[AF-FORUM] 166E 胺碘酮治疗的泌尿生殖系统副作用Miss Long

[AF Symposium]

亲爱的Drs. Yongqiang Zhao, Riera及所有同仁：
Dr. Riera's对Dr. Zhao's的问题（在胺碘酮的应用中我们需 
要注意什么）作了精彩回答，包括药物不良反应表格 
及相关文献。这个表格反映了应用胺碘酮患者群的现 
实性，但却有个明显的遗漏。如你所想的，如果副作 
用将被广泛认知，理解，患者会获得进一步的关于副 
作用的告知。

非感染性的附睾炎：
胺碘酮相关性附睾炎：药物相关的非感染性附睾炎(J  
Urol. 1985 Jun; 133(6):971-2; Gasparich JP, Mason JT, Greene HL,  
Berger RE, Krieger JN.)

在应用胺碘酮（一种有效的新抗心律失常药物）的56 
例患者中，有6例发生了非典型性附睾炎。在发生附 
睾炎的患者中胺碘酮平均剂量是700mg/天，而所有患者 
应用的剂量是377mg/天（P小于0.01）。所有患者均无感 
染史。在胺碘酮治疗中，对发生非感染性附睾炎的患 
者，推荐暂时停药或减少剂量。

上述研究并没有反映出，在我们的患者群中发生胺碘 
酮相关附睾炎的男性比例(ARVD/C)。一个年轻的妻子私 
下里问，她丈夫经受反复所谓睾丸感染，她想知道是 
否应用胺碘酮的其他男性有同样的问题。大约2001年末 
2002年初，我们的研究有11个男性应用胺碘酮。私下里 
询问这些男性：“自从应用胺碘酮后，你有发生睾丸 
感染的经历吗？”

我们研究的非正式结果：11例服用胺碘酮的心律失常 
性右心室发育不良（ARVD）患者中，有4例附睾炎。两 
例男性附睾炎反复发作，两例长期持续发作。所有患 
者在进行抗生素治疗中均报告有难忍的疼痛及抗药 
性。化验结果不支持有感染。附睾炎及疼痛的缓解从 
三周（一次发病）到一年不等。四例患者的年龄在30至 
50岁之间，至少1例患者包括在研究的每十年里。仅仅 
1例患者（两名年轻患者中的一个）因有生育要求而 
检查不育，结果发现不能生育。胺碘酮的剂量不同， 
其使用年限为2-7年。

我们研究的不足：在患者服用胺碘酮前并没有询问其 
附睾炎病史。诚然，假定这些男性有这个问题（一项 
误差），会表现得很震惊和尴尬。不能忽略个人环 
境，如果上面所有人在患附睾炎前，并没有被问到是 
否有混乱的性关系，这个假定是危险的。所有患者只 
有心脏的情况，且有长期的一夫一妻的关系。我们的 
研究中，两例男性在一年内接受了心脏移植，两例男 
性经常停用胺碘酮而间断出现持续性室速，其中一例 
已明确在性交时发生（另一例无）
那名不育的男性和他的妻子非常悲痛：“如果告诉我 
们应用胺碘酮可能出现的副作用，我们会在使用前生 
育（或者考虑精子库）。当这些男性了解到此副作用 
在15年以前就已经被发现后，非常困惑，然而他们并 
没有被告知这会发生。他们觉得自己经受了没有必要 
的，但并不算小的烦恼。

而且，他们经受了对非传染附睾炎的长期抗菌治疗。

尽管我们的研究有不足，但证据证实了胺碘酮诱发附 
睾炎。而且，研究的不足并不能这点。因为信息的缺 
乏导致失去后代是惨痛且没必要的损失。

这封短信的要点是，如果你有兴趣读：
1） 关于四例受累患者的简要说明，包括胺碘酮剂量。

2） 一些其他胺碘酮受累家庭的陈述。

这些临时网页在：
http://ARVD-ARVC-Info.com/WebX/ARVD/Amiodarone

3） 全世界内科医生应该知道至少一个应用的，有经 
验的及顺从性的胺碘酮患者群。

这些临时网页在：
http://ARVD-ARVC-Info.com/WebX/ARVD/Invested

下面是其它的参考文献：

Micheline J. (Tink) Long
国际ARVD家庭救助网络

从：
"男性输精管系统的炎性环境 Part I;" ( P. T. K. Chan and P.  
N. Schlegel; J Androl, July 1, 2002; 23(4): 453 - 460)

