多潘立酮
多潘立酮是一種周邊作用的**多巴胺-2 (D2) 受體拮抗劑**，主要用作促進胃腸動力藥、止吐藥以及催乳劑。 主要臨床應用包括： - **馬**：預防和治療圍產期母馬的高狐茅中毒（fescue toxicosis）、刺激泌乳（無乳症），以及作為馬垂體中葉功能障礙（PPID / 馬庫興氏症）的診斷劑。 - **小動物**：標示外使用於促進胃腸動力和止吐，特別適用於胃排空延遲的疾病。 **臨床要點**：與甲氧氯普胺（metoclopramide）不同，多潘立酮不易穿過血腦屏障。這顯著降低了中樞神經系統（CNS）副作用（如錐體外症候群引起的震顫、抽搐）的風險，使其成為對中樞作用促動力藥敏感的病患的理想替代品。
作用機制: Domperidone exerts its effects through multiple pathways: - **Dopamine-2 (D2) Receptor Antagonism** in the GI tract → enhances gastric motility and accelerates gastric emptying (prokinetic effect). - **D2 Receptor Antagonism** in the **Chemoreceptor Trigger Zone (CRTZ)** → blocks emetic signaling (antiemetic effect). Because the CRTZ lacks a complete blood-brain barrier, domperidone can act here without entering the deeper CNS. - **Alpha-2 and Beta-2 Adrenergic Receptor Antagonism** → provides additional modulatory effects on stomach motility. - **Pituitary Gland Disinhibition** → Dopamine normally inhibits prolactin release. By blocking dopamine receptors, domperidone → increases **prolactin** secretion → stimulates milk production (galactagogue effect). This directly counteracts the dopamine-mimetic alkaloids found in toxic tall fescue.
各物種劑量
- As a prokinetic agent · 0.05-0.1 mg/kg PO once or twice a day · PO · q12-24h · Scant clinical experience; suggested dose based upon experimental data.
- Antiemetic / Prokinetic · 0.1 - 0.5 mg/kg · PO · q8h-q12h · As needed · Administer 15-30 minutes before feeding.
- For fescue toxicity · 1.1 mg/kg PO once daily starting 10 to 15 days prior to Expected Foaling Date (EFD) · PO · q24h · Up to 5 days after foaling if inadequate milk · Treatment may be continued for up to 5 days after foaling if mares are not producing adequate milk.
- As a prokinetic agent · 0.05-0.1 mg/kg PO once or twice a day · PO · q12-24h · Scant clinical experience; suggested dose based upon experimental data.
- For vomiting due to gastritis · 2-5 mg (total dose) PO two to three times a day · PO · q8-12h
- Antiemetic / Prokinetic · 0.1 - 0.5 mg/kg · PO · q8h-q12h · As needed · Administer 15-30 minutes before feeding.
- Leishmaniasis (Treatment and Prevention) · 0.5 mg/kg · PO · sid · 28 days · For prevention, the 28-day course can be repeated every 3-4 months depending on infection risk.
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
- Known hypersensitivity to domperidone
- Presence or suspicion of gastrointestinal obstruction, perforation, or hemorrhage
- Pregnant mares >15 days prior to expected foaling date (unless specifically managed)
- Horses intended for human consumption
- Gastrointestinal hemorrhage
- Mechanical GI obstruction or perforation
- Prolactin-secreting pituitary tumors (prolactinomas)
- Known hypersensitivity to the drug
不良反應
- Galactorrhea (inappropriate milk production)
- Gynecomastia
- Premature lactation in horses (dripping milk prior to foaling)
- Failure of passive transfer in foals
- Rarely: somnolence or dystonic reactions
- Arrhythmias (associated with withdrawn injectable human products, especially with hypokalemia or heart disease)
- Galactorrhea (milk production in females)
- Mammary gland hyperplasia
- Changes in estrus cycle
- Mild gastrointestinal upset
藥物相互作用
- Azole Antifungals (e.g., ketoconazole) · May increase domperidone levels due to metabolic inhibition.
- Anticholinergic Drugs · May reduce the gastrointestinal prokinetic efficacy of domperidone.
- Bromocriptine / Cabergoline · Domperidone may antagonize their dopamine-agonist effects on prolactin.
- Macrolide Antibiotics (e.g., erythromycin, clarithromycin) · May increase domperidone levels.
- Opioids · May reduce the gastrointestinal prokinetic efficacy of domperidone. · moderate
- Sustained-Release or Enteric-Coated Oral Medications · Domperidone may alter the absorptive characteristics of these drugs by decreasing GI transit times.
- Antacids · May decrease the oral absorption of domperidone · minor
- H2-receptor antagonists (e.g., famotidine) · May decrease the oral absorption of domperidone due to altered gastric pH · minor
- Ketoconazole · Inhibits CYP3A4 metabolism of domperidone, potentially increasing plasma concentrations and risk of QT prolongation · major
- Erythromycin · Inhibits CYP3A4 metabolism of domperidone, increasing plasma concentrations. · major
- Anticholinergics (e.g., Atropine) · May antagonize the gastrokinetic effects of domperidone. · moderate
- Antacids and H2 Blockers (e.g., Famotidine, Omeprazole) · Increase gastric pH, which may decrease the oral absorption of domperidone. Administer at least 2 hours apart. · moderate
監測
- Clinical efficacy (resolution of vomiting, improved gastric emptying, or adequate milk production)
- Serum IgG concentrations in foals born to treated mares
- Serum prolactin levels (if indicated)
- Resolution of nausea and vomiting
- Improvement in clinical signs of Leishmaniasis (if used for this indication)
- Signs of galactorrhea, mammary enlargement, or false pregnancy in females
過量
There is no specific antidote for a domperidone overdose. - Employ standard gastrointestinal decontamination procedures if ingestion is recent and the patient is asymptomatic. - Provide supportive and symptomatic care as needed. Monitor for potential neurological signs (especially in MDR1-mutant dogs) or gastrointestinal upset.
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。