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(S)-(5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl)-(6-methoxyquinolin-4-yl)methanol;sulfuric acid | 50-54-4

中文名称
——
中文别名
——
英文名称
(S)-(5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl)-(6-methoxyquinolin-4-yl)methanol;sulfuric acid
英文别名
——
(S)-(5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl)-(6-methoxyquinolin-4-yl)methanol;sulfuric acid化学式
CAS
50-54-4
化学式
C40H50N4O8S
mdl
——
分子量
746.9
InChiKey
RONWGALEIBILOG-KHRUQITBSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    212°C
  • 颜色/状态:
    Occurs as fine, needle-like, white crystals which frequently cohere in masses or as a fine, white powder.
  • 味道:
    Very bitter taste
  • 溶解度:
    WHITE; VERY BITTER; ODORLESS; FINE CRYSTALS; FREQUENTLY COHERING IN MASSES; PH (1% AQUEOUS SOLN): 6.0-6.8 PKA: 4.2, 8.8; SPECIFIC OPTICAL ROTATION: +212 @ 25 °C/D (95% ALCOHOL); ABOUT + 260 @ 25 °C/D (DILUTE HYDROCHLORIC ACID); DOES NOT LOSE ALL OF ITS WATER BELOW 120 °C 1 G DISSOLVES IN ABOUT 90 ML WATER, 15 ML BOILING WATER, 10 ML ALCOHOL, 3 ML METHANOL, 12 ML CHLOROFORM; INSOL IN ETHER, BENZENE; /DIHYDRATE/
  • 稳定性/保质期:
    Quinidine gluconate, quinidine polygalacturonate, and quinidine sulfate darken on exposure to light and should be stored in well closed, light-resistant containers. Solutions of quinidine salts slowly acquire a brownish tint on exposure to light. Only colorless, clear solutions of quinidine gluconate injection should be used. Quinidine gluconate injection should be stored at 15-30 °C. When diluted to a concentration of 16 mg/ml with 5% dextrose injection, quinidine gluconate injection is stable for 24 hr at room temperature and up to 48 hr when refrigerated. /Quindine salts/
  • 旋光度:
    Specific optical rotation: + 212 deg at 25 °C/D (alcohol); prisms; needles from water. /d-quinidine sulfate/
  • 分解:
    When heated to decomposition it emits very toxic fumes of /nitrogen oxides and sulfur oxides/.
  • 折光率:
    INDEX OF REFRACTION ALPHA 1.565; BETA 1.607; GAMMA 1.670. OPTIC SIGN +, EXTINCTION PARALLEL, ELONGATION +

计算性质

  • 辛醇/水分配系数(LogP):
    5.69
  • 重原子数:
    53
  • 可旋转键数:
    8
  • 环数:
    9.0
  • sp3杂化的碳原子比例:
    0.45
  • 拓扑面积:
    174
  • 氢给体数:
    4
  • 氢受体数:
    12

