Exam 4 Analgestics Flashcards
cox1
constitutive, housekeeping, all tissues
cox2
constitutive in kidney, otherwise inducable
NSAIDS prototype
aspirin (prototype)
What enzyme releases arachidonic acid? what is it inhibited by?
What are two pathways?
phospholipase A2; inhibited by glucocoticoids
1) lipooxygenase -> leukotrienes (bronchoconstrictor, inflammation)
2) cyclooxygenase -> prostaglandins, prostacyclins, and thromboxane
cox1 response
1) thromboxane: inhibit cox1 > inhibit thromboxane> inhibit clot formation (why aspirin works)
2) prostacyclins: inhibit cox1 > limit acid secretion control > thinner mucin layer > lining exposure and pain (NSAIDs cause stomach pain)
3) prostaglandins: help fluid movement inkidney
cox 2 constitutive response
prostacyclin in vasculature prevents platlet aggregation and micro clots
so inhibit cox2 > remove micro clot inhibition > you GET clots (why cox2 selective was a bad idea)
cox2 inducible
fever, pain, inflammation
name of aspirin?
acetyl salicyclic acid
basic therapuetic effect of NSAIDs
analgesic
antipyretic
anti-inflam
what is only NSAID to permanently inhibit platlets?
aspirin
1) aspirin lowers ____ plasma levels to reduce inflame?
2) does aspirin have uricosuric action?
1) C-reactive protein due to prostaglandin synthesis inhibition
2) only in high doses
adverse aspirin
respiratory alkalosis "ringing in ears" = tinnitus ulcers hypertension rare hypersenstivity REYE SYNDROME *premature closure of ductus arterisus*
low dose aspirin
aka baby aspirin = 1/4 normal, 82mg
what drug is used to prevent ulcers in pts on NSAIDs?
misoprostol (Cytotec)
- inhibits acid secretion and stimulates mucus production
- get diarrhea
ionized or un-ionized passes through membrane?
UN-ionized, lower pH has more un-ionized so it is absorbed more
why moniter pH in pts of aspirin overdose?
switch from alkalosis to acidosis
why not give a person with gout aspirin?
at low levels it decreases secretion of uric acid making the gout worse
clinical uses of aspirin
pain RA fever cardiovascular prevention dysmenorrhea patent ductus arteriosus reduce cancer and alzheimer's risk
what NSAIDs are approved for pharmacotherapy of patent ductus arteriosus?
indomethacin and ibuprofin
what is the derivative of salicyclic acid?
difluorophenyl
difluorophenyl
long 1/2 life
– similar side effects as aspirin bit more stomach friendly
acetaminophen pathway
acetaminophen converted in liver by CY2E1 into toxic, converted from toxic metabolite by GLUTATHIONE to inactive
* don’t drink alcohol with acetaminophen UNLESS you are an alcoholic, bc they have increased levels of 2E1 and alcohol is it’s preferred substrate
acetaminophen vs aspirin
aspirin pKA=3
- stomach probs
- cox responds in PNS
- more cox1 effects
acetaminophen pka= 9.5, so FASTER bc more un-ionized in stomach
- NOT an NSAID
- no anti-inflam, but has equal analgestic and anti-pyretic to aspirin
- cox responds in CNS
- SEVERE liver toxicity (4g per day FDA) = black box
- equal cox1 & 2
- – CYP2E1 enzyme
avoid acetaminophen with?
alcohol, codeine (depleits liver of glutathione) and warfarin (increases INR and anticoagulation)
gold standard for pain control
400mn of Ibuprofen
what is name for ibuprofen?
propionic acid
ibuprofen has cross-reactivity to?
aspirin (salicylates)
motrin is?
ibuprofen
what is sister drug to ibuprofen
naproxen
ibuprofen vs naproxen
ibuprofen- rapidly absorbed, 1/2 life is 2 hrs, 6x daily
naproxen- 1/2 life of 12 hrs, 2x daily, and safety concern due to hypertension
propionic acid drugs
ibuprofen
naproxen
ketoprofen
Celecoxib (celebrex)
used for osteoarthritis and acute pain
- long 1/2 dose
- stomach friendlier than aspirin
- CAUSES HEART ATTACKS
meloxicam (Mobic)
cox2 preferrential
- black box: heart probs
List cox2 blockers
Celecoxib (celebrex)
meloxicam (Mobic)
