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S ??? @?   ? ?  ? ????藿h????? ? ???????33烫?膊#0 ????  ? C ??   ? S ???? @?   ? ?  ? ????藿h????? ? ???????33烫?膊rP?+锉鄢堑 撤 c[?咏卓O吐?IMQ[_仔OSaYW厢G夸75-%!聃坯?mA??e9   ?? ?]9?|(??    / 0DDTimes New Roman??|dv 0|( 0 D?[SOes New Roman??|dv 0|( 0?  D?ck?SO New Roman??|dv 0|( 0? 0D?fNSO New Roman???c action ⊙ 兴奋-收缩脱偶联,心肌收缩性减弱 ⊙ 心肌耗氧减少 ⊙ 硝苯地平表现为轻微的正性肌力作用 ⊙ 维拉帕米和地尔硫卓负性肌力作用强△ 负性频率和负性传导作用 negative chronotropic and conductive actions ⊙ 窦房结和房室结等慢反应细胞的0相除极和4相缓慢除极都是Ca2+内流所引起 ⊙ Calcium anatagonists : 降低窦房结自律性,心率减慢; 房室结传导速度减慢; 延长有效不应期,消除折返激动.△ 保护缺血心肌作用☆ 对其它平滑肌的作用☆ 改善组织血流的作用a☆ 其它作用 △ 抗动脉粥样硬化: A. 减少细胞内Ca2+离子的超负荷 B. 抑制血小板聚集; Ca2+拮抗药的作用方式 Clinical uses ☆ 心血管系统疾病: △ 高血压: 理想的抗高血压作用 △ 心绞痛 (angina pectoris) 变异型:休息时发作,冠脉痉挛引起,首选药 稳定型:劳累、激动时发作,可选维拉帕米、地尔硫卓 不稳定型:无明显诱因,昼夜都可发作,较严重,维拉帕米和地硫尔卓效果好 △ 心律失常:室上速首选 verapamil; 房颤和房扑。 △ 慢性心功能不全:长效钙拮抗剂,首选 amlodipine △ 肥厚性心肌病:☆ 脑血管疾病:nimodipine、flunarizine等用于脑血管痉挛及血管性头痛 ☆ 其他: 雷诺病—nimodipine、nifedipine 支气管哮喘、食管贲门失弛缓症、急性胃肠痉挛性腹痛、痛经等—verapamilAdverse reactionsContraindications第3节 常用钙拮抗药nifedipine-商品名心痛定Clinical uses AmlodipineNimodipine-尼莫通) Verapamil-异搏定(isoptin) Diltiazem 幻灯片 30`Brief description ☆ 正常心律: 窦性心律 频率:60-90bpm 规则:一般每2个心动周期间隔时间均相等☆ 心律失常(arrhythmia): 由于冲动起源、冲动传导异常所致的心跳节律和频率的紊乱,是一种严重的心脏疾病。 ☆ 分型:缓慢型心律失常 快速型心律失常 幻灯片 33 幻灯片 34 幻灯片 35☆ 心律失常发病和治疗 ? 发病:很多疾病可引起,25%使用强心苷,50%的麻醉病人,80%心肌梗死病人,美国每年因心律失常猝死者约有45-60万人; ? 治疗问题: ⊙ 不同的心律失常治疗方法不同; ⊙ 抗心律失常药物控制心律失常,但亦可导致心律失常。 第1节 心律失常的电生理基础心肌细胞 ☆ 自律细胞:窦房节、房室节和传导系统心肌细胞; ☆ 非自律细胞:心房和心室肌细胞。 心肌细胞特性 ☆ 自律性 ☆ 传导性 ☆ 兴奋性 ☆ 收缩性按照动作电位特征分类-有效不应期 Effective Refractory Period,ERP 幻灯片 41/ Electrophysiological basis of the arrhythmias ?$y0lb!?=财?~?A⒛@~?兀Qn卫烹啡?眈 kk??[?}?g鼽掭茨#wvw>蟓啐*???\ y|Z?G???? ???>????蛙o吼?wx?????命?C??酌}?w珙??羼r??w缇?鞣??w钗]脔v钗?y~??饱??圹???m?O国??珧剥腔r?\卩:[rQWnP??Dv??贻かx?T.?r?莞+麽v\?晗?a'.C觚??钔鲢ポ?~溶?+j?[夙/??殓???a?4???足7膪???r7yZtQ?u{酾G|)??j蹲?PQ??}:谆Q观] -I?;X?K篑??=.C?D?骷??坟_?uE{7w:H??=n?K??U\oKn ?A?????r?搞j7=[??袍 6oe3??? ?:K赋^e 獠^,??=富?N?K??;胪z??积品?qG籴lz???翱?;d?仂?q愚l?keS?????p痈w濡?骋V??该Yk]谑?A7???