Gout and Hyperuricemia

Question 1

Gout is

Answer 1

Hyperuricemia + recurrent attacks of acute arthritis

Question 2

Define hyperuricemia

Answer 2

Serum uric acid >7 in men and >6 in women

Question 3

Acute arthritis caused by

Answer 3

Deposition of monosodium urate crystals in joints

Question 4

Gout leads to

Answer 4

Pain, joint destruction and loss of function

Question 5

Define Uric Acid nephrolithiasis

Answer 5

Kidney stones of uric acid

Question 6

Define Tophi

Answer 6

Depositis of monosodium urate crystals in soft tissues of the body -> joint destruction and nerve compression and deformity

Question 7

Gout Epidemiology

Answer 7

Males
Increases with age
Incidence in women after menopause

Question 8

Serum urate concentration correlates with

Answer 8

Males
Age
Body weight obesity
Renal insufficiency
Alcohol intake
Genetics
Lead exposure

Question 9

Xanthine oxidase

Answer 9

Reduces hypothanthine to xanthine to uric acid

Question 10

Urate is the

Answer 10

predominate species of uric acid in plasma

Question 11

Hyperuricemia causes

Answer 11

Diet
Overproduced by increased breakdown of nucleic acids (cancer)
Increased cytotoxic drugs
Genetics

Question 12

Genetics

Answer 12

Overactivity of PRPP synthetase (purine accumulation)
HGPRT deficiency (accumulation of PRPP)

Question 13

PRPP Synthetase

Answer 13

Superactive PRPP leads to excessive purine

Five genetic mutations associated with superactivity

Question 14

HGPRT deficiency

Answer 14

Involved in purine salvage pathway

Usually takes purines and makes monophosphates but deficiency = more to uric acid

Question 15

Other causes of Hyperuricemia

Answer 15

Underexcretion

Renal elimination/reabsorption

Question 16

Joint Response to Urate

Answer 16

Local vasodilation, pain, heat, edema, inflammation, tissue damage via IL-1beta

Question 17

Acute Gouty Arthritis

Answer 17

Sudden onset of sharp/intense pain, erythema, swelling

First attack is usually monoarticular and usually the big toe

Question 18

When do acute attacks usually occur?

Answer 18

During the night bc water reabsorption from joint space

Question 19

Uric Acid Nephrolithiasis

Answer 19

Uric acid kidney stones

Excessive urinary excretion

Question 20

Gouty Nephropathy

Answer 20

Acute leads to acute renal failure

Chronic: protein in the urine

Question 21

Tophaceous gout

Answer 21

SQ deposits –> late complication

Damage soft tissue and compress nerves

Question 22

Treatment of Gout

Answer 22

NSAIDS
Corticosteroids
Colchicine

Question 23

Prophylactic therapy

Answer 23

Allopurinol
Febuxostat
Rasburicase
Pegloticase
Probencid
Sulfinpyrazone

Question 24

NSAIDs

Answer 24

Sulindac, Indomethacin, Naproxen
Relief from pain and inflammation
Consider coadmin of PPIs

Question 25

Corticosteroids Intraarticular

Answer 25

Limited to 1 or 2 joints

Question 26

Corticosteroids Systemic

Answer 26

Multiple joints | Risk of osteoporosis, HPA suppresion

Question 27

Colchicine MOA

Answer 27

Inhibits cell division and migration of neutrophils | Decreases their inflam activity

Question 28

Colchicine | Test question

Answer 28

Relieves acute gout attacks with low benefits to toxicity ratio

Question 29

Uric Acid Lowering Therapy

Answer 29

Block Uric acid formation Enhance urate excretion Enhance Urate elimination

Question 30

Enhance urate excretion drug

Answer 30

Uricosuric agents

Question 31

Block Uric acid formation | drugs

Answer 31

Allopurinol or Febuxostat

Question 32

Enhance Urate elimination drugs

Answer 32

Rasburicase | Pegloticase

Question 33

Allopurinol

Answer 33

Inhibitor of xanthine oxidase Feedback inhibition of purine synthesis NOT with azathioprine SJS

Question 34

Febuxostat

Answer 34

Xanthine Oxidase inhibitor Non-purine CYP metabolism

Question 35

Rasburicase

Answer 35

Uricase Uric acid to allatoin (more soluble) Antibodies can form against the drug

Question 36

Pegloticase | Test question

Answer 36

Uricase Increase excretion and immunogenicity against allatoin No data on drug interactions

Question 37

Probenecid

Answer 37

OAT binds to uric acid so no reabsorption can occur | NOT with salicylates

Question 38

Sulfinpyrazone

Answer 38

Inhibits reabsorption Longer acting and more potent then probenacid Higher GI distress