Anti Angina (Hany)
-
Upload
angga-ahadiyat -
Category
Documents
-
view
225 -
download
0
Transcript of Anti Angina (Hany)
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 1/51
ANTI ANGINA
Hany Yusmaini dr Mkes
Dept Farmakologi FKUPN Veteran Jakarta
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 2/51
ANGINA PECTORIS
Manifested by sudden, seere, pressingsubsternal pain t!at often radiates to t!e left
s!oulder and along t!e fle"or surfa#e of t!e leftarm$
Usually pre#ipitated by e"er#ise, e"#itement ora !eay meal$
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 3/51
YPE OF ANGINA PEC ORIS
%$ &'())*& (N+*N( (t!erosklerosis Pre#ipitating fa#tor -.
/$ P0*N1M23(')
Vasospasm Pre#ipitating fa#tor 4.
5$ UN)3(6'2
( rapid in#rease in fre7uen#y and intensity of
anginal pain o##urs, 8!i#! is t!oug!t to !eraldimminent myo#ardial infe#tion$
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 4/51
TYPES OF ANGINA
%$ &lassi#al angina9 )table
Unstable
/$ Variant or Prin:metal;s angina
Myocardial infarction – what is it ? Acute and co!lete occlusion of a coronary artery
"ue to coronary thro#osis
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 5/51
STA$%E ANGINA
)table angina is also kno8n as92"ertional angina<3ypi#al or #lassi# angina<(ngina of
effort<(t!eros#leroti# angina
3!e underlying pat!ology is usually at!eros#lerosisredu#ed o"ygen deliery. giing rise to is#!emiaunder #onditions 8!ere t!e 8ork load on t!e !eart
in#reases in#reased o"ygen demand.
(nginal episodes #an be pre#ipitated by e"er#ise,#old, stress, emotion, or eating
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 6/51
&NSTA$%E ANGINA Unstable angina is also kno8n as9
Preinfar#tion angina&res#endo angina(ngina at rest
&aused by re#urrent episodes of small platelet#lots at t!e site of a ruptured at!eros#leroti#pla7ue 8!i#! #an also pre#ipitate lo#alasospasm
(sso#iated 8it! a #!ange in t!e #!ara#ter,fre7uen#y, and duration of angina in patients8it! stable angina, and episodes of angina atrest
May be asso#iated 8it! myo#ardial infar#tion
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 7/51
'ASOSPASTI( ANGINA
Vasospasti# angina un#ommon form. is also
kno8n as9Variant anginaPrin:metal=s angina
&aused by transient asospasm of t!e
#oronary essels (tta#k o##urs een at rest or during sleep
&!est pain may deelop at rest
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 8/51
PA HOPHYSIOLOGY
>/ supply >/ demand
*)&H2M*(
P(*N
Pre#ipitating fa#tors
(ngina Pe#toris
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 9/51
S D
sehat angina angina
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 10/51
RISK FAC OR
(ge )moking
DM
+eneti# ?
Hypertension
Hyper#!olesterolemia
>ral #ontra#eption
at!erosklerosis
>6)30U&3*>N a$#oronary.
