Obat Kardiovaskular

DRUG AFFECTING CARDIOVASCULAR FUNCTION Peter Kabo

Drug Affecting Cardiovascular Function

Physiology & pathophysiology of the cardiovascular system

Jantung

Pembuluh darah

ANATOMI SSO

FAAL SSO

Acetyl choline Adrenaline/nor adrenaline

Transmisi Neurohormonal

Respon Efektor terhadap perangsangan SSO Organ Jantung Nodus SA AV Atrium/ Ventrikel otot Sist – konduksi Arteri & Vena

Resptor

Respon Perangsang Adrenergik

Respon Perangsang Kolinergik

β1

Nadi ↑

Nadi ↓

β1 β1 β1

Kontraktilitas ↑ Konduksi ↑

Kontraktilitas ↓ Kondulsi ↓ ↓

α1 & α2 β2

Konstriksi Dilatasi

?

β2

Relaksasi

Konstriksi Sekresi ↑ ↑

α2/β2

Sekresi ↓ / ↑ Mediator inflam ↓

Paru-paru Otot bronkus + trankea Kelenjar bronkus Sel mast

β2

Sal cerna Otot pls lambung & usus Otot Sfingter Kelenjar

α1 & α2 β2 α1 α2

Relaksasi Relaksasi Kontraksi Sekresi ↓

Kontraksi

α1 β1

↓ ↑

-

β2 α1

Relaksasi Kontraksi

Kontraksi Relaksasi

Prostat Mata Hati

α1 β2 α1 α1 α1, β 2

Pankreas Sel β

α2 β2

Kontraksi (hamil) Bervariasi Relaksasi Kontraksi Midriasis Miosis Glikogenolisis & glikoneogenesis Sekresi insulin ↓ Sekresi insulin ↓

Ginjal Sekresi renin Kandung kemih Otot detrusor Trigon & Sfingter Uterus

Sel lemak Kelenjar liur

β3 α1

Relaksasi Sekresi ↑ ↑

Lipolisis ↑ ↑ Sekresi ↑ Sekresi ↑

Transmisi Adrenergik Fenilalanin Hidroksiterase

↓

Tirosin Hidroksilase

↓

Dopa

Dekarboksilase

↓

β Hidroksilase Dopamin

↓

Metiltrasferase Noradrenalin

↓ Adrenalin

↓ ↓

↓ Comt

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

Denervasi Nikotin

kurase

respon

Anti Hypertensive Agents

Diuretics

Pharmacological Effects

Adverse effect

Therapeutic uses

Diuretic Resistance

Sympatholytic agents (Anti Adrenergic)

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

Pharmacological Effects:

Indication

Pharmacological Effects Adverse Effects

Kardioselektif

ISA

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

Bio Metabolism t1/2 (jam) Availibilitas e lintas I Oral (%) (Hati)

Farmakodinamik

Sistem kardiovaskular (-) inotropik (-) kronotropik ↓ resistensi perifer (non-selektif) ↓ sekresi renin ↓ cardiak output ↓ resistensi perifer (pengguna kronis)

Turunkan TD

indikasi

Efek samping

Takikardi Gagal jantung Takiaritmia Bradikardi Hipertensiangina pektoris Infark miokard HOCM Feokromasitoma Tirotoksikosis Glaukoma

Saluran nafas

Bronkokonstriksi

Bronkospasme

Efek metabolik

↓ Asam lemak ↓ Trigliserida ↓ HDL ↓glikogenolisis

Hipertrigliserid Hipoglikemi !! Putus obat

Penghambat saraf adrenergik

Clonidine Methyl Dopa Negative Feed back mechanism

Calcium Channel Blockers (CCB)

Relative Cardiovascular Effects Vasodilatasi Nifedipin Diltiazem Verapamil

5 3 4

Supression of Contractility

Automaticity

Conduction

1 2 4

1 5 5

0 4 5

ANGIOTENSIN CONVERTING ENZYME (ACE) - INHIBITORS

Pharmacodynamic

Adverse effect

Bradikinin system

Angiotensin system

Kinino gen

Angitensinogen

Bradykinine

Angiotensin I

Endothelium

Prostaglandin NO

Va

ACE-I Inactive peptide

so

di

la

ta

tio

Angiotensin II

n

AT 1

s Va

G AT 2

PLC

DAG

IP3

Proteinkinase C Contraction

oc

n tio c i st r on

Angiotensin receptor antagonists AT1 - antagonists

PENGHAMBAT ACE & ANGIOTENSIN RECEPTOR ANTAGONIST

Sel juxtaglomerolus

Angitensoinogen Renin Bradikinin AI

Non ACE

ACE-I AI

Vasokinstriksi

Mekanisme Kerja ACE-I

ACE Peptide maktif

↑ Aldosteron

Efek samping:

Angiotensin antagonis:

Kegunaan : Preparat

ACE - Inhibitors

Pharmacological Treatment of Hypertension Compelling indication & drug of choice (except contraindication)

First line: 1. Diuretics 2. β blocker

VASODILATO RS

ANGINA PECTORIS

Isosorbid 5 – Mononitrat Penta Eritritol Tetranitrat Eritritil Tetranitrat

Mekanisme kerja h ac

ad

Nitrat

B 2

M

G

T -H

S

P AD

P

bi m o Tr n

T

in es r p so a V

V Endotel

EDRF NO?) GS P

Toleransi

- SH

GMP CGMP Relaksasi

Farmakokinetik :

Farmakodinamik :

Indikasi

Rebound fenomena Kontraindikasi: Syok &Hipersensitif

Cardiac Glicoside William Withering (1789)

Digitalis lanata (foxglove putih) Digitalis purpura (foxglove ungu)

Farmakokinetik

Sign & Symptoms of Cardiac Glycoside Toxicity Drug interaction with Digoxin

Pharmacodynami c

Management of Digoxin toxicity

Efek pada Jantung

Efek pada organ lain

Anti Arrhytmic drugs

Mechanism of anti arrhythmias drug action

Ant arrhythmic drugs can cause arrhythmias Some arrhythmias should not be treated

Classification of anti arrhythmia drugs

Farmakokinetik O

P

Dosis

Kadar puncak

Metab

Eks

Indikasi

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 hipotensi infark)

PROPAFENON

+

+

3 x(150 -300) mg

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

60 – 180’

VES

Efek samping

Amiodaron Farmakokinetik

indikasi

O

P

T1/2

+

+

25 – 60 jam

Dosis

VT, AF

Loading 600 s/d 800 mg/ hari Maintenance 300mg/ hari

Efek samping Pro aritmik, Hipotensi, gangguan fungsi: hati, tiroid, paru & mata

Sotalol Farmakokinetik

indikasi

O

P

T1/2

+

-

11 jam

Dosis 800 s/d 320 mg/hari

SVT, VT

Efek samping Gagal jantung

Bradicardy Sinus Bradicardy 1.Ephedrine 2.Aminophyline 3.Atropine (I.V.)

Heart Block 1. Atropine (I.V.) 2. Temporary Pacemaker 3. Permanent Pacemaker

Permanent Pacemaker