[AF-FORUM] 126E 胺碘酮的治疗地位 Dr. Perez Riera

[AF Symposium]

尊敬的Yongqiang Zhao，胺碘酮的化学成分属于碘化的苯 
并呋喃衍生物，其化学成分不归于其他抗心律失常药 
物。术后心律失常的预防可在静脉弹丸式输注胺碘酮 
后再予以口服高剂量的胺碘酮，这用于冠脉搭桥术后 
患者是安全、实用、可行、有效的方法。

胺碘酮明显减少患者术后房颤的发生率(1)。可有效进 
行房颤转复后窦律的维持，而与心律失常持续的时间 
无关。甚至在房颤发作较长时间的患者以及存在心 
房-电重构的患者中，胺碘酮仍能有效维持转复后的 
正常窦律(2)。

根据最新的ACC/AHA/ESC指南，运用标准剂量的美托洛尔 
或胺碘酮预防术后房颤的发生，为证据A级水平。

Pappone等进行的APAF研究比较了射频消融治疗与抗心律 
失常药物治疗对于阵发性房颤患者的比较。作者的结 
论是：肺静脉口消融比抗心律失常药物治疗对于预防 
阵发性房颤更有效，合并症也较少(3)。



胺碘酮药物的不良反应：

1）         眼睛异常：包括视神经病变，视神经炎， 
视乳头水肿，角膜沉积，光敏感，晶状体混浊，以及 
黄斑变性。角膜沉积实际上在所有服用胺碘酮超过6 
个月的患者中都存在。角膜沉积是由于泪腺分泌胺碘 
酮的累积作用，并被角膜上皮吸收所导致的。这类患 
者中大约10%存在眩目和重影，但仅有这些症状通常不 
足以需要采取治疗。

2）         甲状腺功能不全：由于胺碘酮会抑制5'-脱 
碘酶的活性，导致T4转换为T3的减少，同时rT3产物增 
多以及清除能力减退，从而引起甲状腺功能异常。

  胺碘酮治疗的患者中存在明显的甲状腺功能不全， 
表现为胺碘酮引起的甲状

腺功能亢进（AIT）或甲状腺功能减退（AIH）。甲亢主 
要是与碘过量引起异常

的甲状腺体合成过多甲状腺素有关（I型甲亢），或 
者是胺碘酮相关的破坏性

甲状腺炎（II型甲亢）。胺碘酮引起的甲减的病因学 
与服用大剂量碘后,甲状腺激素合成受抑有关，导致 
甲状腺素生成缺乏。或是在那些甲状腺自身抗体阳性 
的患者中，伴随存在Hashimoto's甲状腺炎。甲亢和甲减 
表面上甲状腺都可能正常，临床上也可无异常情况。 
在碘不足的地区，胺碘酮引起的甲亢较常见，而在碘 
充足的地区，甲减更多见。与甲减相比，甲亢的诊断 
和治疗更困难，通常是推荐停用胺碘酮。在停用胺碘 
酮数月后也可能出现胺碘酮引起的甲亢。

3）心血管不良反应：

致心律失常作用：在器质性心脏病患者和房颤患者中 
运用胺碘酮治疗通常会合并运用β-受体阻断剂和地高 
辛治疗，这样可能增加胺碘酮相关的致心律失常的危 
险性。虽然胺碘酮治疗过程中很少出现尖端扭转性室 
速(TdP)，但在长期药物治疗的患者中观察到尖端扭转 
性室速(TdP)的出现。出现尖端扭转性室速者通常合并 
存在电解质紊乱，或药物剂量的改变，或合并有其他 
药物治疗。

其他心血管方面的不良反应主要是右心衰竭和肺动脉 
高压。

4）与肺有关的副作用：胺碘酮所致的肺毒性是使用 
胺碘酮最严重的不良反应，但至今尚未有诊断标准， 
其临床表现变化较多。老年人群使用胺碘酮所致肺毒 
性的危险性增加。因此，临床医生对于老年患者应尽 
可能使用最低剂量的胺碘酮，对于任何无法解释的疲 
劳、呼吸困难、咳嗽、体重减轻，都应该停用胺碘 
酮。胺碘酮所致肺损害的另一种表现是急性呼吸窘迫 
综合症。药物引起的肺炎，过敏性肺炎在老年患者治 
疗过程中可能出现。