De#reased @/ supply
(ngina Pe#toris
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 11/51
PRINCIPLES IN HE REA MEN OF ANGINA
PEC ORIS
%$ >/ supply to t!e tissue
/$ >/demand of t!e tissue
5$ risk fa#tor
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 12/51
ANTIANGINA% AGENTS
3!ree maAor #lasses of agents are used indiidually orin #ombination to treat angina9
%$ >rgani# nitrates9 Vasodilate #oronary arteries
0edu#e preload and aferload
/$ &al#ium #!annel blo#kers9 Vasodilate #oronary arteries 0edu#e afterload 3!e non4di!ydropyridines erapamil and diltia:em. also
de#rease !eart rate and #ontra#tility
5$ 6eta4adrenergi# blo#kers9 De#rease !eart rate and #ontra#tility 4 de#rease in #ardia#
8ork and >/ #onsumption *mproe myo#ardial perfusion due to de#rease in !eart rate B
de#reased in entri#ular 8all tensi
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 13/51
CLASSIFICATION OFANTIANGINAL AGENTS1. Nitrates
a) Short acting (10 minutes): Glyceryl trinitrate (GTN and
Nitroglycerine) - EMERGENCY
b) Long acting (1 Hour): Isosorbide dinitrate Isosorbidemononitrate
2. Calcim C!annel "loc#ers$
a) Non dihydro!yridines : "era!amil #iltia$em
b) #ihydro!yridines: Ni%edi!ine &elodi!ine 'mlodi!ine
Nitrendi!ine and Nimodi!ine
%. "eta&adrener'ic "loc#ers$ ro!ranolol eto!rolol'tenolol and others
(. Ot!ers$ 'nti!latelet anti*oagulan tromboliti*+,brinoliti*
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 14/51
NIT)ATES 'll Nitrates share same action only
di.erence is on )!armaco#inetic*ro*erties (duration o% action and onset)
He!atic ,rst-!ass metabolism is high andoral bioa/ailability is lo %or nitroglycerin(GTN) and isosorbide dinitrate (IS#N)Sublingual or transdermal administration o%
these agents a/oids the ,rst-!ass e.ect
Isosorbide mononitrate is not subect to,rst-!ass metabolism and is 1002a/ailable a%ter oral administration
He!atic blood 3o and disease can a.ectthe !harmaco*inetics o% GTN and IS#N
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 15/51
Me#!anism of (#tion of Nitroasodilators
Nitric Oxide
activates
converts
Guanylate Cyclase*
GTPcGMP
activates
cGMP-dependent protein kinase
Activation of PKG results in phosphorylationof several proteins that reduce intracellular calciu
causin! sooth uscle relaxation
Nitrates "ecoe denitrated "y !lutathione #-transferase
to release
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 16/51
Mekanisme anti angina
• 4%e* langsung – #ilatasi arteri *oroner su!lai 56 ↑
• 4%e* ta* langsung – "enodilatasi !reload ↓ –
'rteriodilatasi
a%terload ↓ – Ejection time ber*urang *ebutuhan 56 mio*ard ↓
ada dosis besar: Te*anan darah ↓ aliran darah *oroner(su!lai) ↓
7e3e* ta*i*ardi *ebutuhan 56 mio*ard ↑#a!at teradi 'NGIN' '7'#58S'L
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 17/51
$arakokinetik
• Mudah dia"sorpsi saluran cerna% ukosa dan kulit• $irst pass eta"olis "esar pada pe"erian per
oral "ioavaila"ilitas "ervariasi• Pe"erian su"lin!ual&spray&iv dapat en!hindari
first pass eta"olis • Transderal' a"sorpsi la"at% tapi dapat "ertahan
() a• Pe"erian an!ka panan! dapat eni"ulkan
toleransi• Pen!hentian endadak dapat eni"ulkan re"ound
phenoen
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 18/51
NIT)ATES
harmaco*inetic9om!arison:
• "ioa+ailabilit,$
NG: elo 12
I#N: 602
ISN: 1002
• )lasma clearance$
NG: ;0L+min
I#N: <L+min
ISN: 0=>L+min
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 19/51
• +ndikasi'
– An!ina sta"il – An!ina tidak sta"il – An!ina ,ariant
• #eran!an akut' Nitrat kera cepat su"lin!ual% iv.
• Terapi kronik' Nitrat kera sedan!&la"at oral%transderal.
– Ga!al antun! kon!estif – +nfark iokard
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 20/51
/fek sapin!
