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MSK 2-Pharmacology > Pharm of Gout & Hyperuricemia (Fitz) > Flashcards

Pharm of Gout & Hyperuricemia (Fitz) Flashcards

1
Q

a decrease in pH has what effect on Urate?

A

shifts rxn to left and precipitates uric acid crystals

determinant of acute gout (inflamm)

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2
Q

list factors contributing to gout attacks in the first MTP joint:

A
  • temp: lower temp in the joint which favors crystallization
  • pH: trauma can cause acidosis, low pH favors uric acid crystallization
  • joint hydration: nocturnal intra-articular dehydration may cause nocturnal crystallization, and nocturnal onset of pain
  • presence of altered matrix proteins, exposed cartilage fragments and nucleating debris: enhanced by joint trauma and/or pre-existing osteoarthrtitic damage in ellderly
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3
Q

symptoms of hyperuricemia?

A

none

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4
Q

symtpoms of acute gout flare?

A

joint inflammation

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5
Q

symptoms of advanced/chronic gout?

A

CONSTANT joint pain, inflamm, tophi

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6
Q

this drug class can be used for prompt termination of acute gout attack, prevention of recurrences of acute gout

A

Anti-inflamm drugs

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7
Q

this drug class is used for prevention & reversal or urate crystal deposits in joints, urinary tract, renal interstitium, and tissues and parenchymal organs

A

anti-hyperuricemic (urate-lowering) drugs

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8
Q

this anti-inflammatory binds to tubulin & depolymerizes microtubules. It disrupts granulocyte function and inhibits LTB4 formation

A

Colchicine

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9
Q

__ are the mainstay of tx of acute attacks of gout in pts who have no contraindication to them.

A

NSAIDs

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10
Q

caution with NSAIDs for tx of acute attacks of gout in pts with what?

A

ulcers
HTN
coronary disease
fluid retention

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11
Q

what type of gout is colchicine good for? therapeutic index? adverse effects?

A

specific tx for ACUTE gout

NARROW therapeutic index: doses should be decreased in renal and hepatic dysfunction

GI toxicity (diarrhea, ab pain); Risk for BM suppression

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12
Q

analgesic properties of colchicine? effect on uric acid levels?

A

NOT an analgesic: but indirectly relieves pain by blocking degranulation

does NOT modify uric acid levels

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13
Q

corticosteroids for gout attacks? risks?

A

prednisone and methylprednisolone

long-term risks such as osteoporosis and infx, BUT risk for short-term tx in gout relatively LOW

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14
Q

allopurinol and febuxostat are what type of hyperuricemic drugs?

A

XO inhibitors–> INHIBIT urate biosynthesis

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15
Q

Probenecid (USA), sulfinpyrazone, and benzbromarone are what type of hyperuricemic drugs?

A

URAT1 inhibitors –> enhance urate excretion

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16
Q

pegloticase and rasburicase are what tyype of hyperuricemic drugs?

A

Recombinant urate oxidase enzyme –> enhance urate metabolism

17
Q

1st line ULT drugs in gout?

A

XO inhibitors –> allopurinol and febuxostat

18
Q

what combo is appropriate in some pts to achieve serum urate target (<6 mg/dl)?

A

Combo of ORAL ULT with an oral URICOSURIC agent

19
Q

what drug combo is appropriate for severe disease, failure, or intolerance to appropriately dosed XO inhibitors?

A

ULT with a Urate oxidase recombinant enzyme (pegloticase)

20
Q

allopurinol acts by inhibiting what enzyme?

A

Xanthine oxidase

Blocks conversion of BOTH Hypoxanthine to Xanthine and Xanthine to Uric acid

21
Q

t1/2 of allopurinol and oxypurinol (active metabolite)? dosing interval for both

A

t1/2 allpurinol=2 hrs
t1/2 oxypurinol=16 hrs

Once daily, PO

22
Q

febuxostat acts by inhibiting what enzyme?

A

XO

23
Q

this drug is NOT a purine analog, has a better and different adverse effect profile (liver function) vs allopurinol, and can be used in pts with RENAL DISEASE

A

febuxostat

24
Q

paradox for initial phase of ULT?

A

early increase in acute gout attacks

this may contribute to non-compliance in long-term gout tx

25
Q

Explain the NSAIDs and ULT paradox:

A

recommended to administer oral colchicine or a NSAID in pts who are beginning ULT to decrease acute gout associated with initiation of ULT

26
Q

risk associated with use of allopurinol/febuxostat alongside xanthine drugs (i.e., 6-MP, azathioprine, theophylline)?

A

allopurinol and febuxostat inhibit metabolism of xanthine drugs used in cancer chemo, immunosuppression, asthma conferring RISKS of overexposure and requiring DOSE ADJUSTMENTS

27
Q

black box warning of allopurinol?

A

not recommended for tx of ASYMPTOMATIC hyperuricemia

should be discontinued at 1st apearance of skin rash or other signs of allergic rxn

28
Q

pts with this HLA genotype should avoid allopurinol d/t severe hypersensitivity

A

HLA-B*5801

populations with high allele frequency include Han chinese and Thai descent

29
Q

probenecid effects in kidney?

A

Probenecid=URAT1 inhibitor (blocks URAT on APICAL side)

BLOCKS tubular re-absorption > tubular secretion –> NET EFFECT=ENHANCE urate excretion

normal urate excretion=10% of filtered load
urate excretion with Probenecid=20% of filtered load

30
Q

uricosuric agents (2nd line agents in pts with tophaceous gout or hyperuricemia) should be avoid in who?

A

pts with risk/hx of nephrolithiasis or uric acid nephropathy

31
Q

urate-lowering tx are of no benefit for __

A

acute gout –> should generally not be initiated during acute attack

32
Q

paradox of aspirin use during acute gout attack?

A

do not use standard dose ASA as anti-inflamm agent for acute gout attacks

ASA blocks tubular secretion > tubular absorption and thereby AGGRAVATES HYPERURICEMIA

33
Q

what effect do thiazides and loops have on urate clearance?

A

interfere with urate clearance by effects on multiple transporters in PCT –> uric acid retention

34
Q

what drugs augment metabolic degradation of uric acid into allantoin?

A

Recombo enzyme uric acid oxidase:
Pegloticase
Rasburicase

35
Q

indication for pegloticase?

A

hyperuricemia associated with MALIGNANCY (TUMOR LYSIS syndrome)

IV q 2 wks

36
Q

indication for Rasburicase?

A

gout-associated hyperuricemia

IV qdx5 days

37
Q

Boxed warning for both pegloticase and rasburicase?

A

severe hypersensitivty rxns (including anaphylaxis) have been reported

Rasburicase: contraindicated in G6PD deficiency d/t risk for hemolysis

MSK 2-Pharmacology (7 decks)

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