Lecture 12: NSAIDs/Aspirin Flashcards
ASA: mechanism
IRREVERSIBLY inhibits COX-1 and COX-2 = NON-SELECTIVE COX INHIBITOR
Antiplatelet effect of aspirin lasts…(DAYS)
8 to 10 days (once they’ve lost their COX they’ve lost them forever)
ASA: clinical indication –> antiplatelet (mechanism)
PGE2 and TXA2 enhances pla aggregation –> MI (acute and prophylactically), unstable angina, CVA, TIA
ASA: clinical indication –> anti-inflammatory (mechanism)
PGE2 and PGI2 increase vascular permeability & leukocyte infiltration
ASA: clinical indication –> analgesic (mechanism)
PGE2, PGI2 in PNS and PGE2 in CNS increase neuron membrane excitability/pain sensitization
ASA: clinical indication –> anti-pyretic (mechanism)
PGE2, PGF2alpha, PGI2 increase body temperature
ASA: 4 clinical indications (summary)
Antiplatelet, anti-inflammatory, analgesic, anti-pyretic
ASA: adverse Effects
GI: pain, N/V, ulcer; Heme: bleeding; Respiratory: brochospasm; Renal: increased creatinine and acid/base disorders; CV: HTN, fluid retention
ASA: adverse Effects –> explain GI
PGE2 decreases stomach acid and increases mucus
ASA: adverse Effects –> explain creatinine
PGE2 and PGI2 cause afferent arteriole vasodilation and increased renin –> both increase GFR, so inhibition DECREASES GFR and INCREASES creatinine
COX inhibitors and blood pressure (increase/decrease)
INCREASE
Other adverse effects of aspirin
Tinnitus (effect on cochlear hair cells), rash, Reye’s syndrome
Describe Reye’s syndrome
Acute onset encephalopathy, liver dysfunction, fatty infiltration of liver and other organs
Because of Reye’s, aspirin is contraindicated in…
Individuals under 20 years of age who have a fever
Describe aspirin hypersensitivity
Anapylactic response with rhinitis, angioedema, urticaria, bronchospasm, nasal polyposis
Samter’s triad
- Aspirin sensitivity, 2. Asthma, 3. Nasal polyps
How to treat aspirin overdose
Urine alkalinization to increase excretion of ionised salicylate
Aspirin and dialysis
Aspirin is highly protein bound AND widely distributed, so dialysis will not remove medicine from the body
Aspirin is metabolized __________ but excreted __________
Hepatically and renally
Why does aspirin’s half life increase in overdose?
Conjugation enzyme becomes saturated
ASA: overdose sx
Hearing issues: cochlear hair cells; decreased vision/headache; N/V; bleeding; fever (uncoupling of oxidative phosphorylation –> heat release)
ASA: overdose –> acid base derangements (3)
ASA stimulates resp medullary drive center –> respiratory alkalosis; uncoupling of oxidative phosphorylation results in lactic acid –> metabolic acidosis , late stage intoxication results in decreased mental status –> respiratory acidosis
T/F: ASA overdose can cause death
True
Ibuprofen: mechanism
REVERSIBLE non-selective COX inhibitor
Ibuprofen: clinical indications (4)
Anti-inflammatory, analgesic, anti-pyretic, antiplatelet (but not used for this purpose)
Ibuprofen: adverse effects
GI (pain, N/V, ulcer), heme (bleeding), renal (increased creatinine), CV (HTN, edema), allergy (angioedema, rash)
Ibuprofen: BP
Increases
Celecoxib: mechanism
SELECTIVE COX-2 inhibitor
Celecoxib: clinical indications (3). What’s missing?
Anti-inflammatory, analgesic, anti-pyretic; NO ANTIPLATELET BECAUSE THIS IS MEDIATED BY COX-1
Celecoxib: adverse effects
GI (fewer, 1/2 as many ulcers), respiratory (fewer bronchospasm), renal (increased creatinine), CV (HTN, edema, MYOCARDIAL INFARCTION, allergy (angioedema, rash)
Celecoxib: BP
Increases
Acetaminophen: mechanism
WEAK COX-1 and COX-2 inhibitor with poorly understood mechanisms
Acetaminophen: clinical indications (2). What’s missing?
Analgesic, anti-pyretic; NO ANTIPLATELET OR ANTI-INFLAMMATORY ACTIVITY
Acetaminophen: adverse effects, contraindications
Severe, fatal hepatotoxicity, renal failure (acute tubular necrosis)
What AE is NOT seen with acetaminophen?
GI bleeds
