NSAIDS - Slattery Flashcards
What is the most potent COX inhibitor?
Why isn’t it often used?
What should you use it for when you do?
Indomethacin
It has significant toxicity
(GI distress, abdominal pains, ulcers, blood loss, headache)
Used when other NSAIDS are ineffective
(fevers, arthritis not controlled by other NSAIDS)
(Congential disorder ductus arteriosis)
Why is acetaminophen not an NSAID?
It is NOT anti-inflamaotry.
It is analgesic and antipyretic
ADvantage vs Disadvantage of acetaminophen?
Advatnage: Minimal GI irritation , no effect on bleeding, no effect on respiration
Disadvantage: therapeutic index much lower than other OTC drugs
Too high of doses can causes hepatic necrosis especially when combined with alcohol
How does acetaminophen cause hepatotoxicity, how does N-acetylcystein treat it?
A free radical is created when the dose is too high, which reacts with cells to create hepatic necrosis
N-acetylation is a scavenger drug that can pick up those free radicals
-Exogenous equivalent of glutathione (nice!)
Pros and Cons of NSAIDS vs Opioids:
NSAIDS Pros -inflammation pain gone -few adverse effects Cons -Only mild or moderate pain
Opioids Pros -Intense ain Cons -drowsy -tolerance -phys. dependence -abuse potential -resp depression
What are differences between the two forms of Cyclooxygenase
COX1: normal physiology
Gastric cytoprotection, vasodilation, platelet aggregation
COX2: inducible
Induced by acute inflammation
Inhibited by glucocorticoids
NSAIDs inhibit both COX1 and COX2
How is temperature elevated in infection?
Machanism.
How does NSAID lower it again?
Hypothalamus sets body temperature
- Temperature elevation mediated by cytokines
- COX2 induction and PGE2 synthesis, in epithelial cells of brain vasculature
- PGE2 crosses BBB, promotes elevation of body temperature by hypothalamus
NSAIDs decrease prostaglandin synthesis (PGE2) = decrease body temperature
Why can NSAIDS create gastrointestinal distress?
NOT hypersensitivity
Its cuz prostaglandins inhibit secretion of gastric acid and promote mucus secretion
SO, you get too much acid and not enough mucus when NSAIDs block prostaglandin synthesis
Capillary damage leads to necrosis and bleeding
Cyclooxygenase generates what? from arachidonic acid?
Prostaglandins - to modify nociception threshold
Thromboxane - To increase platelet aggregation
Prostacyclin - Inhibits platelet aggreagation
How can high doses of NSAIDS cause respiratory and electrolyte disturbances?
Hyperventilation - caused by stimulation of medulla respiratory center
Metabolic Acidosis - High doseuncouples oxidative phosphorylation, causing lactic acid to accumulate in blood and decrease pH
Body hyperventilates more in order to blow off acid through CO2
Treatment for aspirin overdose:
Gastric decontamination
Sodium carbonate to balance pH
Tranfusion or dialysis?
What causes asprinin hyersensitivity
Probably due to shunting of arachidonic acid into the leukotriene pathway
Treat with epinephrine
Why is aspirin use not reccommended in kids with chicken pox?
Slight possibilty of Reye’s syndrome.
Caused by asprinin use in the presence of a viral infection. Mechanism not known
What cox-inhibitor is used for arthritic diseases?
Indomethacin
What drug is a selective Cox-2 inhibitor?
Why is this an advantage?
Celecoxib (Celebrex)
COX2 inhibition responsible for NSAID therapeutic effects
The cox-1 inhibition is wht is responsible for side effects.
Unfortunately there are complications with heart attacks and stroke…
