[LEC18_S2.5] Thuốc điều trị đau thắt ngực và bệnh mạch vành (2).pdf

Bài giảng thuốc điều trị đau thắt ngực và mạch vành, bộ môn Dược lý - Trường Đại học Y Hà Nội

1. >
THUOCDIEUTRI
DAUTHATNGLTCVA
BENHMACHVANH
• •
TSMaiPhiFongThanh

2. MUCTIEUHOCTAP
# • •
Saukhihocxongbainay,sinhviencokhanang:
1.Phanbietdu’o’
cvjtrftacdungchuyeucuacacnhom
thuocdu’o’cSIKdungdedieutrjdauthatngi/cvabenh
machvanh
2.Trinhbaydu’o’ccochetacdung,doocdonghoc,tacdung
du’
o’
clyvatacdungkhongmongmuoncuanhomthuoc
nitrat.thuocchenbetagiaocamvathuocchertkenhcalci
trongdieutrjdauthatngocvabenhmachvanh

3. DAICITONG
#
Benhmachvanh(Coronaryarterydisease-CAD)
Artery
CoronaryArteryDisease
Plaquesforminliningofartery
Ptaquegrows,liningofarterydamaged
coronary
artery
-
r
Plaque
" Plaqueruptures
\
Bloodclotforms,
limitingWoodflow
BenhlyDMV-benhlydohephay
taccacDMcungcapoxyvachat
dinhdu’o’ngchotim
OMAVOFOUNDATIONFORMECCALEDUCATIONANDRESEARCH ALLRIGHTSRESERVED

4. DAICITONG
Benhmachvanh(Coronaryarterydisease-CAD)
Tightnessor
paininchest
\
!£
\\
\
\
\\j\
XV\
^
x
\
'W,f
C,--
\
J
Blocked
CoronaryArtery
L

5. DAICITONG
Condauthatngipc(angina)

6. DAICl/CNG
Condauthatngipc(angina)
Chest,leftand Backoftheneck, Jaw,upper
nghtarm,neck shoulderblades,back abdomen

7. DAICU’aNG
Condauthatngipc(angina)
Xayrakhitim
thieuoxydpt
ngptdomat
thangbangnhu
cauoxyvakha
nangcapoxy
cuamachvanh
Oxygen
demand
Oxygen
demand
Oxygen
supply
Oxygen
supply
Normalmetabolism
Requiresoxygensupply
Myocardialischemia
Insufficientoxygensupply
•Dauthatngircondjnh(Stableangina)
•Dauthatngi/ckhongondjnh(Unstableangina)
•Dauthatngycbienthe(Variantangina,
Prinzmetalangina)(đau do co thắt mạch)

8. DAIaTONG
#
Condauthatngu’c(angina)
Angina
i[ I
ChronicStableVariant(Prinzmetal)Unstable
* **
atherosclerosis
leadstoafixed
narrowingof
bloodvessels
thrombosis,
theformation
andbreak-
downofclots
coronary
vasospasm
(vesselscan
looknormal)
**
Demand
Ischemia
Supply
Ischemia
Supply
Ischemia

9. DAICl/CNG
CondauthatngiPc(angina)
A a
Nguoncungcapo\y Nhucautieuthuoxyco
*tim
NongdooxymauDM Suecangthanhthat
p
=—
2h
LuulugmgDMV
+ApluctuoimauDMV
+Suecanthanhmach
+Sueeptirbenngoai
+Cochet\rdieuhoanpisinh
+Chatchuyenhoataicho
+YeutonQimac
+Phanbothankinhtim
Nhiptim
Suecobopcatim
>c >%
r s
Hinh1.1:Cacyeutochinhquyetdjnhcung-cauoxycatimf26J
(P:dpluctrongtarnthat,r:bankinhtamthat,h:chieudaythanhthat)
2 mũi tên trên thể hiện mong muốn
điều trị ở BN đau thắt ngực

10. DAICITONG
Condauthatngipc(angina)
Angina
Treatment
•Tangcungcap
02chotim
•Giamnhucau
02
cuatim
•Phanbolai
t\j&\mauvung
6ir&\noimac
i
rACOIEUTRI
Giam Kiem
dau soat
trieu
chum

11. OIEUTRIDAUTHATNGITC
• •
Cacnhomthuoc
•Kiemsoattrieuchu’ng
-LoaichongCOT:nitrathCmccy
-Loaidieutricungco:chenbeta,chenkenhcalci,nitrat,thuoc
khac(m&kenhkali,tiechekenhIpranolazine,trimetazidine)
•PhongngOathu*phat:
-Chongdongvachong
^
kettaptieuc
'
au:aspirin,clopidogrel
-Thuocticcheenzymchuyen(ACEIs)
-Thuochalipidmau:statin
(Cắt cơn, giảm đau tức thời)
dự phòng
tái phátvastarelức chế
kênh Na chậm

12. NITRATHOUCO
Cautruehoahoc
O
!U
No
-
o
-
w
o
Nitroglycerin
(glyceryltrinitrate,GTN)
CacnitrathCaica-esterpolyolcuaacidnitric(C-O-NO2)
CacnitrithCruca-estercuaacidnita(C-O-NO)
Cacthuocnhomnayhoacladungdjehbayhai(amylnitrit),hoacladung
djehbayhainhe(nitroglycerin),hoaclatheran(isosorbiddinitrat).
Ti
'
enthuoccungcapNOtaimodfch
Isosorbidedinitrate
(ISDN)
lsosorbide-5-mononitrate
(ISMN)
Tác dụng trên mạch

13. NITRATHl/UCO
C<
ychetacdung
humanvein
segmentNitrateMechanism Muscletension
Nitrates(NTG) 10mN|
Vascular
smoothmuscle
OO
NorEpiNTG
Nitrate
mtALDH
2
Guanylyl
cyclase
NO
bindstoGC
hemegroup
GTP >cGMP GMP
myosm-LC
phosphatase
mtALDHjf:mitochondrial
aldehydedehydrogenase2
Myosin-LC-P04 Myosin-LC
i
/ actin-myosin
crossbridges
\
*
Contraction Relaxation AdaptedfromKatzung(2015)
TB cơ trơn
thành mạch
khử phosphoryl
hóa của chuỗi
nhẹ myosin

14. NITRATHUXICO
Tacdung
•Lamgianmoiloaicatrcmdobatkynguyennhangay
tangtrironglirenao.Khongtacdungtrirctieptrenca
timvacavan.
Nitrates
*
02
supply
bydilationof
largeEpicardial
coronaryarteries
TTnhmach
Arteries
Dong
machCapacitance
vessels
Resistancej
vessels
Themajoranb-ischemic
mechanism*
\
/
/
HighdosesLowdoses
r
'
i
'
Afterload
^
Myocardial02demand
v y
^
Preload
^
Myocardial02demand Maomach
AdaptedFromChong&Michel(2012)
giảm nhu cầu O2 của tim
cơ chế chính là giãn TM
Liều thấp Liều cao
giãn ĐM và MM
- Giãn ĐM vành => tăng cung cấp oxy cho cơ tim.

