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MSK II Midterm > Fitzy: Pharmacology of Gout and Hyperuricemia > Flashcards

Fitzy: Pharmacology of Gout and Hyperuricemia Flashcards

1
Q

What transporter in the kidney will let us reabsorb urate?

A

-URAT1

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2
Q

Where does Uric acid come from?

A
  • Purines
  • fructos
  • alcohol
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3
Q

What enzyme makes uric acid?

A

-Xanthine Oxidase

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4
Q

What are some other factors besides hyperuricemia that contribute to gout attacks in the first metatarsal phalangeal joint?

A
  • temperature
  • pH
  • joint hydration: this is why there’s nocturnal pain
  • Presence of altered matrix proteins, exposed cartilage fragments and nucleating debris
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5
Q

What are the two XO inhibitors?

A
  • Allopurinol

- Febuxostat

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6
Q

What are the drugs that turn uric acid into a more soluble form?

A
  • rasburicase
  • pegloticase
  • uricosolytics
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7
Q

What is the one anti inflammatory gout specific drug?

A

-colchicine

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8
Q

What is that unique MOA for Colchicine?

A
  • binds to tubulin and depolimerizes microtubules
  • disrupts granulocyte function; inhibits LTB4 formation
  • *kind of paralyzes neutrophils… they can’t migrate to the site inflammation… this is used specifically for gout
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9
Q

what is the mainstay of therapy of acute gout attacks in patients who have no contraindications to them?

A

-NSAIDS!

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10
Q

when do we have to use caution with NSAIDs?

A
  • ulcers
  • htn
  • coronary disease
  • fluid retention
  • remember that the dose of NSAIDs needed to resolve gout attack are on the higher side
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11
Q

How much ibuprofen should a person with gout take?

A

-2 tabs three times a day is often insufficent! so they need to take a shit ton

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12
Q

What does colchicine do again?

A
  • binds to tubulin, depolymerizes microtubules, and imparis migration of granulocytes
  • thereby blunting inflammation
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13
Q

What is the maximum does for colchicine?

A

-12 tablets per episode

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14
Q

Is colchicine an analgesic?

A

-no

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15
Q

Does colchicine modify uric acid levels?

A

-no

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16
Q

What confers long term risks, such as osteoporosis and infection, but has low risk for short-term risks?

A

-corticosteroids

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17
Q

What aer the adverse effects of corticosteroids that we have to worry about?

A
  • adverse effects on bp and blood sugar

- so if they have htn or uncontrolled diabetes mellitus

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18
Q

What are the 2 XO inhibitors?

A
  • allopurinol
  • febuxostate
  • they inhibit urate biosynthesis
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19
Q

What are the 2 drugs that are uricosuric agents (URAT1 inhibitors)?

A
  • Probenecid
  • Sulfinpyrazone
  • they enhance urate excretion
20
Q

What are the recombinant urate oxidase enzymes?

A
  • pegloticase
  • rasburicase
  • they enhance urate metabolism
21
Q

What is the only uricosuric agent available in US?

A

-Probenecid

22
Q

What is the 1st line urate lowering therapy (ULT) in gout?

A
  • XO inhibitors
  • allopurinol
  • febuxostat
23
Q

What accumulates as a result of tx with allopurinol and febuxostat?

A

-hypoxanthine is the best answer

24
Q

What is the active metabolite of allopurinol?

A
  • oxyurinol

- has long ass half life

25
Q

Why is febuxostat better than allopurinol?

A
  • has better and different adverse effect profile vs allopurinol
  • can be used in patients with renal disease
26
Q

What is that one wierd paradox thing with ULT?

A

-during the initial phase of ULT, there is an early increase in acute gout attacks

27
Q

What do we give as well to people who are beginning ULT to decrease acute gout associated with initiation of ULT?

A

-colchicine or an NSAID

28
Q

What is a big thing that we have to worry about with allopurinol and febuxostat?

A

-they inhibit metabolism of Xanthine drugs use in cancer chemotherapy, immunosuppression, asthma conferring risk of overexposure and requiring dose adjustments

29
Q

What were the Xanthine drugs that build up when we inhibit XO?

A
  • 6 mercaptopurine
  • Azathioprine
  • Theophylline
30
Q

Which xanthine drug makes people edgy when they don’t clear it?

A

-theophylline

31
Q

What is the black box warning with allopurinol?

A
  • Allopurinol should be discontinued at the first appearance of skin rash or other signs of an allergic rxn
  • it is not recommended for tx of asymptomatic hyperuricemia
32
Q

What genotype do we have to worry about and make them avoid allopurinol?

A
  • HLA-B*5801
  • severe hypersensitivity to allopurinol
  • Han Chinese, Thai descent
33
Q

What drug combo is appropriate in some patients to achieve the serum urate target (<6mg/dL)?

A
  • oral ULT

- oral uricosuric agent (probenecid)

34
Q

What are uricosuric drugs?

A
  • weak organic acids that promote renal clearance of uric acid by inhibiting urat-anion exchangers in the proximal tubule that mediates urate reabsorption
  • Probenecid remember that
35
Q

What does probenecid do specifically?

A
  • blocks URAT1 transporter on apical membrane of epithelium

- promotes excretion

36
Q

When should uricosuric agents (probenecid) be avoided?

A

-in pts with risk/hx of nephrolithiasis or uric acid nephropathy

37
Q

Should urate-lowering therapies be initiated during an acute attack?

A
  • no

- they are of no benefit for acute gout

38
Q

What is the paradox thing with aspirin?

A
  • do not use standard dose aspirin as an anti-inflammatory agent for acute gout attacks
  • aspirin blocks tubular secretion>tubular absorption and thereby aggravates hyperuricemia
39
Q

What kind of a dose of aspirin do we need to give them to have a uricosuric effect?

A

-a very high dose

40
Q

Will thiazide and loop diuretics help?

A
  • no!
  • they interfere with urate clearance by effects on multiple transporters in the prox renal tubule
  • this causes uric acid retention
41
Q

What is kind of the last stitch effort we use for gout?

A

-ULT with a urate oxidase recombinant enzyme (pegloticase) is appropriate for severe disease, failure, or intolerance to appropriately dosed XOI options

42
Q

What does Pegloticase and rasburicase do?

A

-these drugs augment metabolic degradation of uric acid into allantoin

43
Q

What do we use pegloticase for?

A

-hyperuricemia associated with malignancy (tumor lysis syndrome)

44
Q

What do we use rasburicase for?

A

-approved for gout-associated hyperuricemia

45
Q

How is pegloticase and rasburicase given to patients?

A

-IV… not a pill

46
Q

What is rasburicase contraindicated in?

A
  • G6PD deficiency

- gives them hemolysis

MSK II Midterm (15 decks)

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