环;r?C??u湮曜(熘???]?T?[q?o??#镂莨;w??v榧sw钗莨;w?X塬v林燹????? ?y??"Am义?HD?v腺?{>圜p迫 ?pS.G.匡Ea???{?M 9{4$瑭呲佰A ?i莪?8?dA?>?钇笏???~.??禽貉|福?》瘸?熠M?鲐????璩)橹??炖??瞽坟噎?梯}?????~?P-U1w]V?-?唠?囹@会@-猩??峨A??VcM??.?B:?\b_躯0T???c躅_貂?q?E?{??+.4??吼`愎???楝?~$墙?细?wd??跟J炽5??:SY鲐?-?u??学?觯JW?F:K???EY加?k顼???0铒?沽P}P罡体?]?ポ馗%琨烟U?镔罡??v??5n8筛??L?u{v?ol l滑*??寰?I?*s?︹e]锔桕?L:o魈脑刁?汴??刽:?e??斯????M_??^???,*?耱???????很碾啄???伯.槛 A?k?N恫tn??岁蒴C?~T?n~9×臻,lW]??6??=??啄?9彦?薹m*?亿酱??.??庶??t[nY:???③*尴[???M?E7M??+???Q??捻[???谦氙巍?l?E??走a?i?????YⅩ诏q抽芊\S疫-q?s?骘????v??苦?毯f?vI??=+u苛5?????包グ??Xpo?Jw?镏?-q?划U?畹q???倒N???\;k?透A将P?+泾OQ,W+规A?JP??[甫jd?%褛??胝.?跸?Pp?3坼n!?SWO,?&^? ??/??裙i晃谳?嗖/阏????妖???汴x拚??柠?阃?/T+I纾% ??p'%?3.^圣??!筛??&????S??渴?}?]?|Q?眄?x???K寒??尔nI:圪鞅%]?iK7lp]?? 7(蝴?射?u???胼??:???墨?7*?g:X?kU?%V??*?/?晤r.Z??5阜lw茑??-?x?????qIk7 *??j?表???f\\忖?^?J?制?焊??w剞u????u褛埽??(d室n??殪/贲Y?q?\R?e.?癃p苏?a苣n?q棰n&?k獾?5W7}稼弯?~?+LgQS7h殁\S??;{舶??z?4关???w??r{ ?7X磐?hQ??+VwE;7)q???T?y6|%?.)q??wE7l?n???福?]?[工?沛??┛嘉??硖??w忆仓nRR??/?V?焊?V嘿#?%??,绮j??%钆J*愕? **??{Z怫m髫?Q⑨认jo?W,旌+??%d[??^o7?{堠[?郡蜂? ん4? ??钤u\ w??????n6?Ce8螽'6s漭?\?w钗莨;w珙荃?薰;w珙??w钗莨;w?v?/?q??迓:J?o洛A?? ?2^???o$??????p????[苏m"^~W? ???鼗?yN?+??R???wD忸w/7?z痃效?Cr?^|L??SA}嵘0??L??X\-烀???H2?yMn "?CacK??jW?H7??测?琵??,z8???.)忝裟?5\ ]?)喊?/~暄p*,7$厦w献衿?ge2*?间?x'柽窿?v?嗍??力?瞒??/:t w?搜-?D?,? ]蛑r??=?UL屣?尾. a??我?嫉?eu?7??2徼skr)????X肚hO?qW5?L?l劈蹈?稽@?7?-~)]?M孽黑?zs?萄A洼?0漪聃8?胆/?ol???R/?>????筘遂t?塑?叭?I???+?? z??G时?kq?? ???%29?铭??/BC?_??G??^)?nC?"c? ?娠F?u??(??攫d%??纶?j衮D?阜C梵?r ?%?厅>?"奚:?0?;?gU?rp???I???pC?wO?生ja?3W訇?迓??YS|?麽? 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"?4?&l|  ?0e???0e?????? ??????A??????????????????@????屏5%狭?怂8c8c     ??????1??瘗??d0u0盱?@T?????y?2 NP'p????'p??@A?BCD|E???????@8;?<?]唯 ?;2N蜕?;g4IdIdv 0p??????ppp@ <4!d!d` 0,?@<4dddd` 0,?@? <4BdBd?亵 0,??___PPT9? ???(???"???(,??????+???7???><?????????@???? %ei??,{?NASN? ?P[?S??i? $ ??O??_????P[?S?xvz?{? (??1955t^ HodgkinI{???S??i? ?T???5u?S????Rf[!j?W ???_1963t^??\utf[VY0 1976t^?v??Gr??b/g?^(u?N?\???v5u;m??TUS*N?S? ?@b? ?Neher??_1991t^?v??\uirf[VY0 0E???P[?S??vR{|(??r5u?S???P[?S? Sf[???P[?S? 9hnc?P[ ??'