15. NITRATHUXICO
Tacdung
•Lamgianmoiloaicatrandobatkynguyennhangay
tangtraanglacnao.Khongtacdungtractieptrenca
timvacavan.
•Catrommach
#
-Hi£uqualamgianTM>DM>MM
•TMgian—giamtienganh
~
•DMgian—giamhauganh
•DMvanhgian—>Tangcungcap02chocatim
-Phanbolailimliftingmachvanhtu*vungbinhthaorng
sangvungthieumaucuebo,giamcothatmachvanh
•Catrorikhac:Giancagianphequan,ongtieuhoa,daorig
mat,du'o'ngtietnieusinhdue.
•Tieucau:Hoathoaguanylylcyclase—>|cGMP—giamket
,A.•
A*
V
taptieucau
-Giamnhucau02
cuacatim
(chủ yếu)

16. NITRATHU’UCO
Du'
o
'
cdonghoc
Hapthutotquadu'6'ngtieuhoa
ChuyenhoaquaganIandaumanhthanhdangbat
hoat—>SKDdtroriguongthap(<10-20%)
Ou'o
’
ngdungtranhchuyenhoaquaganIandau:
SDu’dngdipdiliFdi:hapthunhanh,lieudungthapdetr
^
nhtac
dungquamere,dangxjtdu'd’
ilu’o'
ikhdiphattacdungnhanh
hondpngviend|tdifdilu’di,thdigianticdyngngan(i5-3oph)
SOu'
dngapniemm?cma:thuocgiaiphongch$mhon,keodai
thdigiantacdungcuathuoc
SBiPcmghapthuquada:hapthutotquada,giaiphdngthuoctir
tu*duytrinSngdpondjnhtrongm3uftnhat24gidsaukhidung
trenda.
SOiFdngtTnhmach:thdigiantacdungngancuaGTNlamotu*u
diemtrongchuandolieuTM
t/2ngan(GTNs2-8phut;ISDNs;
45phut),motso
chatchuyenhoacohoatti
'
nhcot/2daihorn(to'i3h)
Thaitn>quathan
O
Nitroglycerinn
0
'
ONO
2
02NO/«.„
isosorbidedinitrate

17. NITRATHOUCO
Du’o’cdonghoc
°
-NO2
isosorbidedinitrate Isosorbidemononitrate
•Chatchuyenhoac6hoattinhcuaISDN,tacdungmanhhornISDN
•KhongbichuyenhoaquaganIandau—SKDdironguongcao100%)
•Kho'iphattacdungchamhorn
•t/2JS3-7gio'
•Dangglaiphongbiendoi(modified-releaseformulations)thirongdu'o'c
sirdungdekeodaitho’igiantacdungcuathuoc
trong cơ thể
chuyển hóa thành
Đặc điểm của ISMN

18. NITRATHl/UCO
Tacdungkhongmongmuon
haHAtu’the,chongmat,ngatvanhiptim
nhanhdophanxaK-SLTdungdongth&ithuocdoi
khang6-adrenoceptorlamgiamnhipnhanh
daunhoid
'
auvadobung,cothedungnap
TDKMMnaykhidieutrjbangnitrattacdungkeodai.
•Phatbandothuoc.
•Miengdannitroglycerincothegaycamgiacbongrat
trenvitrfdancacmiengdienci/ccuamaykhirrung
gabomiengdantrw&ckhisirdung
phwcmgphdpkhirrungtimbenngoaidenganngira
bongnong.
•GianTM
•GianDM
timngoai

19. NITRATHOUCO
Tacdungkhongmongmuon
•Quenthuoc(Tolerance)
-Dungthirongxuyen/lientuclieucaonitrathCruccr
-Baogom:
GiathuyetveccheHientiFc
^
ngdungnap
Giamkhanang
chuyennitrat
thanhNOcuacor
tranmachmau
Dungnapthatsir
cuamachmau
(truevascular
tolerance)
Giamdirtrirnhomthiols
taiTBdich
TanggianghoaNObcricac
goctirdotaiTBdfch
Kichhoatcacccr
chegaydungnap
khonglienquan
denthanhmach
*
Hoathoahegiaocamva
renin-angiotensindedap
ungv&\hahuyetap
Giadungnap
(pseudotolerance)

20. NITRATHl/UCO
Tacdungkhongmongmuon
•Quenthuoc(Tolerance)
Nitroglycerin.
OrganicNitrates
i
NL\tracelluhr
SH SH
Membrane
Cysteine
Giam
Intracellular
* Dung
S-NilrauHhiol.NO
i
<+>
SolubleGuonylalcCyeluM?
I
(I
f
CyclicOMP
.
trCKnitrat
<->
CytosolicFree
*
Ca*
f
i<->
thiol
VwcalarSinmnh
MuscleRelaxation
V
FIGURE 17.1
Proposedmechanismbywhichnitroglycerinandtheorganic
nitratesproducerelaxationinvascularsmoothmuscle.
NitratesinduceendothelialcellstoreleaseNOora
nitrosothiol(endothelium-derivedreleasingfactor,orEDRF).
EDRFactivatestheenzymeguanylatecyclase,whichcauses
thegenerationofcyclicguanosinemonophosphate(GMP),
producingadecreaseincytosolicfreecalcium.Theend
resultisvascularsmoothmusclerelaxation.SH.sulfhydryl.

