Pharm of Gout & Hyperuricemia (Fitz)

Question 1

a decrease in pH has what effect on Urate?

Answer 1

shifts rxn to left and precipitates uric acid crystals

determinant of acute gout (inflamm)

Question 2

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

Answer 2

• 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

Question 3

symptoms of hyperuricemia?

Answer 3

none

Question 4

symtpoms of acute gout flare?

Answer 4

joint inflammation

Question 5

symptoms of advanced/chronic gout?

Answer 5

CONSTANT joint pain, inflamm, tophi

Question 6

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

Answer 6

Anti-inflamm drugs

Question 7

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

Answer 7

anti-hyperuricemic (urate-lowering) drugs

Question 8

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

Answer 8

Colchicine

Question 9

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

Answer 9

NSAIDs

Question 10

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

Answer 10

ulcers
HTN
coronary disease
fluid retention

Question 11

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

Answer 11

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

Question 12

analgesic properties of colchicine? effect on uric acid levels?

Answer 12

NOT an analgesic: but indirectly relieves pain by blocking degranulation

does NOT modify uric acid levels

Question 13

corticosteroids for gout attacks? risks?

Answer 13

prednisone and methylprednisolone

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

Question 14

allopurinol and febuxostat are what type of hyperuricemic drugs?

Answer 14

XO inhibitors–> INHIBIT urate biosynthesis

Question 15

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

Answer 15

URAT1 inhibitors –> enhance urate excretion

Question 16

pegloticase and rasburicase are what tyype of hyperuricemic drugs?

Answer 16

Recombinant urate oxidase enzyme –> enhance urate metabolism

Question 17

1st line ULT drugs in gout?

Answer 17

XO inhibitors –> allopurinol and febuxostat

Question 18

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

Answer 18

Combo of ORAL ULT with an oral URICOSURIC agent

Question 19

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

Answer 19

ULT with a Urate oxidase recombinant enzyme (pegloticase)

Question 20

allopurinol acts by inhibiting what enzyme?

Answer 20

Xanthine oxidase

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

Question 21

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

Answer 21

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

Once daily, PO

Question 22

febuxostat acts by inhibiting what enzyme?

Answer 22

XO

Question 23

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

Answer 23

febuxostat

Question 24

paradox for initial phase of ULT?

Answer 24

early increase in acute gout attacks

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

Question 25

Explain the NSAIDs and ULT paradox:

Answer 25

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

Question 26

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

Answer 26

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

Question 27

black box warning of allopurinol?

Answer 27

not recommended for tx of ASYMPTOMATIC hyperuricemia should be discontinued at 1st apearance of skin rash or other signs of allergic rxn

Question 28

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

Answer 28

HLA-B*5801 populations with high allele frequency include Han chinese and Thai descent

Question 29

probenecid effects in kidney?

Answer 29

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

Question 30

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

Answer 30

pts with risk/hx of nephrolithiasis or uric acid nephropathy

Question 31

urate-lowering tx are of no benefit for __

Answer 31

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

Question 32

paradox of aspirin use during acute gout attack?

Answer 32

do not use standard dose ASA as anti-inflamm agent for acute gout attacks ASA blocks tubular secretion > tubular absorption and thereby AGGRAVATES HYPERURICEMIA

Question 33

what effect do thiazides and loops have on urate clearance?

Answer 33

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

Question 34

what drugs augment metabolic degradation of uric acid into allantoin?

Answer 34

Recombo enzyme uric acid oxidase: Pegloticase Rasburicase

Question 35

indication for pegloticase?

Answer 35

hyperuricemia associated with MALIGNANCY (TUMOR LYSIS syndrome) IV q 2 wks

Question 36

indication for Rasburicase?

Answer 36

gout-associated hyperuricemia IV qdx5 days

Question 37

Boxed warning for both pegloticase and rasburicase?

Answer 37

severe hypersensitivty rxns (including anaphylaxis) have been reported Rasburicase: contraindicated in G6PD deficiency d/t risk for hemolysis