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分类名称
一级分类：循环系统药物 二级分类：心血管扩张药物 三级分类：钙拮抗剂
药品英文名
Nisoldipine
药品别名
硝苯异丙啶、易立、尼索的平、BayK-5552、Baymycard、Nisoldipinum、Syscor、3,5-Pyridinedicarboxylicacid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, methyl(2-methyl)-propyl diester
药物剂型
片剂：5mg。
药理作用
本品是第二代二氢吡啶类钙通道阻滞药，结构类似硝苯地平，具有高度的血管平滑肌选择性。血管选择性增高与其亲脂性增加有关，亲脂性增加则易于进入血管壁，也更易于阻滞电压依赖型钙离子通道。与其他钙离子通道阻滞药相似，本药通过阻滞细胞膜的电压依赖型钙通道而抑制钙离子内流，从而导致血管平滑肌舒张，肌肉收缩力下降及负性变时作用。
研究证明，本药扩张周围血管的作用至少是硝苯地平的10倍。另外，扩张冠状动脉作用更强、选择性更高。本药对无活性的钙离子通道的亲和力比硝苯地平高，分离速度更慢，分配系数更大，因而作用时间比硝苯地平更长。当本药引起周围血管和冠状血管明显扩张时，对电生理的影响甚微。
研究显示，本药对房室结和窦房结功能正常的心血管疾病患者的传导时间和不应期无明显影响。静脉给药不影响房室传导阻滞患者房室结的传导功能。用药后引起周围血管扩张可导致反射性交感神经兴奋，心脏输出量和心脏指数明显增加。本药主要引起后负荷下降，也可引起患者左室舒张末压和肺毛细血管楔压(前负荷)间接下降。每搏量和射血分数增加可改善左心功能。服药后所致的反射性心率增加，在休息时比运动时更明显，长期给药时未观察到心动过速。研究发现，缺血性心脏病致左心室功能障碍的患者静脉用本药对心肌收缩力的负性影响，低于静脉应用等效剂量的硝苯地平，原因主要是因为本药的血管特异性更高。有研究表明，本药产生的急性血流动力学作用对左心室功能障碍的患者有益。本药可明显扩张心血管疾病患者的冠状动脉，降低冠状血管阻力，但不改变心肌氧耗。中-重度充血性心力衰竭患者静脉滴注或推注本药可明显降低平均动脉压、全身血管阻力，增加心脏指数，而心率改变不明显。另外，本药还可促进尿钠排泄，长期用药一般可以代偿。对醛固酮和肾素血浆水平可能有影响，但长期用药的影响很小。
药动学
口服速释剂治疗心绞痛的最大效应时间为3h，治疗高血压为1～3h。降压效应与血药浓度有关。达峰时间为1～1.5h。治疗心绞痛时，给药一次持续时间为7～8h，治疗高血压为6～8h，多次给药治疗高血压时持续时间为12h。缓释剂的达峰时间为6～12h，多次给药治疗高血压的持续时间为24h。口服几乎完全吸收，缓释剂的生物利用度为4%～8%。食物可减慢本药的吸收，但不影响吸收量。高脂饮食可改变某些包衣剂型的释放特性，使在近端小肠的释放增加，总吸收量降低，因此本药包衣片应在餐前1h或餐后2h服用。蛋白结合率为99%。静脉给药的分布容积为4～5L/kg，口服为2.3～7.1L/kg。在肝脏广泛代谢，肠壁也参与了首过代谢，近端小肠代谢率高，远端小肠代谢率低。本药已发现了18种代谢产物，尚不清楚这些代谢产物是否具有药理活性。肾脏排泄70%～75%。尿液中排出的是代谢产物，几乎没有原药。是否分泌入乳汁尚不清楚。10%～15%原形和代谢产物由粪便排出体外。母药清除半衰期为7～12h，个体差异较大。血液透析不能清除本药。
适应证
用于心绞痛和冠状粥样硬化性心脏病(冠心病)，尤为适用于合并高血压和(或)充血性心力衰竭的患者。
禁忌证
孕妇、哺乳期妇女、心源性休克者及过敏者。
注意事项
1.慎用：
(1)主动脉狭窄。
(2)低血压。
(3)充血性心力衰竭，特别是与β受体阻滞药同时使用时。