21. NITRATHU’UCO’
Tacdungkhongmongmuon
•Quenthuoc(Tolerance)
-Dungthuwigxuyen/lientuclieucaonitrathCmccy
-Tranhdungnapbangeach:
0Sirdunglieuthapnhatcohieuqua
0Sirdyngftlan/ngay
0Tranhsirdunglientuc
0Taokhoangthcrigian“nitrate
-low”8-12gicymoingay
Khongchiad
'
eutho'i
giandungthuoc:
uongISMNd$nggp*
tirethl2lan/ngayluc
8hvaI3h
Gdbomiengdan
GTNmottho'igian
(VD:bandem)moi
24gicx
Dungdanggp*keo
daicuaISMN1
lan/ngay(nongdo
nitratgiamvedem)

22. NITRATHl/UCO
Tacdungkhongmongmuon
•Methaemoglobin
-Nitriteion(khongphainitrate)phanumgv&\
hemoglobinhinhthanhnenmethaemoglobin.
-Hiemgapvo’
icacnitrattrenLS
-UYigdungamylnitritetrongdi
'
eutringodoccyanide
(xyanua),vlmethaemoglobinlienketvalambat
hoatcacioncyanide.
V
VOc3902X
I
dạng hít
(Chủ yếu)

23. NITRATHi/UCO
Chidinh
Dauthatngipcondjnh
-Dieutricatconvcyinitratetacdungngan:
GTNhoacISDNdiroiliroi.
-Dirphong:lirachpnhangth&2sau/?blocker
&GTNdiKoiliroingaytrimckhigangsire
&GTNdanggiaiphongkeodai
*
ISDNvaISMNdanggiaiphongkeodai
dung2lan/ngayeachnhau6-7gio',sau
dolakhoangtho'
igiannitrate-freeft|
nhat8gia
A
Oauthat
ngirckhong
ondinh
•GTNdi/ongttnhmach
¥
Kiemsoat
HAtrong
phauthuat
•GTNdu'd’ngttnhmach
¥
Suytimcap•GTNdirongttnhmach
¥
•ISMN,vo'ihydralazine
cfBNngiroiMygocSuytimman
Phi
còn ISMN có tác dụng dài
Một số chỉ định khác

24. NITRATHOTJCO
Chongchidjnh
•Quamin
•Giamthetfchtuanhoan
•GiamHAnang(HAtamthu<90mmHg)
•HepvanBMChoacvanhaila,benhcotim
phidaidotacnghen
•
A
'
f r
*
/V.
•Thieumauroret
•Tangapli/cnoiso(dochanthircmgsonao
hoacchaymaunao).
•Glaucomagocdong(thantrong).
•Sirdungdongtho’ivdithuocirechePDE5,
chatkichthichguanylatecyclase(riociguat)
(xem cơ chế)

25. NITRATHOTJCO
TiFcyngtacthuoc
humanveto
segmentNitrateMechanism Muscletension
Nitrates(NTG) 10mN|
Vascular
smoothmuscle
oo
NorEpINTG
Nitrate
mtALDH
2
Guanylyl
cyclase
NO.
©
bindstoGC
hemegroup sildenafilUi
y
PDE
GTP cGMP GMP
myostn-LC
phosphatase
mtALDHj:mitochondrial
aldehydedehydrogenase2
Myosin-LC-P04 Myosin-LC
actin-myosin
crossbridges
>
f \<
Contraction Relaxation AdaptedfromKatzung(2015)
, tadanafil
viagra: rối loạn CD

26. NITRATHimCO
Tipongtacthuoc
Organicnitrates
P2H—CH-ONO
7
I
H—C—0N02
ISDN
I
H—CH-0N02
ONO
2Nitroglycerine
Hahuyetapdangke
-Khongnenkethuoci>cchePDE5choBNdungbatkydang
nitratnao
-Khongnendungthuoc(rcchePDE5trongvongftnhat24gib*
trirdc/saukhidungnitrat
-Sirdungchatchuvanavadichtruyenneucan

27. NITRATHOUCO
Motsochepham-Tacdungngan
DC28596-r?012
Nitroglycerin
LingualSpray
iwogr
^
errmguaispratf
IB'
lire
*
C0meg;rfSprayI.J
21
)0Mefer«JSpraysI
.=
•PHARMACISTONLYMEDICINE
Z
<
TOOUTOFREACHOFCHN.0REN
Isordil
»*
Pi
W
*
wiamK«Sirw5(!20
5
^
t4i0fwaaiNi
*
I?isosorbidedinitrateo
'
00NOTSHAKE
H010CONTAINERUFWGHT
PRIMEBEFOREUSE
FORANGINALATTACKS
^
tooSublingualTablets AO$TA'tf\
>Eaefttabletcontainsisosorbidedfltrafe5“5?
AmusPn\RMWUTK4lS
V

28. !.i
NITRO-B1D
t
*
i|I3
®ii
I55
^
i
NilroulyrerinOiiUmonlU5P,2%
hlti
*
111n
^
ly
NtTWT JOgram
iii
HOC01«8-03»-30
NITRO-BID
(NitroglycerinOintmentUSI\2%)
13only NETWT30grams
"
PI
u
o
SQJ
W)
c
3*
TD
O
u
u
I
|
f.If:1-
51-
:¥<,
uliWII'IJ
E
<b
\rv
!
CL
s
<o
f -O
SE
#«>
Iu
Si3 \
IGC
Hil/*
s
<o
!,iii ^
0)
|-£Prs o
!oin)
o)
*
2
?JJ
'rJ}£
^^
sj£>5»2
®
Js
N
to
I
<o-
/
•
»J3
I
>„-
r-ia:ar

29. THUOCCHENBETA
#
Tacdung
AAGiannopoulasrtal./Phamiocob&&Theivpruric
;163(2016)118-131
•Giamnhjptim
•Giamlirecobopco
1
tim
•HaHAdogiamcunglu'p
’ng
tim(ketquacuagiamnhjptim
valirecobopco"tim)
o
I
o:o
L-Type
Cardiac
SmoothMuscleCell O
oO
o
[Intracellular
Ca
2
’
Noradrenaline
^
PK-A
cAMP
Giamnhjptim—k£o
d£ithdigiantarn
troong,tangthdigian
tu’d'
im2umachv£nh
Giamnhiptim,giam
lirecob6pcotim,
giamhauganh
Sympathetic
nerve
Beta-blockers
Tangcung
cap02cho
cc?tim
fi
Increasediastolic
perfusionGiamnhucau
02cuaccytim
.ContractilityiHeartrate lAfterload
i i\
t02
supply
i02demand
Tác dụng trên tim

