Gout Treatment Overview

Gout Treatment Overview

• Gout is a metabolic disorder marked by high uric acid levels.
• Hyperuricemia (high uric acid) can lead to sodium urate crystal deposits in tissues, primarily joints and kidneys.
• Gout isn't always a consequence of hyperuricemia, but hyperuricemia always precedes gout.
• Sodium urate is the final product of purine metabolism in humans.

Treating Gout

• Acute Gout Attacks: Treated with indomethacin to reduce granulocyte movement to the affected area. Other NSAIDs (nonsteroidal anti-inflammatory drugs) are also effective for pain and inflammation. Aspirin is contraindicated as it competes with uric acid for kidney secretion. Initial NSAID dose can be doubled within 24-48 hours, then tapered.
• Chronic Gout:
  • Treatment strategies aim to lower uric acid levels below saturation point to prevent urate crystal deposition.
  • Techniques include:
    • Inhibiting uric acid synthesis using allopurinol.
    • Increasing uric acid excretion, using probenecid or sulfinpyrazone.
    • Inhibiting leukocyte entry into affected joints with colchicine.
    • Administering NSAIDs.
• Prophylactic Therapy: Patients with more than two gout attacks annually are candidates for preventative treatment. Intra-articular glucocorticoids may be used for single or double-joint involvement.

Chronic Gout Causes

• Genetic Defects: Increased purine synthesis.
• Renal Deficiency: Impaired kidney function.
• Lesch-Nyhan Syndrome: Rare inborn error of purine metabolism (lack of enzyme HPRT).
• Cancer Chemotherapy: Associated with increased uric acid production.

Treating Chronic Gout (continued)

• Uricosuric Drugs: Increase uric acid excretion, reducing plasma concentration. Allopurinol is a selective inhibitor of uric acid biosynthesis. Often the preferred choice in patients with excessive uric acid synthesis, prior uric acid stones or renal insufficiency. Uricosuric agents are first-line for patients with decreased uric acid excretion.

Colchicine

• Mechanism of Action: Binds to tubulin, causing depolymerization and disrupting granulocyte mobility, reducing their migration to affected areas. It also blocks cell division. Colchicine inhibits the synthesis and release of leukotrienes.
• Therapeutic Uses: Effective for alleviating acute gout pain within 12 hours (best if administered within 24-48 hours of onset). Often replaced by NSAIDs for acute gout attacks. Now commonly used for the prophylaxis of recurrent attacks, effective in over 80% of patients.
• Pharmacokinetics: Administered orally → rapid absorption → recycled in the bile → excretion in feces or urine. Avoid in patients with low creatinine clearance (<50 mL/min).
• Adverse Effects: Nausea, vomiting, abdominal pain, diarrhea, myopathy, neutropenia, aplastic anemia, alopecia (with chronic use). Not recommended in pregnancy and caution advised with liver, kidney or cardiovascular issues.

Allopurinol

• Mechanism of Action: Competitive inhibitor of xanthine oxidase, reducing uric acid production.
• Therapeutic Uses: Primarily to treat primary gout and hyperuricemia related to other factors (e.g., malignancies, chemotherapy). Preferred in patients with a history of uric acid stones or renal insufficiency.
• Pharmacokinetics: Absorbed orally, primary metabolite is also a xanthine oxidase inhibitor (alloxanthine, oxypurinol). Both are excreted in feces and urine.
• Adverse Effects: Skin rashes (most common), acute gout attacks, nausea, diarrhea (common). Generally well tolerated compared to other treatments but may interact negatively with certain chemotherapeutics (6-mercaptopurine, azathioprine).

Uricosuric Agents (Probenecid & Sulfinpyrazone)

• Mechanism of Action: Promote uric acid excretion by inhibiting the urate-anion exchanger in the proximal tubule.
• Uses: Appropriate for patients with decreased renal excretion, and patients who do not have a history of kidney stones. Probenecid commonly used to enhance the effects of other drugs due to its inhibition of tubular secretion. Probenecid also blocks penicillin tubular secretion and can be used to increase its serum concentration.
• Adverse Effects: Gastric distress is a common side effect, especially with sulfinpyrazone. Also inhibits excretion of some other drugs (naproxen, ketoprofen, and indomethacin).

This quiz explores the key concepts of gout treatment, including acute and chronic strategies. It highlights the role of uric acid in gout and the medications used to manage acute attacks and prevent future episodes. Test your knowledge on this metabolic disorder and its management options.