青黴胺
青黴胺是一種強效的**螯合劑**，在獸醫學中主要用於治療**銅儲積性肝病**（如貝林登㹴、拉布拉多犬和大麥町犬）。它也可用於鉛或汞中毒的長期口服治療，以及胱氨酸尿石症的溶解與預防。由於其具有抗纖維化特性，可能對慢性肝炎有益，但所需劑量通常難以耐受。
作用機制: Penicillamine exerts its effects through multiple distinct mechanisms depending on the target condition: * **Heavy Metal Chelation**: Contains sulfhydryl groups that bind to heavy metals (copper, lead, iron, mercury) → forms stable, water-soluble complexes → facilitates rapid excretion via the kidneys. * **Cystine Urolithiasis**: Combines chemically with cystine via a disulfide interchange reaction → forms a stable, highly soluble penicillamine-cysteine mixed disulfide complex → readily excreted in urine, preventing stone formation. * **Antirheumatic Activity**: Mechanism is not fully elucidated, but it improves lymphocyte function and decreases **IgM rheumatoid factor** and immune complexes in serum and synovial fluid. * **Antifibrotic Activity**: Inhibits **lysyl oxidase** and collagen crosslinking → renders newly synthesized collagen more susceptible to enzymatic degradation.
各物種劑量
- Lead poisoning · 125 mg q12h PO for 5 days. · PO · q12h · 5 days · After initial therapy with CaEDTA and if blood lead is greater than 0.2 ppm at 3-4 weeks post-treatment.
- Copper toxicity · 52 mg/kg daily for 6 days · PO · q24h · 6 days · FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Copper toxicity · 26-52 mg/kg PO once daily for 6 days. · PO · q24h · 6 days
- Lead or mercury toxicity · 110 mg/kg PO for 1-3 weeks. · PO · Unknown · 1-3 weeks · Must clear GI tract of toxic metal before therapy.
- Adjunctive treatment of lead poisoning · 55 mg/kg PO q12h for 1-2 weeks. · PO · q12h · 1-2 weeks · Suggested to combine CaEDTA and penicillamine for several days until symptoms dissipate followed by a 3-6 week treatment with penicillamine.
- Lead or mercury toxicity · 110 mg/kg PO for 1-3 weeks. · PO · Unknown · 1-3 weeks · To prevent continued metal absorption, must clear GI tract of toxic metal before therapy. FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Copper toxicity · 52 mg/kg daily for 6 days · PO · q24h · 6 days · FARAD recommends a minimum milk withdrawal time of 3 days after the last treatment and a 21-day preslaughter withdrawal.
- Copper toxicity · 26-52 mg/kg PO once daily for 6 days. · PO · q24h · 6 days
- Lead or mercury toxicity · 110 mg/kg PO for 1-3 weeks. · PO · Unknown · 1-3 weeks · Must clear GI tract of toxic metal before therapy.
- Copper-associated hepatopathy · 10-15 mg/kg PO q12h on an empty stomach. Do not give concurrently with any medication, including zinc or a vitamin-mineral supplement. · PO · q12h
- Copper-associated hepatopathy · 15 mg/kg PO twice daily 30 minutes before meals. Give supplemental pyridoxine. Chelate at least 6 months, and then use a second liver biopsy to determine efficacy and chronic treatment plan. · PO · q12h · At least 6 months · If patient is zinc intolerant, use chronic penicillamine at a dose restriction of 50%. Do not use chelation and zinc together.
- Copper-associated hepatopathy · 10-15 mg/kg PO two times a day 30 minutes prior to food. Start low and increase. · PO · q12h
- Copper-associated hepatopathy · 15 mg/kg PO twice daily on an empty stomach. · PO · q12h
- Cystine urolithiasis · 15 mg/kg: PO twice daily. If nausea and vomiting occur, mix with food or give at mealtime. Some dogs may need to have the dosage slowly increased to full dose in order to tolerate the drug. · PO · q12h
- Cystine urolithiasis · 15 mg/kg: PO twice daily with food · PO · q12h
- Lead poisoning · 110 mg/kg/day, PO divided q6-8h for 1-2 weeks. If vomiting, depression, and anorexia occur, may reduce dose to 33-55 mg/kg/day divided q6-8h, which should be better tolerated. · PO · q6-8h · 1-2 weeks · After initial therapy regimen with CaEDTA and if continued therapy is desired at home.
- Lead poisoning · 110 mg/kg/day divided q6-8h PO 30 minutes before feeding for 1-2 weeks. If vomiting a problem may premedicate with dimenhydrinate (2-4 mg/kg PO). Alternatively, may give 33-55 mg/kg/day divided as above. · PO · q6-8h · 1-2 weeks · As an alternate or adjunct to CaEDTA. Dissolving medication in juice may facilitate administration.
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
- Patients with a history of penicillamine-related blood dyscrasias
- Presence of lead in the gastrointestinal tract (can enhance absorption)
- Pregnancy (unless benefits outweigh teratogenic risks)
- Moderate to marked renal impairment
- History of penicillamine-related blood dyscrasias
不良反應
- Nausea
- Vomiting
- Depression
- Anorexia
- Dietary mineral deficiencies (zinc, iron, copper, calcium) with long-term use
- Fever (rare)
- Lymphadenopathy (rare)
- Skin hypersensitivity reactions (rare)
- Immune-complex glomerulonephropathy (rare)
- Teratogenicity
- Pyrexia
- Nephrotic syndrome
- Leucopenia (human data)
- Thrombocytopenia (human data)
- Lymphadenopathy (human data)
- Skin hypersensitivity reactions (human data)
藥物相互作用
- 4-Aminoquinoline drugs (e.g., chloroquine, quinacrine) · Concomitant administration may increase the risks for severe dermatologic adverse effects.
- Oral Cations (Zinc, Iron, Calcium, Magnesium) · May decrease the effectiveness of penicillamine if given orally together due to chelation in the gut.
- Food and Antacids · The amount of penicillamine absorbed from the GI tract may be reduced by concurrent administration.
- Gold Compounds · May increase the risk of hematologic and/or renal adverse reactions.
- Immunosuppressant drugs (e.g., cyclophosphamide, azathioprine) · May increase the risk of hematologic and/or renal adverse reactions.
- Phenylbutazone · May increase the risk of hematologic and/or renal adverse reactions.
- Antacids · Decreased gastrointestinal absorption of penicillamine · moderate
- Food · Decreased gastrointestinal absorption of penicillamine · moderate
- Iron salts · Decreased gastrointestinal absorption of penicillamine · moderate
- Zinc salts · Decreased gastrointestinal absorption of penicillamine · moderate
- Cytotoxic drugs · Increased renal and haematological adverse effects · major
- NSAIDs · Increased risk of renal damage · major
監測
- Clinical efficacy (e.g., resolution of neurologic signs in lead poisoning)
- Liver enzymes (ALT) and liver copper levels via biopsy (for hepatopathy)
- Urinalysis and stone dissolution (for cystine urolithiasis)
- Complete blood count (CBC) and urinalysis to monitor for rare blood dyscrasias or glomerulonephropathy
- Full blood count (weekly initially)
- Urinalysis (weekly initially)
- Renal function
- Dietary mineral levels (zinc, iron, copper, calcium) during long-term use
過量
No specific acute toxic dose has been established for penicillamine. Toxic effects generally occur in patients taking the drug chronically. Any relationship of toxicity to dose is unclear; patients on small doses may develop toxicity. Management of overdose would be largely supportive and symptomatic.
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