心臓を守る！　ミネラルコルチコイド受容体拮抗薬

出版社： 文光堂
著者：
発行日： 2019-03-05
分野： 臨床医学：内科  >  循環器一般
ISBN： 9784830619465
電子書籍版： 2019-03-05 （第1版第1刷）
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ミネラルコルチコイド受容体拮抗薬（MRA）は従来アルドステロン拮抗薬と言われていたものである．近年，ミネラルコルチコイド受容体（MR）の新たな作用機序が続々と明らかになり，高血圧，CKD，メタボ，2型糖尿病，動脈硬化，そして心不全の病態進展に重要な役割を果たすことがわかってきた．本書では，MRの最新の病態生理からMRAの臨床エビデンス，そして次世代の非ステロイド型MRAの可能性までをエキスパートによる解説でまとめた．

目次

  • PART 1 アルドステロンとMRを理解する
    Q1　ミネラルコルチコイド受容体（MR）はどのようなものでしょうか？
    　　その働きとともに教えてください
    Q2　MRの腎上皮細胞における作用を教えてください
    Q3　MRは腎臓以外に広く分布すると聞きました．どのような臓器に分布するのか，
    　　そしてその役割についても教えてください
    Q4　アルドステロンは副腎皮質だけでなく他の組織でも産生されると聞きました．
    　　それに関して教えてください
    Q5　組織にはコルチゾールが高濃度存在し，アルドステロンとほぼ同じ親和性で
    　　MRに結合すると聞きました．
    　　なぜ，腎上皮細胞ではMRにアルドステロンのみ作用するのでしょうか？
    Q6　組織にはコルチゾールが高濃度存在し，アルドステロンとほぼ同じ親和性でMR に
    　　結合すると聞きました．
    　　心筋のMRではコルチゾールとアルドステロンがどのような関係になるのでしょうか？
    Q7　なぜアルドステロン拮抗薬ではなく，ミネラルコルチコイド受容体拮抗薬（MRA）と
    　　呼ぶようになったのでしょうか？
    Q8　アルドステロンの非上皮作用（腎上皮以外）に関して教えてください
    Q9　アルドステロンとアンジオテンシンIIおよび交感神経系との相互作用に関して教えてください
    Q10　アルドステロンのゲノム作用と非ゲノム作用を教えてください
    Q11　MRはどのようなとき，あるいは刺激で活性化されるのでしょうか？
    Q12　心不全，CKDや2型糖尿病でMRは活性化されているのでしょうか？
    Q13　MRAに抗炎症作用効果があると聞きました．その機序に関して教えてください
    Q14　MR活性化の中枢神経に対する生理的そして病的作用について教えてください
    Q15　MR活性化の血管に対する病的作用に関して教えてください
    Q16　MR活性化の心臓に対する病的作用に関して教えてください
    Q17　MR活性化の腎臓に対する病的作用に関して教えてください
    Q18　ACE阻害薬そしてARBでも出現するアルドステロンブレークスルーの機序と
    　　　病的意義を教えてください

