Penicillamine
Penicillamine is a potent **chelating agent** primarily utilized in veterinary medicine for the management of **copper-storage hepatopathies**, particularly in susceptible dog breeds like Bedlington Terriers, Labrador Retrievers, and Dalmatians. Key clinical highlights: * **Slow Onset**: Clinical improvement in copper-associated hepatopathy may require weeks to months of continuous therapy. * **Versatility**: Beyond copper, it is effective for long-term oral treatment of lead or mercury poisoning, and for the dissolution/prevention of **cystine urolithiasis**. * **Anti-fibrotic Properties**: May offer benefits in chronic hepatitis by inhibiting collagen crosslinking, though the required doses are often poorly tolerated. > **Clinical Pearl**: Because penicillamine can chelate dietary minerals, it should not be administered concurrently with zinc or vitamin-mineral supplements unless specifically staggered under a strict protocol.
กลไกการออกฤทธิ์: 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.
ขนาดยาตามชนิดสัตว์
- 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.
วิธีการให้ยา
ข้อห้ามใช้
- 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
อาการไม่พึงประสงค์
- 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)
อันตรกิริยาระหว่างยา
- 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
การติดตาม
- 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
การได้รับยาเกินขนาด
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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