シルデナフィル
シルデナフィルは強力な**ホスホジエステラーゼ5型（PDE5）阻害薬**です。人医療では主に勃起不全の治療薬として知られていますが、獣医薬理学においては**肺高血圧症（PH）**治療の要となる薬剤です。 * **臨床のポイント**: 慢性僧帽弁疾患、犬糸状虫症（フィラリア症）、または原発性肺疾患（肺線維症など）に続発する肺高血圧症の犬猫に対して特に有効です。 * 肺動脈血管床を選択的に拡張することで、右室後負荷を著しく軽減し、失神、運動不耐性、右心不全などの臨床症状を改善します。 * 肺血管に対する特異性が高いため、他の血管拡張薬と併用しない限り、通常は重篤な全身性低血圧を引き起こすことはありません。
作用機序: 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**.
動物種別の用量
- 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.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- 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
有害事象
- 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)
薬物相互作用
- 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
モニタリング
- 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)
過量投与
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 の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。