Gout

Question 1

Explain purine metabolism and how we get uric acid?

Answer 1

AMP is deamidated to IMP. IMP and GMP are dephosphorylated to Guanosine and inosine. Ribose is taken from both to make hypoxanthine and guanine. Guanine is dephosphorlyated to xanthine and hypoxanthine is converted to xanthine via xanthine oxidase. Xanthine oxidase is then converted to uric acid via xanthine oxidase. Primarily this happens in the liver.

Question 2

Talk about the two ways we can salvage purines?

Answer 2

APRT converts free adenine to AMP

HGPRT converts hypoxanthine to AMP and guanine to GMP

Question 3

Explain Lesch Nyhan syndrome and the three clinical signs?

Answer 3

Absence/deficiency of HGPRT

Retardation, self mutilation and severe gout.

Question 4

1 uric acid underexcreter causing primary hyperuricemia? Causes of sedonary hyperuricemia?

Answer 4

Lower fractional excretion of filtered urate

Impaired renal function and drug induced inhibition

Question 5

2 urate overproduction situations causing primary hyper uric acid? 2 urate overproduction situations causing secondary hyper uric acid?

Answer 5

Metabolic disorders and idiopathic

Excessive purine intake and tumor lysis syndrome

Question 6

What 2 things will cause the plasma urate concentration to increase?

Answer 6

Fractional excretion is less than normal

GFR falls

Question 7

3 mechanisms by which we will treat gout?

Answer 7

Anti inflammatory drugs
Drugs to increase uric acid renal excretion
Drugs to reduce uric acid production

Question 8

What do we use for treatment of acute gout?

Answer 8

First, NSAIDS
If NSAIDS are contraindicated, then use colchicine.
If colchicine is contraindicated, then use glucos. If its one joint, you can it in the joint. If greater than two, need to be more systemic.

Question 9

MOA of colchicine and common adverse effect?

Answer 9

Blocks formation of microtubules and leads to inhibition of leukocyte migration and phagocytosis.
GI distress

Question 10

MOA of allopurinol, clinical application, and adverse effect ?

Answer 10

Competitive inhibitor of xanthine oxidase leading to hypoxanthine and xanthine being excreted
Recurrent gout
Skin rash (hypersensitivity reactions can be fatal)

Question 11

MOA for febuxostat and clinical application?

Answer 11

Non purine xanthine oxidase inhibitor

Recurrent gout for those who cannot tolerate allopurinol

Question 12

MOA of pegloticase, clinical application and 1 adverse effect?

Answer 12

Uricase, so it converts uric acid to more soluble allantoin.
Chronic gout
Infusion reactions

Question 13

MOA for rasburicase, clinical application.

Answer 13

Uricase

Prevents acute uric acid nephropathy due to tumor lysis syndrome in patients with high risk lymphoma or leukemia

Question 14

MOA of probenecid and clinical application?

Answer 14

Blocks urate reabsorption and encourages urate secretion

Use in underexcreters with GFR over 60 and no stones.

Question 15

3 lifestyle modifications to advise patients on for gout?

Answer 15

Diet, weight, and avoid alcohol