胺碘酮作用机制的多样性

对心律失常的药物治疗方法近10年中发生了很大变化。CAST(心律失常抑制试验)和SWORD(口服d-索他洛尔生存试验)等大规模临床试验提示，以抑制Na^ 通道为主的药物和单纯K^ 通道抑制药物可使心律失常患者预后恶化，这些药物的副作用使其应用受到限制。而近年来对胺碘酮研究的不断深入，逐渐显示出其巨大的应用潜能。胺碘酮的早期(20     

加强对胺碘酮副作用的认识

胺碘酮作为抗心律失常和心绞痛的药物 ,临床应用已久 ,在使用过程中 ,发现了不少与治疗无关的副作用 ,并不乏致人死亡的报道。因此 ,加强对胺碘酮毒副作用的认识 ,不但能更全面的了解此药 ,也能使医生在使用中避免不必要的后果发生。本文复习了此前关于胺碘酮副作用的一些报道 ,现综述如下。1　肺毒性 (APT) [1 ]APT是 1980年 Rothmensch首次提出 ,以后不断有许多类似的报道。发病率各家报道不一 ,Olson[2 ]等报告肺毒性的发生率高达 18% ,Wilson[3 ] 报道发病率为 5 %～ 10 % ,死亡率为5 %～ 10 % ,Darmanata等认为比较少 ,在 6 %左右 …     

乙胺碘呋酮的临床副反应

乙胺碘呋酮(简称胺碘酮)用于抗心律失常已20多年，是一种很有效的广谱抗心律失常药。其主要电生理学特点是延长心肌细胞的动作电位时间，不改变膜息电位；抑制4相位除级，延长心肌复极，并且有除颤的作用，故其为Ⅲ类抗心律失常药。不仅能终止室上性心律失常，且能成功地治疗致命性心律失常。近年来有人提出此药尚能预防室颤的发生。因本药疗效高，毒性小，安全性大，抗心律失常广谱等特点，目前临床上不恰当地选择应用现象日增，以至引起一些不必要的致命的不良反应。本文将乙胺腆呋酮的毒副反应作以综述，借以引起临床医生注意。     

长期应用乙胺碘呋酮的老年病人药物管理问题的探讨

乙胺碘呋酮是治疗心律失常的常用药 ,在老年人群中应用较为广泛。但长期服用可产生一些副作用 ,特别是引起甲状腺机能亢进或甲状腺机能减退。据研究报道 ,在人群中 ,发生甲状腺机能亢进的为 1%～ 2 3% ,发生甲状腺机能减退的为 1%～ 32 % ,其中 4 9%的病人服用乙胺碘呋酮[1] 。本文回顾调查了 15例因心律失常而服用乙胺碘呋酮的老年病人 ,发生甲状腺机能减退 1例 ,甲状腺功能指标异常 3例。可见在老年人群中 ,对服用乙胺碘呋酮药物的管理应给予高度的重视。1　临床资料15例病人均为男性。年龄在 6 1～ 90岁 ,平均年龄 78岁。患有房颤 11例 ,…     

胺碘酮同时静脉和口服给药治疗心律失常临床疗效观察

目的评价胺碘酮同时静脉和口服给药对心律失常患者的疗效。方法口服胺碘酮600～800mg/d,同时深静脉注射胺碘酮,首剂150mg,15～20分钟注毕,续之1.0mg/min,维持静脉滴注(1.5±1.2)天。结果72小时总有效率73.1%。静脉用药期间2例出现一过性I度房室传导阻滞,3例出现窦性心动过缓,1例出现一过性II度房室传导阻滞,经减量后恢复。结论同时静脉和口服胺碘酮治疗心律失常安全有效。     

胺碘酮的不良反应

１引言胺碘酮作为一种广谱抗心律失常药物，其疗效早已公认。随着临床的广泛应用，越来越多的不良反应相继被报道，本文围绕胺碘酮这些不良反应加以综述。２心脏毒性２．１心脏传导阻滞、心律失常心脏毒性发生率约为０．６％～３０．０％。心脏毒性主要表现为窦性心动过缓、窦性停搏及心脏各部位传导阻滞、QT间期延长，低血压，各种心律失常等犤１犦。虽然胺碘酮可引起QT间期延长，但由于胺碘酮可使心肌复极过程均匀一致，所以，此种QT间期延长大大减少了致尖端折返性室性心动过速的机会。郭新雯等犤２犦对１２４例由于各种原因引起的继…     

乙胺碘呋酮致碘甲亢12例分析

我院1998～2004年共收治因各种心律失常而服用胺碘酮(AMD)致甲亢患12例，其治疗与预后同一般甲亢殊多不同，现报告并分析如下。     

胺碘酮的毒副反应

胺碘酮(Amiodarone)在国外于1961年合成,1967年开始用于治疗心绞痛,1970年开始用于治疗心律失常。过去认为该药疗效高,尤其对顽固性和危及生命的快速室性心律失常,抗心律失常谱广,毒性小、安全度大,被认为是较理想的抗心律失常药物。但随着近年来的广泛使用,关于该药的毒副反     

