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DRUG AFFECTING CARDIOVASCULAR

FUNCTIONPeter Kabo

Physiology & pathophysiology of the cardiovascular system

Drug Affecting Cardiovascular Function

JantungPembuluh darah

ANATOMI SSO

FAAL SSO

Transmisi Neurohormonal

Acetyl choline

Adrenaline/nor adrenaline

Respon Efektor terhadap perangsangan SSO

Organ Resptor Respon Perangsang Adrenergik

Respon Perangsang Kolinergik

Jantung

Nodus SA

AV

Atrium/ Ventrikel otot

Sist – konduksi

Arteri & Vena

Paru-paruOtot bronkus + trankea

Kelenjar bronkus

Sel mast

β1

β1

β1

β 1

α1 & α2

β 2

β 2

α 2 / β 2

β 2

Nadi ↑

Kontraktilitas ↑

Konduksi ↑

Konstriksi

Dilatasi

Relaksasi

Sekresi ↓ / ↑

Mediator inflam ↓

Nadi ↓

Kontraktilitas ↓

Kondulsi ↓ ↓

?

Konstriksi

Sekresi ↑ ↑

Sal cerna

Otot pls lambung & usus

Otot Sfingter

Kelenjar

Ginjal

Sekresi renin

Kandung kemih

Otot detrusor

Trigon & Sfingter

Uterus

Prostat

Mata

Hati

Pankreas

Sel β

Sel lemak

Kelenjar liur

α1 & α2

β 2

α1

α2

α1

β 1

β 2

α1

α 1

β 2

α1

α1

α1, β 2

α2

β 2

β 3

α1

Relaksasi

Relaksasi

Kontraksi

Sekresi ↓

↓

↑

Relaksasi

Kontraksi

Kontraksi (hamil)

Relaksasi

Kontraksi

Midriasis

Glikogenolisis & glikoneogenesis

Sekresi insulin ↓

Sekresi insulin ↓

Lipolisis ↑ ↑

Sekresi ↑

Kontraksi

Relaksasi

Sekresi ↑ ↑

-

Kontraksi

Relaksasi

Bervariasi

Miosis

-

Sekresi ↑

Transmisi Adrenergik

Fenilalanin

↓ Tirosin

↓ Dopa

↓ Dopamin

↓Noradrenalin

↓Adrenalin

↓ ↓ Comt

↓ NormetanefrinMetanefrin

3 – metoksi 4 –hidroksi femilglikol asam 3, 4 – dihidroksi mandelat

Hidroksiterase

Hidroksilase

Dekarboksilase

β Hidroksilase

Metiltrasferase

Denervasi kurase Nikotin respon

Anti Hypertensive Agents

Diuretics

Pharmacological Effects

Adverse effect

Therapeutic uses

Diuretic Resistance

α-methyldopa (Dopamet 250 mg/tab)↓α-methyl dopamine↓α-methyl Noradrenaline

Sympatholytic agents (Anti Adrenergic)

Pharmacological Effects:

Pharmacological Effects

Indication

Adverse Effects

Kardioselektif ISA

Bio Availibilitas Oral (%)

Metabolisme lintas

I (Hati) t1/2 (jam)

ACEBUTOLOL + + 30 - 50 + 3

METOPROLOL + - 40 - 50 +  3 - 6

ATENOLOL + - 40 - 60 - 6 - 8 

BISOPROLOL +++ - 90 10%  11

PROPANOLOL - - 25 - 35 +  2 - 6

PINDOLOL - ++ 95 - 100 -  3 - 4

OKSPRENOLOL - + 25 - 50 + 2

SOTALOL - - 90 - 100 - 10 - 15 

TIMOLOL - - 50 - 75 +  4 - 5

LABETOLOL (Alfa blocker) - + 25 +  5 - 8

CARVEDILOL          

Farmakodinamik indikasi Efek samping

Sistem kardiovaskular

(-) inotropik(-) kronotropik↓ resistensi perifer

(non-selektif)↓ sekresi renin↓ cardiak output↓ resistensi perifer

(pengguna kronis)

Turunkan TD

TakikardiTakiaritmiaHipertensiangina pektorisInfark miokardHOCMFeokromasitomaTirotoksikosisGlaukoma