ADMET

代谢
奎尼丁在人体内代谢产生2'-羟基奎尼丁。/奎尼丁;来自表格/
QUINIDINE YIELDS 2'-HYDROXYQUINIDINE AS METABOLITE IN MAN. /QUINIDINE; FROM TABLE/
来源:Hazardous Substances Data Bank (HSDB)
代谢
大多数尿液代谢物只在一个位点发生羟基化,要么在喹啉环上,要么在喹诺环上;也可以找到少量二羟基化合物。奎尼丁剂量的代谢部分和代谢途径似乎在患者之间有相当大的差异。
MOST URINARY METABOLITES ARE HYDROXYLATED AT ONLY ONE SITE, EITHER ON THE QUINOLINE RING OR ON THE QUINUCLIDINE RING; SMALL AMOUNTS OF DIHYDROXY COMPOUNDS ARE ALSO FOUND. THE FRACTION OF A DOSE OF QUINIDINE THAT IS METABOLIZED & THE METABOLIC PATHWAY APPEAR TO VARY CONSIDERABLY FROM PATIENT TO PATIENT.
来源:Hazardous Substances Data Bank (HSDB)
代谢
奎尼丁在肝脏中被代谢,主要是通过羟基化反应生成3-羟基奎尼丁和2-喹尼啶酮。这些代谢物可能具有药理活性。大约10-50%的剂量在24小时内以原药形式通过尿液排出(可能是通过肾小球滤过)。/奎尼丁/
Quinidine is metabolized in the liver, principally via hydroxylation to 3-hydroxyquinidine and 2-quinidinone. The metabolites may be pharmacologically active. Approximately 10-50% of a dose is excreted in urine (probably by glomerular filtration) as unchanged drug within 24 hr. /Quinidine/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 毒性总结
鉴定:奎尼丁是一种IA类抗心律失常药物。物质来源:奎尼丁是奎宁的D-异构体。奎尼丁是一种生物碱,可以从多种金鸡纳树皮中提取。金鸡纳树皮含有0.25至3.0%的奎尼丁。奎尼丁也可以从奎宁中制备。奎尼丁是一种无味、苦味的粉末或白色结晶。硫酸奎尼丁是无色结晶,无味且苦。葡萄糖酸奎尼丁是一种无色、无味、苦味的白色粉末。聚半乳糖醛酸奎尼丁是一种粉末。硫酸奎尼丁是一种无味、苦味的白色粉末或结晶。 适应症:描述:室性早搏和室性心动过速;室上性心律失常;心房扑动或心房颤动电复律后维持窦性心律。 人体暴露:主要风险和靶器官:心脏毒性是奎尼丁中毒的主要风险。奎尼丁可能引起中枢神经系统症状。 临床效果摘要:毒性效应通常在摄入后2至4小时内出现,但根据奎尼丁盐类和制剂形式的不同,潜伏期可能会有所变化。症状可能包括心律失常(特别是在有基础心血管疾病的患者中)、神经毒性和呼吸抑制。 诊断:心脏干扰:心脏停搏、休克、传导障碍、室性心律失常、心电图改变、神经系统症状:耳鸣、嗜睡、晕厥、昏迷、抽搐、谵妄。呼吸抑制。奎尼丁浓度对于诊断可能有帮助,但对于临床管理没有用处。 禁忌症:对金鸡纳生物碱过敏或特异反应;房室传导阻滞或完全性心脏阻滞;室内传导缺陷;无房性活动;洋地黄中毒;重症肌无力和尖端扭转型室性心律失常。注意事项包括以下内容:充血性心力衰竭、低血压、肾脏疾病、肝衰竭;同时使用其他抗心律失常药物;老年和哺乳期妇女。 进入途径:口服:口服吸收是中毒最常见的原因。parenteral:静脉注射后中毒很少见,但已在接受静脉注射奎尼丁治疗心律失常的患者中有报道。吸收途径:口服:奎尼丁几乎完全从胃肠道吸收。然而,由于肝脏的首过效应,绝对生物利用度约为摄入剂量的70至80%,并且可能因患者和制剂而异。血浆峰浓度时间为硫酸奎尼丁1至3小时,葡萄糖酸奎尼丁3至6小时,聚半乳糖醛酸奎尼丁约6小时。缓释奎尼丁持续吸收8至12小时。parenteral:肌肉注射后奎尼丁的吸收可能不稳定且不可预测,可能由于药物在注射部位的沉淀导致不完全吸收。 分布途径:口服:蛋白结合:约70至80%的药物与血浆蛋白结合。慢性肝病患者血浆蛋白结合降低。组织:肝脏中奎尼丁浓度是血浆的10至30倍。骨骼和心肌、大脑和其他组织含有中间量。红细胞血浆分配比率为0.82。 生物半衰期:消除半衰期:半衰期约为6至7小时。在慢性肝病患者和老年人中增加。在充血性心力衰竭或肾功能衰竭中似乎没有改变。 代谢:50至90%的奎尼丁在肝脏代谢为羟基化产物。代谢物包括3-羟基奎尼丁、2-氧代奎尼啶酮、0-去甲基奎尼丁、奎尼丁-N-氧化物。主要代谢物是3-羟基奎尼丁,它产生与奎尼丁相似的效应,可能部分负责观察到的抗心律失常效果。羟基奎尼丁的消除动力学似乎与奎尼丁相似。 消除途径:肾脏:尿液中未改变的排出量可变,但约为给药剂量的17%。多达50%的奎尼丁剂量(未改变+代谢物)在给药后24小时内通过尿液排出。肾排泄取决于尿液的pH。排泄与尿液pH成反比。在肾功能不全和充血性心力衰竭中排泄减少。肝脏:50至90%的奎尼丁剂量在肝脏代谢。胆汁:大约1至3%通过胆汁在粪便中排出。乳汁:奎尼丁在乳汁中排出。 作用模式:毒效动力学:奎尼丁减少了心肌对电解质的通透性(膜稳定剂)并且是一种普遍的心脏抑制剂。它具有负性肌力作用;抑制自发舒张去极化;减慢传导;延长有效不应期;并提高电阈值。这导致收缩力下降、传导性受损(房室和室内)和兴奋性降低,但可能存在异常刺激再入机制。奎尼丁具有抗胆碱能效应和周围血管扩张剂特性。在实验研究中观察到以下进展变化:心电图:心动过缓,PR间期延长,QT间期延长,QRS增宽,发展成室性自主心律,
IDENTIFICATION: Quinidine is a class lA antiarrhythmic drug. Origin of the substance: Quinidine is the d- isomer of quinine. Quinidine is an alkaloid that may be derived from various species of Cinchona. Cinchona barks contain 0.25 to 3.0% quinidine. Quinidine is also prepared from quinine. Quinidine is a powder or white crystals, odorless with a bitter taste. Quinidine bisulfate is colorless crystals which is odorless and has a bitter taste. Quinidine gluconate is a white powder which is odorless and has a bitter taste. Quinidine poly-galacturonate is a powder. Quinidine sulfate is a white powder or odorless crystals with a bitter taste. Indications: Description: Premature ventricular extrasystoles and ventricular tachycardia; supraventricular arrhythmia; maintenance of sinus rhythm after cardioversion of atrial flutter or fibrillation. HUMAN EXPOSURE: Main risks and