| 简介：
部份中文米力农处方资料（仅供参考）
商品名：Milrila K
英文名：Milrinone
中文名：米力农注射剂
剂 型：注射剂
生产商：安斯泰来
ミルリーラK注射液22.5mg
药用类别名称
急性心力衰竭治疗剂
批准日期：1998年6月
商標名
Milrila K Injection 22.5mg
一般名
ミルリノン（Milrinone）
化学名
1,6-Dihydro-2-methyl-6-oxo[3,4'-bipyridine]-5-carbonitrile
構造式
分子式
C12H9N3O
分子量
211.22
性状
米力农是一种结晶性粉末, 微带为淡黄色, 白色至细黄色。易溶于甲酸、醋酸(100) 或N, 几乎不溶于n-二甲基甲酰胺, 几乎不溶于甲醇或乙醇(95), 非常溶于水, 几乎不溶于二乙醚。 它融化成0.1moll盐酸检测溶液。
药用药理学
1. 药理作用
(1) 心脏作用
1) 在切除的豚鼠肌和右心房标本, 但增强了浓度依赖性的产生张力 , 增加了对节拍数量的影响较弱。 提高张力增强效果比安林内强10至30倍左右。
2) 在麻醉犬和非麻醉犬, 允许增强剂量依赖性肌肉收缩力, 低血压作用和心率增加效果较弱。心肌收缩力增强效果比安林尼强10~30倍。
(2) 对心脏和血管系统的影响
1) 在麻醉犬, 剂量依赖性Max.dpation, 以及增加心脏输出量和一个节拍体积, 降低肺动脉楔形压力, 以降低总周围血管阻力。
2在切除的兔主动脉标本和切除的犬隐静脉标本中, 血管由KCl收缩, 去甲肾上腺素被允许放松与浓度有关。 血管舒张效应是安利酮的5至6倍。
3) 麻醉犬颈总动脉、椎动脉、冠状动脉、肠系膜动脉和股动脉的血管阻力降低。
(3) 对实验性心力衰竭的影响
1) 在麻醉犬心力衰竭模型中, 用普萘洛尔诱导, 降低左心室舒张压和总外周血管阻力, 增加 Max.dpw 和心输出量, 改善急性心力衰竭状态。
2) Max.dpjdt, 心脏输出量在急性心力衰竭模型中通过麻醉犬冠状动脉结扎, 左心室舒张压, 以及增加心跳量和冠脉窦血流, 以降低总外周血管阻力和冠状动脉阻力, 改善急性心力衰竭状态。
3) 在无麻醉犬的起发心力衰竭模型中, 最大++Dp/dt, 以及增加Max.-dpet和心脏输出量, 以降低左心室舒张压降低和总外周血管阻力, 改善了心力衰竭状态。此时, 在不影响血浆儿茶酚胺浓度的情况下, 也没有诱发心律失常。
(4) 对心肌代谢的影响
1) 在麻醉犬中, 在不增加心肌耗氧量的情况下表达心肌作用。
2) 在急性心力衰竭模型中, 麻醉犬冠状动脉结扎, 在不进一步降低乳酸摄入量的情况下降低缺血, 也不会加重心肌缺血。
(5) 电生理对心脏刺激传导系统的影响
1) 在切除犬Purkinje纤维标本中, 静止膜电位、作用势的振幅、0相的最大上升速率、传导时间、四相梯度、作用电位持续时间, 不影响难治期和兴奋期。
2) 在麻醉犬中, 它不影响第二诱导心电图。加重了麻醉犬肾上腺素诱导的心律失常, 但对冠状动脉结扎和乌阿布所致心律失常没有影响。
2. 作用机制
通过选择性抑制磷酸二酯酶III, 选择性地增加细胞内循环AMP量, 表达心肌收缩力增强作用和血管舒张作用。
3. 一般药理学
中枢神经系统、呼吸和心血管系统、自主神经系统、消化系统以及对泌尿生殖系统特别有问题的影响没有显示出来。
适应症
当效果不足时, 即使在以下状态下服用其他药物
急性心力衰竭
用法与用量
该制剂每体重超过50微克, 注射10分钟, 继续静脉注射0.5μkg/分/分钟。
另外, 根据临床症状, 患者的静脉注射剂量可以适当增加或减少在0.25~0.75μkg的范围内每分钟。另外, 根据患者的病情, 可能会从静脉给药开始。
临床结果
对日本急性心力衰竭患者进行的双盲试验和一般临床试验中, 72例(93.1%) 的67例进行了改进或改善。
包装
注射液22.5mg/150mL：5袋
制造和销售
安斯泰来制药有限公司
注：以上中文不够完整，使用者以原处方资料为准。
完整说明附件：http://www.info.pmda.go.jp/go/pack/2119408G1027_1_15/
Milrila K Injection 22.5mg（Milrinone,米力农 K,ミルリーラK注射液）
Name of drug classification
Acute heart failure treatment
Sales name
Milrila K injection solution 22.5 mg
Molecular formula
C12 H9 N3 O
Molecular weight
211.22
Property
Milrinone is a fine-grain yellow-white to slightly yellow crystalline powder. It is easily soluble in formic acid, slightly soluble in acetic acid (100) or N, N - dimethylformamide, hardly soluble in methanol or ethanol (95), very insoluble in water and hardly soluble in diethyl ether. It dissolves in 0.1 mol / L hydrochloric acid reagent solution.
composition
Active ingredient (in 1 bag of 150 mL)
Milrinone 22.5 mg
Additives (in 1 bag of 150 mL)
7.43 g of glucose, L-lactic acid, pH regulator
Contraindication
Patient with hypertrophic obstructive cardiomyopathy [possibility of outflow tract obstruction]
Patients with a history of hypersensitivity to the ingredients of this drug
Indication or effect
When the effect is insufficient even if another drug is administered under the following conditions
Acute heart failure
This drug is intravenously administered as milrinone intravenously over 10 minutes in an amount of 50 μg per kg body weight, followed by intravenous drip infusion at 0.5 μg / kg per minute.
