GABAとベンゾジアゼピン系薬
GABA(γ-アミノ酪酸)
GABAはGABAA受容体に結合することで細胞内にClイオンを流入させて神経細胞膜電位を過分極にすることで、活動電位発生を抑制して神経抑制効果を発揮するという抑制性神経伝達物質である。興奮性神経伝達物質であるグルタミン酸からグルタミン酸脱炭酸酵素の働きによって作られる。
GABAA受容体
GABAA受容体にはGABA結合部位のみではなく、ベンゾジアゼピン系薬やバルビツール酸系薬やアルコール・揮発性麻酔薬など多くの薬剤との結合部位が存在する。これらの薬剤はGABAA受容体の作用を増強させることで効果を発揮する。
ベンゾジアゼピン系薬
ベンゾジアゼピン系薬には抗不安作用・催眠作用(傾眠作用)・抗けいれん作用・筋弛緩作用などの臨床的薬理作用がある。これらの作用に伴って、海馬の活動性を抑制してしまうことで服用後の記憶が障害される前向健忘やふらついて転倒するといった有害事象が起こる。
また、アルコール離脱症状に対しては敢えてベンゾジアゼピン系薬を用いることで身体を偽飲酒状態にして騙す。これはベンゾジアゼピン系薬とアルコールのGABA受容体に結合する部位が一緒だということを利用している。
一般的なせん妄は抗精神病薬で治療するのに対してアルコール離脱せん妄はベンゾジアゼピン系薬で治療する。アルコール離脱せん妄に対する予防投与としてベンゾジアゼピン系薬が用いられることが医師国家試験ではしばしば出題される。
ベンゾジアゼピン離脱症候群
ベンゾジアゼピンには依存性と耐性があることが分かっている。使用するにつれて薬剤の用量がどんどん増えていくのにも関わらずどんどん効かなくなっていき、飲むのを止めるとベンゾジアゼピン離脱症候群が起こるので止めることができないという状況に陥ることがある。
深刻な睡眠障害・不安の増加・けいれん発作・自立神経過活動(発汗・動悸)といった症状が出る。
参考文献
GABAA受容体応答の制御機構:https://www.jstage.jst.go.jp/article/hirosakiigaku/66/2-4/66_105/_pdf/-char/ja
GABA-A受容体作動薬における薬物依存:https://www.kyorin-pharm.co.jp/prodinfo/useful/doctorsalon/upload_docs/161160-1-23.pdf
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