Medications for Gout Flashcards
Urate/ uric acid?
end product of purine metabolism
Hyperuricemia cause?
underexcretion, overproduction
Gout?
deposition of monosodium urate crystals in tissues (joints and tendons)
cause inflammatory response/ mediator release
what happens when synoviocytes phagocytose urate crystals?
secrete inflammatory mediators, attract polymorphonuclear leukocytes (PMN) and mononuclear phagocytes (MNP) (macrophages)
drugs active in gout inhibit crystal phagocytosis and polymorphonuclear r lecukocyte and macrophage release on inflammatory mediators
Acute treatment of gout goal?
relieve pain, not stop the cause
dampen immune response, otherwise cause eroision and permanent damage
Chronic treatment of gout goal?
lower and prevent recurrent uric acid
Characteristics of gout?
exquistely painful typically single joint -podagra(big toe), first MTP joint result of an imbalance btw uric acid production and renal excretion -hyperuricemia Asymptomatic hyperuricemia -does not always cause gout
Characteristics of gouty arthritis?
sudden onset intense inflammation distal joints severe pain middle aged males recurrent episodes influenced by diet and comorbidities bony eroisions on xray hyperuricemia -durgs may exacerbate, thaizedes, loops, salicylates
Acute gouty arthritis?
precipitation of monosodium urate crystals
acute inflammatory response
Chronic?
chronic arthritis joint destruction tophi renal calculi and damage -nephrlithiasis and neuropathy
First attack?
short duration
-resolves within a few days to several weeks (if untreated)
typically involves one joint
subsequent attacks may last weeks and involve many joints
Without prophylaxis?
asymptomatic periods become shorter
more frequent attacks
chronic joint symptoms cause permanent erosive joint deformity
Manage asymptomatic hyperuricemia?
lifestyle mod and risk reduction
-diet, alcohol
Comorbid disease management
-hypertension, obesity, diabets, alcoholism, hyperlipidemia
Treatment aims for Gout?
- prompt relief of acute attacks
- prevention of recurrent attacks
prevent/ reverse crystal depositis in
-joints, urinary tract, renal intersitium, tissue and paranchymal organs (tophi)
Acute treatment?
inhibit immune response
-nasaids, corticosteroids, colchicine
Prevention?
inhibit uric acid synthesis
-allopurinol
increase uric acid elimination
-probenecid
NSAIDs?
first line therapy for most patients
fast-acting (hrs)
decrease inflammtory response
MOA Nsaids?
mainly inhibit prostaglandin synthesis
General properties of NSAIDS?
analgesic
antipyretic
anti-inflammatory
Indomethacin?
drug of choice for acute attacks
significant GI and CN side effects
prostaglandin synthase inhibitor
Other nsaids?
ibuprofen, naproxen
Avoid aspirin with gout?
low dose- cause renal retention of uric acid
high dose- uricosuric action increases risk of renal calculi
Colchicine?
treat acute attacks slower onset than NSAIDS GI side effects (narrow therapeutic index) Antiinflammtory- blocks cellular response to crystals not an analgesic not uricosuric -not effect uric acid serum levels -not stop destructive aspects of gout
Colchicine MOA?
binds to tubulin
cause antimitotic effect, interferes with microtubules and spindle formation, neutrophils and GI epithelium
inhibits luekocyte migrattion, phagocytosis, and leukotriene B4 formation
can’t activate immune cells, cant cause inflammatory response
High dose of colchicine?
treat gouty arthritis, can do even with narrow TI, because only short use, acute
Low does colchicine?
prevent recurrent attacks, particularly in early stages of antithyperuricemic therapy, better tolerated
Colchicine toxicity?
GI (primary) -drug use for acute attacks -diarrhea (can be severe), nausea, vomit, ab pain Hematological -bone marrow suppression myopathy (chronic use)
Corticosterioids?
for acute attacks
antiinflammatory steroids
intra-articular injections (one or 2 joints)
PO/parenteral (systemic) use
-can’t take nsaids or colchicine
-pts not candidates for intra-artiuclar injections
toxicity limits chronic use (last resort)
Xanthine oxidase?
prevent uric acid formation by inhibiting it
Hypoxanthine and xanthine?
they will accumulate because of inhibited xanthine oxidase but is water soluble
Indications for uric acid lowering drug therapy?
frequent/diabling attacks clin/radiographic signs of joint disease tophaceous deposits gout with renal insufficiency recurrent uric acid stones not recommend for asymptomatic no role in managing acute attacks
Allupurinol clin use?
chronic treatment of gout (1st choice) prevent stone formation protect kidneys eliminate tophi cancer chemo
Allupurinol effectiveness?
in both underexcetors/ overproducers
ease of use (once daily)
effective in renal insufficiency (elderlu, dose adj)
Hypoxanthine analog?
competitive inhibitor of xanthine oxidase
inhibits uric acid production
Allupurinol inhibits metabolism of? (caution with these other drugs)
6-mercaptopurine (anticancer agent)
Azathioprine (immunosuppressive agent)
Both metabolized by xanthine oxidase
reduce doses of these drugs
Allopurinol adverse effects?
generally well tolerated
most common issue is hypersentivity
can cause acute gouty attacks
hypersensitivity?
mostly rashes but can be more serious
may occur after months or years
desentization possible in 50% pts
acute gouty attacks? prevent them?
mobilizes tissue stores of uric acid
use NSAIDs or colchcine (low dose) when starting therapy
Febuxostat?
xanthine oxidase inhibitor may be better for pts with mild to moderate chronic kidney disease -no dose adjust -allupurinol- watch GFR and adjust dose may have increased CV risk high cost
Uricsuric agents?
second line
patients that are underexcretors
acoid use where nephrolithiasis or neprhropathy might occur, likely ineffective in pts with renal impairment, less effective in elderly pts
requires bid or tid dosing (less compliant)
for patients resistant to or intolerant of allopurinol(hypersensitivity)
Uricosuric agents?
urate excretion
reabsorption redominates, trasnporter mediated
these drugs are weak organic acids
inhibit urate-anion exchangers in proximal tubule
decrease uric acid reabsorption
Probenecid?
decrease serum uric acid level
block tubular reabsorption or uric acid
enhance urine uric acid excretion (increase uric acid level in urine, increase risk of nephrolothiasis) not used in pts with renal disease
frequent but mild, side effects
Contraindications Probenecid?
history of nephrolithiasis
existing renal disease
avoid use in pts that excrete a large amount of UA already, renal calculi is a risk (DONT USE IF URINARY URATES ARE TOO HIGH)
urine flow is low/history or renal calculi
less effective in elderly
2-3 times a day dosing (compliance)
Drug Drug interactions Probenecid?
can interfere with renal excretion of other drugs
-penicillin, cephalosprins, quinolones, loops, NSAIDs
aspirin can diminish probenecid’s effect
Adverse effects Probenecid?
generally well tolerated (some GI, hypersentivity, uric acid stone formation)
May cause acute attack of gout
- until theurpeutic levels are reached, may happen
give nsaids/ colchicine before to reduce risk