target organs: Cardio-toxicity is the main risk of quinidine poisoning. Quinidine may induce central nervous system symptoms. Summary of clinical effects: Toxic effects appear within 2 - 4 hours after ingestion but the delay may vary according to the quinidine salt and to the preparation forms. Symptoms may include disturbances of cardiac rhythm (especially in patients with underlying cardiovascular disease), neurotoxicity and respiratory depression. Diagnosis: Cardiac disturbances: circulatory arrest, shock, conduction disturbances, ventricular arrhythmias, ECG changes, Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsions, delirium. Respiratory depression. Quinidine concentrations may be helpful in diagnosis but are not useful for clinical management. Contraindications: Allergy or idiosyncrasy to cinchona alkaloids; atrioventricular or complete heart block; intraventricular conduction defects; absence of atrial activity; digitalis intoxication; myasthenia gravis and ventricular dysrhythmia of the torsades de pointes type Precautions include the following: Congestive heart failure, hypotension, renal disease, hepatic failure; concurrent use of other antiarhythmic drugs; old age and breast-feeding. Routes of entry: Oral: Oral absorption is the most frequent cause of intoxication. Parenteral: Intoxication after IV administration is rare but has been reported in patients treated with IV quinidine for cardiac dysrhythmia. Absorption by route of exposure: Oral: Quinidine is almost completely absorbed from the gastrointestinal tract. However, because of hepatic first-pass effect, the absolute bioavailability is about 70 to 80% of the ingested dose and may vary between patients and preparations. The time to plasma peak concentration is 1 to 3 hours for quinidine sulfate, 3 to 6 hours for quinidine gluconate and about 6 hours for quinidine polygalacturonate. Sustained-release quinidine is absorbed continuously over 8 to 12 hours. Parenteral: Absorption of quinidine after intramuscular injection may be erratic and unpredictable with incomplete absorption of the administered dose, probably due to precipitation of drug at the site of injection. Other studies indicate no difference between the rate of quinidine absorption when given by intramuscular injection or oral absorption. Distribution by route of exposure: Oral: Protein binding: About 70 to 80% of the drug is bound to plasma protein. Plasma protein binding is decreased in patients with chronic liver disease. Tissue: Quinidine concentrations in liver are 10 to 30 times higher than those in plasma. Skeletal and cardiac muscle, brain and other tissues contain intermediate amounts. The red cell plasma partition ratio is 0.82. Biological half-life by route of exposure: Elimination half-life: The half-life is about 6 to 7 hours. It is increased in chronic liver disease and in the elderly. It does not appear to be altered in congestive heart failure or renal failure. Metabolism: 50 to 90% of quinidine is metabolized in the liver to hydroxylated products. Metabolites include 3-hydroxyquinidine, 2 oxoquinidinone, 0-desmethylquinidine, quinidine-N-oxide. The principal metabolite is 3 hydroxyquinidine which exerts similar effects to quinidine and may account for part of the observed antiarrhythmic effects. The elimination kinetics of hydroxyquinidine appear to be similar to those of quinidine. Elimination by route of exposure Kidney: The amount excreted