2015年06月

Dr.水谷の女性と妊婦講座 No.61 張り止めの薬を使われた妊婦は赤ちゃんに鬼乳を飲ませるのを避けるのがなぜ望ましいのでしょうか?  副作用発生を“自供”する使用上の注意文書



▽妊娠して、しかも早産になりかけたりしない限り、妊婦さんが切迫早産の治療薬のことを知る機会は少ないと思います。この薬は、よく「子宮の張り止めの薬」と呼ばれています。お腹の張りを訴える妊婦さんに、産婦人科医がこともなげに「じゃあ、張り止めのお薬を出しましょうか?」と言ったという話はよく耳にします。



▽良く使われている張り止めの薬は「基本的に喘息のくすりであるべ-ター2刺激剤」です。今では先発薬は特許切れなので、その特許が失効した後に発売されたゼネリック(後発薬)と呼ばれる薬が多数あります。

▽私は、先発も後発も張り止め薬を使った経験がないので知らなかったのですが、名古屋市内のある会合に出席した際、そのゼネリック(後発薬,A社)の「使用上の注意」という添付文書を読む機会がありました。一般の人も読もうと思えば読めるのですが、普通はお医者さんしか読みません。



▽その添付文書の内容に、びっくり仰天しました。そこには次の様に記載されていました。1. 妊娠16週未満の症例(妊婦のことです)に関する安全性及び有効性は確立していないので,投与しないこと(使用経験が少ない)2.出産直前に本剤を投与した場合には,出産直後の授乳を避けることが望ましい.[動物実験(ラット)で乳汁中への移行が報告されている.]。

▽興味を持たれた方はURL:http://www.info.pmda.go.jp/go/pack/2590004F1273_1_02をクリックしてください。これは、独立行政法人医薬品医療機器総合機器のホームページです。



▽話を戻します。この「子宮の張り止めの薬」を使われる先生方は、「出産後の授乳は避けるのが望ましい」という表現に違和感を覚えませんか? 張り止めの薬が、妊婦に投与されると、点滴薬でも錠剤でも、薬の有効成分は胎盤を簡単に通過して胎児の血液濃度は、妊婦の血液濃度と同じになります。この子宮の「張り止めの薬」の発売以前から良く知られていた事実です。



▽産婦人科医なら常識ですが、褥婦(じょくふ=分娩後2週間までの妊婦の呼び方)の乳汁の分泌が始まって1週間は、新生児が免疫力を母からもらえる唯一の機会なのです。母乳の初乳(鬼乳=きにゅう)は、免疫の大切なタンパクがあるため、是非とも新生児に飲ませるべきなのです。詳しくは次のURLをクリックしてください。URL:http://p-lap.doorblog.jp/archives/40080325.html 



▽ところが、「張り止めの薬」を投与されている妊婦さんは、貴重な初乳を赤ちゃんに飲ませない方が良いことになります。「子宮の張り止めの薬」の「使用上の注意」の「出産後の授乳は避けるのが望ましい」という表現は、「張り止めの薬」が胎児に移行すると、副作用が発生する可能性が高いのを“自供”しているようなものでしょう。



▽仮にそうではないとするなら、分娩直後の赤ちゃんに欠かせない鬼乳はなぜ避けるのが望ましいのか。そこまで書かないと、使用上の注意文書にはならないと思うのですが。どうでしょうか。


 


 


 


 


 


 


 


 

Lecture on human pregnancy No.14 Is Antithrombin (ATⅢ) a hopeful treatment for preeclampsia sure enough ? :Gestational hypertension- the result doesn’t draw the treatment.


 “innga ouhou” in Buddhism term, meaning “results are creation of causes” in brief.

Why gestational hypertension occurs, there is no clear explanations for its causes until now, so various treatments emerge without meeting causal cure, unfortunately.

Surprising enough, this incurable disease disappears when the fetus was -very low weight though- forced to be delivered, or otherwise died due to aggravating of severe preeclampsia.

The fact of, fetus living in the uterus, straightforwardly tells us the direct cause, or the etiology, of the disease. Therefore the results will be as follows.

Symptoms appeared in the mothers’ body are the results. Firstly, edema, abnormal weight gain. Normally, pregnant woman puts her weight about 400g per week, irrespective of her gestational term. Any additional weight gain should be taken suspiciously as the omen of edema.

The second symptom is the rise of blood pressure i.e., hypertension. I wrote, in the previous blog, that the pressure should become lower, compared to pre-gestation state, in the mid-term of gestation, which is around 14th to 30th weeks.

http://livedoor.blogcms.jp/blog/plap/article/edit?id=38627969

The third symptom is proteinuria, which is the condition of protein substances are excreted into the urine. This means, dysfunction of the kidneys and it must be thought aggravation of the disease.

When the disease status aggravates, various other symptoms may appear. In other words, variety of physiological (pathologic) changes start to occur. They are the body’s defense reactions, one of which is inflammatory reaction.

When I was working for the University of Nagoya, I had an opportunity to attend the scientific congress for gestational hypertension in Europe. There, I was listening to the lecture given by a professor of well-known University in the UK. His lecture was about,” the cause of gestational hypertension is inflammation.”

I asked him of a question from auditorium that, my clinical experiences with many cases of gestational hypertension, I never encountered the fever of the patients, though undoubtedly, inflammation should cause fever. The lecturer didn’t give a clear answer to my question.