30. THUOCCHENBETA
Phanloai
Beta-Blockers
I
r I l
Selective Withalpha-blocking
activity
Non-selective
I1
I 1 I I
NegativeISA PositiveISA NegativeISA PositiveISA -Carvedolol
-Labetolol
-Atenolol
-Metoprolol
-Bisoprolol
-Celiprolol
-Acebutolol
-Pindolol
-Oxprenolol
-Propranolol
-Sotalol
-Timolol
HighLipophilicity
Pindolol
Penbutolol
ModerateLipophylicity
Acebutolol
Betaxolol
LowLipophilicityorHydrophile
<
CO Beta-1selective Carteolol
£ Non-selective Labetalol
S
Metoprolol
Bisoprolol
Nebivolol
<
Atenolol
Fsmolol
Beta-1selective
o
Propranolol
Timolol
Nadolol
Sotalol
Non-selective Carvedilol
legend:ISA=
IntrinsicSympathomimeticActivity.
Đtrị CĐTN bệnh mạch vành

31. THUOCCHENBETA
DIPOCdonghoc
•6-adrenoceptorantagoniststannhieutronglipid
(propranololvametoprolol):hapthutotquadirong
tieuhoa,chuyenhoaquaganIandaunhieu,thcrigian
banthaingan
•6-adrenoceptorantagoniststannhieutrongnu'd'c
(atenolol):hapthukhonghoantoanquadirdngtieu
hoa,thaitrirquanu'd'ctieudirdidangkhongdoi,
phamvilieudeduytrinongdohieuquatronghuyet
tu'o'nghepho'
nsovo'inhCrngthuoctraiquaquatrinh
chuyenhoa,thoigianbanthaidaiho'n

32. w
THUOCCHENBETA
Dacdiemmotsothuocchenbeta
• • •
TABLE10-2Propertiesofseveralbeta-receptor-blockingdrugs.
PartialAgonist
Activity
LocalAnesthetic
Action
Elimination
Half-life
Approximate
BioavailabilityLipidSolubilitySelectivityDrugs
Acebutolol P Yes Yes 3-4hoursLow 50
i
Atenolol 6-9hoursP
No No Low 40
i
14-22hoursBetaxolol
Bisoprolol
Carteolol
P, SlightNo Low 90
9-12hoursP. No No Low 80
Yes 6hoursNone No Low 85
Carvedilol Moderate 7-10hoursNone No No 25-35
Celiprolol
Esmolol
Labetalol
Metoprolol
Nadolol
4-5hoursP.
Yes No Low 70
P. No LowNo 10minutes 0
i
5hoursNone Yes Yes Low 30
P, Moderate 3-4hoursNo Yes 50
14-24hoursNoNone No Low 33
Nebivolol P
11-30hoursLowNo 12-96
i
Penbutolol Yes High
Moderate
5hoursNone No >90
Pindolol 3-4hoursYes YesNone 90
303Propranolol
Sotalol
Timolol
High
Low
Moderate
3.5-6hoursNo YesNone
No 12hoursNone No 90
4-5hoursNone No No 50
'Carvedilolandlabetalolalsocausea,-adrenoceptorblockade,
agonist.
}
BioavaiIabilityisdose
-dependent.

33. THUOCCHENBETA
Tacdungkhongmongmuon
•Chen(3i-adrenoceptor:nhiptimchamquamiKc,nangthemRL
tuanhoandongmachngoaivi.
•Chenp2-adrenoceptor:cothatphequan,keodaitlnhtrangha
difOTghuyet(trenBNdunginsulin),chelapdauhieuha
di/onghuyet(dacbietlanhjptimnhanh)
•TKTI/:RLgiacngu,aogiac(chen(3i/alipid),RLcuwigduOTig
•Lipidmau:tangTG,giamHDL(chenpkhongchonIpc)
•Hoichungngimgthuocdptngpt:dieutrikeodaivoicac
thuocchenp—dieuhoatangp-adrenoceptor—timtang
nhaycamvoicatecholaminkhingimgthuoc!COT0TNKOO
hoacNMCTkhingumgthuocd§tngQt.
•Tumigtacthuoc:hiepdongtangmiKcvoicacthuocchen
kenhCacotacdunggiamli/ccobopcatim(verapamil,
diltiazem)—haHAnang,suytim.

34. THUOCCHENBETA
Apdungdi
'
eutrj
ChongchidinhChidinh
•Dauthatngirc00,KOD
•Dauthatngi/ckhongdapung
nitrate
•NMCT(canthiepsomtrong
giaidoancaptinh)
•Hen,COPD
•Hoichimgsuynutxoang,nhjp
chamcotrieuchung,blockAV,
haHAnang
•BenhDMngoaivinang
•Suytimchiradirc
^
ckiemsoat
Atenolol
150mgFilm-coated
Tablets
MeloprololTat
*
^
1
^£OrdUt#
CiP*
i
'j
pctU
«4

35. Kenhcalci
Calciumchannel
VoltagegatedReceptoroperatedStretchoperated
calciumchannel
CALCIUMCHANNEL
BLOCKERS
sMR
calciumchannelcalciumchannel
T-typeN-typeP-typeR-type
j
i
MangPurkinjeMothankinh,tinhtrung
Mothankinh,tinhtrung
TBthankinhtipdongcuatim,dacbietanutxoangvanutnhTthat
Co?tim,co?tron,co?van,noron(vongmac),TBnoitiet,xirang
Kênh Calci rò
chủ yếu
Kênh phụ thuộc V Kênh phụ thuộc receptor

36. THUOCCHENKENHCALCI
Phanloaitheocautruehoahoc
• •
CalciumChannelBlockers
DihydropyridinesPhenylalkyliminesBenzothiazepines
a.1
1stGen.2ndGen.3rdGen.XVerapamil
m'
Nifedipinef Amlodipine
Diltiazem
*
CardiacEffects
DecreaseContractility
DecreaseHeartRate
DecreaseConductionVelocity
4
th
Gen.
Cilnidipine
VascularEffects
SmoothMuscleRelaxationIsradipineNicardipineFelodipine
o/?mo
điển hình

37. THUOCCHENKENHCALCI
Ccychetacdung
CALCIUMCHANNELMODEL
Opie2012
Ca
2
*
TatcacacCCBdeuganvao
tieuph
'
ana,cuakenhtypeL
D:Vitrfgancuadiltiazem
N:Vjtrfgancuanifedipine
vacacDHP
V:Vjtrfgancuaverapamil
«
2/?•
4
0
*II
V
P
p
p
p