/fek sapin! nitrat% terutaa dise"a"kan oleh
vasodilatasi eksesif pe"uluh darah ' #akit kepala% sinkope% di00ines Takikardi% hipotensi ortostatik An!ina paradoksal
$lushin! $enoena re"ound pada pen!hentianendadak
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 21/51
• Kontraindikasi –
1ipersensitivitas terhadap nitrat
• 1ati-hati pada' – Penin!katan tekanan intrakranial – 1ipotensi% hipovoleia – Takiaritia – Ko"inasi den!an vasodilator lain
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 22/51
NIT)ATE TO%E)AN(E 9ontinuous or %re?uent e@!osure to
nitrates can lead to the de/elo!ment o%com!lete tolerance
The mechanism o% tolerance is not
com!letely understood:ay be related to the en$ymes in/ol/ed in
con/erting the nitrates to N5or to the en$yme that !roduces cG
Industrial (occu!ational) e@!osure to
organic nitrates has been associatedith -Monda, disease and !hysicalde!endence mani%est by /ariant anginaoccurring 1-6 days a%ter ithdraal
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 23/51
N+T2AT O2GAN+K
• Ailnitrit' inhalasi• Nitro!liserin' oral% parenteral% spray% transderal•
+sosor"id ononitrat +#MO.' oral• +sosor"id dinitrat +#3N.' oral• Penta eritritol tetra nitrat' oral
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 24/51
Drug Usual single dose Route ofadministration
Duration of action
Short acting
Nitroglycerin
0.15-1.2 mg sublingual 10 - 30 min
sosorbide dinitrate 2.5-5 mg sublingual 10 ! "0 min
#myl nitrite 0.1$ ! 3 ml inhalation 3 ! 5 min
Long acting
Nitroglycerin sustainedaction
".5 ! 13 mg % "-$ hrs oral " ! $ hrs
Nitroglycerin 2&ointment 1 ! 1.5 inches % hr to'ical 3 ! " hrs
Niroglycerin slo(released
1 !2 mg 'er ) hrs *uccal mucosa 3 ! " hrs
Nitroglycerin slo(released
10 ! 25 mg +2)hrs ,one 'atch+day
transdermal $ !10 hrs
sosorbide dinitrate 2.5 ! 10 mg 'er 2 hrs sublingual 1.5 ! 2 hrs
sosorbide dinitrate 10 !"0 mg 'er )-" hrs oral ) ! " hrs
sosorbide dinitrateche(able
5 ! 10 mg 'er 2-) hrs oral 2 ! 3 hrs
sosorbide mononitrate 20 mg 'er 12 hrs oral " !10 hrs
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 25/51
ANTAGON+# KA4#+5M
1= Golongan dihidro!iridinNi%edi!in nicardi!in nimodi!in %elodi!in
amlodi!in nitrendi!in lacidi!in
6= Golongan %enilal*ilamin: "era!amil
A= Golongan ben$otia$e!in: #iltia$em
e*anisme *era:enghambat masu*nya *alsium *e dalam sel
embuluh darah: "asodilatasi io*ard: inotro!i* negati% Nodus S' nodus '": *ronotro!i*
dromotro!i* negati%
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 26/51
MECHANISM OF ACTION
*n!ibit t!e influ" of &al#ium into &(0D*(& CV()&U'(0 #ells MU)&'2 3>N2
&&6
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 27/51
EFFECTS (I)
&&6
Vas#ular 2ffe#ts &ardia# 2ffe#ts
'asodilatation
↑ >/ supply (fter load↓ 6P ↓
↓ >/ demand
Heart 0ate ↓ &ondu#tion
&ontra#tion
↓ >/ demand
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 28/51
EFFECTS (II)
&&6
henylal/ylamines# ,era'amil
Dihydro'yridines
*,Nifedi'ine ,Nimodi'ine
*enothiae'ines
D,Diltiaem
asodilatation
eri'heraloronary
erebral
4eart Rate
S# Node
# Node
ontractility
↓
↓
↓↓↓↓
↑-
-↑
-
-
--
↓
↓↓
↓↓
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 29/51
ANTAGONIS *A%SI&M
Efek kardiovaskular Nifedipin Verapamil Dilia!em
(N) (V) (D)
