
NSAIDs cause afferent arteriole vasoconstriction, decreasing
GFR
NSAIDs cause _____ _______ vasoconstriction decreasing GFR
afferent arteriole
NSAIDs cause afferent arteriole ________ decreasing GFR
vasoconstriction
NSAIDs can increase serum _____ concentrations
lithium
NSAIDs (indomethacin most commonly) can cause
Aplastic anemia
NSAID induced hypoaldosteronism can cause
hyperkalemia
Aspirin irreversibly inhibits
COX- 1 and COX-2
Aspirin acetylates COX-1 and COX-2 resulting in
irreversible inhibition
Aspirin is useful in treating what childhood disease
Kawasaki disease
Kawasaki disease is the most common
vasculitis syndrome of childhood
Aspirin use in children can lead to development of
Reye’s syndrome
Reye’s syndrome
rapidly progressive encephalopathy with hepatic dysfunction
Reye’s syndrome occurs when
a child is given aspirin in the setting of a viral illness
Reye’s syndrome encephalopathy
- Confusion
- Seizure
- Coma
Reye’s syndrome hepatic dysfunction
hepatic steatosis and hepatomegaly
Aspirin toxicity causes what metabolic disturbance
- anion gap metabolic acidosis
2. respiratory alkalosis
Aspirin can cause
- anion gap metabolic acidosis
- respiratory alkalosis
- Reye’s Syndrome
- Tinnitus
______ ______ can be used to absorb aspirin in setting of acute toxicity
Activated charcoal
Alkalinization of the serum and urine with a basic solution (e.g. sodium bicarbonate) increases the renal excretion of
aspirin
Minimize NSAID use in patients at risk for
acute kidney injury
Avoid NSAIDs in which trimester of pregnancy
3rd trimester
Avoid NSAIDs in 3rd trimester due to
risk of premature closure of ductus arteriosus
Which NSAIDs have the highest risk of premature closure of ductus arteriosus in the 3rd trimester of pregnancy
- Indomethacin
2. Ibuprofen
Celecoxib is a
- Selective COX-2 inhibitor
2. Sulfa drug
Celecoxib has a reduced ulcer and bleeding risk by avoiding
COX-1 inhibition
Celecoxib may increase the risk of
ischemic cardiovascular disease
Celecoxib decreases the risk of
ulcer and bleeding
Acetaminophen inhibits
COX-2
Acetaminophen inhibits COX-2, acting as an
antipyretic and analgesic (not anti-inflammatory)
Toxic levels of acetaminophen
deplete glutathione in the liver (inactivates the toxic metabolite: NAPQI)
Acetaminophen can cause
hepatotoxicity
Acetaminophen causes hepatotoxicity via the
toxic metabolite: NAPQI
______ ________ can be used to absorb acetaminophen in setting of acute toxicity
activated charcoal
_________ restores hepatic glutathione stores to treat acetaminophen hepatotoxicity
n-acetylcysteine