The intravenous drip dose can be appropriately increased or decreased in the range of 0.25 to 0.75 μg / kg per minute depending on the patient's hemodynamics and clinical symptoms. Depending on the condition of the patient, it may be started by intravenous drip infusion.
If the clinical symptoms improve with the administration of this drug, and the patient's condition is stable (in case of getting out of the acute phase), change to other treatment method without being ordered. The administration period varies according to the patient's reactivity, but if it becomes necessary to administer for more than 48 hours, careful administration should be administered while adequately controlling the hemodynamics and general condition. The total daily dose should not exceed 1.13 mg / kg (equivalent to 24 hours administered at the upper limit of the approved dose).
This drug is a drug of renal excretion type, and patients with reduced renal function (chronic renal failure, diabetic nephropathy, elderly people
Patient with severe tachyarrhythmia [Arrhythmia may get worse]
Patients with impaired renal function [This product is a renal excretory type drug, plasma concentrations may be high in patients with decreased renal function. (See <Notes on usage related to usage and dose>)]
Patient with markedly low blood pressure [There is a risk that blood pressure may further decrease]
Elderly (see "Administration to the elderly" section)
Patient with serum potassium decline [If correction is difficult, serious arrhythmia may occur. ]
Serious side effects
Ventricular tachycardia (including Torsades de Pointes), ventricular fibrillation, hypotension (less than 0.1 to 5% each)
Ventricular tachycardia (including Torsades de Pointes), ventricular fibrillation, and blood pressure reduction may occur, so observe thoroughly and if these are observed, take appropriate measures such as weight loss or discontinuation.
Renal function deterioration (less than 0.1 to 5%)
Since patients with impaired renal function (chronic renal failure, diabetic nephropathy, elderly, etc.) may cause deterioration of renal function, observation should be done sufficiently, in such cases administration Canceling.
Medicinal pharmacology
Pharmacological action
Cardiac action
In the isolated guinea pig papillary muscle and right atrial specimen, the generated tension was increased in a concentration-dependent manner, but the increasing effect on the pulsation number was weak. The generated tension enhancing action was about 10 to 30 times stronger than that of amrinone.
In anesthetized dogs and anesthetized dogs, myocardial contractility was enhanced in a dose-dependent manner, but blood pressure lowering action and heart rate increasing activity were weak. The myocardial contractile potentiating action was about 10 to 30 times stronger than that of amrinone.
Action on the cardiovascular system
In anesthetized dogs, pulmonary artery wedge pressure was decreased and total peripheral vascular resistance was decreased, while max.dp / dt, cardiac output and stroke volume were increased in a dose-dependent manner.
Blood vessels contracted by KCl and noradrenaline were relaxed in a concentration-dependent manner in isolated rabbit aorta specimens and excised canine saphenous vein specimens. The vasodilating effect was 5 to 6 times stronger than that of amrinone.
In anesthetized dogs, the vascular resistance of the common carotid artery, vertebral artery, coronary artery, mesenteric artery and femoral artery was decreased.
Action on experimental heart failure
In anesthetized dog heart failure model induced by propranolol, max.dp / dt and cardiac output were increased and left ventricular end diastolic pressure and total peripheral vascular resistance were decreased to improve acute heart failure condition.
Increased max.dp/dt, cardiac output, stroke volume and coronary sinus blood flow rate in the acute heart failure model of coronary artery ligation of anesthetized dogs as well as left ventricular end diastolic pressure, total peripheral vascular resistance and coronary vascular resistance , And improved the acute heart failure condition.
Increased max. + Dp/dt, max.-dp/dt and cardiac output, decreased left ventricular end diastolic pressure and decreased total peripheral vascular resistance in a pacing-induced heart failure model of anesthetized dogs, I improved the condition. At this time, it did not affect plasma catecholamine concentration and did not induce arrhythmia.
Work against myocardial metabolism
In anesthetized dogs, cardiotonic action was developed without almost increasing myocardial oxygen consumption.
In an acute heart failure model with coronary artery ligation of anesthetized dogs, it did not further decrease lactate intake declined by ischemia and did not exacerbate myocardial ischemia.
Electrophysiological action on cardiac stimulation conduction system
In the excised canine Purkinje fiber specimens, there were no effects on resting membrane potential, amplitude of action potential, maximum rising rate of 0 phase, conduction time, gradient of 4 phases, duration of action potential, refractory period and excitability.
In the anesthetized dog, it did not influence the II lead ECG. It exacerbated adrenaline-induced arrhythmia in anesthetized dogs, but had no effect on coronary artery ligation and ouabain induced arrhythmia.
Mechanism of action
It is considered that selective inhibition of phosphodiesterase III selectively increases the intracellular cyclic AMP level, and exerts a myocardial contractility enhancing action and a vasodilating action.
General pharmacology
It did not show any particular problematic effects on central nervous system, respiratory / cardiovascular system, autonomic nervous system, gastrointestinal system and urogenital/reproductive system. |