Gagal jantungBradikardi

Saluran nafas Bronkokonstriksi Bronkospasme

Efek metabolik ↓ Asam lemak↓ Trigliserida↓ HDL↓glikogenolisis

HipertrigliseridHipoglikemi!! Putus obat

Penghambat saraf adrenergik

Clonidine

Methyl Dopa

Negative Feed back mechanism

Relative Cardiovascular Effects

Vasodilatasi Supression of

Contractility Automaticity Conduction

NifedipinDiltiazemVerapamil

534

124

155

045

Calcium Channel Blockers (CCB)

Kinino gen

Bradykinine

Angitensinogen

Angiotensin I

Angiotensin IIInactive peptide

Endothelium

Prostaglandin NO

ACE-I

Bradikinin system Angiotensin system

Contraction

AT1

AT2

G

PLC

DAG IP3

Proteinkinase C

Vasoco

nstrict

ion

Vasodilatation

Pharmacodynamic

ANGIOTENSIN CONVERTING ENZYME (ACE) - INHIBITORS

Adverse effect

Angiotensin receptor antagonistsAT1 - antagonists

PENGHAMBAT ACE & ANGIOTENSIN RECEPTOR ANTAGONIST

Angitensoinogen

Renin

AI

AI

Vasokinstriksi ↑ Aldosteron

Non - ACE

ACE

Bradikinin

Peptide maktif

ACE-I

Sel juxtaglomerolus

Efek samping:Mekanisme Kerja ACE-I

Preparat

Kegunaan:

Angiotensin antagonis:

ACE - Inhibitors

First line:1. Diuretics2. β blocker

Pharmacological Treatment of Hypertension

Compelling indication & drug of choice (except contraindication)

VASODILATORS

Isosorbid 5 – Mononitrat

Penta Eritritol Tetranitrat

Eritritil Tetranitrat

ANGINA PECTORIS

Mekanisme kerja

BB22

MM SS PP TT VV

EDRF EDRF NO?)NO?)

GSGS

CGMPCGMP

RelaksasiRelaksasi

ToleransiToleransi

adad ach

ach

G - HT

G - HT

ADPADP

Trom

bi

Trom

bi

nnVas

opre

sin

Vasop

resin

EndotelEndotel

NitratNitrat

GMPGMP- SH- SH

PP

Rebound fenomenaKontraindikasi: Syok &Hipersensitif

Farmakokinetik :

Farmakodinamik :

Indikasi

William Withering (1789) Digitalis lanata (foxglove putih)

Digitalis purpura (foxglove ungu)

Cardiac Glicoside

Farmakokinetik

Sign & Symptoms of Cardiac Glycoside Toxicity

Drug interaction with Digoxin

Pharmacodynamic

Management of Digoxin toxicity

Efek pada organ lain

Efek pada Jantung

Anti Arrhytmic drugs

Mechanism of anti arrhythmias drug action

Ant arrhythmic drugs can cause arrhythmiasSome arrhythmias should not be treated

Classification of anti arrhythmia drugs

O P Dosis Kadar puncak

Metab Eks Indikasi Efek samping

KINIDIN + + 3 X 200 mg 60 – 90’ H G/H AF, SVT

PROKAINAMID + + 3X (250000 – 500) mg

45 – 70’ H G VES, SVT Lupus like syndrome, leukopeni

DIISOPIRAMID + - 3X 100 mg 60 – 120’ H G VES, SVT Mulut kering, konstipasi, penglihatan kabur

LIDOKAIN - + 1 MG/ KG bb =1mg/ jam

H VT (pasca miokard infark)

hipotensi

PROPAFENON + + 3 x(150 -300) mg

60 – 180’ VES

Cinchonism

•Demam•Tinitus•Penglihatn kabur•Diplopia•Sakit kepala•Delirium•Prikosis•Gangguan GIT

Farmakokinetik

AmiodaronFarmakokinetik indikasi Efek samping

O P T1/2 Dosis VT, AF Pro aritmik,Hipotensi, gangguan fungsi: hati, tiroid, paru & mata+ + 25 – 60 jam Loading 600

s/d 800 mg/ hariMaintenance 300mg/ hari

Farmakokinetik indikasi Efek samping

O P T1/2 Dosis SVT, VT Gagal jantung

+ - 11 jam 800 s/d 320 mg/hari

Sotalol

Bradicardy

Heart Block1. Atropine (I.V.)2. Temporary Pacemaker3. Permanent Pacemaker

Sinus Bradicardy1.Ephedrine2.Aminophyline3.Atropine (I.V.)

Permanent Pacemaker