5）内分泌方面的不良反应：异常的抗利尿激素分泌 
综合症(SIADH)。

6）神经系统方面的不良反应：20-40%的患者中有报道 
存在神经系统异常，包括震颤、共济失调、周围神经 
病变、抑郁或疲乏、睡眠障碍、眩晕以及头痛。

7）胃肠道不良反应：在4-25%的患者中出现肝功能异 
常，特别是转氨酶和碱性磷酸酶水平升高。长期使用 
胺碘酮可出现假性酒精性肝病和肝硬化。

8）皮肤的不良反应：已经报道过几种不同类型的皮 
肤反应，包括过敏性皮疹、光敏感、皮肤蓝-灰变 
色。蓝色人：胺碘酮所导致的皮肤变色。

9）过敏反应：胺碘酮所引起的血管性水肿。



参考文献：

1) Zebis LR, Christensen TD, Thomsen HF et al. Practical  regimen for  
amiodarone use in preventing postoperative atrial fibrillation. Ann  
Thorac Surg. 2007;83:1326-1331.

2) Komatsu T, Tachibana H,Sato Y,  et al. Efficacy of  amiodarone for  
preventing the recurrence of symptomatic paroxysmal and persistent  
atrial fibrillation after cardioversion. Circ J. 2007; 71:46-51.

3) Pappone C, Augello G, Sala S,  et al.A randomized trial of  
circumferential pulmonary vein ablation versus antiarrhythmic drug  
therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll  
Cardiol. 2006;48:2340-2347.

向全体人员致意

Andrés Ricardo Pérez Riera MD

Chief of Electro-Vectocardiology Sector of the Discipline of   
Cardiology,

ABC Faculty of Medicine (FMABC), Foundation of ABC (FUABC) - Santo  
André São Paulo - Brazil.



--

Dr. Sergio Dubner

科委会主席

Dr. Edgardo Schapachnik

组委会主席


赵勤华译 王玲洁校


原文：



Dear Yongqiang Zhao: Amiodarine chemically, it is classified as an
iodinated benzofuran derivate antiarrythmal drug not chemically
related to any other available antiarrhythmic drug.Postoperative
prophylaxis with a high dose of oral amiodarone after an intravenous
bolus infusion is a safe, practical, feasible, and effective regimen
for coronary artery bypass grafting patients. It significantly
diminishes the occurrence of postoperative AF (1) Efficacy for
maintaining SR after cardioversion of AF was not biased by the
duration of arrhythmia. Amiodarone is effective in maintaining normal
SR after cardioversion, even in patients with long-lasting AF and
electrical atrial remodeling(2) .

According to newly released ACC/AHA/ESC guidelines, use of standard
beta-blockers or amiodarone to prevent postoperative AF have a level
of evidence of A.

The APAF Study conducted by Pappone et al compared ablation strategy
with antiarrhythmic drug therapy in patients with paroxysmal AF. The
authors conclude that circumferential pulmonary vein ablation is more
successful than antiarrhythmic drug therapy for prevention of
paroxysmal AF with few complications (3).

Adverse drug reactions

1)       THE OPHTHALMIC ABNORMALITIES include optic neuropathy, optic
neuritis, papilledema, corneal deposits, photosensitivity, lens
opacities, and macular degeneration. Corneal microdeposits are seen
in virtually all patients who receive amiodarone for more than 6
months. Corneal microdeposits result secondary to the secretion of
amiodarone by the lacrimal gland with accumulation on, and absorption
by, the corneal epithelium. Approximately 10% of these patients
become symptomatic with glare and halos; however, that alone is
usually not enough to precipitate intervention

