這本書的用詞會讓人產生混淆 就我的理解, 參考braunward 9th ch35 像Na/K/Ca 這一類voltage gated ion channel皆以三種形式存在 (有些藥理的書也會提到 e.g. Katzung) (voltage gated意指channel 打開受cell membrane potential 影響 cell membrane depolarization時才打開) 1. open/activated state (cell membrane depolarization才打開 這本書上寫成:open, depolarized channels) 2. closed/inactivated state (Ca channel 在打開後, 就會直接進入 closed/inativated state, 這個state 無法再度被活化) 3. closed/resting state(cell membrane repolarization後, Ca channel 才會從closed inativated state進入close resting state 此狀態下的channel 才可以再度被活化) 就因為Verapamil and ditiazem 只會抑制open/activated calcium cnannel 所以才叫use-dependent,而且不讓open/ativated calcium channel 回到 close/resting state (原文寫prevent repolarization,應該就是不讓calcium channel回到closed/resting state, 而不是指prevent cell menbrane repolarization) 因為verapamil/diltaizem主要的作用就是抑制Ca流入細胞, 整體而言是會"加速" cell membrane repoalrization, 但因為抑制calcium channel回到 close/resting state, 對下一個actional potential cycle而言, 可 以活化的calcium channel變少了, 因此會增加effective refractory period, 亦即傳導速度變慢) ※ 引述《hpw01 (hpw)》之銘言： : 在Lippincotts Illustrated Reviews Pharmacology第十七章提到 : 關於第四類抗心律不整藥物Verapamil and diltiazem的機轉: : Actions: Calcium enters cells by voltage-sensitive channels and by : receptor-operated channels that are controlled by the binding of agonists, : such as catecholamines, to membrane receptors. Calcium-channel blockers, such : as verapamil and diltiazem, are more effective against the voltage-sensitive : channels, causing a decrease in the slow inward current that triggers cardiac : contraction.以上可以讀懂 : Verapamil and diltiazem bind only to open, depolarized channels, : thus preventing repolarization until the drug dissociates from the channel. : 這邊開始不懂了 : 為什麼只接在打開跟去極化的通道會防止通道的再極化? : These drugs are therefore use-dependent; that is, they block most effectively : when the heart is beating rapidly, because in a normally paced heart, the : calcium channels have time to repolarize and the bound drug dissociates from : the channel before the next conduction pulse. : 不太理解甚麼叫做鈣離子通道的再極化 : 書上講動作電位有一個圖將Action potential of a Purkinje fiber分成 : 0 1 2 3 4 五個phase : 其中phase3再極化時作用的不是主要是鉀離子嗎?跟鈣離子有甚麼關係呢? : 最後一段(前面的問題解決了應該就懂了,打上來幫助理解) : By decreasing the inward current carried by calcium, : verapamil and diltiazem slow conduction and : prolong the effective refractory period in tissues that are dependent on : calcium currents, such as the AV node. These drugs are therefore effective in : treating arrhythmias that must traverse calcium-dependent cardiac tissues. : 書上還提到Verapamil and diltiazem治療心房性心律不整比心室性心律不整有效 : 請問是為什麼呢? 最後一個問題, 我的理解是verapamil and diltiazem主要作用於SA node and AV node, 心房性心律不整, 一定要經過AV node 傳到心室, 才會造成心搏過快 因此只要抑制AV node整體速度就會降下來, 反觀心室性心律不整並不需要AV node就可以跳, 因此你抑制SA node or AV node,對心室性心律不整沒有幫助. --

※ 發信站: 批踢踢實業坊(ptt.cc) ◆ From: 114.34.109.233 ※ 編輯: sophiajoan 來自: 114.34.109.233 (07/30 20:45)