56: NSAIDs and Treatment of Gout Flashcards
4 classic inflammatory symptoms
redness/rubor
swelling/tumor
heat/calor
pain/dolor
molecular inflamamtory mediators
bradykinin substance histamine 5HT arachidonic acid metabolites: prostaglandin, thromboxanes, prostacyclin cytokine TNF-a
functional characteristics of NSAIDs
analgesia
antipyretic
anti-inflammatory
target prostaglandin production
therefore… acetaminophen is not and NSAID because it is not anti-inflammatory
convert arachindonic acid to prostaglandins
COX
consituitve, protective COX
v.
inducible, inflammatory COX
COX-1
COX-2
what can be used for antipyretic in children and viral diseases?
acetaminophen
aspirin and other PG synthesis inhibitors NOT recommended; can be used in adults
MOA aspirin
irreversible COX inhibitor and therefore inhibitor of PG synthesis
significant portion hydrolyzed to salicylic acid (reversible COX inhibitor)
travels bound to plasma prtns
low dose v. high dose aspirin
low dose: analgesic antipyretic
high dose: antiinflammatory
how does aspirin produce an anti-pyretic effect?
blocks production of PG in CNS to reset temperature control at hypothalamus, facilitating heat dissipation by vasodilatation
ASA ______- bleeding time
prolooongs
anti-thrombotic and anti-coagulant effects
phophylactic uses of ASA
inhibit platelet hyperaggregaion
protective against CAD, MI, DVT post op
adverse effects ASA
- GI tract upset due to COX1 inhibition **
- GI irritation due to inhibition of cytoprotective PG (PGE2 and PGI2 decrease acid secretion)
- platelet inhibition –> prolonged bleeding time
- hepatic and renal toxicity
- hypersensitivity (pruritus)
- tinnitus
- reye’s syndrome (encephalopathy)
what kinds of hepatic and renal toxicity may occur with ASA?
aymptomatic hepatitis
decreased kidney function with chronic use
- decreased renal blood flow
- sodium retention/edema
NSAID for gout and ankylosing sponylitis
indomethacin
have analgesic, antipyretic, and anti-inflammatory effects but with less GI adverse effects
COX2 inhibitors
no impact on platelet aggregation (COX1) - incidence of thrombotic events associated with COX2 inhibitors
celecoxib is FDA approved for ..
RA and osteoarthritis
black box warning- cardiovascular
actions of acetaminophen
pain reliever and fever reducer (analgesic and anti-pyretic only) not anti-inflammatory
acetaminophen might react with
ethanol, isoniazid etc
because metabolized by cP450
therapeutic dose of acetaminophen
15mg tid
narrow therpeutic index, 150 - liver necrosis, 350 - liver failure
how is capsaicin used to treat RA, osteoarthritis, and neuralgia?
topically
binds and activates vanilloid receptor –> release substance P
prolonged activation of these neurons depletes and prevent re-accumulation of substance P
limitations for each NSAID
ketorlac- GI and renal adverse effects limit use
Indomethacin and tolmetin - greatest toxicity
Salicylate, ASA and ibuprofen - least toxic
Diclofenac and sulindac - increased liver function abnormalities
celecoxib - safest for pts with high risk GI, more risk CV toxicity and $
metabolic disease characterize dby recurrent episodes of acute arthritis due to deposits of monosodium urate (uric acid crystals) in joints and cartilage
gou
usually associated with hyperuriciemia
first line treatment gout
NSAIDs - indomethacin
can use other NSAID (not asa), corticosteroids or intra-articular steroid injection as well
how does colchicine treat gout?
reduces pain and inflammation without altering metabolism or excretion of uric acid
(inhibits leukocyte migration and phagocytosis)
adverse effect = diarrhea
