帕米膦酸二鈉
**帕米膦酸二鈉 (Pamidronate disodium)** 是一種第二代含氮雙膦酸鹽類藥物，在獸醫學中主要用於治療嚴重或難治性**高血鈣症**，特別是與惡性腫瘤（如淋巴瘤或頂泌腺肛門囊腺癌）及維生素D類似物中毒（如膽鈣化醇殺鼠劑、卡泊三醇）相關的高血鈣症。 主要臨床應用包括： * **高血鈣症管理**：當標準療法（靜脈注射生理食鹽水、呋塞米、皮質類固醇）效果不佳時，能迅速降低危險的高血清鈣濃度。 * **骨肉瘤與骨骼腫瘤**：被研究作為輔助治療以直接針對微小轉移，並廣泛用作姑息治療藥物，以減輕與溶骨性病變相關的嚴重骨痛。 > **臨床要點**：由於帕米膦酸二鈉是強效的骨吸收抑制劑，其對血清鈣的影響深遠且持久。必須將其稀釋於不含鈣的晶體溶液中，並進行緩慢的靜脈輸注（通常歷時 2 至 4 小時），以盡量降低急性腎毒性的風險。
作用機制: Pamidronate is a nitrogen-containing bisphosphonate that strongly binds to **hydroxyapatite crystals** in the bone matrix, specifically targeting areas of active bone turnover. * **Inhibition of Bone Resorption**: Once internalized by osteoclasts during bone resorption, pamidronate inhibits the enzyme **farnesyl pyrophosphate synthase (FPPS)** in the mevalonate pathway. * **Osteoclast Apoptosis**: Inhibition of FPPS prevents the prenylation of small GTPase proteins (like **Ras** and **Rho**) → disruption of osteoclast cytoskeletal function and ruffled border formation → **induction of osteoclast apoptosis**. * **Antineoplastic Effects**: In vitro, it exhibits direct cytotoxic and cytostatic effects on human osteosarcoma cell lines, potentially exerting antiangiogenic effects and inhibiting tumor cell migration.
各物種劑量
- Control of hypercalcemia · 1.5-2 mg/kg IV over 4 hours · IV · From a retrospective study of 2 cats.
- Refractory hypercalcemia · 1 mg/kg IV given over 2 hours in 250 mL of normal saline · IV · every 4 weeks
- Control of hypercalcemia · 1.32 mg/kg in 150 mL of 0.9% saline with a 2 hour IV infusion · IV · can repeat in 1-3 weeks · Consider if parenteral saline, furosemide and corticosteroids do not resolve the issue.
- Treatment of cholecalciferol-induced toxicosis · 0.65-2 mg/kg in 0.9% NaCl · IV · on days 1 and 4 post-ingestion
- Attempting to reduce bone pain associated with osteosarcoma in combination with an NSAID · 1-2 mg/kg; diluted into 250 mL of 0.9% sodium chloride and administered as a CRI over 2 hours · IV · every 28 days
- Pain associated with skeletal neoplasias · 1-2 mg/kg IV over 2 hours · IV · every 21-28 days · Has been shown to provide pain relief in ~50% of dogs with skeletal neoplasia.
- Calcipotriene toxicosis · 1.3-2 mg/kg slow IV infusion · IV · single dose · In most cases, a single dose will lower calcium levels back to normal. Monitor calcium daily for at least 10 days after returning to normal.
- Control of hypercalcemia · 1.05-2 mg/kg IV over 4 hours · IV · From a retrospective study of 7 dogs.
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給藥途徑
禁忌症
- Hypersensitivity to pamidronate or other bisphosphonates
- Severe renal impairment (use with extreme caution; not tested in humans with serum creatinine > 5 mg/dL)
不良反應
- Electrolyte abnormalities (hypomagnesemia, hypocalcemia, hypophosphatemia)
- Cardiac arrhythmias (secondary to electrolyte shifts)
- Renal toxicity (especially with rapid infusion)
- Transient bone pain
- Anemia
- Thrombocytopenia
- Granulocytosis
- Ophthalmic syndromes (e.g., scleritis - reported in humans)
藥物相互作用
- Calcium-affecting drugs (e.g., furosemide, corticosteroids) · Can affect calcium levels; requires careful monitoring when used concurrently.
- Nephrotoxic drugs (e.g., cisplatin, aminoglycosides) · Potential for increased risk of nephrotoxicity; use with caution.
監測
- Renal function (serum creatinine, BUN) and hydration status before treatment and prior to each dose
- Serum calcium (ionized preferred), phosphate, magnesium, and potassium
- CBC (baseline and continued if ongoing treatment)
- Urinalysis
過量
Overdosage of pamidronate may cause profound **hypocalcemia**, which can manifest clinically as muscle tremors, facial rubbing, seizures, or **tetany**. * **Treatment**: Should severe hypocalcemia occur, treat immediately with short-term, intravenous calcium supplementation (e.g., calcium gluconate) while monitoring the ECG.
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