unchanged in urine is variable but is about 17% of an administered dose. Up to 50% of a dose of quinidine (unchanged + metabolites) is excreted in urine within 24 hours after administration. Renal excretion is dependent upon the pH of the urine. Excretion varies inversely with urine pH. Excretion is reduced in renal insufficiency and in congestive heart failure. Liver: 50 to 90% of a dose of quinidine is metabolized in the liver. Bile: Approximately 1 to 3% is excreted in the feces via the bile. Breast milk: Quinidine is excreted in breast milk. Mode of action Toxicodynamics: Quinidine reduces the permeability of heart muscle to electrolytes (membrane stabilizer) and is a general cardiac depressant. It has a negative inotropic effect; inhibits the spontaneous diastolic depolarization; slow conduction; lengthens the effective refractory period; and raises the electrical threshold. This results in depression of contractility, impaired conductivity (atrioventricular and intraventricular) and decreased excitability but with possible abnormal stimulus re-entry mechanism. Quinidine has an anticholinergic effect and peripheral vasodilator properties. In experimental studies the following progression changes was observed: ECG: bradycardia, prolongation of the PR interval, lengthening of the QT interval, widening of the QRS with development of an idioventricular rhythm and then in ventricular standstill. Sometimes the terminal event was ventricular fibrillation. Blood pressure decreases progressively. A significant decrease of blood pressure was noted with the appearance of QRS widening and blood pressure was close to zero when slow idioventricular rhythm appeared. Electrolytes abnormalities: decrease in plasma concentrations of potassium, sodium and magnesium with the development of acidosis. Electrolytes: Hypokalaemia may occur and is probably related to an intracellular transport of potassium by a direct effect on cellular membrane permeability. Neurologic symptoms: Syncope and convulsions may represent a direct toxic effect on CNS or may be related to cerebral ischaemia due to circulatory or respiratory failure. Pharmacodynamics: Quinidine slows the rate of firing of the normal and of ectopic rhythmic foci; it raises the threshold for electrically induced arrhythmias; it protects against ventricular arrhythmias; and it prevents or terminates circus movement flutter. Teratogenicity: Quinidine has been implicated as a cause of light cranial nerve damage to the fetus at doses much larger than those needed to treat arrhythmias. Interactions: Several interactions have been reported. Quinidine has a synergistic action with warfarin (decrease of prothrombin level). Quinidine potentiates both non-depolarizing and depolarizing neuromuscular blocking agents. The cardiodepressant effects of other antiarrhythmic agents are increased by concurrent use of quinidine; amiodarone increases quinidine concentrations in the blood. Quinidine concentrations are reduced by: rifampicin, anticonvulsants, nifedipine and acetazolamide. Quinidine concentrations are increased by antacids, cimetidine, verapamil and amiodarone; the risk of quinidine toxicity is increased by terfenadine, astemizole, and thiazide and loop diuretics. Quinidine increases the plasma concentrations of propafenone and digoxin. Main adverse effects: Numerous adverse effects during quinidine therapy have been reported. Cardiovascular: Hypotension after