应用胺碘酮诱发药物性附睾炎报道 (Gasparich et al, 1984;  
Hutcheson et al,1998),..." ---  (Gasparich JP, Mason JT, Greene HL,  
Berger RE, Krieger JN.

胺碘酮相关的非感染性附睾炎的治疗. Lancet. 1984;  
2:1211–1212) ---(Hutcheson J, Peters CA, Diamond DA. 儿童应用 
胺碘酮导致附睾炎. J Urol. 1998;160:515–517)

尽管仍不知道此疾病的确切机制，但研究已经发现在 
许多身体组织中的药物浓度，例如附睾，比血浆水平 
高300倍(Sadek et al, 1993)，且副作用同药物剂量及应用 
时间相关---(Greene HL, Graham EL, Werner JA, Sears GK, Gross BW,  
Graham GB, Kudenchuk PG, Probaugh GB.
胺碘酮在治疗心律失常中的疗效及毒性。 J Am Coll  
Cardiol.1983;2:1114–1128)

尽管有报道说，如果重新应用相同剂量的胺碘酮会导 
致综合征的再发，但减少和停用胺碘酮可以迅速减轻 
症状(Gabal-Shehab and Monga, 1999)." --- (Gabal-Shehab LL, Monga  
M. 胺碘酮相关性双侧附睾炎复发. J Urol. 1999;161:921.)

Dr. Sergio Dubner
科委会主席
Dr. Edgardo Schapachnik
组委会主席

赵宏伟译 王玲洁校

166E Amiodarone therapy/genitourinary side effect. Miss Long

Dear Drs. Yongqiang Zhao, Riera and All,
Dr. Riera's excellent response to Dr. Zhao's question ("What cautions  
should we take during the implication of amiodarone?")  included a  
list of adverse drug reactions and supporting references.  The list  
reflects the reality of our patient group's "Amiodarone experience,"  
with one glaring omission.  As you can imagine, those affected would  
ike to make sure that the side effect is widely known, understood,  
and that they (the patients) are given advanced warning that it could  
occur.

Noninfectious Epididymitis:
"Amiodarone-associated epididymitis: drug-related epididymitis in the  
absence of infection;" (J Urol. 1985 Jun;133(6):971-2; Gasparich JP,  
Mason JT, Greene HL, Berger RE, Krieger JN.)

"An atypical epididymitis syndrome developed in 6 of 56 men (11 per  
cent) treated with amiodarone, an effective new anti-arrhythmic  
agent. Of the 6 patients 5 (87 per cent) had bilateral epididymal  
enlargement and pain. The mean dosage in the patients with  
epididymitis was 700 mg. per day compared to 377 mg. per day in all  
patients (p less than 0.01). No infectious etiology was implicated in  
any patient. Temporary discontinuation or decrease in dosage is  
recommended for patients who suffer noninfectious epididymitis while  
on amiodarone therapy."

The above study does not reflect the percentage of men found to be  
affected by Amiodarone related epididymitis in our patient community  
(ARVD/C).  A young wife whose husband suffered repeated "so-called"  
testicular infections queried in private.  She wondered if other  
males taking Amiodarone had a similar experience.  In approx. late  
2001 or early 2002, our group included 11 men taking Amiodarone.  The  
men were privately interviewed, "Have you experienced a testicular  
infection since taking Amiodarone."

