(cardiovascular pharmacology)

82655188Oljt@xjtu.edu.cnofficeNo.9169th floorLibrary Building

24 (drugs acting on ion channels in cardiovascular system )

permeationselectivitygatingRPAP

1(voltage gated channels): (ligand gated channels)(mechanically gated ion channels)(nongated background/leak channels2 ionchannelpathies

(calcium channel blockers,)

()1.2. LTNPQR LT :

calcium antagonist () Ca2+,Ca2+(calcium channel blocker)()1.WHO(1987) PDC PDC

2.IUPHAR(1992)L4 a b c d T N P

()1. (1), (2),, (3)Ca2+2. (1), (2) (3)

3. (1) (2) (3) (4)(, 4. ,,5. ASVSMC6. ;; 7.;;;

()1.2.

()1.(1),(2),(3),(4)(5),,,,,,(6)As2.,

()

+++ ++ ++ +++ ++ ++ 0+ 0+ 0 0 0 0 +0

(drugs acting on potassium channel)

(potassium channel modulators). (potassium channel blockers) : (potassium channel openers) ,

(drugs acting on sodium channel)

(sodium channel blockers) I

25 (antiarrhythmic agents)

1.*2. RPAP AP AP APNa+K+Ca2+3.,,

1.2.* RPAP AP AP APNa+K+Ca2+3.,,

1.2. RPAP AP AP APNa+K+Ca2+3.,,*

1. (1):, (2)2.(afterdepolarization)(triggered activity) AP,TP,,

: (EAD)AP23* (DAD)AP :K+ ,TP,,Ca2+AP Ca2+Na+Na+TP,

: (EAD)AP23 (DAD)AP*: K+,TP,, Ca2+AP Ca2+Na+Na+TP,

: (EAD)AP23 (DAD)AP. : K+,TP,, Ca2+ AP Ca2+Na+Na+TP,

3. (1):,, AP (2)(reentry) : : ERP *

reentry

4.

RPAP 1. Na+Ca2+K+2. (1) K+

(2) Na+(Ca2+K+) 3.ERPAPD (1)ERP: Na+Ca2+K+ERP (2)ERP/APD (3)ERP4. ,,

:Na+ a, b, c::APD():

pro-arrhythmia

()a(quinidine)1.Na+,K+,Ca2+ Na+(, ) (1) (2) (3)APDERP (4)

2.1.,2.,,3.,1.chichonic reaction2.3.:,,,4.

(procainamide) :1.2.,,,3.,,;4.,,

() b(lidocaine)K+,Na+,K+ 1.2.ERPAPD,ERP/APD,ERP,*3.

() B(lidocaine)K+,Na+ 1.2.ERPAPD,ERP/APD,ERP,3.

(1)(2) (),1.2.

(phenytoin sodium)1.,;Na+-K+-ATP,2.,ERPAPD,,3.,,4.

mexiletine

,,,

()C(propafenone)1.Na+2.APDERP;3.4.

(flecainide),(encainide)

(,propranolol) CA1Na+Ca2+ ,,ERP(1)()1(2)Na+ : : 1.: 2. 3.ERP

CA()(1)(2)(3),, (4),;(5)

APD (amiodarone )T3T41.APDERP2.:,3.4.,,

,1.2.3.,4.

sotalol12APDERP

LERP ,,(verapamil)Ca2+ :1. 2. 3.ERP

1.2.,3.4. ,;

:P291

27 [Drugs used in treatment of chronic congestive heart failure(CHF)]

RAAI :,

1.*2.3.:,,4. (1) (2)ACEI

1.2.*3.:,,4. (1) (2)ACEI

1.2.3.:,,4. 507070ACEI8090AVPET

RAAI: ACEI, AT1, : :,(1)(2)ACEI

RAAI(renin-angiotensin-aldosterone inhibitor) ACEIAT1

ACEI 1.12

2CHF(1)ACE ACEAng Ang NOPGI2

(2): ACEAng (3) (ventricular re-modeling)4 CA1AC5VEC

AngACEIAngNOPGI2 3.CHF 4.5. (captopril) (enalapril) (cilazapril) (benazapril)

AT1(ARB)1.Ang2.CHF( Ang)3. ACEI4.(losartan)(valsartan)(erbesartan)

(aldosterone antagonists) VSMC PAI (spironolacton) ACEI

(diuretics) 1VSMC2ACEI CHF CHF CHF3RAASNA

1. 2.(1) Ang II CACa2+

CA RAAS (2) (3) (4)3.CHF()CHF,,CHF,

(carvedilol)()(metoprolol)(bisoprolol)4.(1)ACEI(2)(3) 3(4)(5)

(cardiotonic agents) 1.,2. (1), (2)1, , (3)PDEPDEcAMP (4)(calcium sensitizer),;PDE-III

(cardiac glycosides)

1.(1) :,, :, ,,*(2) , ,

1.(1) :,, :, ,,(2) , ,

(3) +(Na+-K+-ATP)Na+K+Na+Na+Na+Ca2+ ,Na+Ca2+Ca2+*2.(1)(2)

(3) +(Na+-K+-ATP)Na+K+Na+Na+Na+Ca2+ ,Na+Ca2+Ca2+2.(1)(2)

(3) ,; ;

3.(1)(2) () (3)

4. ,5. ERP (1)Na+-K+-ATP(2) ACh,,ERP

6.P-P,P-R,Q-T,T,S-T,

NA CNSCTZCHFII

(1) (2)Na+-K+-ATPNa+

1.CHF(1), ; ; (2),

(1)(2)(3)B1,(4),,(5),

1.2.3.1997

2.(1) ,(2) ERP, , ,, ,(3)

(1),(2) ,;K,, , , :,;,,,K , ,,K,,

1. (1) (2)CNS (3) 2.

