Allopurinol
**Allopurinol** is a potent **xanthine oxidase inhibitor** widely used in veterinary medicine. Key clinical applications include: * **Urate Urolithiasis:** Used primarily in dogs (especially predisposed breeds like Dalmatians) to dissolve and prevent uric acid stones. It must be combined with a low-purine diet to prevent the formation of xanthine stones. * **Canine Leishmaniasis:** Acts as a leishmaniostatic agent. It is often used in combination with meglumine antimoniate or miltefosine for long-term management. * **Avian and Reptilian Medicine:** Used to manage hyperuricemia and treat gout in birds and reptiles. *Clinical Pearl:* Because allopurinol increases the urinary excretion of xanthine, prolonged high doses without dietary purine restriction can paradoxically lead to the formation of xanthine uroliths.
Mecanismo: Allopurinol and its primary active metabolite, **oxypurinol** (alloxanthine), competitively inhibit the enzyme **xanthine oxidase**. * **Normal Pathway:** Hypoxanthine → **xanthine oxidase** → Xanthine → **xanthine oxidase** → Uric Acid * **Inhibition:** By blocking this enzyme, allopurinol prevents the conversion of oxypurines to uric acid. This decreases serum and urine concentrations of uric acid, while increasing the levels of the more water-soluble precursors (hypoxanthine and xanthine). **In Leishmaniasis:** Allopurinol acts as a purine analogue. *Leishmania* organisms mistakenly incorporate allopurinol metabolites into their RNA, which disrupts protein synthesis and inhibits parasite multiplication.
Dosificación por especie
- Urate uroliths (dissolution) · 15 mg/kg PO q12h; only in conjunction with low purine foods. · PO · q12h
- Urate uroliths (prevention) · 10-20 mg/kg/day · PO · Daily · Preferable to minimize recurrence with dietary therapy to avoid xanthine uroliths.
- Urate uroliths (dissolution and prevention) · 7-10 mg/kg PO three times daily · PO · TID · Goal is to reduce urine urate:creatinine ratio by 50%.
- Leishmaniasis (First line treatment) · 10 mg/kg PO twice daily · PO · BID · 6-12 months · Used plus Meglumine antimoniate 75-100 mg/kg once daily for 4-8 weeks.
- Leishmaniasis (Second line treatment) · 10 mg/kg PO twice daily · PO · BID · 6-12 months · Used plus Miltofosine 2 mg/kg PO once daily for 4 weeks OR allopurinol alone.
- Leishmaniasis · 20 mg/kg PO q12h · PO · q12h · 9 months · With Meglumine antimoniate (100 mg/kg/day SQ) until resolution.
- Leishmaniasis (Alternate protocol alone) · 10 mg/kg PO q8h or 10-20 mg/kg PO q12h · PO · q8h or q12h · 1-4 months
- Leishmaniasis · 10 mg/kg PO twice daily · PO · BID · If possible use with meglumine antimoniate, if not, use alone.
- Leishmaniasis (with renal insufficiency) · 5 mg/kg PO twice daily · PO · BID
- Leishmaniasis · 15 mg/kg PO twice daily · PO · BID · months
Vías de administración
Contraindicaciones
- Known hypersensitivity to allopurinol
- Red-tailed hawks (anecdotal reports of severe toxicity)
Efectos adversos
- Xanthine urolithiasis (especially with high doses or non-restricted diets)
- Hypersensitivity reactions (rash, erythema)
- Lethargy
- Gastrointestinal upset
- Hepatotoxicity (rare)
- Bone marrow suppression (rare)
Interacciones farmacológicas
- Chlorpropamide · May increase risks for hypoglycemia and hepato-renal reactions
- Cyclophosphamide · Increased bone marrow depression may occur
- Cyclosporine · Allopurinol may increase cyclosporine levels
- Diuretics (Furosemide, Thiazides, Diazoxide) and Alcohol · Can increase uric acid levels, antagonizing allopurinol's effect
- Oral Anticoagulants (e.g., Warfarin) · Allopurinol may reduce the metabolism of warfarin thereby increasing its effect
- Trimethoprim/Sulfamethoxazole · Thrombocytopenia has occurred in a few human patients when used concurrently
- Uricosuric Agents (e.g., Probenecid, Sulfinpyrazone) · May increase the renal excretion of oxypurinol and thereby reduce xanthine oxidase inhibition; additive effects on blood uric acid may be beneficial
- Urinary Acidifiers (e.g., Methionine, Ammonium Chloride) · May reduce the solubility of uric acid in the urine and induce urolithiasis
- Azathioprine · Allopurinol inhibits the metabolism of azathioprine, leading to severe, potentially fatal myelosuppression. · major
- Mercaptopurine · Allopurinol inhibits the metabolism of mercaptopurine, significantly increasing toxicity risk. · major
- Amoxicillin / Ampicillin · Concurrent use increases the risk of cutaneous rash. · moderate
Monitoreo
- Urine uric acid (for urolithiasis)
- Adverse effects (rash, lethargy)
- Periodic CBC, liver and renal function tests (e.g., BUN, Creatinine, liver enzymes); especially early in therapy
Sobredosis
Information on acute overdosage in veterinary species is limited. Massive overdoses may cause gastrointestinal distress (vomiting, diarrhea). Treatment should consist of supportive care and monitoring of renal function. Adequate hydration is important to promote diuresis and excretion.
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