` N T?R:N?'Y{| 10???S? 20??S? 30???S? 40/l?S?((" :?? ???S?yr?_??45u?S?OV?'` ?;m?T1Y;m??? gyr_'`?;mBR?T;??BR?????S???L-?W?\O(uc???? ??;m5u?S? ?5u?'Y ?/f??tQKY?Y???QAm?vg;N????_0 yr?_?5u?S?OV?'` ?;m??ba ??P[ ??'`??NO(4\Z????S???h?N?WgY ?\O(ug YBg?vN{|?P[?S? ?R^^?0 R{|? 5u?S?OV?'`??S? ???OV?'`??S? ?QTteAm??S?54   ??<& Classifications of the drugs@'?$%?%???NLukSu??(WHO)?vR{| N0 ??'`Ca2+??bo? \O(u?NL-?WCa2+?S? 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B   ? ??Ca2+??bo??v\O(u?_T &?0.?0&?0??0 ??& ???S??HT N??` & 5u?S?OV?'` 5u?S??'`Ca2+?S??v?R??To?ir?KN\O(u;N???5u?S?vq_? N??R??`?Y?o``(nif)0_>e`(ver) 01Y;m`(dil) & ???s?OV?'` ?S?_>ea??A~ ?o?ir?v;??\O(u1\a:_?Eeo?ir????d??g?v???:N gHe?? ??? ? ?? ?>? ??#??#"?Adverse reactions'?6??4Y?0)wUf0YhT4l??vQ-N:Nib _??@??MR@?? ?^???4ltoYu@b? ]x?0Ws^?4Y?0b??0??0??4l?0)wUf0ON?RI{ ??^s|???0)wUf04Y?0YhT4l?0??? 0W\kxSS?4Y?04l?0)wUf0??? N?dex ????????d?Contraindications'?6??n??^s|00W\kxSS??y(u?N%N??p?0???T?_0II-III?AVB0?'`???? ]x?0Ws^??y(u?NNO@??S?P8 ?  !??  ?4??N Clinical uses & ?@??????? ? ?@??S? t??v?b?@??S\O(u ? ??? (angina pectoris) ?_?W?Oo`??\O ??Q ??c_w? ??? ?o? 3z?[?W??/}0????\O ?? ???^s|00W\kxSS N3z?[?W??f>f?? ?fq_? ?N8^?vQ?\'`tQKY @?Am??Rf[He?^?M?YhT;??R ???M??S ???c???X?R ?b@?\gZ???T?b6R@??s^??????Xu?|??((?'?? ????,*O%? Clinical uses'?0??J???:@?????'`:@??T???? ?? N3z?['`????[Nnf?m\T(u ?@??S?{?0-N0???@??S?qSa? 4O??U ?? N?O(u?SO;??o??v?@??S?T????? YhT@???c'`?????? nf?BR?W?]x?0Ws^/???[ ? 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N??R??`?Y?o``(nif)0_>e`(ver) 01Y;m`(dil) & ???s?OV?'` ?S?_>ea??A~ ?o?ir?v;??\O(u1\a:_?Eeo?ir????d??g?v???:N gHe?? ??? ? ?? ?>? ??#??#"?Adverse reactions'?6??4Y?0)wUf0YhT4l??vQ-N:Nib _??@??MR@?? ?^???4ltoYu@b? ]x?0Ws^?4Y?0b??0??0??4l?0)wUf0ON?RI{ ??^s|???0)wUf04Y?0YhT4l?0??? 0W\kxSS?4Y?04l?0)wUf0??? N?dex ????????d?Contraindications'?6??n??^s|00W\kxSS??y(u?N%N??p?0???T?_0II-III?AVB0?'`???? ]x?0Ws^??y(u?NNO@??S?H8 ?!???4??N Clinical uses & ?@??????? ? ?@??S? t??v?b?@??S\O(u ? ??? (angina pectoris) ?