1. Vasodilatasi koroner 5 4 3
2. Vasodilatasi perifer 5 4 3
3. Inotropik negatif 1 4 2
4. Kronotropik negatif 1 5 5
5. Dromotropik negatif6. Refleks takikardi
03
50
40
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 30/51
e*anisme anti angina
•NI&4#IIN – 4%e* langsung:
• #ilatasi *oroner su!lai 56 ↑ – 4%e* ta* langsung:
• 7esistensi !eri%er ↓ T# ↓ *ebutuhan 56 mio*ard
↓ – /a*at ter0adi ree#s ta#i#ardi dan
an'ina *arado#sal
• "47''IL #ILTI'B4 – 4%e* langsung:
• Inotro!i* *ronotro!i* (-) *ebutuhan 56 mio*ard ↓ – 4%e* ta* langsung:
• Inotro!i* (-) tegangan dinding /entri*el ↓• 8ronotro!i* (-) a*tu !engisian arteri *oroner ↑
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 31/51
$ETA+$%O(*E)S
Though most beta-bloc*ers do not causecoronary /asodilatation li*e the
nitro/asodilators or calcium channelbloc*ers beta-bloc*ers are im!ortant inthe treatment o% angina because o% theire.ects on the heart
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 32/51
• 4%e* langsung: – 8ronotro!i* C inotro!i* negati%
menurun*an *ebutuhan 56 mio*ard
• 4%e* ta* langsung:
– Inotro!i* (-) mengurangi tegangandinding /entri*el
– 8ronotro!i* (-) meme!r!anang a*tudiastol !egisian a= *oroner ↑ (su!lai ↑)
• Indi*asi: 'ngina stabil *roni*
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 33/51
PROPANOLOL
*s t!e prototype β adrenergi# blo#ker
β (drenergi#
blo#ker
↓*notropi# #!ronotropi# domotropi#
↓0enin → (g → perip!eral →6P ↓ resistan#e
aldosteron
↓ )odium, 8aterretention
6P ↓
O, deand
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 34/51
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 35/51
O$AT %AIN PA"AANGINA "ANSIN")OM *O)ENE)
A*&T•(ntiplatelet antitrombosit.
•(ntikoagulan
•Fibrinolitik trombolitik.
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 36/51
5
(N3*P'(32'23), (N3*&>(+U'(N3,3H0>M6>'Y3*&
• (ntiplatelets9 – Drugs t!at preent platelet ad!esion, a#tiation,
and aggregation
• (nti#oagulants9 – Drugs t!at preent blood #oagulation #as#ade
t!roug! modifi#ation of #oagulation fa#tors
• 3!rombolyti#s< fibrinolyti#s9 – Drugs t!at degrade t!e t!rombus
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 37/51
5E
(N3*P'(32'23
• Platelet9
Dense Parti#le9(DP, 3!rombo"ane(/, serotonin
(DP4re#eptor
+ly#oprotein**b<***a9fibrinogenre#eptor
0e#eptor of F+p *bre#eptor. #ollagen
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 38/51
Platelet a#tiation9
Platelet ad!esion *nAured endot!elium releases on illebrand fa#tor
#ollagen re#eptor.
Platelet a#tiation by93!rombin, (DP, serotonin, t!rombo"ane (/
(#tiation of re#eptors on platelet surfa#e9 3"(/ re#eptor, (DP4re#eptor, +ly#oprotein **b<***a re#eptor
fibrinogen re#eptor.
Platelet aggregation 'inking of platelet by fibrinogen
5G
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 39/51
5
P'(32'23 (&3*V(3*>N
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 40/51
ANTI P%ATE%ET
%$ *n!ibitor of &y#loo"ygenase9 ()P*0*N
(( 444444444444 3!rombo"ane4(/
&>I
(spirin irreersibly blo#ks &>I4% in t!e platelet 3"(/ ↓ Preent platelet a#tiation by 3"(/
(lso in!ibits formation of P+s in gastri# mu#osa irritation
)!ould be gien immediately in a#ute #oronary syndrome
'ife long use in all is#!emi# as#ular disease #oronary,#erebral, perip!eral.
