乙胺嘧啶與磺胺嘧啶
**乙胺嘧啶與磺胺嘧啶 (Pyrimethamine and sulfadiazine)** 是一種具有協同作用的抗菌與抗原蟲複方藥物，在獸醫學中主要用於治療由 *Sarcocystis neurona* 引起的**馬原蟲性脊髓腦炎 (EPM)**。 * **協同作用：** 透過結合磺胺類藥物與二氨基嘧啶類藥物，此配方能對葉酸合成途徑產生連續阻斷作用，對易感原蟲與細菌具有致命性。 * **仿單標示外使用 (Off-label Uses)：** 雖然 FDA 僅核准用於馬匹，但此複方（或類似的葉酸拮抗劑組合）有時會在小動物臨床上用於治療嚴重的原蟲感染，例如貓的**弓形蟲症 (Toxoplasmosis)** 與狗的**新孢子蟲症 (Neosporosis)**。 * **臨床注意事項：** 治療 EPM 需要長期的療程（通常為 3 到 9 個月）。由於可能引發全身性葉酸缺乏，臨床獸醫師必須密切監測骨髓抑制的風險。
作用機制: This combination exerts its antiprotozoal and antibacterial effects through a **sequential blockade** of the folic acid synthesis pathway, which is essential for nucleic acid (DNA/RNA) production in the parasite: 1. **Sulfadiazine** acts as a structural analogue of para-aminobenzoic acid (**PABA**). It competitively inhibits the enzyme **dihydropteroate synthase**, blocking the conversion of PABA → **dihydrofolic acid (DFA)**. 2. **Pyrimethamine** specifically targets and inhibits the enzyme **dihydrofolate reductase**, blocking the conversion of DFA → **tetrahydrofolic acid (THFA)** (the active form of folate). > **Pharmacological Pearl:** Pyrimethamine has a much higher affinity for protozoal dihydrofolate reductase compared to bacterial or mammalian forms, making it highly effective against protozoal parasites like *Sarcocystis neurona* and *Toxoplasma gondii*.
各物種劑量
- Treatment of EPM · 20 mg/kg sulfadiazine with 1 mg/kg pyrimethamine; equivalent to 4 mL of ReBalance suspension per 50 kg (110 lb) body weight · PO · once daily · 90-270 days (based upon clinical response) · Administer at least 1 hour before feeding with hay or grain. Administer using a suitable oral dosing syringe; insert nozzle through the interdental space and deposit the dose on the back of the tongue.
- Maintaining clinical remission (for horses that have had two relapses) · pyrimethamine/sulfadiazine · PO · twice weekly (first and fourth day of each week) · Ongoing · After completing regular therapy for EPM.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Hypersensitivity to pyrimethamine or sulfadiazine
- Horses intended for human consumption
不良反應
- Bone marrow suppression (anemia, leukopenia, neutropenia, thrombocytopenia)
- Reduced appetite or anorexia
- Loose stools or diarrhea
- Urticaria (hives)
- Treatment crisis (temporary worsening of neurologic signs due to parasite die-off)
- CNS effects (seizures, depression - though often secondary to the underlying EPM)
藥物相互作用
- Antacids · May decrease the bioavailability of sulfonamides if administered concurrently.
- Highly protein-bound drugs (e.g., methotrexate, phenylbutazone, thiazide diuretics, salicylates, probenecid, phenytoin, warfarin) · Sulfonamides may displace other highly bound drugs, potentially increasing their free (active) plasma concentrations and risk of toxicity.
- p-Aminobenzoic acid (PABA) · Reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear.
- Trimethoprim · Use with pyrimethamine/sulfa is not recommended in humans as adverse effects may be additive; however, this combination has been used clinically in horses.
監測
- CBC (including platelets): baseline and at least monthly during therapy
- GI adverse effects (appetite, stool consistency)
- Clinical Efficacy: Improvement in neurologic signs
- CSF Western Blot test (monitoring for negative status)
過量
Acute overdosage information (>2X) in horses is not well documented. When administered at **2X the labeled dose for 92 days**, signs included loose stools, slight increases in ALP, declines in red blood cell parameters (RBC, HCT, Hgb, PCV), and depressed appetite. Treatment should be supportive and symptomatic.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。