NSAID Analgesics Flashcards
How does aspirin affect COX?
It irreversibly inhibits both COX1 and COX2. In order to regain platelet activity, they must be remade.
How do other NSAIDS affect COX (other than aspirin)?
They reversibly inhibit cyclooxygenase
All NSAIDs are. . .
- Analgesic
- Antipyretic (fever reducer)
- Anti-inflammatory
How are NSAIDS analgesic?
- Prostaglandins (PGE2 and PGI2) cause peripheral sensitization of nociceptors
- –Decrease threshold for nociceptor stimulation
- NSAIDs decrease prostaglandin synthesis = reversal of peripheral sensitization
- Prostaglandins may also contribute to sensitization in the CNS
How are NSAIDS antipyretic?
- Hypothalamus sets body temperature
- Temperature elevated by infection
- Mediated by cytokines
- Mediated by COX2 induction, and PGE2 synthesis, in epithelial cells of brain vasculature - PGE2 crosses BBB, promotes elevation of body temperature by the thalamus
- NSAIDS decrease prostaglandin synthesis = decrease in body temp.
Tell me about aspirin
-Fever
-Headache
-Dysmenorrhea
-Osteoarthritis
-Rheumatoid arthritis
-Prophylaxis against heart attack
-Low dose (81 mg) preferentially synthesis of thromboxane
-Thromboxane promotores platelet aggregation
-Prostacycline decreases platelet aggregation
[??If you use large dose, it inhibits both of the above and there will be less effect on heart attack prevention]
-Avoid concurrent use of other NSAIDs
Tell me about ibuprofen
- Analgesic, antipyretic, anti-inflammatory
- Fewer GI adverse effects than aspirin
- Clotting effects are reversible
- Naproxen: similar, longer acting than ibuprofen
Tell me about Indomethacin:
- Analgesic, antipyretic, anti-inflammatory
- The most potent COX inhibitor
- Primarily used when other NSAIDS are ineffective
- Fever intractable to other NSAIDS, antipyretics
- Arthritic diseases not responsive to other NSAIDs
- Significant toxicity
- GI distress, abdominal pains, ulcers, blood loss, headache
- Used to treat patent ductus arteriosus
- Congenital disorder, ducturs arteriosus failes to close after birth
- Possibly mediated by effect on PGE2
- Congenital disorder, ducturs arteriosus failes to close after birth
Tell me about Ketorolac:
- NSAID, can be injected (IM, IV)
- Can replace morphine if opioid addiction is an issue
- When combined with opioid, can decrease opioid requirement by 25-50%
Tell me about Celecoxib:
- A selective COX2 inhibitor
- COX1: normal physiology, constitutive activity
- COX1 inhibition responsible for NSAID side effects
- COX2: induced during inflammation
- COX2 inhibition responsible for NSAID therapeutic effects
- COX1: normal physiology, constitutive activity
- Additional selective COX2 inhibitors
- Rofecoxib and Valdecoxib
- Both removed from market
- Increased risk of heart attack and stroke
Tell me about Acetaminophen use:
- Not anti-inflammatory
- Analgesic and and antipyretic
- Mechanism unclear
- Very weak COX inhibition
- Possible effect in CNS (hypothalamus)
- Minimal GI irritation (advantage over NSAIDS)
- No effect on bleeding (advantage over NSAIDS)
- No effect on respiration (advantage over NSAIDS)
Tell me about acetaminophen toxicity (what happens when someone tries to OD on it):
- Therapeutic index much lower than other OTC medications
- Toxic, free radical metabolite in liver
- Hepatic necrosis!!
- Ethanol shifts liver metabolism toward toxic product
- Increased incidence of hepatotoxicity in presence of ethanol
- Treatment: N-acetylcysteine as scavenger drug
- Exogenous equivalent of glutathione
- Effective if <24 hours since overdose