If we try to grasp biological reactions based on the progression of the disease, -the inflammation theory-, such a n elusive and bizarre explanation, was preached.

The ultimate change of the worsening of blood pressure is, eclampsia, the major symptom in gestational hypertension. Abrupt rise of the pressure give rise to aggravated cerebral circulation, causing unconsciousness, systemic convulsion follows. HELLP, a kind of disseminated intervascular coagulation (DIC) may sometimes be developed. HELLP is the abbreviation for hemolysis, elevated liver enzyme and, low platelets.

In obstetric circumstances, common symptoms of DIC are, bleeding or dysfunction of maternal organs, such as the liver for example, due to vascular occlusion of the capillaries in the whole body. Further progression of the disease may cause hemolytic anemia and shock.



Anti-hypertensives, such as methyldopa, calcium channel blockers, and magnesium sulfate are usually prescribed.

You may think lowering the blood pressure for the treatment of high blood pressure is a natural approach, however, the fetus increases blood pressure in preeclampsia and thus respond to the stress in the feto-placental unit.

In fact, the situation may seem to be alleviated when maternal blood pressure was lowered by anti-hypertensive medication, however, this kind of situation should be interpreted as being the worsening of fetal environment.

Most of you may have experienced that drugs were not effective to treat severe cases.

http://livedoor.blogcms.jp/blog/plap/article/edit?id=21419968  http://livedoor.blogcms.jp/blog/plap/article/edit?id=21777330

As I described in my blog, magnesium sulfate is the compound for stop convulsion. Since long time, it has been used to suppress systemic convulsion at the onset of eclampsia, therefore a onetime treatment but not for relieving gestational hypertension itself.

http://livedoor.blogcms.jp/blog/plap/article/edit?id=7222558  http://livedoor.blogcms.jp/blog/plap/article/edit?id=8423797  http://livedoor.blogcms.jp/blog/plap/article/edit?id=10156761  http://livedoor.blogcms.jp/blog/plap/article/edit?id=15554285  http://livedoor.blogcms.jp/blog/plap/article/edit?id=18924144  http://livedoor.blogcms.jp/blog/plap/article/edit?id=28941608  http://livedoor.blogcms.jp/blog/plap/article/edit?id=40098448

Having said that, is there any possible - effective treatment?  Straight to the conclusion, there is none, if we take result-oriented approach.

Antithrombin (AT) is on the clinical trials by well-known University in the US in alliance with a venture capital.

http://www.wbjournal.com/article/20150205/METROWEST01/150209973/framingham-biopharma-hopes-to-rewrite-the-rules-of-preeclampsia-treatment

Let’s think about blood coagulation. It starts with prothrombin, a kind of blood protein, is activated and transformed into thrombin, a kind of protease.  Thrombin transforms fibrinogen, or a fiber-like material, into fibrin which forms a mass of aggregated fibrin. Briefly, this is the coagulation process.


AT is a kind of blood protein and it’s function is to suppress coagulation. As it literally says “anti”, it resists against thrombin, therefore, it is a result-oriented approach for the disease. Can we then expect a good result?

Urokinase is another protease which transforms plasminogen (a precursor of inactive enzyme) into plasmin.(also a protease) It is excreted into urine.

Plasmin degrades fibrin or fibrinogen, AT blocks formation of thrombus, urokinase degenerates thrombus. All of these activities are related to thrombin.

I do remember that one of the well-known obstetrician proposed an optional treatment for gestational hypertension with urokinase.

In May this year, the following literature was published. (Ann Intern Med) Dysfunction of epithelial cells requires aspirin to prevent the onset of preeclampsia. The literature said that “it is recommended to prescribe aspirin for high-risk pregnant patients as there is no alternatives”. I mentioned in my blog that aspirin could pose risk to the pregnant mother. Is it meaning-full at all?

In the Ann Intern Med May version, the results of the randomized trial of low molecular weight heparin (LMWH) for the treatment of   repeated abortion patients (434 cases) who aborted at five to eight gestational week, were shown.

Heparin is a physiological substance which inhibits blood coagulation and synthesized in the liver. It inhibits thrombi formed by blood coagulation. In this report, heparin did not demonstrate efficacy for preventing miscarriage.

There is a line of thought that anti-coagulation treatment using heparin or aspirin in the treatment of miscarriage where hyper-coagulative condition is often seen. Cochrane Database Syst Rev. 2009

Anti-coagulation therapy, in the recurrent miscarriage, in the early phase of pregnancy, may be as same as in the situation of anti-coagulation therapy for gestational hypertension.


In the past, gestational hypertension was named gestational toxemia. This naming, in a sense, captures the essence of the disease.

The mother incurred into toxemic status while in the pregnant (fetus grows in the uterus) this may be easier to conceptually capture the situation that, diarrhea after eating toxic food.

After knowing that the clinical trials for AT in the US,I thought again about the naming of gestational toxemia. Now I think fundamental approach for the treatment of gestational hypertension as well as miscarriage need to be investigated.

http://livedoor.blogcms.jp/blog/plap/article/edit?id=38573481  http://livedoor.blogcms.jp/blog/plap/article/edit?id=42977235  http://livedoor.blogcms.jp/blog/plap/article/edit?id=43673641



 

 

 

 

 

 

 

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