    PART 2 MRAの臨床効果を検証する
    降圧薬としてのMRA
    Q19　欧米，日本の高血圧ガイドラインにおけるMRAの位置づけを教えてください
    Q20　スピロノラクトンとエプレレノンの使い分けに関して教えてください
    Q21　ACE阻害薬・ARBにMRAを加えるときのメリットと注意点を教えてください
    Q22　MRAと併用するとより強い降圧効果が得られる組み合わせを教えてください
    Q23　原発性アルドステロン症の病態と治療方針を教えてください
    心不全
    Q24　MRAの多施設共同試験を解説する（HFrEF）：RALES試験
    Q25　MRAの多施設共同試験を解説する（HFrEF）：EMPHASIS-HF研究とJ-EMPHASISHF研究
    Q26　HFrEF患者にはtriple blockadeが必要といわれています．
    　　　なぜ，ACE阻害薬やβ遮断薬にMRAを加えると相加効果を出すのでしょうか？
    Q27　HFrEF患者ではACE阻害薬やARBを最大限まで使用しないとMRAを
    　　　併用してはいけないのでしょうか？
    　　　あるいは，MRAの先行投与はいけないのでしょうか？
    Q28　HFrEF患者の入院急性期からMRAを使用したほうがよいでしょうか？
    Q29　HFrEF患者にMRAを用いる場合に徐々に増量したほうがよいでしょうか？
    Q30　ガイドラインではNYHA II度からMRAが推奨されていますが，
    　　　NYHA I度の患者には使用すべきでしょうか？
    Q31　超重症のHFrEF患者にもMRAは使うべきでしょうか？
    Q32　MRAはHFrEF患者の突然死を減少させると聞きました．そのエビデンスと機序を教えてください
    Q33　MRAの多施設共同試験を解説する（HFpEF）：TOPCAT試験
    Q34　HFpEF患者にはMRA は無効なのでしょうか？ 軽症例に使用するメリットはあるでしょうか？
    Q35　MRAの多施設共同試験を解説する（心筋梗塞）：EPHESUS試験
    Q36　MRAには交感神経抑制作用があるのでしょうか？
    Q37　どのような心筋梗塞患者にMRAが推奨されるのでしょうか？
    Q38　MRAの心肥大抑制効果に関して教えてください
    Q39　MRAでしばしば高K血症が問題になりますが，心不全患者における
    　　　適正な血清K値に関して教えてください
    血管保護作用
    Q40　MRAの血管内皮機能とスティフネスに対する効果を教えてください
    Q41　MRAの心血管イベント予防効果とその機序に関して教えてください
    利尿薬としてのMRA
    Q42　ループ利尿薬単独よりもMRAを加えたほうがよいといわれています．
    　　　なぜなのでしょうか？ その理由を教えてください
    Q43　慢性心不全患者の利尿におけるMRAそしてサイアザイドの役割を教えてください
    腎保護効果
    Q44　MRAは腎不全患者で使いにくい印象があります．腎保護効果はあるのでしょうか？
    Q45　MRAは糖尿病性腎症の蛋白尿に対する効果があると聞きました．
    　　　そのエビデンスと機序を教えてください
    状況別使用法
    Q46　75歳以上の高齢高血圧患者に対するMRAの適応と注意点に関して教えてください
    Q47　高血圧を合併する2型糖尿病患者にMRAを使用するメリットと注意点を教えてください
    MRA の副作用とその対策
    Q48　MRAで誘発される高K血症の機序とそのハイリスク群を教えてください
    Q49　MRAの高K血症対策：どこまで許容し，どのように対応したらよいのか教えてください
    Q50　MRAの禁忌に関して教えてください
    PART 3次世代MRAの可能性を探る
    Q51　非ステロイド型MRAとはどのようなものでしょうか？
    Q52　非ステロイド型MRAはスピロノラクトン，エプレレノンと異なり，
    　　　どのような利点があるのでしょうか？
    Q53　非ステロイド型MRAにはどのようなものがあるのでしょうか？
    Q54　非ステロイド型MRAの降圧効果に関して教えてください
    Q55　非ステロイド型MRAの腎保護効果の機序と糖尿病性腎症に対する効果に関して教えてください
    Q56　非ステロイド型MRAの心不全に対する効果に関して教えてください
    Q57　非ステロイド型MRAの副作用に関して教えてください

この書籍の参考文献

参考文献のリンクは、リンク先の都合等により正しく表示されない場合がありますので、あらかじめご了承下さい。

本参考文献は電子書籍掲載内容を元にしております。

PART 1 アルドステロンとMRを理解する

P.4 掲載の参考文献
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P.22 掲載の参考文献
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P.24 掲載の参考文献
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P.27 掲載の参考文献
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P.29 掲載の参考文献
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P.31 掲載の参考文献
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P.33 掲載の参考文献
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P.35 掲載の参考文献
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2) Yamamuro, M et al : Direct effects of aldosterone on cardiomyocytes in the presence of normal and elevated extracellular sodium. Endocrinology 147 : 1314-1321, 2006
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P.40 掲載の参考文献
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P.42 掲載の参考文献
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5) Sato, A et al : Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension 41 : 64-68, 2003
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PART 2 MRAの臨床効果を検証する

P.45 掲載の参考文献
1) 日本高血圧学会 : 高血圧治療ガイドライン 2014. ライフサイエンス出版, 東京, 2014
 
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P.47 掲載の参考文献
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2) Pitt, B et al : The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341 : 709-717, 1999
 
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4) Zannad, F et al : Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 364 : 11-21, 2011
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1) Pitt, B et al : The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 341 : 709-717, 1999
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PART 3 次世代MRAの可能性を探る

P.125 掲載の参考文献
1) Sato, A : Mineralocorticoid receptor antagonists : their use and differentiation in Japan. Hypertens Res 36 : 185-190, 2013
PubMed
2) Sato, A : The necessity and effectiveness of mineralocorticoid receptor antagonist in the treatment of diabetic nephropathy. Hypertens Res 38 : 367-374, 2015
PubMed
3) Dietz, JD et al : A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension 51 : 742-748, 2008
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