長春新鹼
長春新鹼是一種源自長春花（*Catharanthus roseus*）的細胞週期特異性（M期）抗腫瘤藥物。它是獸醫腫瘤學中的基石，主要用於淋巴和造血系統腫瘤（如淋巴瘤）的聯合化療方案（如CHOP）。 主要臨床重點： * **骨髓保護性**：與許多其他化療藥物（如其類似物長春花鹼）不同，長春新鹼在標準劑量下對骨髓的抑制作用較小，這使其在聯合方案中極具價值。 * **傳染性性病腫瘤 (TVT)**：作為單一藥物治療犬隻TVT具有極高的療效。 * **免疫介導性血小板減少症 (IMT)**：長春新鹼獨特地用於治療難治性IMT。它能促進巨核細胞的碎裂，導致血小板快速釋放到血液循環中。 * **發泡劑**：它是一種嚴重的組織發泡劑；必須透過完美放置的導管嚴格進行靜脈注射，以防止毀滅性的藥物外滲損傷。
作用機制: Vincristine is a cell-cycle specific agent that acts during the **M-phase** (mitosis). * **Antineoplastic Action**: It binds specifically to **tubulin** dimers → inhibits microtubule polymerization → prevents the formation of the mitotic spindle → arrests cell division in **metaphase**, ultimately leading to apoptosis. * **Metabolic Effects**: It interferes with amino acid metabolism by inhibiting glutamic acid utilization and preventing purine synthesis, citric acid cycle, and urea formation. * **Thrombocytosis**: The exact mechanism is unknown, but it is believed to stimulate megakaryocyte fragmentation, accelerating the release of platelets into the peripheral blood. * **Immunosuppression**: Exhibits mild immunosuppressive activity, which may contribute to its efficacy in immune-mediated conditions.
各物種劑量
- Neoplastic diseases · 0.5-0.75 mg/m2 · IV · every 1-3 weeks · Dosed in mg/m2, NOT mg/kg. Consultation with an oncologist recommended.
- Neoplastic diseases (particularly lymphoproliferative disorders) · See Appendix for chemotherapy protocols and conversion of body weight to body surface area. · IV · Not specified · Not specified · Must be administered i.v. through a carefully pre-placed catheter.
- Neoplastic diseases · 0.5 mg/m2 (usually 2.5-3 mg total dose per horse) · IV · weekly · Often used in CAP protocol with cytarabine and cyclophosphamide.
- Neoplastic diseases (usually in combination protocols) · 0.5-0.75 mg/m2 · IV · every 1-2 weeks · Dosed in mg/m2, NOT mg/kg. Consultation with an oncologist recommended.
- Transmissible venereal tumor (TVT) · 0.5 mg/m2 (maximum dose 1 mg) · IV · once weekly · for 4-6 weeks · Used as sole therapy.
- Adjunctive treatment of immune-mediated thrombocytopenia (IMT) · 0.5 mg/m2 · IV · once · If platelet count <10-20,000 cells/mcL or bleeding; consider bone marrow aspiration to document megakaryocytes.
- Adjunctive treatment of immune-mediated thrombocytopenia (IMT) refractory to prednisone · 0.5-0.7 mg/m2 · IV · once · Given as an IV bolus or as an infusion over 4-6 hours.
- Adjunctive treatment of immune-mediated thrombocytopenia (IMT) · 0.02 mg/kg · IV · once · Generally single use.
給藥途徑
禁忌症
- Preexisting neuromuscular disease
- Severe leukopenia
- Uncontrolled infection
- No specific absolute contraindications listed, but requires extreme caution in specific disease states
不良反應
- Peripheral neuropathy (proprioceptive deficits, spinal hyporeflexia)
- Paralytic ileus and severe constipation
- Mild leukopenia
- Tissue necrosis and sloughing (if extravasated)
- Anorexia, vomiting, diarrhea
- Impaired platelet aggregation
- Increased liver enzymes
- Syndrome of inappropriate ADH secretion (SIADH)
- Jaw pain
- Alopecia
- Stomatitis
- Seizures
- Pulmonary edema (rare, reported in cats)
- Peripheral neuropathy
- Ileus
- GI tract toxicity
藥物相互作用
- Asparaginase · Additive neurotoxicity may occur; less common if asparaginase is administered after vincristine.
- Mitomycin · Severe bronchospasm has occurred in humans receiving mitomycin-C with Vinca alkaloids.
- Amiodarone · Inhibits P-glycoprotein; may increase vincristine toxicity, especially in MDR1/ABCB1 mutant dogs.
- Azole Antifungals (e.g., ketoconazole) · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Carvedilol · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Cyclosporine · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Diltiazem · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Erythromycin · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Clarithromycin · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Quinidine · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Spironolactone · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Tamoxifen · Inhibits P-glycoprotein; may increase vincristine toxicity.
- Verapamil · Inhibits P-glycoprotein; may increase vincristine toxicity.
監測
- Efficacy (tumor burden reduction or platelet count)
- Peripheral neuropathic clinical signs (e.g., gait abnormalities, constipation)
- Complete blood counts (CBC) with platelets
- Liver function tests (prior to therapy and repeated as necessary)
- Serum uric acid
- Complete Blood Count (CBC) prior to each dose
- IV catheter site for any signs of extravasation during administration
- Gastrointestinal signs (monitoring for ileus or severe constipation)
- Neurological exams (monitoring for peripheral neuropathy, e.g., dragging paws, loss of reflexes)
過量
Vincristine has a narrow therapeutic index. * **Dogs**: The maximally tolerated dose is reported as 0.06 mg/kg every 7 days for 6 weeks. Toxicity signs include slight anemia, leukopenia, increased liver enzymes, and neuronal shrinkage in the peripheral and central nervous systems. * **Cats**: The lethal dose is reportedly 0.1 mg/kg. Toxic signs include weight loss, seizures, leukopenia, and general debilitation. A reported 10X overdose (5 mg/m2) resulted in death within 72 hours despite intensive care (including calcium folinate). * **Treatment**: Primarily supportive. Includes cardiovascular and hematologic monitoring, anticonvulsants for seizures, and prevention of ileus. Fluid restriction and loop diuretics may be needed to manage SIADH. Leucovorin calcium has been used in humans, but efficacy is unconfirmed.
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