IV administration; Syncope; proarrhythmic effect: "torsades de pointes"; and ECG: widening of QRS interval; prolongation of PR and QT intervals. CNS: Cinchonism: headache, fever, visual disturbances, mydriasis, tinnitus, nausea, vomiting and rashes. Gastrointestinal: Nausea, vomiting, diarrhoea, colic have been reported. Hepatic: Granulomatous hepatitis or hepatitis with centrilobular necrosis. Skin: Skin rashes with drug fever and photosensitivity may result. Hematologic: Thrombocytopenia (immunologic reaction) has been noted. Clinical effects: Acute poisoning: Ingestion: Severity of quinidine poisoning is related to the cardiotoxic effects. Symptoms appear usually within 2 to 4 hours and may include: cardiovascular symptoms: hypotension, cardiogenic shock, cardiac arrest. ECG may show: decrease of T wave; prolongation of QT and QRS intervals; atrioventricular block; ventricular dysrhythmia (torsade de pointes). Neurological symptoms: tinnitus, drowsiness, syncope, coma, convulsion, blurred vision and diplopia. Respiratory symptoms: hypoventilation and apnea. Cardiotoxicity may be enhanced if other cardiotoxic drugs have been ingested (antiarrhythmic drugs, tricyclic antidepressants). Parenteral exposure: After IV administration symptoms appear more rapidly. Chronic poisoning: Ingestion: The most relevant symptoms of chronic poisoning are: ECG disturbances; syncope due to ventricular dysrhythmia, (torsade de pointes) and cinchonism gastrointestinal disturbances Course, prognosis, cause of death: The usual course of quinidine poisoning is dominated by the cardiovascular disturbances which usually occur within 2 to 4 first hours but may first appear as late as 12 hours after exposure (and perhaps even later after ingestion of a slow- release preparation). Symptoms may last for 24 to 36 hours. Patients who survive 48 hours after acute poisoning are likely to recover. Death may result from cardiac arrest by asystole or electromechanical dissociation and, rarely, by ventricular fibrillation. Systematic description of clinical effects: Cardiovascular: Acute: Cardiovascular symptoms are the major features of quinidine toxicity. Tachycardia due to anticholinergic effects is usually observed initially or in moderate intoxication. In severe intoxication, bradycardia due to atrioventricular block may occur. Hypotension and shock: hypotension due to peripheral vasodilation is common. In severe intoxication, cardiogenic shock with increased central venous pressure is usually observed and is related to decreased cardiac contractility. Cardiac arrest may occur, which may be related to electromechanical dissociation, ventricular dysrhythmia or asystole. Cardiac dysrhythmias are common and may include: atrioventricular block, idioventricular rhythm, ventricular tachycardia and fibrillation, torsades de pointes. ECG changes are always present in symptomatic intoxication: repolarization abnormalities, decreased T wave, increase of U wave, prolongation of QT and PR intervals, widening of QRS complexes (> 0.08 sec), atrioventricular block. Syncope due to torsade de pointes may occur. Chronic: ECG changes with repolarization abnormalities, decreased T wave and increase of QT interval are a common feature during quinidine therapy. Syncope is related to transient torsade de pointes and occurs in 1 to 8% of patients receiving quinidine. The occurrence of torsade de pointes is not correlated with plasma quinidine