anti angina (hany)

7/23/2019 Anti Angina (Hany)

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ANTI ANGINA

Hany Yusmaini dr Mkes

Dept Farmakologi FKUPN Veteran Jakarta



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$



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$



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



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



&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



'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



PA HOPHYSIOLOGY

>/ supply >/ demand

*)&H2M*(

P(*N

Pre#ipitating fa#tors

(ngina Pe#toris



S D

sehat angina angina



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



PRINCIPLES IN HE REA MEN OF ANGINA

PEC ORIS

%$ >/ supply to t!e tissue

/$ >/demand of t!e tissue

5$ risk fa#tor



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



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*



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



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



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



$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



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



• +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



/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



• Kontraindikasi –

1ipersensitivitas terhadap nitrat

• 1ati-hati pada' – Penin!katan tekanan intrakranial – 1ipotensi% hipovoleia – Takiaritia – Ko"inasi den!an vasodilator lain



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



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



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



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%



MECHANISM OF ACTION

*n!ibit t!e influ" of &al#ium into &(0D*(& CV()&U'(0 #ells MU)&'2 3>N2

&&6



EFFECTS (I)

&&6

Vas#ular 2ffe#ts &ardia# 2ffe#ts

'asodilatation

↑ >/ supply (fter load↓ 6P ↓

↓ >/ demand

Heart 0ate ↓ &ondu#tion

&ontra#tion

↓ >/ demand



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

↓

↓

↓↓↓↓

↑-

-↑

-

-

--

↓

↓↓

↓↓



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



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 ↑



$ETA+$%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



• 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*



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



O$AT %AIN PA"AANGINA "ANSIN")OM *O)ENE)

A*&T•(ntiplatelet antitrombosit.

•(ntikoagulan

•Fibrinolitik trombolitik.



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



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



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



5

P'(32'23 (&3*V(3*>N



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.

@



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$

%



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

/



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



*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



)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



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.



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



G



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*



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"



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

anti angina (hany)

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