gout drugs Flashcards
what is the prevalence of gout?
Most common cause of inflammatory arthritis in the US (not autoimmune)
Most common rheumatic disease of adults
how is gout dx?
synovial aspiration (gold standard) :Seen via monosodium urate crystals more commonly- can see on PE
what is gout?
protein metabolism product–>uric acid
too much protein breakdown or the diminished kidney function (where uric acid is excreted)
–> uric acid increases ( in blood tissues)
When it deposits in the joint it is called gout.
can you have hyperuricemia without gout?
yes! (if uric acid >6 = hyperuricemia) BUT if its not in the joints then its NOT gout
common presentation of gout
Painful, red, swollen inflammation of a joint (common area is first toe)
who usually gets gout?
poor diet (alcohol, fish, red meat, soda)
sedentary
older, male
what drugs can CAUSE hyperuricemia?
Thiazide diuretics (HCTZ) Nicotine Cyclosporine Ethambutol (TB drug) Pyrazinamide (TB drug) Salicylates
“C SPENT”
what is a Ddx that must be ruled out when suspecting gout?
septic arthritis
3 drugs for acute txt of gout
Colchicine (Colcrys)
NSAIDs
Corticosteroids
prophylatic urate lowering therapy
- uricosuric agents
- xanthine oxidase inhibitors
- Recombinant Urate-Oxidase Enzyme
what are the three uricosuric agents?
Probenecid - no longer used
Losartan (Cozaar)
Fenofibrate
what are the two xanthine oxidase inhibitors?
Allopurinol (Zyloprim)
Febuxostat (Uloric)
what are the two recombinant urate-oxidase enzyme drugs?
Pegloticase (Krystexxa)
Rasburicase (Elitek)
“-icase”
MOA of allopurinol
MOA: Inhibits Xanthine Oxidase (XO) preventing the conversion of xanthine to uric acid
what is allopurinol or febuxostat (uloric) used for?
uric-acid lowering therapy, as prophylaxis for gout
but of the two, allopurinol ALWAYS better choice.
ADRs of allopurinol
SJS, Hepatotoxicity, Hemolytic anemia (G6PD)
dosing for allopurinol
starts at 100mg daily and titrated to maximum 800mg/day
***Goal is Uric Acid < 6
(full effect 2-3 months)
why should allopurinol ONLY be used for prophylaxis of gout?
Can precipitate flare if given during active flare d/t mobilization of uric acid
MOA of febuxostat (uloric)
MOA: similar to Allopurinol (XO inhibitor) - just more specific but DOESNT mean its better
ADRs of febuxostat
Hepatotoxicity, SJS, CV events
worse CV -thrombotic- events than allopurinol
MOA of probenecid?
Inhibits tubular reabsorption of urate causing excretion of uric acid (uricosuric drug)
when is probenecid used for gout?
really not ever anymore
due to need for adequately functioning kidneys, adequate hydration, and drug-drug-interactions
MOA of pegloticase
Enhances the oxidation of uric acid to allantoin which is readily excreted through the urine (uricosuric drug)
what do you need to do to preven the MAJOR adr of pegloticase ?
premedicated with antihistamines and corticosteroids before administration (b/c of anaphylaxi risk)
2 ADRs of pegloticase
Anaphylaxis, CHF exacerbation
what is rasburicase used for? MOA?
similar MOA to pegloticase and only indicated for Tumor Lysis Syndrome (TLS) - chemotherapy use
NSAIDs for gout?
relieving the inflammation gout crystals cause
*Indomethacin, *naproxen, and sulindac favored but any will do
corticosteroids for gout?
Intra-articular injections indicated if gout present in a single joint
Oral steroids indicated for multiple joints or large joint involvement
MOA of colchicine?
inhibits polymerization of beta-tubulin into microtubules (dis-assemble structure- so more neutrophils can’t be assembled and draw more to the area)
main ADR of colchicine?
BAD GI upset (N/D)
dosing for colchicine- gout acute flare?
“do not repeat course of txt more than every __ weeks”
first ign of flare: 1.2 mg ORALLY
one hr later: 0.6 mg (MAX 1.8 mg over 1 hour)
Then 0.6 mg once or twice daily until attack resolves
*2 weeks
gout- 3 phases of txt
Treat acute inflammation:
Prevent acute inflammation
Lower uric acid
1st phase: acute inflammation txt:
mild-moderate affecting 1 or few small joints or 2 large joints
monotherapy
1st phase: acute inflammation txt: severe pain or multiple large joints
combination therapy
NSAIDs
Oral Corticosteroids:
Colchicine
corticosteroids: one joint vs multiple
One joint do a corticosteroid injection. Multiple joints give oral steroids
2nd phase: prevention of acute inflamm. (3 options)
- Colchicine : Oral low dose (once or twice a day) is first line option
- NSAIDs: Also first line option, must use low-dose
If using long term, consider PPI for suppression of peptic ulcer disease - urate lowering therapy: allopurinol
Urate lowering therapy can be initiated during an acute gout attack as long as concomitant ________ is given.
anti-inflammatory therapy is given
*colchicine txt dose
1.2mg x 1 then 0.6mg one hour later
*allopurinol: common ADR? ddi?
Rash common, DDI w/ Azathioprine
*febuxostat: ADR? ddi?
CV warning, DDI w/ azathioprine
*uses for pegloticase vs rasburicase
which has a risk? how do you avoid it?
Pegloticase : only refractory gout, anaphylaxis risk (must pre-medicate prior to administration)
Rasburicase : only for TLS
*which drug? … Blocks renal elimination of penicillins increasing serum concentrations and half life (block tubular reabs)
probenecid
A 49 year old alcoholic businessman complains of 2 days of severe worsening pain with redness and swelling of his first metatarsophalangeal joint. He has no history of injury or trauma. He is afebrile with no other symptoms. Which of the following drugs is the most appropriate pharmacotherapy?
Indomethacin (NSAID- add PPI b/c an alcoholic)