levels but is favored by an increase in the QT interval. Respiratory: Acute: Respiratory depression or apnea is mostly associated with severe cardiac disturbances such as shock or ventricular dysrhythmia. Pulmonary edema with normal pulmonary capillary wedge pressure following an attempted suicide has been documented. Neurological: CNS: Acute: Drowsiness, delirium, coma and convulsions may appear without cardiac symptoms. However, cardiac failure should always be considered when CNS symptoms appear. Cinchonism may sometimes appear. Chronic: Cinchonism. Delirium has been reported. Peripheral nervous system: Chronic: Quinidine can potentiate the neuromuscular blocking action of some skeletal muscle relaxants and may cause the return of respiratory paralysis if it is given shortly after recovery from neuromuscular blockade. Autonomic nervous system: Acute: Quinidine has an anticholinergic effect. However, this effect is usually limited to the vagal system. Skeletal and smooth muscle: Chronic: An increase in serum concentrations of skeletal muscle enzymes has been reported in a man treated with quinidine. Gastrointestinal: Acute: Nausea and vomiting may occur. Chronic: Gastrointestinal toxicity (nausea, vomiting, diarrhea and colic) is the most frequent side effect of quinidine. Hepatic: Chronic: Hepatotoxicity has been reported, with an increase in serum concentrations of transaminases, LDH, alkaline phosphatase, and cholestasis. Renal: Acute: No direct nephrotoxic effect has been reported. Acute renal failure related to cardiogenic shock may occur. Dermatological: Chronic: Skin lesions have been attributed to the use of quinidine and include skin rash, photosensitivity and lichen planus. Eye, ear, nose, throat: local effects: Acute: Cinchonism is rarely observed in acute poisonings. Toxic amblyopia, scotoma and impaired color perception may occur at toxic doses. Chronic: Chronic cumulative overdose may cause cinchonism: headache, tinnitus, vertigo, mydriasis, blurred vision, diplopia, photophobia, deafness, and corneal deposits have been reported in a patient who took quinidine for two years. Hematological: Chronic: Thrombocytopenia and hemolytic anemia of immunologic origins have been reported. Immunological: Chronic: Quinidine may cause several immunologic mediated reactions: thrombocytopenia, hemolytic anemia, angioneurotic edema, skin rash, fever. Metabolic: Acid-base disturbances: Acute: Metabolic acidosis may occur in severe intoxication with shock. Fluid and electrolyte disturbances: Acute: Hypokalemia is frequently observed. Special risks: Pregnancy: Chronic: Quinidine has been implicated as a cause of cranial nerve damage to the fetus at doses much larger than those needed to treat arrhythmia. In a neonate born to a woman taking quinidine throughout pregnancy, serum levels were equal to that of the mother. The child's ECG was normal and there was no evidence of teratogenicity. Breast-feeding: Chronic: Quinidine is present in breast milk at levels slightly lower than serum levels. The dose of quinidine received by an infant taking 1l of milk would be below therapeutic doses. However, breast-feeding is not recommended because of potential quinidine accumulation in the immature newborn liver. /Quinidine/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
洋地黄糖苷在90%以上的洋地黄化患者中的血浆浓度增加。变化程度与奎尼丁的剂量成比例;平均变化约为两倍。奎尼丁的初始效应可能是由于洋地黄从组织结合位点被置换。/奎尼丁/