The results of our informal study:
4 out of 11 ARVD diagnosed males (36%) taking Amiodarone reported  
epididymitis.  Two men had repetitive bouts of epididymitis, two had  
suffered long continuous bouts.  All reported disabling pain and  
resistance to repeat courses of antibiotic therapy.  Lab work defied  
infection.  Relief from the epididymitis and its pain varied from 3  
weeks (at a time), to nearly a year.  The ages of the 4 affected men  
were mid 30s to mid 50s, with at least 1 man in each decade at the  
time of the study.  Only one of the affected men (one of the 2  
younger men) was tested for sterility due to a desire for progeny  
with no success, he was sterile. Amiodarone dosages differed, years  
on Amiodarone spanned approximately 2 - 7.

Shortcomings of our study:  The patients were not asked if they had  
ever experienced epididymitis prior to Amiodarone. To be honest, the  
men appeared to be so shocked and confounded by this problem that  
this was presumed (an error.)  Not ignoring the human condition, and  
while presumptions are dangerous, none of the above men were asked if  
they had been been involved in promiscuous relationships in the time  
period previous to their epididymitis.  All men were quite ill with  
their heart conditions and were in what were known to be long term  
and loving monogamous relationships.  Two of the men received heart  
transplants within 1 year of our study.  Two of the men often broke  
through Amiodarone and experienced intermittent exercise induced  
sustained VT, one was known to have done so during intercourse.  
( another error)

The sterile man and his wife mourned, "If we had been told that this  
was a possible side effect of Amiodarone, we could have planned our  
children before this could occur" (or considered the  banking of  
sperm.)  All affected men were nonplussed when they learned that this  
side effect had been known for over 15 years, yet  they had never  
been informed that it could occur.  In their estimation they suffered  
needlessly, and with no small amount of embarrassment. Moreover, they  
were exposed to long periods of antibiotic treatment for non-infections.

  Despite the shortcomings of our study, the evidence pointed toward   
Amiodarone-induced Epididymitis.  Additionally, theshortcomings do  
not negate the important point.  The loss of one's progeny due to an  
avoidable lack of information is a

painful and unnecessary loss.
In the essence of mercifully truncating this email, if you are
interested in skimming/reading:

1) brief notes pertaining to the 4 affected men, including Ami dosages
2) a few brief words from several other Amiodarone affected families
****This temporary webpage is offered:
****http://ARVD-ARVC-Info.com/WebX/ARVD/Amiodarone

3) that which at least one invested, experienced and compliant
"Amiodarone taking" patient community would like the physicians of

the world to know
****This temporary webpage is offered:
****http://ARVD-ARVC-Info.com/WebX/ARVD/Invested

Additional references are below.

Micheline J. (Tink) Long
International ARVD Family Support Network

====================
From, "Inflammatory Conditions of the Male Excurrent Ductal System.  
Part I;" ( P. T. K. Chan and P. N. Schlegel; J Androl, July 1, 2002;  
23(4): 453 - 460)

"Drug-induced epididymitis has been reported with the use of  
amiodarone (Gasparich et al, 1984; Hutcheson et al, 1998),..." ---   
(Gasparich JP, Mason JT, Greene HL, Berger RE, Krieger JN. Non- 
infectious epididymitis associated with amiodarone therapy. Lancet.  
1984; 2:1211–1212) ---(Hutcheson J, Peters CA, Diamond DA.  
Amiodarone induced epididymitis in children. J Urol. 1998;160:515–517)

"Although the exact mechanism of this disease is unknown, studies  
have shown that the drug concentration in many body tissues, such as  
epididymis, may be up to 300-fold greater than the serum level (Sadek  
et al, 1993) and that the side effects are dose-dependent and  
duration-dependent." ---(Greene HL, Graham EL, Werner JA, Sears GK,  
Gross BW, Graham GB, Kudenchuk PG, Probaugh GB. Toxic and therapeutic  
effects of amiofarone in the treatment of cardiac arrhythmias. J Am  
Coll Cardiol.1983;2:1114–1128)

"Reduction or discontinuation of amiodarone provides rapid relief of  
symptoms, although symptoms have been reported to recur if the drug  
is reinstituted at the same dosage (Gabal-Shehab and Monga, 1999)."  
--- (Gabal-Shehab LL, Monga M. Recurrent bilateral amiodarone induced  
epididymitis. J Urol. 1999;161:921.)


--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee