pain pharmacology Flashcards
(52 cards)
three major pathways in arachidonic acid metabolism
5-LOX
COX
CYP450
all iron containing
aracadonic acid is metabolized in what part of the COX enzyme
cyclooxygenase
parts of COX enzymes
peroxidase
cyclooxygenase
features of COX-1
- expressed in most tissues
- inhibition leads to renal and GI toxicity
- not induced by cytokines
features of COX-2
- expressed in low levels in most tissues
- highly induced by cytokines
prostacyclin (PGI2) is located where
endothelium
kidney
platelets
brain
thromboxane A2 (TxA2) is located where
- platelets
- vascular smooth muscle
- macrophages
- kidney
activation of prostacyclin causes
- vasodilation
- declumping of platelets
activation of thromboxane causes
- vasoconstriction
- platelet aggregation
analgesia effect
inhibition of prostanoid production which sensitize pain receptors
antiinflammatory effect
inhibit prostanoid synthesis at site of inflammation
antipyresis effect
inhibit prostanoid production in CNS
pyresis development process
- infection/inflammation
- leukocytes activated
- pyrogenic cytokines are released
- PGE2 is produced
- set point is elevated
FEVER
most common AE of pain medications
gastric or intestinal ulceration
drugs that promote bleeding
aspirin and NSAIDs
renal effects of pain medication
-may result in hypertension by decreasing kidney blood flow and increasing water retention
COX2 hypothesis
COX-2 selective inhibitors will cause less GI AEs than nonselective COX inhibitors
COX-2 expression in colorectal cancer
- higher expression
- NSAIDs thought to have benefit
COX enzyme with the larger active site
COX-2
COX enzyme associated with housekeeping
COX-1
prostaglandin G/H synthases also known as
cyclooxygenases
aspirin MoA
unique
-acetylates proteins (a ser residue in COX)
aspirin cardiovascular benefit
-reduces platelet aggregation via irreversible inhibition of COX-1 in platelets
aspirin absorption
- primarily in the small intestine
- peak concentrations 1-2 hrs