38. THUOCCHENKENHCALCI
Co*chetacdung
Calcium
Calciumchannelblocker
n
0
Depolarisation
l-typcvottage
^
atcO
calciumchannel
o
o
Contractile
mechanism
\
0
Ryanodine
—^receptor
Sarcoplasmicreticulum

39. THUOCCHENKENHCALCI
Tacdung
Chenkenhtype
L(ccytim)
Chenkenhtype
T(nutSA,AV)
CalciumChannelBlockers
ventricularmyocardium
^
Contractility
u demand
SAnode
4
*
heartrate
demand
Giamco
bopcatim
Giamnhipcoronaryarteries
'
fvasodilation
^
02
supply
tim
&w
Arlenes
ChenkenhtypeLtrenmach
TieuDM
ngoaivi
peripheralveins
[minimalvasodilation Machvanh
Resistance
vessels „
1
arterioles
Giamcothat,
tanglu'ulu’ang
machvanh
Giamsirecan
ngoaivi,giamHA
'
I
'
Bloodpressure(afterload)
^
Myocardial0
-,demandAdaptedFromChong&Michel(2012)
cung cấp O2
giảm nhu cầu O2
Giống chẹn beta
(chủ yếu trên động mạch)
Tác dụng cả trên tim và trên mạch (chủ yếu động mạch)

40. THUOCCHENKENHCALCI
Co*chetacdungcuacilnidipine
Sympatheticnerve
ending
PureL-type
Ca
2+channel
blockers
Cilnidipine
\
\7
(N-typoCa*
*channels).*
Norepinephrine
Release
(L-typoCa** Ca
2
*channels Vessels Kidney
Vessels
Decreaseof
ronalbloodflow(cn)
IncreaseofheartrateReninsecretion(pi)
Increaseofcardiac
contraction
VasoconstrictionVasoconstriction
(thuộc nhóm DHP thế hệ 4th)

41. THUOCCHENKENHCALCI
Tacdung
Smoothmusclecells|Heart
|myocardialcontractility
’
I|AYconductionvelocity
II
Vasodilationofmainlyarteriolarsmooth
muscle
|Ca
:~entry
i
fi
?
i „frequencyofCCopening
inresponsetodepolarization
I
CCB
I
II
TTTTtTTTTTTTTTTT
......
TTTTT
......
I
^
StimulationofCa
:*
rclease
^^
ff
^
f^
‘.frominternalstore
l
i
Activationofmyosinlightchainkinase
IPhosphorylationoflightchainmyosin
I
Actin-myosiucross-bridgmg
I
I I
Vasoconstriction
I

42. THUOCCHENKENHCALCI
Tacdung
Dantruyentim
Ccytrcyn
thanh
mach
Nhom Ccytim
SA AV
Dihydropyridines
(nifedipine)
ii >1>t>1
*
V
Phenylalkylamine
(verapamil) ^
f N/
^^
Benzothiazepine
(diltiazem)
O
^
EIO
tim = mạch
mạch > tim
tim > mạch

43. THUOCCHENKENHCALCI
Tacdung
Nifedipine
DecreaseinArterial
Resistance:reflex
tachycardia
©
DecreasedAfterload
o
DecreaseinArterial
Resistance:noreflex
tachycardiadueto
concomitanteffect
onheartrate
©ReducedHeartRate
^
and/orcontractility
Diltiazem
Verapamil
Giãn mạch gây
Nhịp nhanh phản xạ
(td trên tim làm trung hòa
nhịp nhanh phản xạ)

44. THUOCCHENKENHCALC1
Tacdungkhac
•Nimodipinegiamtothatmachnaovanhoi
\
xuathuyetdu’
O’inhen
•Verapamil&cchegiaiphonginsulinv&ilieu
caohemlieudungtrongtimmach
•VerapamilvacacCCBkhacu’cP-glycoprotein
chiutrachnhiemvanchuyenthuo
'
crakhoiTB
ungthu*(vacacTBkhac)
mausau

45. THUOCCHENKENHCALCI
Chidinh
•Oauthatngi/condjnh,Prinzmetal
•Tanghuyetap
•Loannhjpnhanhtrenthat(non-
DHPs)
•Cothatmachnaosauxuathuyet
diro'inhen(nimodipine)
•HoichumgRaynaud(nifedipine)
•0auni>adau(verapamil,off-label)
Indications,USADrug Proprietaryname
Hypertension;Chronic,stable,and
vasospasticangina
Hypertension;chronic,stable,and
vasospasticangina;atrialfibrillation
orflutter;paroxysmal
supraventriculartachycardia
Hypertension
Hypertension
Hypertension;angina
Hypertension;angina
Hypertension
Hypertension
Angina
Atrialfibrillation
Orflutter
Paroxysmalsupraventricular
Tachycardia
Amlodpine Norvasc
Tiazac;Cardizem;
Cartia;Dilacor
Diltiazem
Felodipine
Isradipine
Nicardipine
Nifedipine
Nisoldipine
Verapamil
Plendil
Dynacirc
Cardene
Adalat;Procardia
Suiar
Calan;Covera;Verelan
cả DHPs và non-DHPs
do DHPs không có tác dụng trên tim

46. THUOCCHENKENHCALCI
DLFOCdonghoc
•Hapthutotquadu'cvngtieuhoa—thi/ongdung
dironguong(PO),tru’nhungCOdacbiet(tiemIV
trongxuathuyetdu’d
’
inhen)
•ChuyenhoamanhquaganIandau,SKDthap
•Ganmanhvdiproteinhuyettuwig
•Tho'
igianbanthai^2-12gift-dangbaochegiai
phongcodi
'
euchinhgiupkeodaitho
’
igiantacdung
•Amlodipinhapthucham,khongbjchuyenhoaqua
ganIandau,tho’
igianbanthaidai(1-2ngay).
(nimodipine)
(nhịp nhanh phản xạ ít gặp với amlodipin nhất)