THE ADMIN OF QUINIDINE RESULTS IN AN INCREASE IN THE PLASMA CONCN OF THE GLYCOSIDE IN OVER 90% OF DIGITALIZED PATIENTS. THE DEGREE OF CHANGE IS PROPORTIONAL TO THE DOSE OF QUINIDINE; THE AVERAGE CHANGE IS ABOUT TWO-FOLD. ... THE INITIAL EFFECT OF QUINIDINE MAY BE DUE TO THE DISPLACEMENT OF DIGOXIN FROM BINDING SITES IN TISSUES. /QUINIDINE/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
药物...例如苯巴比妥或苯妥英...可能会通过增加消除速率显著缩短奎尼丁的作用持续时间。...硝酸甘油可能会导致服用奎尼丁的患者出现严重的体位性低血压。/奎尼丁/
DRUGS ... SUCH AS PHENOBARBITAL OR PHENYTOIN ... MAY SIGNIFICANTLY SHORTEN DURATION OF ACTION OF QUINIDINE BY INCR RATE OF ELIMINATION. ... NITROGLYCERIN CAN CAUSE SEVERE POSTURAL HYPOTENSION IN PATIENTS WHO ARE TAKING QUINIDINE. /QUINIDINE/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
盐酸奎尼丁是一种弱碱,通过肾脏排出...如果尿液的pH值增加,其生物半衰期可能会延长...碳酸酐酶抑制剂、碳酸氢钠和噻嗪类利尿剂,这些都能增加尿液的pH值,可能会增加奎尼丁的脂溶性以及肾小管的再吸收,从而延长其治疗作用。/盐酸奎尼丁/
QUINIDINE IS WEAK BASE EXCRETED ... BY KIDNEY & ITS BIOLOGICAL HALF-LIFE MAY BE PROLONGED ... IF PH OF URINE IS INCREASED. ... CARBONIC ANHYDRASE INHIBITORS, SODIUM BICARBONATE, & THIAZIDE DIURETICS, ALL OF WHICH INCR URINARY PH MAY SERVE TO INCR LIPID SOLUBILITY & TUBULAR REABSORPTION OF QUINIDINE & THUS PROLONG ITS THERAPEUTIC EFFECT. /QUINIDINE/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
  • 相互作用
喹尼丁(300毫克),缓慢静脉注射,导致由琥珀酰胆碱(40毫克静脉注射)诱导的瘫痪恢复。喹尼丁可能会增强或导致筒箭毒碱的神经肌肉效应再次出现。/喹尼丁/
QUINIDINE (300 MG), SLOWLY ADMIN IV, CAUSED RETURN OF PARALYSIS INDUCED BY SUCCINYLCHOLINE (40 MG IV). QUINIDINE MAY ENHANCE OR CAUSE A RECURRENCE OF NEUROMUSCULAR EFFECTS OF TUBOCURARINE. /QUINIDINE/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
关于奎尼丁,大约90%在血浆中与血浆蛋白(酸性糖蛋白和清蛋白)结合。药物进入红细胞并...与血红蛋白结合;在稳态时,血浆和红细胞中奎尼丁的浓度大约相等。奎尼丁在大多数组织中迅速累积,除了大脑,...分布体积为2-3升/千克。/奎尼丁/
ABOUT 90% OF QUINIDINE IN PLASMA IS BOUND TO PLASMA PROTEINS (ALPHA/ACID GLYCOPROTEIN AND ALBUMIN) THE DRUG ENTERS ERYTHROCYTES & ... BINDS TO HEMOGLOBIN; AT STEADY STATE, CONCN OF QUINIDINE IN PLASMA & ERYTHROCYTES ARE APPROXIMATELY EQUAL. QUINIDINE ACCUMULATES RAPIDLY IN MOST TISSUES EXCEPT BRAIN, & ... VOL OF DISTRIBUTION IS 2-3 L/KG. /QUINIDINE/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
代谢物和部分母药(20%)通过尿液排出;消除半衰期约为6小时。/奎尼丁/
METABOLITES AND SOME OF THE PARENT DRUG (20%) ARE EXCRETED IN URINE; ELIMINATION HALF-TIME IS ABOUT 6 HR. /QUINIDINE/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
肝脏代谢和肾脏排泄是消除的主要途径。肠肝循环不会显著改变吸收动力学,这反映在血液浓度上。
LIVER METABOLISM & RENAL EXCRETION ARE THE MAIN ROUTES OF ELIMINATION. ENTEROHEPATIC CIRCULATION WOULD NOT SIGNIFICANTLY ALTER ABSORPTION KINETICS AS REFLECTED BY BLOOD CONCENTRATION.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
血浆中奎尼丁的峰浓度为0.29微克/毫升,在服用缓释胶囊(250毫克硫酸奎尼丁)后4小时测量得到,随后在接下来的8小时内稳步下降,而在服用缓释片(300毫克硫酸奎尼丁)后,它们在服用后2-10小时内相对平稳。与片剂相比,胶囊在较晚时间点的血浆浓度更高。在12小时内,从胶囊中得到的奎尼丁的生物利用度比片剂高184%。在服用胶囊后3、4、6、8和10小时,奎尼丁的平均血浆浓度显著高于服用片剂后的浓度。
PEAK PLASMA CONCN OF 0.29 UG/ML OF QUINIDINE WERE MEASURED @ 4 HR AFTER ADMIN OF SUSTAINED RELEASE CAPSULE (250 MG QUINIDINE BISULFATE) AND DECLINED STEADILY DURING THE NEXT 8 HR, WHILE AFTER ADMIN OF SUSTAINED RELEASE TABLET (300 MG QUINIDINE SULFATE) THEY WERE FAIRLY EVEN DURING 2-10 HR AFTER DOSING. PLASMA CONCENTRATIONS WERE HIGHER AT LATER TIMES FOR THE CAPSULE THAN FOR THE TABLET. THE BIOAVAILABILITY OF QUINIDINE FROM THE CAPSULES DURING 12 HR WAS 184% COMPARED TO THE TABLET. MEAN QUINIDINE PLASMA CONCN WERE SIGNIFICANTLY GREATER @ 3, 4, 6, 8, & 10 HR AFTER ADMIN OF THE CAPSULE THAN AFTER THE TABLET.
来源:Hazardous Substances Data Bank (HSDB)

