gout drugs Flashcards by Jacqui Joseph

what is the prevalence of gout?

Most common cause of inflammatory arthritis in the US (not autoimmune)
Most common rheumatic disease of adults

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how is gout dx?

synovial aspiration (gold standard) :Seen via monosodium urate crystals 
more commonly- can see on PE

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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.

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can you have hyperuricemia without gout?

yes! (if uric acid >6 = hyperuricemia) BUT if its not in the joints then its NOT gout

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common presentation of gout

Painful, red, swollen inflammation of a joint (common area is first toe)

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who usually gets gout?

poor diet (alcohol, fish, red meat, soda)
sedentary
older, male

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what drugs can CAUSE hyperuricemia?

Thiazide diuretics (HCTZ)
Nicotine
Cyclosporine
Ethambutol (TB drug) 
Pyrazinamide (TB drug) 
Salicylates

“C SPENT”

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what is a Ddx that must be ruled out when suspecting gout?

septic arthritis

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3 drugs for acute txt of gout

Colchicine (Colcrys)
NSAIDs
Corticosteroids

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prophylatic urate lowering therapy

uricosuric agents
xanthine oxidase inhibitors
Recombinant Urate-Oxidase Enzyme

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what are the three uricosuric agents?

Probenecid - no longer used
Losartan (Cozaar)
Fenofibrate

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what are the two xanthine oxidase inhibitors?

Allopurinol (Zyloprim)

Febuxostat (Uloric)

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what are the two recombinant urate-oxidase enzyme drugs?

Pegloticase (Krystexxa)
Rasburicase (Elitek)
“-icase”

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MOA of allopurinol

MOA: Inhibits Xanthine Oxidase (XO) preventing the conversion of xanthine to uric acid

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what is allopurinol or febuxostat (uloric) used for?

uric-acid lowering therapy, as prophylaxis for gout

but of the two, allopurinol ALWAYS better choice.

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ADRs of allopurinol

SJS, Hepatotoxicity, Hemolytic anemia (G6PD)

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dosing for allopurinol

starts at 100mg daily and titrated to maximum 800mg/day
***Goal is Uric Acid < 6
(full effect 2-3 months)

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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)

1. Colchicine : Oral low dose (once or twice a day) is first line option 2. NSAIDs: Also first line option, must use low-dose If using long term, consider PPI for suppression of peptic ulcer disease 3. 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)