@
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 41/51
ANTI P%ATE%ETS
/$ (DP4re#eptor blo#kers9 3i#lopidin
0edu#e platelet a#tiation by (DPNo gastri# irritation
)ide effe#ts9 neutropenia, lier abnormalities, t!romboti#t!rombo#ytopenia
&lopidogrel'ess side effe#ts, but #osts mu#! more
Faster onset of a#tion'ess +* aderse effe#tsNo8 be#ome standard t!erapy in a#ute #oronary syndrome$
%
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 42/51
ANTI P%ATE%ETS
5$ +p **b<***a re#eptor blo#kers9ab#i"imab, eptifibatide, lamifiban, tirofiban
Preent t!e final step in platelet aggregation
3o be administered *ntraenously
>nly for limited time and not routinely used &ontraindi#ation
(#tie bleeding or potentially bleeding
3!rombo#ytopenia
/
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 43/51
ANTI(OAG&%ANTS
Heparine
routinely used in (&)Unfra#tionated !eparine UFH.'o8 mole#ular 8eig!t !eparine 'MH.9
Fra"iparine, nadroparine, eno"aparine, dalteparine
)ynt!eti# pentasa##!aride9 Fondaparinu"
Me#!anisms of a#tion96inds to antit!rombin ina#tiate of F Ia and F **a$
Fondaparinu" ina#tiate F Ia only
5
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 44/51
*INETI(S
)!ould be administeed parenterally i, s#. UFH need monitoring of effe#ts aP33. 'MH C fondaparinu"9 no needs of aP33 monitoring 'MH C fonaparinu" !ae a longer !alf life on#e
or t8i#e daily Do not #ross pla#ental barrier safe for pregnant
8omen (ntidote of !eparine to"i#ity9 Protamine sulp!ate
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 45/51
)ide effe#ts
6leeding3!rombo#ytopenia
&ontraindi#ation(#tie bleeding, !aemop!ilia, seere !ypertension,
intra#ranial !emorr!age, adan#e !epati# or renaldisease, t!reatened abortion
L
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 46/51
O)A% ANTI(OAG&%ANT
arfarin, di#umarol itamine K antagonistin!ibits a#tiation of
it K4dependent fa#tors **, V**, *I, I.
Delayed onset of a#tion (dministered orally rarely i. Need monitoring of prot!rombin time *N0.
3arget9 *N0 %$L B 5$L of normal leel redu#tionof P3 by /L.
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 47/51
TO-I(ITY
arfarin #rosses pla#ental barrier readily !emorr!agi# and malformation of t!efetus #ontraindi#ated during pregnan#y
0arely9 #utaneous ne#rosis, infar#tion oft!e breast, fatty tissues, intestines,e"tremities$
*ntera#t 8idely 8it! ot!er drugs N)(*D,
it K, barbiturates, rifampi#in, diureti#,steroids, sulp!a, amiodarone, . and foods
(ntidote9 Vit K
E
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 48/51
G
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 49/51
T.)OM$O%YTI(S /FI$)INO%YTI(S0
Fibrinogen
Fibrin
FDP
PlasminPlasminogen
)treptokinase
Urokinase
(nistreplase
(lteplase tP(.
3!rombin
Main indi#ation9 reperfusion in a#ute )32M*
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 50/51
3!rombolyti# is only effe#tie in ne8ly formedt!rombus 'ess t!an 4%/ !ours.
(dministration9 i infusion)302P3>K*N()2 Produ#ed by )tepto#o##us
U0>K*N()2 2"trated from !uman renal #ells allergi# r"< rare
('32P'()2 tP(. Naturally o##uring fibrinolyti#
L@
SI"E EFFE(TS AN"
7/23/2019 Anti Angina (Hany)
http://slidepdf.com/reader/full/anti-angina-hany 51/51
SI"E EFFE(TS AN"(ONT)AIN"I(ATIONS
)ide effe#ts9Hemorr!age
Hypotension )treptokinase.(llergi# rea#tion )treptokinase.
&ontraindi#ations(#tie bleeding
(ny preious !istory of !emor!agi# stroke
Non !emor$ )troke 8it!in % year
*nternal bleeding 8it!in mo$Hypertension %G@<%%@., pregnan#y
MaAor surgery, trauma
Pregnan#y