Therapeutics - Gout part 2 Flashcards
symptoms of colchicine toxicity begin within…
2-5 hours
may lead to organ failure within 24-72hrs
doses of colchicine as small as___ have been fatal
8mg
name some treatment for colchicine toxicity
stomach pumping (gastric lavage)
activated charcoal
is NOT dialyzable
dose of colchicine as PROPHYLAXIS
0.6mg QD or BID for 3-6 months after starting UA lowering therapy to prevent attacks from starting the XO inhib
if they feel attack - start using flare doses (1.2mg stat and 0.6mg 1 hour later)
in what patients is colchicine used as prophylaxis
pts who have recurrent attacks and NORMAL URIC ACID (allopurinol wont help)
corticosteroids are ____ line for gout
3rd line
what steroid is typically given IA and which 2 typically IM
IA - trimcinolone
IM - triamcinolone or methylprednisolone
approx how long is oral corticosteroid therapy?
what is dose
important considerations
around 10-14 days
0.5mg/kg/day of prednisone for 5-10 days OR 2-5 days and then taper off for 7-10 days
DONT WANT REBOUND FLARES - taper off
corticosteroids should be used in caution in pts with which 3 health conditions
HTN
CHF
diabetes
can cause hyperglycemia and sodium and water retnetion
however, only given short term so not really the biggest concert
if all 3 agents (NSAIDS, colchicine, CS) are ineffective/cant be used, what can be used?
(NAME 2)
IL-1 inhibitors
anakinra and canakinumab
considered off label
give 2 scenarios in which urate lowering therapy (prevention) should NOT BE USED
-if UA is only mildly elevated (like around 8)
-if the first episode was mild and responsed well to treatment
watch and see first if UA levels go down or if they have more attacks 1st
4 scenarios in which UA lowering therapy SHOULD be started
-have frequent attcks (2 or more in a year) - discuss with pt
-have uric acid kidney stones - CKD stage greater than or equal to 2
-evidence of tophi for greater than or equal to a year (sign of more longstanding disease)
-have chronic joint damage from the gout – dont want further disability
definition of hyperuricemia
serum UA is GREATER THAN 7mg/dL
as mentioned - if it’s 8 - dont start urate lowering therapy yet
if a pt has hyperuricemia but no symptoms of flares or tophi, should it be treated with urate lowering therapy?
NOO
MIGHT consider if it’s very severely elevated
scenarios in which we may consider urate lowering therapy in someone that just had 1 gout attack
the UA level greater than 9
have mod-severe CKD
-kidney stones (urolithiasis)
pts on chemo or radiotherapy (tumor lysis syndrome)
if a pt is on chemo and at risk of tumor lysis syndrome, what may they be treated with
allopurinol or rasburicase (specific for hyperuricemia with chemo)
name the 4 classes of drugs approved for urate lowering therapy
XO inhibitors
uricosurices
uricase agents
URAT 1 (uric acid transporter 1) inhibitor
name 2 XOIS
allopurinol and febuxostat
name a uricosuric agent
probenecid
name a uricase agent
pegloticase
name URAT 1 inhibitor
lesinurad
ULT (urate lowering therapy) drugs are given with _____ for _______ to prevent _______
anti-inflammatories for 3-6 months to prevent gout caused by initiating ULT
ex: colchicine, NSAIDS, prednisone
target UA when using ULT
less than 6mg/dL
true or false
ULT treatment is stopped after 3-6 months of improvement
FALSE
it’s continued forever
1st line ULT
allopurinol
true or false
XOIs are useful for BOTH under excreters and over prodicuers
TRUE
can allopurinol be used in CKD?
yes - just need to lower the dosing
regular dosing of allopurinol
100mg/day
increase every 4 weeks to 200-300mg a day
some pts may need 600-800 a day
monitoring parameters for allopurinol
serum UA (obviously)
CBC
hepatic and renal function
why is allopurinol started at low doses of 100mg/day
reduce hypersensitivty reaction risk and risk of causing an acute gout attack
what is AHS
allopurinol hypersensitivity reaction
rare but severe - causes SJS, TEN, rash, eosinophilia
this is why doses are started LOW
which ppl are particularly at risk for AHS due to HLA-B*5801 allele
koreans, han chinese, thai, african americans
BLACK BOX WARNING FEBUXOSTAT
increased risk of CV related deaths like MI, stroke compared to allopurinol
thus, allopurinol should only be used in pts not responding to max dose of allopurinol, or contraindicated
febuxostat should be avoided in patients with severe ____ impairment
hepatic
dosage febuxostat
40mg QD
increase to 80mg after 2 weeks if UA not below 6 – has easier trituation than allopurinol
when would pegloticase be used
as last resort in pts with advanced gout and uncontrollable by the other ULTs
reduces uric acid levels and fixes tophi
pegloticase is contraindicated in what patients
with G6PDH deficiency
true or false
when using pegloticase, it takes a long time to see effects
FALSE - improves rapidly, but also very expensive
how is pegloticase given
via infusion
ppl starting pegloticase should be pretreated with what
antihistamines and corticosteroids to prevent BBW of infusion reaction
also, give colchicine or NSAID for 1 week before and 6 months after treatment
role in therapy for lesinurad
used only in COMBINATION with an XO inhibitor in pts who failed on XO inhib alone
black box warning lesinurad
risk of renal failure
risk decreases when given with XOI (that’s why we do it)
when is lesinurad contraindicated
pts with bad renal function
dosage lesinuard
200mg QD with XOI
what is duzallo
lesinurad + allopurinol
probenecid is a ____ agent
how long to see benefit? when can it NOT be started and why
uricosuric
6-12 months to see effect
NOT started during an acute gout flare bc can cause more kidney stones
imp counseling pt for pts on probenecid
lot of fluids
probenecid is contraindicated in which pts
with history kidney stones or mod-severe CKD
probenecid is used as add-on therapy in what pts?
pts not reaching goal with just XOI treatment
what are fenofibrate and losartan
uricosuric agents
monitoring on probenecid
serum UA (obvious)
CBC
RENAL FUNCTION
what drugs decrease effects of probenecid
salicylates
outline for treating refractory gout
- start with XOI as monotherapy. if serum UA target not achieved….
- ADD URICOSURIC (probenecid). if not achieved still and disease activity is continued….
- add pegloticase or lesinurad (RARE)1
1st and 2nd line for acute gout prophylaxis when starting ULT
1st line - colchicine 0.6mg QD or BID OR low dose NSAID (naproxen 250mg BID) BUT chronic NSAID use not rec. in older pts)
2nd line - low dose prednisone (less than 10mg a day)
continue these therapies for 3-6 months AFTERRRRRRR target uric acid levels have been achieved with ULT
some nonpharm gout treatment
lose weight
proper diet
regular exercse
limit red meats, organ meats, high fructose corn syrup, alcohol, fish, stop smoking
can also ice the joint for pain relief!
true or false
during gouty attacks, alcohol consumption should be totally avoided
true
alcohol intake should be limited to prevent gout flares
explain what this means for men vs women
men - no more than 2 drinks a day
women - no more than 1