安全信息

  • 危险品标志:
    Xn
  • 安全说明:
    S22,S45
  • 危险类别码:
    R22
  • 危险品运输编号:
    UN 1544

SDS

SDS:c8890abc4311c93f7619255d9b478c3b
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制备方法与用途

硫酸奎尼丁 适应症

硫酸奎尼丁是一种抗心律失常药,适用于房性早搏、心房颤动、心房扑动、阵发性室上性心动过速、预激综合征合并室上性心律失常、室性早搏、室性心动过速及心房颤动或心房扑动经电转复后的维持治疗。

作用机制

硫酸奎尼丁主要作用在房室肌和浦肯野纤维,为细胞膜抑制剂。直接作用于细胞膜离子通道,主要抑制Na+内流,亦阻滞K+外流和Ca2+内流,减慢动作电位0相上升速度,降低4相斜率,延长动作电位时程和有效不应期。可使阈电位升高而自律性、传导性及心肌收缩力降低,有利于消除折返激动和异位节律。

此外,硫酸奎尼丁尚有抗胆碱能作用,使心率增快。大量使用时可扩张血管并阻断α受体,引起血压降低。

理化性质

硫酸奎尼丁为白色细针状结晶体,无臭,味极苦。遇光渐变色,并呈右旋光性。溶于沸水、乙醇或丙酮,微溶于冷水及稀碱液。本品主要用于治疗各种心律失常。

不良反应

硫酸奎尼丁的不良反应较多见,常见心血管反应:严重心律失常如室性早搏、室性心动过速、室颤和传导阻滞等。消化道反应包括恶心、呕吐、痛性痉挛、腹泻等症状。其他不良反应还包括特异质反应、过敏反应以及金鸡纳反应。

用法与用量

本药治疗指数低,约1/3的患者会发生不良反应。使用时应注意剂量,并根据具体情况调整用药量。

注意事项

使用硫酸奎尼丁需谨慎,特别是对于原有器质性心脏病的患者。治疗过程中应定期监测心电图及血药浓度,并密切观察患者的临床症状变化。

与其他药物相互作用

本药与多种药物存在相互作用,如抗胆碱药、降压药、β阻滞剂等均可能增加不良反应的风险。

不良反应的处理

对于出现传导阻滞、心室停搏等症状时,可静脉滴注异丙肾上腺素或去甲肾上腺素,也可采用心脏起搏器治疗。对于室性早搏和快速心律失常等情况,则可用心得安、利多卡因、苯妥英钠或电复律等方法进行处理。

如发生扭转型室速时可使用异丙肾上腺素及碳酸氢钠(或乳酸钠)。视力障碍则可通过硝酸酯类及乙酰甲胆碱治疗。对于过量中毒,可用血液透析清除。

总之,硫酸奎尼丁在临床应用中需严格控制剂量并密切观察患者情况以减少不良反应的发生率。如有任何疑问,请咨询专业医师或药师。