(4)胃肠高动力状态或胃肠道梗阻时，慎用缓释剂。
(5)肝功能损害。
2.个别患者在治疗开始或合并饮酒时，可能影响驾驶或操纵机器的能力。
3.可与食物同服以减轻胃肠道不良反应，但在服用糖衣片时应避免高脂饮食。因葡萄柚汁中的黄酮类物质可干扰本药代谢，高血压或稳定性心绞痛患者服普通片前2h到服后3h内不要服用葡萄柚汁，服缓释片前2h到服后5h内不要服用。
4.冠状动脉疾病患者，停药应逐渐进行，以避免发生心肌缺血。
5.钙通道阻滞药对β-受体阻滞药的撤药反应无保护作用。
6.一旦皮肤反应持续或发展为多形性红斑或剥脱性皮炎，应立即停药。
不良反应
偶见少数患者有面部潮红、发热、心悸、头晕、头痛、步履蹒跚、疲倦、腹痛、口干、发汗、畏食和心动过速；丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、尿素氮(BUN)和肌酐值上升，红细胞、血红蛋白、血细胞比容值下降。突然停药可能导致不稳定型心绞痛。
用法用量
口服：每次5～10mg，每天2～3次。与地高辛合用中增加后者的浓度，因此地高辛应减量使用。
药物相应作用
1.与胺碘酮合用可进一步抑制窦性心律或加重房室传导阻滞，因此病窦综合征患者或不完全房室传导阻滞的患者应避免两药同用。
2.虽然与β-受体阻滞药合用对心绞痛或高血压治疗有效，但也可能导致严重低血压或心脏储备下降。在左室功能受损、心律失常或主动脉狭窄的患者更明显。如需合用，应仔细监测心脏功能，特别是对有潜在心衰的患者。
3.在芬太尼麻醉时，合用钙通道阻滞药和β受体阻滞药可导致严重低血压。
4.与咪贝地尔合用可引起严重低血压和心动过缓。在开始使用本药前，咪贝地尔应停用7天。
5.细胞色素P4503A4酶抑制药如地拉费定、奎奴普汀/达福普汀、沙奎那韦、酮康唑等，可抑制本药经细胞色素P4503A4的代谢，使血药浓度升高，毒性增强。如合用，应减小本药的剂量。
6.西咪替丁可干扰许多钙通道阻滞药的肝脏代谢，并可减少胃酸分泌，增加钙通道阻滞药的生物利用度，结果引起钙通道阻滞药血药浓度升高，曲线下面积增大，毒性增强。而雷尼替丁可减小本药的曲线下面积，降低本药疗效。
7.与非甾体抗炎药或口服抗凝剂合用，有增加胃肠出血的可能。
8.奎尼丁可降低本药的生物利用度，同时奎尼丁的毒性增加。如果合用，应监测奎尼丁的血浆浓度，或换用其他钙通道阻滞药。
9.本药可抑制地高辛的肾脏或肾外清除，使地高辛血药浓度升高达50%，毒性增强。
10.苯妥英钠可诱导本药的首过代谢，降低血浆浓度，个体差异较大，因此，使用苯妥英钠的患者应选择其他心血管药物。磷苯妥英钠是苯妥英钠的前体药物，与本药的相互作用与苯妥英钠相似。
11.利福平可诱导一些钙通道阻滞药的代谢，使钙通道阻滞药的疗效下降，如合用可能要增大本药的用量。
12.麻黄含有麻黄碱和伪麻黄碱，可降低抗高血压药疗效。使用本药治疗的高血压患者应避免使用含麻黄制剂。
13.食物可减慢本药的吸收，但不改变吸收总量。高脂饮食可影响某些包衣片的释放特性。
14.葡萄柚汁中的黄酮类物质可抑制本药代谢，引起本药血药浓度升高，毒性增强。橙汁与葡萄柚汁的营养成分相似，但不发生相互作用，因此推荐患者用橙汁代替柚汁。
专家点评
本品为二氢吡啶类钙离子阻滞剂。对冠状动脉有较高的选择性，并有扩张作用，同时亦可扩张周围血管，使外周血管阻力下降、血压降低，其作用也较硝苯地平强而持久。能改善糖代谢，使糖耐量保持稳定水平。
Baymycard - General Information:
A dihydropyridine calcium channel antagonist that acts as apotent arterial vasodilator and antihypertensive agent.
It is also effective in patients with cardiac failure and angina.
