Gout Treatment

Gout Treatment

Gout is a type of arthritis caused by the buildup of uric acid crystals in the joints, leading to recurring episodes of inflammation. This condition arises from elevated uric acid levels in the blood, a consequence of purine metabolism disorders.

Purine Metabolism Process:

Purines are converted into hypoxanthine, which is then further processed by the enzyme xanthine oxidase (XO) to produce xanthine and ultimately uric acid. Uric acid can be eliminated through urine or transformed into water-soluble substances.

Gout medication falls into two categories:

• Anti-inflammatory drugs: Reduce inflammation and pain during acute gout attacks.

• Uric acid-lowering drugs: Decrease uric acid levels in the blood, preventing the formation and deposition of urate crystals.

Colchicine:

• Effects:

• Treats acute gout.

• Does not possess anti-inflammatory effects on other types of arthritis.

• Does not impact uric acid excretion.

• Mechanism of action:

• Inhibits the movement of white blood cells to the site of inflammation.

• Reduces the phagocytic activity of urate crystals, decreasing the release of lactic acid and inflammatory enzymes.

• Blocks cell division, increases vascular wall strength, and decomposes lymphocytes.

• Adverse effects: Nausea, vomiting, diarrhea, abdominal pain, gastrointestinal mucosal epithelial damage, bone marrow suppression, hair loss, neuropathy, renal toxicity.

• Indications: Treatment of acute gout attacks, acute episodes of chronic gout, and gout relapse prevention.

Drugs that Reduce Uric Acid Synthesis:

• Allopurinol: Inhibits the enzyme xanthine oxidase.

• Febuxostat: Has a more selective effect on XO compared to allopurinol.

Allopurinol:

• Mechanism of action:

• Inhibits the enzyme xanthine oxidase.

• Increases the excretion of readily soluble precursors of uric acid.

• Effects: Reduces uric acid levels in the blood, prevents stone formation, and is less likely to cause painful spasms.

• Adverse effects: Can cause Stevens-Johnson syndrome.

• Pharmacokinetics: Metabolized in the liver while retaining activity, the active form being oxypurinol.

• Indications: Chronic gout, urate stones, secondary hyperuricemia.

• Dosage: 1 tablet/day due to the 18-20 hour half-life of oxypurinol.

Drugs that Increase Uric Acid Excretion:

• Probenecid: Inhibits uric acid reabsorption in the renal tubules.

• Lesinurad: Enhances uric acid excretion in urine.

Probenecid:

• Mechanism of action:

• At therapeutic doses: Competitively inhibits the urate transporter.

• At low doses: Competes with the uric acid elimination process.

• Contraindications: Renal insufficiency, kidney stones, hyperuricosuria.

• Drug interactions: Reduces the effectiveness of aspirin, thiazides, cancer drugs, increases the toxicity of antibiotics, carbapenems, and antiviral agents.

Lesinurad: Advantages include fewer drug interactions compared to probenecid.

Drugs that Enhance Uric Acid Breakdown:

• Uricase:

• Rasburicase: Intravenous administration.

• Pegloticase: Subcutaneous administration.

• Drawbacks: Easy to develop resistance, gout relapse, and allergic reactions.

Gout treatment group with the highest risk of kidney stones: The group that increases excretion.

Important Considerations:

• Intravenous colchicine can cause pain and necrosis at the injection site.

• Aspirin should not be used for inflammation in gout treatment as it reduces the effectiveness of other uric acid-lowering drugs and increases gastrointestinal ADRs.

• Colchicine can be combined with allopurinol during the initial months of treatment to prevent acute gout attacks.

• When administering cancer medications, be aware of hyperuricemia due to increased cell destruction.

• Patients with renal insufficiency treated with allopurinol require dose adjustments.

• Patients allergic to probenecid components can consider allopurinol as an alternative treatment.

In conclusion: Gout treatment should be managed under the guidance of a specialist to ensure appropriate medication selection, dosage, and monitoring of side effects.