Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
20 Cards in this Set
- Front
- Back
|
What are the MOA of NSAIDs?
|
All NSAIDs work by inhibiting COX
prevent conversion of Arachidonic Acid into Prostaglandins and Thromboxane anti-inflammatory, analgesic, anti-pyretic, anti-platelet activity |
|
|
What is the difference between COX-1 and COX-2?
|
COX-1
always expressed in all tissues maintains homeostasis made in the ER inhibited by Aspirin (irreversibly) and NSAIDs COX-2 Induced by inflammatory cytokines (TNFa, TGFb, IL-1, etc) expressed at low levels in kidney, endothelium brain, uterus, ovaries, small intestines inhibited by Aspirin, NSAIDs and COX-2 inhibitors responsible for pro-inflammatory responses |
|
|
Name the functions of prostaglandins in
inflammation pain fever |
inflammation
COX-2 -> PGE2 and prostacyclin PGI2 cause increase edema, dilate blood vessels causing increased redness and enhance migration of phagocytes to the area pain inflammatory cytokines induce COX-2 -> prostaglandins which act as pain neuromodulators in the spinal cord fever inflammatory cytokines induce COX-2 which acts on the OVLT of the hypothalamus to cause fever |
|
|
What are the homeostatic functions of prostaglandins?
|
COX-1 in the stomach and GI cause prostaglandin which protects the stomach against gastric acid.
When COX-1 is inhibited then there is no inhibition of gastric acid production. Aspirin and NSAIDs cause ulcer CV response Platelets produce COX-1 produces TXA-2 which causes vasoconstriction and platelet activation and aggregation. Endothelium produces COX-1 and COX-2 which produces PGI2 -> causes vasodilation and inhibits platelet activation Kidney promotes vasodilation thereby increasing renal blood flow and preventing renal ischemia increases the glomerular filtration rate |
|
|
What is the MOA of low-dose aspirin?
|
permanently inhibits COX-1 preventing TXA2 production and inhibiting platelet aggregation
|
|
|
Why doesn't high dose aspirin work to treat CVD?
|
at high doses aspirin inhibits COX-1 and COX-2 which causes less TXA2-less platelet aggrevation but also causes less PGI2 producing less platelet inhibition
|
|
|
SALSALATE
|
dimer of salicylic acid
converted to salicylic acid after absorption competitive inhibitor of COX used in treatment of mild to moderate pain, fever and inflammation |
|
|
DI FLU NISAL
|
derivative of salicylic acid
not converted to salicylic acid competitive inhibitor of COX more potent anti-inflammatory than aspirin cannot cross the BBB --> not antipyretic |
|
|
ASPIRIN/SALICYLATES Pharmacokinetics
|
cross BBB (except diflunisal)
protein-bound (affects Warfarin) metabolized in the liver excreted in the urine as free salicylic acid (10%) or conjugated (90%) ....at low doses decreases uric acid excretion leading to gout eliminated by first order kinetics at low doses eliminated at zero order kinetics at high doses when its metabolic enzyme is saturaged....half-life then becomes greater than 15hrs. |
|
|
Ibuprofen
|
equipotent with aspirin
rapid onset |
|
|
Naproxen
|
20x more potent than aspirin
considered to be one of the safest NSAIDs |
|
|
Oxaproxin
|
very long serum half-life of 50hrs allows once daily dosing
think.. oxen can work long hours so ox-aproxin can work long t1/2 is 50 hours |
|
|
Indomethacin
|
Indo`meth`acin
10-40X more potent than aspirin as an anti-inflammatory most effective NSAID at reducing fever not well tolerated drug of choice to promote closure of patent ductus arteriosus INDO= in doors close the patent duct |
|
|
Sulindac
|
equipotent to aspirin
closely related to indomethacin- less potent |
|
|
Dic lof enac
|
Dic lof enac
relatively selective for COX-2 increased heart/stroke risk similar to Vioxx (↑40%) |
|
|
Keterolac
|
Keterolac
used as i.v. analgesic for moderate/severe post surgical pain can be used to replace opiods eg. aspirin |
|
|
Piroxicam
|
increased incidence (>9.5X) of peptic ulcers and bleeding
|
|
|
Meloxicam
|
preferentially inhibits COX-2
associated with fewer GI problems associated with an increased risk of heart attach and stroke |
|
|
Selective COX-2 inhibitors
|
Three selective COX-2 inhibitors
Celecoxib (Celebrex) Rofecoxib (Vioxx) Valdecoxib (Bextra) |
|
|
Celebrex
|
anti-inflammatory, anti-pyretic and analgesic similary to NSAIDs
fewer GI side effects |