Pharmacology: Baymycard, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Baymycard is similar to other peripheral vasodilators.
Baymycard inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic
reticulum.
The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Baymycard for patients
SULAR is an extended release tablet and should be swallowed whole. Tablets should not be chewed, divided or crushed. SULAR should not be administered with a high fat meal. Grapefruit juice, which has been shown to increase significantly the bioavailability of nisoldipine and other dihydropyridine type calcium channel blockers, should not be taken with SULAR.
Baymycard Interactions
A 30 to 45% increase in AUC and Cmax of nisoldipine was observed with concomitant administration of cimetidine 400 mg twice daily. Ranitidine 150 mg twice daily did not interact significantly with nisoldipine (AUC was decreased by 15-20 %).
No pharmacodynamic effects of either histamine H2 receptor antagonist were observed.
Coadministration of phenytoin with 40 mg SULAR tablets in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Coadministration of SULAR with phenytoin or any known CYP3A4 inducer should be avoided and alternative antihypertensive therapy should be considered. Pharmacokinetic interactions between nisoldipine and beta-blockers (atenolol, propranolol) were variable and not significant. Propranolol attenuatednisoldipine. The blood pressure effect of SULAR tended to be greater in patients on atenolol than in patients on no other antihypertensive therapy. Quinidine at 648 mg bid decreased the bioavailability (AUC) of nisoldipine by 26%, but not the peak concentration. The immediate release, but not the coat-core formulation of nisoldipine increased plasma quinidine concentrations by about 20%. This interaction was not accompanied by ECG changes and its clinical significance is not known. No significant interactions were found between nisoldipine and warfarin or digoxin.
Baymycard Contraindications
SULAR is contraindicated in patients with known hypersensitivity to dihydropyridine calcium channel blockers.
Additional information about BaymycardBaymycard Indication: For the treatment of hypertension.
It may be used alone or in combination with other antihypertensive agents.
Mechanism Of Action: By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Baymycard inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.
Drug Interactions: Not Available
Food Interactions: Do not take with grapefruit juice as this has been shown to interfere with nisoldipine metabolism, resulting in a mean increase in Cmax of about 3-fold (up to
about 7-fold) and AUC of almost 2-fold (up to 5-fold).
Generic Name: Nisoldipine
Synonyms: Nisoldipinum [Inn-Latin]; Nisoldipino [Inn-Spanish]; NisoldipinDrug Category: Vasodilator Agents; Antihypertensive AgentsDrug Type: Small Molecule; ApprovedOther Brand Names containing Nisoldipine: Baymycard; Nisocor; Sular; Syscor; Zadipina; Absorption: Relatively well absorbed into the systemic circulation with 87% of the radiolabeled drug recovered in urine and feces. The absolute bioavailability of nisoldipine is about 5%.
Toxicity (Overdose): Not Available
Protein Binding: 99%Biotransformation: Pre-systemic metabolism in the gut wall, and this metabolism decreases from the proximal to the distal parts of the intestine. Nisoldipine is highly metabolized; 5 major urinary metabolites have been identified.
The major biotransformation pathway appears to be the hydroxylation of the isobutyl ester. A hydroxylated derivative of the side chain, present in plasma at concentrations approximately equal to the parent compound, appears to be the only active metabolite and has about 10% of the activity of the parent compound. Cytochrome P450 enzymes are believed to play a major
role in the metabolism of nisoldipine.
The particular isoenzyme system responsible for its metabolism has not been identified, but other dihydropyridines are metabolized by cytochrome P450 IIIA4.
Half Life: 7-12 hoursDosage Forms of Baymycard: Tablet, coated OralChemical IUPAC Name: O5-methyl O3-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylateChemical Formula: C20H24N2O6Organisms Affected: Humans and other mammals
附件:
20123717343630.PDF
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产地国家: 日本
原产地英文商品名:
BAYMYCARD(バイミカード) 5mg/tab 100tabs/box
原产地英文药品名:
NISOLDIPINE
原产地英文化合物名称:
3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, methyl (2-methyl)-propyl diester
中文参考商品译名:
BAYMYCARD(バイミカード) 5毫克/片 100片/盒
中文参考药品译名:
尼索地平
生产厂家中文参考译名:
拜尔
生产厂家英文名:
bayer
完整处方资料完附件：http://www.info.pmda.go.jp/go/pack/2171019F1027_2_11/ |
