NSAIDS, RA, and gout Flashcards
effect of inflammation?
can be beneficial or deleterious
classic inflammatory sx
redness (rubor), swelling (tumor), heat (calor), pain (dolor)
what are some of the molecular inflammatory mediators?
bradykinins, substance P, histamine, prostaglandin, thromboxanes, prostacyclin, TNF-alpha
what is the fxns of DMARDS?
delay or arrest of diease process
fxnal characteristics of NSAIDS
- analgesia
- antipyretic
- anti-inflammatory
is acetaminophen an nsaid?
NOOOO, but it does have analgesic and antipyretic properties
downstream effects o PGE2 and PGI2?
incr edema, incr vascular permeability
which COX is constitutively expressed, protective, is a housekeeping isozyme?
COX1
which COX is inducible, production of inflammatory molec, expressed in vascular endothelium?
COX-2
which COX promotes synthesis of PG in stomach mucosa that protect stomach lining from gastric acid?
COX-1
which NSAIDS are non-selective (both COX1 & 2)
ASA, ibuprofen, indomethacin
which NSAIDS are COX-2 selective?
celecoxib
is acetylation & inhibition of COX by ASA reversible or irreversible?
irreversible
how does ASA irritate the GI?
inhibit protective PG–>PGe, PGI normally decr gastric acid secretion, maintain mucosal resistance/enhance repair
how does ASA potentially decr kidney fxn?
- inhibition of PG–>decr renal blood flow (tubular necrosis)
- PG inhibition may allow fro enhanced Na/Water reabsorption
what is the major difference b/w ASA and other non-specific NSAIDS?
- duration of action
2. potency
do COX-2 selective inhibitors impact platelet aggregation?
no (this is mediated by COX1)
effects of COX-2 selective inhibitors?
analgesic, antipyretic, anti-inflammatory
major issue assc’d with COX-2 inhibitors?
CV thrombotic events
what is the bad SE effect associated with acetaminophen?
acute liver toxicity
p450 metab–>beware of interactions w/ ethanol, INH
therapeutic goals with gout tx?
- terminate acute gout attacks
- provide control of pain and inflammation
- prevent future attacks
what is the 1st line tx for gout?
indomethacin (NSAID)
which NSAIDS can be used for tx of gout?
indomethacin, ibuprofen, naproxen, sulindac
can you use ASA to tx gout?
NO, it causes renal retention of uric acid at low dose
when to use corticosteroids as tx for gout?
when patients can’t tolerate NSAIDS
what are the 3 stages of RA?
- initiation phase (nonspecific inflammation)
- amplification phase (T cell activation)
- chronic inflammation (tissue injury)
which drugs for RA reduce inflammation, improve sx, slow bone damage, but have a slow onset of action?
DMARDS
what is the 1st line DMARD tx for RA?
methotrexate
what was the First agent for RA indicated for both sympt improvement and retardation of structural joint damage?
leflunomide
Anti-TNFa agent; cytokine receptor fusion protein
Etanercept
Anti-TNFa agent; chimeric monoclonal ab
Infliximab
IL-1 inhib (IL-1 cytokine receptor decoy)
Anakinra
which RA drug is an Antimetaboite & antifolate agent
methotrexate
which RA drug inhibs ribonucleotide synthesis?
leflunomide
how does ASA exert anti-pyretic effects?
blocks production of PG in CNS to reset temperature control at hypothaalmus–>dilation of superfifical blood vessels–>drop in temp
does acetaminophen have anti-inflammatory properties?
nope, just used as pain relief and fever reducer
hepatotoxicity with acetaminophen needs to be monitored with?
high doses, alcohol abuse, CYP450 inducers, elderly
capaisin can be used for what?
RA, osteoartiritis, neuralgia