2)       THYROID DYSFUNCTION: Amiodarone often causes changes in
thyroid function tests mainly related to the inhibition of 5'-
deiodinase activity resulting in a decrease in the generation of T3
from T4 with a consequent increase in rT3 production and a decrease
in its clearance. In a group of amiodarone-treated patients there is
overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis
(AIT) or amiodarone-induced hypothyroidism (AIH). AIT is primarily
related to excess iodine-induced thyroid hormone synthesis in an
abnormal thyroid gland (type I AIT) or to amiodarone-related
destructive thyroiditis (type II AIT). The pathogenesis of AIH is
related to a failure to escape from the acute Wolff-Chaikoff effect
due to defects in thyroid hormonogenesis, or, in patients with
positive thyroid autoantibody test, to concomitant Hashimoto's
thyroiditis. Both AIT and AIH may develop either in apparently normal
thyroid glands or in glands with preexisting, clinically silent
abnormalities. AIT is more common in iodine-deficient regions of the
world, whereas AIH is usually seen in iodine-sufficient areas. In
contrast to AIH, AIT is a difficult condition to diagnose and treat,
and discontinuation of amiodarone is usually recommended. Amiodarone
can -induced AIT months after cessation of therapy.

3)       , CARDIOVASCULAR SIDE EFFECTS: PRO-ARRHYTHMIA: Amiodarone
therapy in pts with structural heart disease and AF that are
concomitantly treated with beta-blockers and digitalis may have an
increased risk of amiodarone-associated pro-arrhythmia. Torsade de
Pointes (TdP) although amiodarone appears to have few pro-arrhythmic
effects, TdP has been observed during long-term drug administration.
TdP occur usually in conjunction with electrolyte disturbances, a
change in drug dosage, or concomitant drug therapy., PREDOMINANT
RIGHT HEART FAILURE AND PULMONARY HYPERTENSION,

4)       PULMONARY SIDE EFFECTS: AMIODARONE PULMONARY TOXICITY
represents the most serious adverse reaction from amiodarone use. It
remains underdiagnosed and can have a variable presentation. The
elderly population is at increased risk for amiodarone pulmonary
toxicity. Thus, clinicians should prescribe the lowest dosage
possible in the elderly and have a low threshold to discontinue the
amiodarone for anyone with unexplained fatigue, dyspnea, cough, or
weight loss. ACUTE RESPIRATORY DISTRESS SYNDROME secondary to
amiodarone-induced pulmonary damage: drug-induced pneumonitis
HYPERSENSITIVITY PNEUMONITIS can appear early in the course of therapy.

5)       ENDOCRINOLOGICAL SIDE EFFECTS: syndrome of inappropriate
antidiuretic hormone secretion (SIADH)

6)       NEUROLOGIC SIDE EFFECTS: were reported in 20-40% of
patients, at times associated with tremor, ataxia, peripheral
neuropathy, malaise or fatigue, sleep disturbances, dizziness, and
headaches.

7)       GASTROINTESTINAL SIDE EFFECTS: Abnormalities in liver
function tests, especially elevated aminotransferase and alkaline
phosphatase levels, are seen in 4-25% of patients. Pseudoalcoholic
liver disease and a cirrhosis after use of amiodarone for a long
period of time.

8)        DERMATOLOGIC SIDE EFFECTS: Several types of dermatologic
reactions have been reported, including allergic rash,
photosensitivity, and blue-gray skin discoloration. The blue man:
amiodarone-induced skin discoloration.

9)       ALERGIC SIDE EFFECTS: Amiodarone-induced angioedema:

References

1)       Zebis LR, Christensen TD, Thomsen HF et al. Practical
regimen for amiodarone use in preventing postoperative atrial
fibrillation. Ann Thorac Surg. 2007;83:1326-1331.

2)       Komatsu T, Tachibana H,Sato Y,  et al. Efficacy of
amiodarone for preventing the recurrence of symptomatic paroxysmal
and persistent atrial fibrillation after cardioversion. Circ J. 2007;
71:46-51.

3)       Pappone C, Augello G, Sala S,  et al.A randomized trial of
circumferential pulmonary vein ablation versus antiarrhythmic drug
therapy in paroxysmal atrial fibrillation: the APAF Study. J Am Coll
Cardiol. 2006;48:2340-2347.


All the best for all
Andrés Ricardo Pérez Riera MD
Chief of Electro-Vectocardiology Sector of the Discipline of
Cardiology,
ABC Faculty of Medicine (FMABC), Foundation of ABC (FUABC) - Santo
André São
Paulo - Brazil.
riera在uol.com.br