Pharmacokinetics of amiodarone in the isolated rat lung

In these studies we examined the kinetics of amiodarone (Am) uptake and efflux in/from the lung, and the influence of other amphiphilics on these processes. We used single-pass perfused isolated lungs from rats. Medium containing Am (30 microM + 1 microCi of [14C]Am) was perfused through the lung for 20 min (uptake), followed by 20 min of perfusion with drug-free medium (efflux). Lack of metabolism enabled us to follow Am by measuring the amount of radioactivity in perfusate and lung. Other concentrations of Am (3, 60 and 120 microM; n = 2-4 each) were also examined. Inhibited uptake and accelerated efflux of Am were attempted with the pneumophilic amphiphilics chlorimipramine, chlorphentermine, chlorpromazine, verapamil and with the main metabolite of Am: desethylamiodarone (60 and/or 240 microM; n = 3-4 lungs each). Lung extracted Am extensively during uptake. The amount of Am accumulated at 20 min (inflowing concentration: 30 microM) averaged 1307 +/- 109 (S.E.) nmol/g, corresponding to a tissue to medium ratio of 43.3 +/- 1.6. Spontaneous efflux of Am was incomplete. At 40 min, 862 +/- 105 nmol of Am remained bound per g of lung, suggesting sequestration of Am in a slowly effluxable pool in which calculations show that more than 50% of the drug will ultimately persist. Uptake and efflux rates obey biexponential kinetics, indicating storage into two pools. Uptake rate and the amount of Am accumulated in lung at 20 min increased in proportion to inflowing concentration up to 60 microM. At 120 microM the increase was less. Neither amphiphilic was capable of inhibiting Am uptake, whereas only chlorphentermine significantly accelerated Am efflux.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of drug overdose

Drugs ingested in overdose can have altered pharmacokinetics of absorption, distribution, and elimination. The pathophysiologic consequences of overdose can also change a drug's pharmacokinetic properties. Many toxicologic interventions are based on modifying the drug's pharmacokinetics (e.g., impairing absorption or enhancing elimination). Serum drug monitoring, even with its limitations, does have a role in managing the patient who has taken an overdose.     

Pharmacokinetics and drug interactions of antidepressive agents

Tricyclic antidepressive agents(TCAs) are conventional antidepressant. Cytochrome P450(CYP) 2D6 is involved in the hydroxylation of TCAs, while N-demethylation of TCAs is mediated by other such as CYP2C19, 3A4 and 1A2. The elimination of TCAs is impaired by CYP2D6 inhibitors such as quinidine. Newer antidepressants, selective serotonin uptake inhibitors(SSRIs), are also metabolized in the liver. Fluvoxamine, an SSRI, is a potent inhibitors for CYP1A2 and CYP2C19, moderate for CYP3A4 and weak for CYP 2D6. Paroxetine, another SSRI, causes substantial inhibition of CYP2D6 activity. Milnacipran, a serotonin and noradrenaline reuptake inhibitor, is mainly excreted unchanged in urine and some part as its glucronide conjugate. In contrast to many SSRIs, milnacipran is devoid of metabolic inhibition.     

Determination of cardiac and plasma drug levels during long-term amiodarone therapy

A study of plasma and cardiac concentrations of amiodarone during the course of long-term oral therapy was made possible by the improvement of analytical high performance liquid chromatography of plasma and tissue extracts. The plasma level was found to increase linearly with the daily dose of the drug, above a threshold value of c. 1 . 9 mg kg-1 day-1. Similarly, the cardiac content increased linearly with the daily dose, with no threshold, showing that the drug is taken up and accumulated in the cardiac tissue, with no obvious difference between atrial and ventricular samples (P greater than 0 . 05). Both plasma and heart showed no saturation at high drug intake, a justification for increasing the oral intake in severe cases. The linear relationship between tissue and blood concentrations allows a prediction of the cardiac level from a simple and routine blood analysis.     

Influence of amiodarone on genetically determined drug metabolism in humans

Amiodarone has been shown to interact with the nongenetically determined hepatic elimination of several drugs, including phenytoin and digoxin. Its influence on genetically determined metabolic pathways has not been studied in humans. We examined the effects of oral amiodarone therapy on the genetically determined metabolism of isoniazid (N-acetyltransferase), mephenytoin (cytochrome P450MEPH), and dextromethorphan (CYP2D6). Eight patients with arrhythmias were studied before and 76 +/- 16 days after amiodarone (loading dose of 1000 mg/day for 10 days followed by a maintenance dose of 200 to 400 mg/day). Genetically determined enzyme activity was assessed indirectly by calculating the metabolic ratio (parent drug/metabolite in 8-hour urine for CYP2D6 and P450MEPH and N-acetylisoniazid/isoniazid in plasma for N-acetyltransferase) after oral administration of the parent compounds. At the time of phenotyping, plasma concentrations of amiodarone and N-desethylamiodarone were 0.66 +/- 0.35 micrograms/ml and 0.65 +/- 0.26 micrograms/ml, respectively. Amiodarone increased the log(metabolic ratio) of dextromethorphan from a median of -2.5 (range, -2.9 to -2.0) to a median of -1.9 (range, -2.5 to -1.5; p less than 0.02) but did not alter the metabolic ratio of mephenytoin or isoniazid. The amount of dextromethorphan excreted in urine increased from a median of 0.084 mumol/8 hours (range, 0.041 to 0.161 mumol/8 hours) to a median of 0.205 mumol/8 hours (range, 0.064 to 0.288 mumol/8 hours; p less than 0.02) and the amount of its metabolite (dextrorphan) tended to decrease from a median of 26 mumol/8 hours (range, 15 to 37 mumol/8 hours) to a median of 20 mumol/8 hours (range, 7 to 27 mumol/8 hours; p less than 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)     

Antidepressant drug action and presynaptic alpha-receptors

Receptors have been demonstrated on the terminations of the sympathetic adrenergic nerves. One type, the so-called alpha 2-receptors, are activated by the norepinephrine that is released from the nerve terminals into the synaptic cleft; this activation causes a reduction in the output of the transmitter (negative feedback). Recent studies have demonstrated that certain antidepressant drugs can block these alpha 2-receptors and thus prevent their inhibitory action on the release of norepinephrine. If this occurs in the brain, the increases in norepinephrine levels could help explain the antidepressant action of these agents.