乙胺嘧啶
乙胺嘧啶是一種強效的**抗原蟲藥**，在獸醫學中主要用於治療小動物嚴重的原蟲感染，如**弓形蟲症 (toxoplasmosis)**、**新孢子蟲症 (neosporosis)** 和 ***Hepatozoon americanum***，以及馬的**馬原蟲性脊髓腦炎 (EPM)**。它幾乎總是與磺胺類藥物合併使用，以達到協同阻斷葉酸合成的效果。 **臨床要點：** 由於其標靶為葉酸代謝，宿主骨髓抑制是一個顯著的風險，特別是在貓。通常建議補充亞葉酸 (folinic acid，而非葉酸，因為原蟲有時能利用葉酸) 或烘焙酵母來減輕血液學毒性。
作用機制: Pyrimethamine is a **folic acid antagonist**. It competitively inhibits the enzyme **dihydrofolate reductase (DHFR)** → blocks the reduction of **dihydrofolic acid** to **tetrahydrofolic acid** (the active form of folate) → depletes folate reserves essential for purine and pyrimidine synthesis → halts protozoal DNA and RNA synthesis. When combined with sulfonamides (which inhibit **dihydropteroate synthase** earlier in the pathway), it produces a synergistic, sequential blockade of the folate synthesis pathway.
各物種劑量
- Toxoplasmosis · 0.5-1 mg/kg PO once daily for 2 days, then 0.25 mg/kg PO once daily for 2 weeks · PO · once daily · 2 days, then 2 weeks · Given with sulfadiazine at 30-50 mg/kg PO divided two to four times a day for 1-2 weeks
- Toxoplasmosis (enteroepithelial cycle) · 2 mg/kg, PO once daily · PO · once daily
- Toxoplasmosis (extraintestinal cycle) · 0.5-1 mg/kg PO divided two to three times daily · PO · divided two to three times daily · Combined with sulfonamides (e.g., triple sulfa, sulfadiazine) at 60 mg/kg PO or IM divided two to three times daily
- Protozoal myocarditis · 1 mg/kg PO once daily for 3 days, then decrease dose to 0.5 mg/kg PO once a day · PO · once daily · 3 days, then ongoing · Given with sulfadimethoxine 25 mg/kg PO, IV, or IM once a day
- Toxoplasmosis · 0.5 mg/kg PO per day · PO · per day · 7-10 days · Given with sulfadiazine at 30 mg/kg, PO q12h. Do not use continuously for longer than 2 weeks. Supplementation with folic acid 5 mg/day or folinic acid 1 mg/kg/day may alleviate toxicity.
- Equine protozoal myeloencephalitis · 1 mg/kg PO once a day for 90-120 days (or longer) · PO · once a day · 90-120 days (or longer) · Given with a sulfa or potentiated sulfa (sulfadiazine 20 mg/kg PO once or twice a day). Monitor CBC's.
- Coccidian organisms in raptors (Toxoplasmosis, Atoxoplasmosis, Sarcocystis) · 0.5 mg/kg PO twice daily for 14-28 days · PO · twice daily · 14-28 days
- Toxoplasmosis · 0.5-1 mg/kg PO once daily for 2 days, then 0.25 mg/kg PO once daily for 2 weeks · PO · once daily · 2 days, then 2 weeks · Given with sulfadiazine at 30-50 mg/kg PO divided two to four times a day for 1-2 weeks
- Toxoplasmosis · 0.25-0.5 mg/kg once daily for 28 days · PO · once daily · 28 days
- Neospora · 1 mg/kg once daily for 28 days · PO · once daily · 28 days · Given with trimethoprim sulfa
- Hepatazoon canis · 0.25-0.5 mg/kg once daily for 2-4 weeks · PO · once daily · 2-4 weeks · Given with trimethoprim sulfa and clindamycin
- Hepatazoon americanum · 0.25 mg/kg PO q24h · PO · q24h · Given with Trimethoprim/sulfa (15 mg/kg PO q12h) and clindamycin (10 mg/kg q8h). Once remission attained, decoquinate can maintain.
- Hepatazoon americanum · 0.25 mg/kg PO q24h for 14 days · PO · q24h · 14 days · Given with Trimethoprim/sulfa (15 mg/kg PO q12h for 14 days) and clindamycin (10 mg/kg q8h for 14 days). Once remission attained, decoquinate can maintain.
- Neosporosis · 1 mg/kg PO daily · PO · daily · Given with trimethoprim/sulfa (15-30 mg/kg PO twice daily).
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Known hypersensitivity to pyrimethamine
- Preexisting hematologic disorders (use with extreme caution)
- Pregnancy (potentially teratogenic, weigh risks vs. benefits)
- Pregnancy (teratogenic)
- Pre-existing bone marrow suppression
- Hypersensitivity to pyrimethamine
不良反應
- Small animals: Anorexia, malaise, vomiting, depression
- Small animals: Bone marrow depression (anemia, thrombocytopenia, leukopenia)
- Cats: Highly susceptible to adverse reactions (noted 4-6 days after starting combination therapy)
- Horses: Leukopenias, thrombocytopenia, and anemias
- Bone marrow suppression (anemia, leukopenia, thrombocytopenia)
- Anorexia
- Vomiting
- Lethargy
- Depression
藥物相互作用
- p-Aminobenzoic acid (PABA) · Reportedly antagonistic towards the activity of pyrimethamine; clinical significance is unclear.
- Sulfonamides · Synergistic with pyrimethamine in activity against toxoplasmosis and malaria. · moderate
- 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. · major
- Phenobarbital · May increase folate deficiency · moderate
- Phenytoin · May increase folate deficiency · moderate
監測
- CBC with platelet count (frequent monitoring recommended)
- Clinical efficacy
- Signs of abnormal bleeding or lassitude
- Complete Blood Count (CBC) every 1-2 weeks
- Appetite and body weight
- Signs of bleeding, bruising, or lethargy
過量
Reports of acute overdosage in animals were not located. In humans, signs include **vomiting, nausea, anorexia, CNS stimulation (including seizures), and hematologic effects**. **Treatment recommendations:** - Standard procedures to empty the gut or prevent absorption. - Parenteral barbiturates for seizures. - Folinic acid for hematologic effects. - Long-term monitoring (at least 1 month) of renal and hematopoietic systems.
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。