47. THUOCCHENKENHCALCI
Du
'
o’cdonghoc
Amlodipine Diltiazem Folodipine Isradipine idipine Nicardipine Nifedipine Nitrendipine Verapaml
6-12 Standardoral:Standard
oral:1.5
Extended
release:3-7
2-3postdose1-2 <0.5-2 Standardoral:
0.5-1
Retardtablets:2
1-2 Standardoral:1-2Timetopeak
plasmalevels
(hours)
2-3
Plasmahalflife
(hours)
10-1135-50 46 25 8.3 8 2-3 2-18 4-10
60-65(1with
reducedliver
function)
40(major
Individual
variability)
15 15-24(twith
age;reduced
liverfunction
2-9(twith
reducedliver
function)
10-17 50(twithage
andreduced
liverfunction)
23-30 20-35(twithage;
reducedliver
function)
Bioavailaoility
(%)
OralabsorptionSlow,complete
first-pass
hepatic
Rapid/extenslve
first-pass
hepatic
90-95
(extensivefirst-
pass
metabolism)
Rapid/extensive
firstpass
hepatic
Rapid/extensive
first-pass
hepatic
Extensive
firstpass
hepatic
Rapid/extenslve
first-pass
hepatic
Rapid/oxti
first-pass
hepatic
Rapid/extenalve
(>95%)firstpass
hepatic
90toinactive
metabolites
>95;active
metabolitewith
25-50%of
parentactivity
>99to
inactive
metabolites
Complete
metaboiisation
toInactive
metabolites
Complete
metaboiisation
>99toinactive
metabolites
>95toinactive
metabolites
80-90to
inactive
metabolites
Activemetabolites
with30-40%of
parentactivitycan
accumulatewith
chronictherapy.
Kineticsaffectedby
food
Metaboiisation
<
%)
97 70-80 99 95 >90 >90 92-98 95 -90Plasmaprotein
binding(%)
Volumeof
distribution
21.4|/kg 5.3l/kg 10l/kg 283iatsteady
state
0.9-2.3l/kg 11.6l/kg 1.42 2.04 4-8.6
10%
unchangedandunchangedvia
metabolites
(60%)via
urine;20-25% (60%)viafaeces
viafaeces
2-4% <0.5% Urine:faeces
ratio70:30%
70%bitary:30%
renal
<1%unchanged
viauhne.
Metabolites
mainlyviabile
andfaeces
3-4%unchangedv»a
urine.Metabolites
viakidneys(65-70%)
and(>16%)via
faeces
Elimination Metabolites
(70-80%)via
kidneys
Viaurine(55%)
andfaecesunchanged
andurine;
metabolites metabolites
(70%)via
urine

48. THUOCCHENKENHCALCI
#
Tacdungkhongmongmuon
\
Tim
•Ciamnhiptim,blocknhtthat(verapamil,diltiazem)
•Giamcobopccrtim,suytim(verapamil)
Mach
•Gianmachquami>c—comnongbimg,nhu*cdau,chbngmat,phumatcachan(DHP)
•HaHA—>nhipnhanhphanxa,danhtrongngirc(DHP,dacbietvdidangbaochegiai
phongtirethl)
Khac
•ThaydoinhudpngruQt:taobon(verapamil>diltiazem),<ynongdogiancathatthi/c
quandi/di(amlodipinevacacDHPkhac)
•Tangsannerdu
•Tirorngtacthuoc:verapamilvadiltiazemcdthelamchamnhiptimquamirekhidung
dongthoivoicacthuockhaccdtacdungtirongtirtrendantruyennhTthat(digoxin,
chenp);ti/omgtacvdicacthuoccamu'ng/u
,
ccheCYP450.

49. THUOCCHENKENHCALCI
Chongchidjnh(tuytungthuoccuthe)
\
\
Nhom
thuoc
Tu’o’ngtac
thuoc
CCDTDKMM
Nhjpnhanhphanxa
0audau,metmoi,
nongbung,phumat
cachan
HepDMnang
Soctim
Benhaytimtacnghen
Cachat
CYP3A4
DHPs
Cochat
CYP3A4
ThuocLtC
chetim
(chenp,
digoxin)
Nhjpcham,giamdinNhjpcham<50nhjp/phut
HCsuynutxoang
GiamphansuattongSuytimsunghuyet
mau
Tangsanloi,taobonmmHg)
truyentim
Non-
DHPs
HAthap(HAtarnthu<90
là 1 trong các P450

50. THUOCBIEUTRIBAUTHATNGl/C
• •
Tacdungcuacacnhomthuocchrnh
Phoihapnitrateva
chenp/kenhCa
Chenp/kenhCaNitrate
Nhiptim
Huyetap
Thetfchcuoitarntrirong
Cobopcatim
Thcyigiantongmau

51. THUOCKHAC
ThuocLFCchechonlockenhLcuanutxoang
(a)Thepacemakerpotentialgradually(b)Ionmovementsduringanaction(c)Statesofvariousionchannels
andpacemakerpotentialbecomeslessnegativeuntilit
reachesthreshold,triggeringan
actionpotential.
20
Ca
2+
channelsclose,
K+channelsopen
0
LotsofCa
2+
i
channelsj
open/
Ca
2+
in K+out
>
E
,
5-20-
Q)
O
a
Threshold
g-40--
\SomeCa
2+
channelsopen,
If
channelsclose
Ca
2+in
D
E
a>
5-60 If
channels
open
K+channelsclose
NetNa+in
t
If
channels
open
**
»
*
Action
potential
Pacemaker
potential
Time Time Time >>
cho Na đi vào
f = funny

52. THUOCKHAC
ThuocLPCchechonlockenhLcuanutxoang
Kenhlfmo’
IvabradineMechanismofAction
IvabradinedivaoTBquakenhlf
Ivabradineganvaokenhlf
Ivabradin
U'cchedongionquakenhlf
>
Action
potential
Lowered
heartrate
Keodaithcyigiancandetaoramot
difnthehoatdongm6i
SAnode
Ivabradine-mediatedslowingofdiastolicdepolarization(/,inhibition)
Giamnhjptim
KoruthJS,etal.JAmCollCardiol.2017;70:1777-1784.
/34

53. THUOCKHAC
ThuocLPCchechonlockenhLcuanutxoang
•Khonganhhu’
O’ngdenlirecobopaytim
•Tacdunggiamnhjpphuthuoclieu,nhiptimban
d
'
aucuaBN(nhipbandaucaohorn—giamnhip
nhi
'
euhon)
•dlieukhuyencao,nhjptimgiam—10nhjp/phut
choduBNdangnghingoihaytapluyen.
•Chuyenhoa(gan,thanhruot)thanhchat
chuyenhoacohoattfnh(N-desmethyl
ivabradine)
•Tho'igianbanthaiphanbola2gicy,thcyigian
banthaihieuqua-6gift
\
i
im
^
llvabradinel
Coralan-5m,
•4
00
9.
*• •
»
m
Wv
^
J5
/ >
•»•• •
/
WW
r<
Ivabradine
Coralan75m,
<•
KM
•-
*
«*
'*
«4|*
*
J
0
9
4k

