PHRM 825: Gout - Hazbun Flashcards
What is strongly correlated with gout?
Hyperuricemia
Why is there a limit of urate solubility in the blood of humans?
Humans lack the enzyme uricase
What serum urate level constitutes hyperuricemia?
> or = 6.8 mg/dL
What gets deposited and where is it deposited in someone that has gout?
Monosodium urate crystals in synovial fluid or tissue
How does uric acid solubility compare to hypoxanthine or xanthine?
Uric acid is ~35 times less soluble than hypoxanthine and ~25 times less soluble than xanthine
What does an increase in PRPP synthetase activity result in?
An increase in De Novo synthesis of Purines
What molecules inhibit De Novo synthesis of purines?
AMP, IMP, and GMP
What enzyme catalyzes the Purine Salvage Pathway
Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase)
What happens with decreased HGPRTase activity?
- Increased hypoxanthine oxidation to uric acid
- Stimulates De Novo synthesis through accumulated PRPP
What is primary gout?
Overproduction or decreased secretion of uric acid
What is secondary gout?
Uric acid increases due to cell death and lysis, releasing nucleic acid
What causes primary gout?
- Ethanol
- Foods high in purines
- Obesity
What causes secondary gout?
- Chemotherapeutic agents
- Myelo-and lymphoproliferative disorders
- Polycythemia vera and anemia
- Psoriasis
What joint is commonly involved in gout?
First metatarsophalangeal joint
What is podagra?
Gout involving first metatarsophalangeal joint; ‘the great toe’
When does gouty arthritis occur?
When aggregation of MSU crystals (tophi) over several years of recurrent acute attacks
What is tophi?
Deposits of monosodium urate in cartilage, tendons, synovial membranes, and elsewhere
What is the gold standard for diagnosing gout?
VIsualization of urate crystals from the joint or tophi through aspiration
What is uric acid nephrolithiasis?
- Acidic urine, uric acid is less soluble and risk of stone formation
- 10-25% of patients with gout
- More common when urine pH < 6
- Long-term complication of gout
What is tophaceous gout?
- Late complication of gout
- Base of great toe, helix of ear, bursae, achilles, knee, wrists, and hands
- Joint destruction, pain, and nerve compression syndrome
- Long-term complication of gout
What is acute gouty nephropathy?
- Urine flow is blocked by precipitation of uric acid crystals in collecting ducts and ureters
- Acute renal failure can ensue
- Common with ALL, CLL, and CML patients
What is chronic gouty nephropathy?
- Long-term deposition of urate crystals within the renal system
- Proteinuria may occur
- Often associated with HTN, DM, and atherosclerosis
What 3 immunosuppressants are used to treat gout?
- Colchicine
- NSAIDs
- Corticosteroids
What medications treat gout by reducing serum urate levels?
- Uricosuric agents
- Xanthine oxidase inhibitors
What is the MOA of allopurinol?
Inhibits the synthesis of uric acid by inhibition of xanthine oxidase
What is allopurinol an isomer of?
Hypoxanthine
When is Feboxustat advantageous?
- Patients with allopurinol hypersensitivity
- Patients with reduced kidney function
- Patients not responding to high doses of allopurinol
What is the MOA of Febuxostat?
Non-purine inhibitor of Xanthine Oxidase
When is Pegloticase contraindicated?
In patients with G-6-P dehydrogenase deficiency
What is the MOA of Pegloticase?
Uricase oxidizes uric acid to allantoin (soluble and more easily excreted)
What is the MOA of Rasburicase?
Enzyme that catalyzes oxidation of uric acid to allantoin (soluble and more easily excreted)
What is the MOA of Lesinurad?
Selective uric acid reabsorption inhibitor that blocks the URAT1 transporter
What is the target serum uric acid concentration when gout is treated?
< 6 mg/dL