(1),,,,(2), 3. (1) (2) (3) , (4)

1.+ , ,24h, ,24 , 1.251.5mg 0.1250.5mg2. ,0.25mg/1

(1)(digitoxin),(2)(digoxin),(3) Clanatoside Ccedilanid) K(strophantin K)

( receptor agonists) 1. AdNAIP (1) (2) (3)

2.1,,,,,

(1) ,,(2)(xamoterol) (3)DA 1 ,1DR 12DR(4):()

(PDEI) (1)+(2)PDEVSMCcAMP; VSM,,(3)(4),(5)(milrinone),

calcium sensitizer PDE-III

(vasodilators) 1. (1)AV , (2)2., 3. (1)

(2) (3) 4.(1)(2)(3) ;(4)

4. (1)(nitrovasodilator) (V>A),(A=V) (2)(A>V) (3) (A>V) (4) A>V (5)ACEI

ACEIACEIACEIACEIACEIACEI(:2002)

28 (antianginal drugs)

1.2. (1) (2) 3 3.,

4. , , 5.: (1) (2) (3)4

(nitrates) (nitroglycerin),,(8%),(80%),

,VSMNOGCcGMP cGMPPK *1.VSM,AV, V2.., , 3.,, ,,

,VSMNOGCcGMP cGMPPK 1.VSM,AV, V2.., , 3.,, ,,

1.: A,V,2., (1)AV (2),,,,,()3. NOPGI2CGRP 4.NO

1.,,,2.:,3.1.2.VSMC,,

(receptor blockers) 1. 1,2.(1)1(2)2,3.FFAGS

1.()2.?3. 4., (1),

(2) (1),(2)(3)(4)

(calcium antagonists) (nifedipine)(verapamil)(diltiazem)Ca2+1. ,

2.(1),(2)3. Ca2+Ca2+4. ,,,

1.2.3.,4.,,5.,,,,

/

29 (anti-atherosclerotic drugs) 1.As2.(1)LDL ; (2)TGVLDL. A 3.

lipidemic-modulating drugs 1. cholTG cholTGPL HDLLDLIDLVLDLCM2. () (-) (ab) -() -() ()()*

AS I CM TGTC a LDL TC b VLDLLDL TGTC III IDL TGTC IV VLDL TG V CMVLDL TGTC

3.(1)(2)(3)LDLVLDLTCTGapo BHDLapo A

LDL ()HMG CoA(HMG CoA reductase inhibitors)(statins)1.(1)TCLDLVLDLapo B,HDL(2) VSMC As CAs

2.HMG CoAchol,cholLDLLDLVLDLapo BVLDL3.(ab)4.ALP5.

(cholestyramine,)(colestipol,)TCLDL(1)chol (2)chola1.2.3.,,,,,

TGVLDL(nicotinic acid)1.TG,VLDLLDL(TGVLDL)2.HDL3.TXA2PGI2TG B,,1.2.,3.

fibrates,1.TGVLDLLDLTCHDL2.3.(1)VLDLTG (2),VLDLTG (3)PPAR b,,,III1.2.,,,,

(probucol)1.1ox-LDL2TCLDLHDL3As2.3.

:E(vitmin E)

(polyenoic fatty acid)

(unsaturated fatty acids)

:1.TGcholLDLVLDLHDL2.3.4.

(heparin)AsTCTGLDLVLDLHDLVSMC As

(

30 (antihypertensive drugshypotensive drugs)

1. ,140/90mmHg2.VECAsAs 3. (1)/ (2)///3/*

4.

1.2.- (1)ACEI (2)AT1 (3):3. (1) (2) (3) (4) 4.5. (1):, (2):,*

(duretics) ,,1. 2. Na+VSMC Na+ Na+-Ca2+Ca2+VSM

1.,2.3..ACEI (,)Na+()()

-renin-angiotensin inhibitors ACEI1.10 2.,3.,4.5.6.

ACE 3,,,,+(),+,+

1.ACE,2.,PGI2NO3.4.5.,6.

1.:++2.,1.()2.3.4.(captopril)(enalapril)(ramipril)(benazapril)

ACEI1.2.ACEI3.AT11.AT AT4AT12. AT1AT-II3.:ACEI4.(losartan),(valsartan) (irbesartan)

(clonidine,)1. (1), (2), (3) 2.,

1.I12.2,()3.NA2NA

1. 2.1.2.3.

1.(1) 2. 3.

(prazosin)1.(1), (2) (3) (4), (5) 2.3.TGTCLDL-cVLDL-cHDL 1

1.,2.1.2.

(propranolol)1.,,2.3.,4.1.12.NA3.24.()5.6.

1.2. (1) (2) (3),,3.,

(labetalol,)1.,1212112.,3.

VSMCCa2+Ca2+VSM

(nifedipine) (nitrendipine) (lacidipine) (amlodipine)

(nifedipine)1.,2.3.,4.ACEI4.,,5.,,

(nitrendipine)(lacidipine)(amlodipine)

1. 2.

(hydralazine,)1.,2.,,,3.,4.,,Ca2+Ca2+

1.2.,1.2.3.

(diazoxide)1.2.,3. VSM4.,5.,,

,

(sodium nitroprusside)1.,2.3.NOGCcGMP VSM4.,5.,

1., ACEI ,*

2. (1) (2)+ (3)++ (4)+++3. (1)-,,ACEI (2)-,, ACEI, (3),,, ACEI, (4),,

(5), (6) (7) (8) (9)(10)4.5.6.7.ACEIAT18.(ACEI)

Thanks for your cooperation

11111