西地那非
西地那非是一種強效的 **第5型磷酸二酯酶 (PDE5) 抑制劑**。雖然在人類醫學中主要用於治療勃起功能障礙，但在獸醫藥理學中，它是治療 **肺動脈高壓 (Pulmonary Hypertension, PH)** 的基石藥物。 * **臨床要點**：對於因慢性二尖瓣疾病、心絲蟲病或原發性肺部疾病（如肺纖維化）引起肺動脈高壓的犬貓特別有效。 * 透過選擇性擴張肺動脈血管床，它能顯著降低右心室後負荷，進而改善暈厥、運動不耐及右側充血性心衰竭等臨床症狀。 * 它對肺部血管具有高度專一性，這意味著除非與其他血管擴張劑併用，否則通常不會引起嚴重的全身性低血壓。
作用機制: Sildenafil exerts its effects via the **nitric oxide (NO) pathway** in smooth muscle cells: * Endothelial cells release **Nitric Oxide (NO)** → activates the enzyme **guanylate cyclase** → converts GTP to **cyclic guanosine monophosphate (cGMP)**. * **cGMP** acts as a secondary messenger causing smooth muscle relaxation and vasodilation. * **PDE5** is the enzyme responsible for degrading cGMP, and it is found in high concentrations in the pulmonary vasculature and corpus cavernosum. * **Mechanism**: Sildenafil competitively inhibits **PDE5** → prevents cGMP breakdown → intracellular cGMP accumulates → resulting in prolonged and enhanced **NO-mediated pulmonary vasodilation**.
各物種劑量
- Moderate to severe PH secondary to either left heart disease or primary lung disease · 1 mg/kg · PO · q8h
- Pulmonary arterial hypertension · 1.6 mg/kg · PO · q12h · Reported dose tolerated and clinically efficacious.
- Pulmonary hypertension · 1.9 mg/kg (range from 0.5-2.7 mg/kg) · PO · q8-24h · Median dose from a retrospective study. Dogs may have been also treated with oxygen, ACE inhibitors, furosemide, amlodipine, diltiazem, theophylline, phenobarbital and/or antibiotics.
- Pulmonary hypertension documented by Doppler, chronic pulmonary disease, right-sided heart failure (HW disease; congenital) · 0.5-1 mg/kg (higher dose of 2 -3 mg/kg three times a day may be tolerated and needed) · PO · two times daily
- Moderate to severe PH secondary to either left heart disease or primary lung disease · 1 mg/kg · PO · q8h
- Pulmonary hypertension · 1-2 mg/kg · PO · three times daily
- Pulmonary arterial hypertension · 0.5-2.7 mg/kg (suggested median dose from clinical studies is 3 mg/kg/day) · PO · q8-24h · Improves quality of life despite lack of significant echocardiographic reduction in pressures.
劑量為合格獸醫專業人員的臨床參考。請務必對照最新藥品仿單及個別病患確認。
給藥途徑
禁忌症
- Concurrent use with organic nitrates
- Known hypersensitivity to sildenafil
- Pulmonary veno-occlusive disease (PVOD)
- Systemic hypotension
- Significant hepatic impairment
- Significant renal impairment
- Bleeding disorders
- Concurrent use of nitrates
不良反應
- Cutaneous flushing of the inguinal region
- Gastrointestinal effects (possible)
- Headache, visual disturbances, dyspepsia, nasal congestion, myalgia, priapism, dizziness, and back pain (reported in humans)
- Vomiting
- Dizziness / weakness
- Raised intraocular pressure
- Systemic hypotension (especially if combined with other vasodilators)
藥物相互作用
- Alpha-adrenergic blockers (e.g., phentolamine, phenothiazines, phenoxybenzamine) · May increase hypotensive effects
- Amlodipine · Potential to increase hypotensive effects
- Antihypertensive, hypotensive drugs · Potentially could increase hypotensive effects
- Azole antifungals (ketoconazole, itraconazole) · May reduce sildenafil metabolism and increase AUC
- Cimetidine · May reduce sildenafil metabolism and increase AUC · moderate
- Erythromycin, Clarithromycin · May reduce sildenafil metabolism and increase AUC
- Heparin · May increase bleeding risks
- Nitrates (e.g., NTG, Isosorbide) · Significant potentiation of vasodilatory effects; life-threatening hypotension possible
- Nitroprusside sodium · Significant potentiation of vasodilatory effects; life-threatening hypotension possible
- Phenobarbital · May decrease sildenafil concentrations · moderate
- Rifampin · May decrease sildenafil concentrations
- Erythromycin · Increases plasma sildenafil concentration · moderate
- Itraconazole · Increases plasma sildenafil concentration · moderate
監測
- Clinical efficacy (improved syncope, cough, respiratory effort)
- Pulmonary artery pressure
- Systemic blood pressure
- Adverse effects
- Clinical signs of pulmonary hypertension (exercise tolerance, syncope, respiratory rate/effort)
- Echocardiography (to monitor right heart function and pulmonary pressures)
- Intraocular pressure (if pre-existing ocular disease)
過量
Little information is available in veterinary species. In humans, massive overdose (2000 mg) resulted in tachycardia, nonspecific ST-T changes on ECG, headache, dizziness, and flushing. It is expected that overdoses in animals would mirror the drug's adverse effect profile (e.g., profound hypotension, tachycardia, cutaneous flushing). **Treat supportively.**
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。