Pharmacology
Summary
Gout arises from uric acid crystal deposition, a product of purine metabolism that transforms purines into hypoxanthine, then xanthine, and finally, with xanthine oxidase, to uric acid. This uric acid is mainly excreted by the renal tubules, but drugs aspirin can impede this. Acute gout episodes are treated with glucocorticoids and colchicine, the latter of which acts via binding to intracellular tubulin . Distinctly, pseudogout features unique rhomboid-shaped crystals.
Chronic gout is most commonly managed with allopurinol, a xanthine oxidase inhibitor that reduces uric acid formation. Allopurinol drug also acts to prevent uric acid crystal buildup in scenarios like tumor lysis syndrome following cytotoxic chemotherapy. However, allopurinol carries several risks, including the potential for Stevens-Johnson syndrome and the DRESS syndrome. Probenecid, a sulfa drug and uricosuric agent, increases the renal clearance of uric acid and is also useful in the treatment of chronic gout. Probenacid can increase the risk of renal stone formation due to amplified uric acid excretion, and can also inhibit the renal excretion of penicillin. Pegloticase, administered intravenously, changes uric acid into water-soluble allantoin. Pegloticase carries significant risks, such as anaphylaxis, as well as potentially triggering hemolysis in patients with G6PD deficiency.
Lesson Outline
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FAQs
Gout originates from the accumulation of uric acid crystals in the joints, a byproduct of purine metabolism. When blood levels of uric acid rise, a condition known as hyperuricemia, it often leads to gout. Gout medications manage this through different strategies: xanthine oxidase inhibitors, such as allopurinol limit uric acid production, uricosurics like probenecid facilitate uric acid excretion through the kidneys, and other drugs such as NSAIDs and cholchicine work through various mechanisms to alleviate gout symptoms and reduce the frequency of acute gout attacks.
Acute gouty attacks, characterized by sudden and severe joint pain with redness and swelling, arise from the accumulation of uric acid crystals in the joint linings. Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally the first line of treatment. Should NSAIDs be ineffective or contraindicated, glucocorticoids or colchicine may be prescribed. Additionally, long-term management with drugs like allopurinol or probenecid is often implemented to prevent future episodes.
Pseudogout, characterized by calcium pyrophosphate crystal deposition, is a chronic condition in which the goal of treatment is symptom management. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often first-line agents to alleviate pain and inflammation. In cases where NSAIDs are contraindicated or ineffective, corticosteroids (either oral or injected directly into the affected joint) can be employed. Colchicine, also used in gout management, can be effective for acute pseudogout attacks and as prophylaxis. Gout treatments aim to reduce uric acid levels using medications like allopurinol or probenecid, while pseudogout focuses more on symptom management since there's no specific drug to dissolve calcium pyrophosphate crystals.
Tumor lysis syndrome (TLS) is a life-threatening condition that occurs when large numbers of cancer cells are killed rapidly, leading to the a surge of potassium, phosphate, and uric acid released into the bloodstream, which can lead to acute kidney injury, arrhythmias, and seizures. Allopurinol or febuxostat can be administered to inhibit xanthine oxidase, reducing the production of uric acid from purines released during cell lysis.
Pegloticase is a recombinant uricase enzyme that converts uric acid into a more easily excreted substance, allantoin. It typically reserved for severe, refractory gout where standard treatments such as xanthine oxidase inhibitors or uricosurics are ineffective or inappropriate. By lowering uric acid levels in the blood, pegloticase helps to relieve gout symptoms, decrease the occurrence of gout attacks and preventing related complications, such as urate nephrolithiasis.
