Fitzy: Pharmacology of Gout and Hyperuricemia Flashcards

1
Q

What transporter in the kidney will let us reabsorb urate?

A

-URAT1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where does Uric acid come from?

A
  • Purines
  • fructos
  • alcohol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What enzyme makes uric acid?

A

-Xanthine Oxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the two XO inhibitors?

A
  • Allopurinol

- Febuxostat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

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

A
  • rasburicase
  • pegloticase
  • uricosolytics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the one anti inflammatory gout specific drug?

A

-colchicine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

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

A

-NSAIDS!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does colchicine do again?

A
  • binds to tubulin, depolymerizes microtubules, and imparis migration of granulocytes
  • thereby blunting inflammation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the maximum does for colchicine?

A

-12 tablets per episode

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Is colchicine an analgesic?

A

-no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Does colchicine modify uric acid levels?

A

-no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

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

A

-corticosteroids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the 2 XO inhibitors?

A
  • allopurinol
  • febuxostate
  • they inhibit urate biosynthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
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
Why is febuxostat better than allopurinol?
- has better and different adverse effect profile vs allopurinol - can be used in patients with renal disease
26
What is that one wierd paradox thing with ULT?
-during the initial phase of ULT, there is an early increase in acute gout attacks
27
What do we give as well to people who are beginning ULT to decrease acute gout associated with initiation of ULT?
-colchicine or an NSAID
28
What is a big thing that we have to worry about with allopurinol and febuxostat?
-they inhibit metabolism of Xanthine drugs use in cancer chemotherapy, immunosuppression, asthma conferring risk of overexposure and requiring dose adjustments
29
What were the Xanthine drugs that build up when we inhibit XO?
- 6 mercaptopurine - Azathioprine - Theophylline
30
Which xanthine drug makes people edgy when they don't clear it?
-theophylline
31
What is the black box warning with allopurinol?
- 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
What genotype do we have to worry about and make them avoid allopurinol?
- HLA-B*5801 - severe hypersensitivity to allopurinol - Han Chinese, Thai descent
33
What drug combo is appropriate in some patients to achieve the serum urate target (<6mg/dL)?
- oral ULT | - oral uricosuric agent (probenecid)
34
What are uricosuric drugs?
- 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
What does probenecid do specifically?
- blocks URAT1 transporter on apical membrane of epithelium | - promotes excretion
36
When should uricosuric agents (probenecid) be avoided?
-in pts with risk/hx of nephrolithiasis or uric acid nephropathy
37
Should urate-lowering therapies be initiated during an acute attack?
- no | - they are of no benefit for acute gout
38
What is the paradox thing with aspirin?
- 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
What kind of a dose of aspirin do we need to give them to have a uricosuric effect?
-a very high dose
40
Will thiazide and loop diuretics help?
- no! - they interfere with urate clearance by effects on multiple transporters in the prox renal tubule - this causes uric acid retention
41
What is kind of the last stitch effort we use for gout?
-ULT with a urate oxidase recombinant enzyme (pegloticase) is appropriate for severe disease, failure, or intolerance to appropriately dosed XOI options
42
What does Pegloticase and rasburicase do?
-these drugs augment metabolic degradation of uric acid into allantoin
43
What do we use pegloticase for?
-hyperuricemia associated with malignancy (tumor lysis syndrome)
44
What do we use rasburicase for?
-approved for gout-associated hyperuricemia
45
How is pegloticase and rasburicase given to patients?
-IV... not a pill
46
What is rasburicase contraindicated in?
- G6PD deficiency | - gives them hemolysis