_?W?Oo`??\O ??Q ??c_w? ??? ?o? 3z?[?W??/}0????\O ?? ???^s|00W\kxSS N3z?[?W??f>f?? ?fq_? ?N8^?vQ?\'`tQKY @?Am??Rf[He?^?M?YhT;??R ???M??S ???c???X?R ?b@?\gZ???T?b6R@??s^??????Xu?|??((?'?? ????,*O%? Clinical uses'?0??J???:@?????'`:@??T???? ?? N3z?['`????[Nnf?m\T(u ?@??S?{?0-N0???@??S?qSa? 4O??U ?? N?O(u?SO;??o??v?@??S?T????? YhT@???c'`?????? nf?BR?W?]x?0Ws^/???[ ? No???^?u?s???(17-20%)???BR(control-release formunation ??? T)?u?s??x??? ?#????????X=@ & ? 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Ia0?N"l!TvU{|?]x?0Ws^ nifedipine Ib00W\kxSS{|?0W\kxSS Diltiazem Ic ???{|???^s| verapamil I{ 30?N0^? ??'`Ca2+??bo? 10?N???{|?Bh)R?0lBh)R?I{ 20nf<\?f{|?nf<\?fI{ 30vQ?[{|??KQf?gI{(Z?? ?? ?? ?? ???? ???? ?????H        5  ??,{2?? Actions and clinical uses pharmacological actions ?????v\O(u ?@???v\O(u ?vQ?[s^????v\O(u 9e?U??@?Am vQ?[\O(u v[}%?%?'?0%#? ?? ,2$?  ??& ?????v\O(u: &?$$????F?'`???R\O(u ?'`???s?T?'` O?\O(u ??:@????\O(u ?b?????S\O(u $f?3??$# ??? ?'`???R\O(u negative inotropic action ?" tQKY-6e)1?vPT? ????6e)'`?1_ ?" ????'l?\ ?" ]x?0Ws^h??:N{???vck'`???R\O(u ?" ??^s|?T0W\kxSS?'`???R\O(u:_j?? ?????$? ?$??$??$ ?$D   8 ?  ??H? ?'`???s?T?'` O?\O(u negative chronotropic and conductive actions ?" ??b??T?b??I{ba??^???v0?d??g?T4?bad??g?/fCa2+?QAm@b_w? ?" Calcium anatagonists ? M?NO??b???_'` ???s?ba; ?b?? 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Actions and clinical uses pharmacological actions ?????v\O(u ?@???v\O(u ?vQ?[s^????v\O(u 9e?U??@?Am vQ?[\O(u v[}%?%?'?0%#? ?? ,2$?  ??& ?????v\O(u: &?$$????F?'`???R\O(u ?'`???s?T?'` O?\O(u ??:@????\O(u ?b?????S\O(u $f?3??$# ??? ?'`???R\O(u negative inotropic action ?" tQKY-6e)1?vPT? ????6e)'`?1_ ?" ????'l?\ ?" ]x?0Ws^h??:N{???vck'`???R\O(u ?" ??^s|?T0W\kxSS?'`???R\O(u:_j?? ?????$? ?$??$??$ ?$D   8 ?  ??H? ?'`???s?T?'` O?\O(u negative chronotropic and conductive actions ?" ??b??T?b??I{ba??^???v0?d??g?T4?bad??g?/fCa2+?QAm@b_w? ?" Calcium anatagonists ? M?NO??b???_'` ???s?ba; ?b?? 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