54. THUOCKHAC
ThuocLFCchechonlockenhLcuanutxoang
CHiDjNH
,»i.
MAS
•V
MM
V.V fe
M
•
’
•.Vj»
0ieutritrieuchungcondauthatngirc00man
tfnho'ngu'6'
iI6nmacbenhmachvanhconhip
xoangbinhthirongvanhjptim70nhjp/phut.
n
L
< 5S
•>>!
t:•
r.
.
V
v •
A
V
'Xri
*
v‘
r5i>
v? r
v
va
•BNkhongdungnaphoacCC0vo\chen(2
•PhoihopvdithuocchenpaBNkhongdu’Q'c
kiemsoatdayduvdilieutoiirucuachenp
m mIm
'«
/
%.rVr
«
^
rfigp®
.N
M
r
,v-:
*
9
-
*
v>
ijLrcwe
'
xj
v
Iriff
1
ColoursFaritOactt(Red)USP-NF,
|JW
^
,iA
FemeC«
4
s•
'
Vella
*
-
1U$P-Nf ®fegortflidtMJ*Igr
~
TiurnwrferiNIP
ocs
^
e
SUR;>iPMMiesHep
^
un
SuniMiM
^
tawiroiiifidn.vw
~
*
2n'f&
^
u'i
^
Js
«
Mjeprtut4r<
jall
^
pdicjaioneu! k'
^
MUiQM 4fc
^->
ftjrfcnascnlidfen
I
*
A
*
U
**
®
5SJJ
*j
^
Ivao:Ki.ieTaPleis5mg[*S£
Sjr
’£
p
»
'
V.
^^
8?
£5-
x
-rtib,?2SA -O
?£n1•
'
•IH
2 A-oi
r>
50
0ieutrisuytimmantfnhNYHAdpIIdenIVco
RLchircnangtarnthuangiro'iIonconhip
xoangvanhiptim75nhjp/phut
O
W
•Phoihopvdilieuphapdieutritieuchuanbao
gomcalieuphapchenp
•LieuphapchenpbiCC0hoackhongdungnap
1E3325ES311
UchWrv
^
HteOWDiefcorUlioc
iwbrac.n^
jorocntonoc
wbrxtot5mg
EiXipienh
’
341:1

55. THUOCKHAC
ThuocLFCchechonlockenh
lf
cuanutxoang
•Quaman
•Nhjptimkhinghi<70nhjp/phuttrirdcdieutrj
•Soctim,NMCTcap,suytimcaphoacKOD,
dauthatngircKOD
•HaHAnang(<90/50mmHg)
•Suygannang
•Hpichungsuynutxoang,blockxoangnhT,
blocknhTthatdo3
•Phuthuocmaytaonhjp(tansotimphuthuoc
ho£ntoanvaom3ytaonhjp)
•Keth(
?pvdichati>cchemanhCYP3A4;voT
verapamilhoacdiltiazem(chati>ccheCYP3A4
trungbinh,cotacdunglamgiamnhjptim)
•PNCT,PNCCB,PNcc5khanangmangthai
khongsirdungcacBPTTphuh<?p
4x14tablets
$
ivaoraainenyarocnonaeiaoeis
Coralan5mg
^
'SERVtER
4445
'
^
1* ^
5
m
W
•WJ
CHONGCHiDINH

56. THUOCKHAC
ThuocLPCchechonlockenhLcuanutxoang
-Nhipcham,blocktimdoI.
-Ngoaitarnthuthat.
-Nhi/cdauvachongmat.
-Cactrieuchumgo’
matlienquandenlieu,baogom
phosphenes(domdommat,choisang),vamb’
matdo
LKCcheI,trenmat.
SIDE
9
*
srCT
/
04utim«d(Mtr+r~
>
C
^
rpoutof of
R
* ^
Procoralan5mg
TW7nm
Ivabradioe
Vi
*
or>enbaoph
*
m-Filmcoatedtablet
Otf&ngu6ng
Oralroute
4i74»Vnvntoop#vm
4»14coatedfatten

57. THUOCKHAC
o
0.
®,0
e
Thuocmo*kenhkali-Nicorandil
^
N
H
O
N
NICORANDIL
f-
GianTM
giamti
'
enganh
TWOMECHANISMSOPEN
GianDM
giamhauganh
NITRICOXIDE
PATHWAY
tffR
ATPSENSITIVEK
+
CHANNEL(OPEN)
Ca
++
VOC
(CLOSED)
ftS
ft
80
HYPERPOLARIZATION
&
o
&
Q
INHIBIT
o
oICa~—
4
TONE&
/
o
Ca
44
o
a
ENDOPLASMIC
RETICULUM o
o
mở kênh
kali

58. THUOCKHAC
Thuocmo’kenhkali-Nicorandil
CHIOjNH:Dauthatngi/condinhkhongdu'Q'ckiem
soatdayduhoaccoCCDhoackhongdungnapvoicac
lieuphaptrilieudautay(nhu'thuocchenbetava/hoac
thuocchenkenhCa).
CHONGCHiDINH:
•
•Soc(baogomcasoctim),haHAnghiemtrong,hoac
RLchticnangthattrai.
"
SIPdungchatLPCchePDE5
"
SIPdung(cac)chatkfchthichsolubleguanylate
cyclase(riociguat)
•Giamthetichmau.
•Phuphoicap.
(có tác dụng như NO)

59. THUOCKHAC
Thuocmo’kenhkali-Nicorandil
•Tacdungkhongm
'
qngmuon:
-Daudau,danhtrongngi/c,dobung
-Chongmat
-Buonnonvanon
-Loetda,mat,vaniemmac,baogomca
loetdu
'
&ngtieuhod9kNgirngthuoc
ngaylaptu’c

60. THUOCKHAC
Phase“1”
KVC1-effluxa«oi)
Phase“2
W
-Plateauphas
K-"efflux(IKS)
—5
LateIN,Ca
2T
influxinflux
(lot)
Phase“3”
Phase“0”-
Depolarization
phase
PeakIN,influx K"efflux(IK,,Ixr,IKI)
Phase“4”-Restingpotential
FigureI.Phasesofcardiacactionpotentialinnonpacemakercells.Abbreviations:lea-L.L-typeCaJ
+
channels;lKi,inwardlyrectifierK
+channels;iKr.rapid
delayedrectifierK+channels;lKs,slowdelayedrectifierKchannels;lNa,sodiumcurrent;lt0l,cardiactransientoutwardpotassiumcurrent.

61. THUOCKHAC
ThuocLPCchekenhNacham
LateiNaCS
)
Na+/Ca2+
n.
n
\
rY
11
n
exchan6e
PIPH|pl
y
.
/"(Na+) © (Ca2
^
)
<$E
)
Ischemia
#
Sodiumoverload Calciumoverload
\
o MechanicalDysfunction
*
diastolictone 4^contractility4
>flow
Impaired02
Demand/Supply
Ranolazine
Tangthirgianccrtimtrongthenkytamtrirong
Caithientiroimauccttimtrongthcrikytamtrirorng\
Angina
thiếu oxy
Tên thuốc

62. THUOCKHAC
ThuocLPCchekenhNacham
\
Chidinh
•DieutritrieuchumgchoBNngifoiIoncoconDTNOD
khongdo’o'ckiemsoatdayduhoackhongdungnapvdi
cacli£uphaptrjli£udautay(nhifthuocch
^
npva/hoac
thuocch$nkenhCa).
•t/2ngan 2gicy)—danggiaiphdngk£odii
Chongchidjnh
•Quamin
•Suythannang(Clcrea<30mL/phut)
•Suyganvirahoacnang
•DungdongthoivdicacticchemanhCYP3A4
TDKMM
•Buonnon,khotieuvataobon.
•Nhircdau,chongmatvahonme.
•KeodaikhoangQTtrenECGcokhananggayroiloan
nhiptimneudiracstidungvdicacloaithuockhacco
cungtacdyng.

63. THUOCKHAC
Trimetazidine
FigVe2:MetabolicAlterationsDuringSustainedPeriodof
Ischaemia
Figure1:CardiacMetabolisminNormalConditions
t
Glucose Glucose
Fattyacids Fattyacids
il
44
Glycolysis
Glycolysis
Glycolysis
n
ADPGlycolysis
t
ADP
i
ATP
i
ATP Beta-oxidation
Lactate
andH
*
PyruvateBeta-oxidation
Fatty
acid
oxidation
Pyruvate
'
^J
l
Glucose
oxidation
Fatty
l
Pyruvate
dehydrogenase
Glucose
oxidation
aod
Pyruvate
dehydrogenase
i
oxidation
i
AcetylCoA AcetylCoA
AcetylCoA AcetylCoA
Electron_v transport
chain
Electron
4
transport
chain
ADP ATP
Contractile
functionbasal
metabolism
Theheartderivesmostofitsenergyfromtheoxidationoffattyacids,butnutritionalstatus
(e.g.fasting,substrateavailability)aswellasexerciseandhormonescanmodifyfuel
selection.ADP-
adenosinediphosphate;ATP«adenosinetriphosphate;CoA=co-enzymeA
Glycolysisisthemamcatabolicpathwayduringischaemia,whereasfattyacidoxidation
isenhancedinthisperiod.Asaconsequence,lessATPisgeneratedattheexpenseof
moreprotonsproduction,whichareultimatelyresponsibleformyocardialacidosisandthe
accumulationofions(mainlycalcium).Purplearrows:enhancedpathway;palebluearrows:
almostabolishedpathways.ADP-
adenosinediphosphate.ATP-
adenosinetnphosphate;
CoA
*
co-enzymeA
ATPinADP
(điều hòa quá trình chuyển hóa cơ tim trong đk thiếu máu)

64. THUOCKHAC
Trimetazidine
Decreases
Acidosis
Glucose FreeFattyAcid
TrimetazidineLactate
Fatty
’AcylCoAPyruvicAcid
PyruvateDehydrogenaseH+
3-KetoacylCoA
Tbiolase
Ca+
Carbohydratemetabolism POxidation
Decreasescalcium
overload
&
AcetylCoA
Improves
Contractilefunction *
Improves
Contractilefunction
IncreasesATPproduction 1%
điều hòa:
- giảm quá trình OXH chất béo
- tăng quá trình OXH glucoso

65. THUOCKHAC
Trimetazidine
gidiphongcobrtotfi
toifftmcooledtobkts
Hop2vixtomtomboo
Betof2bintffxtomodifh
J
PJ
JJ
PHANDUOCLIEUT12DMNKC0N6TY
24NGUYENTHINGHIA.Q1-TPHOCHItill
*
#
VASTARELy
Trimetazidinedihydrochlonde3Smg
0
*
utomv<na
*
triem
Keepoutofreocbofchildrr-
Khongdungcbolrfem
^
rS£ftvtEXNotforchildren
CHONGCHIOINHCHieiNH
•Quamin
•Suythannang(Clcrea<30mL/phut)
•BenhParkinson,cactrieuchumg
parkinson,run,hoichungchankhong
yenvacacbatthironglienquandenvan
dongkhac.
•Dieutr|trieuchimgchoBNngu'6'iIonco
con0TNO0khongdu'o'
ckiemsoatday
duhoackhongdungnapvoicaclieu
phaptrilieudautay(nhirthuocchen/?
va/hoacthuocchenkenhCa)

66. w V
THUOCBIEUTRIDAUTHATNGI/C
• •
Vjtrftacdung
Drugsusedinanginapectoris
Vasodilators Cardiacdepressants Otherdrugs
1I
Calciumblockers
(verapamil)
Betablockers
(propranolol)
Metabolism
modifiers;
rateinhibitors
Nitrates
1
Longduration
(transdermal
nitroglycerin)
Intermediate
(oralnitroglycerin)
Shortduration
(sublingual
nitroglycerin)
Source:AJ.Trevor,B.G.Katzung,M.Kruidering-Hall:Katzung&Trevor'sPharmacology:Examination&BoardReview,11thEd.
www.accesspharmacy.com
Copyright®McGraw-HillEducation.Allrightsreserved.
Z
'

67. w V
THUOCDIEUTRIDAUTHATNGl/C
• •
Vjtrftacdung
(i-Adrenoceptor
antagonists
Diltiazem,Verapamil,
Ivabradine,
Ranolazine
Nifedipine,
Nitrates,NicorandilReducedheart
rateand/or
Arterialresistance
decreases:reflex
tachycardia
contractility
Venousreturn
(preload)
decreases
Arterialresistance
decreases:noreflex
(2)
tachycardiadueto
jconcomitanteffecton
heartrate
Diltiazem,Verapamil
Dilate
venous
capacitance
vessels
Reflex
tachycardia
Nitrates