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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 Resptor Respon Perangsang Respon Perangsang
Adrenergik Kolinergik

Jantung
Nodus SA β1 Nadi ↑ Nadi ↓
AV
β1 Kontraktilitas ↑ Kontraktilitas ↓
Atrium/ Ventrikel otot
β1 Konduksi ↑ Kondulsi ↓ ↓
Sist – konduksi β1

Arteri & Vena α1 & α2 Konstriksi ?


β2 Dilatasi
Paru-paru
Otot bronkus + trankea
Kelenjar bronkus β2 Relaksasi Konstriksi
Sel mast Sekresi ↑ ↑
α2/β2 Sekresi ↓ / ↑
β2 Mediator inflam ↓
Sal cerna
Otot pls lambung & usus α1 & α2 Relaksasi Kontraksi
Otot Sfingter β2 Relaksasi
Kelenjar α1 Kontraksi Relaksasi
α2 Sekresi ↓ Sekresi ↑ ↑
Ginjal
Sekresi renin α1 ↓ -
β1 ↑
Kandung kemih
Otot detrusor β2 Relaksasi Kontraksi
Trigon & Sfingter α1 Kontraksi Relaksasi

Uterus α1 Kontraksi (hamil) Bervariasi


β2 Relaksasi
Prostat α1 Kontraksi
Mata α1 Midriasis Miosis
Hati α1, β 2 Glikogenolisis & glikoneogenesis -
Sekresi insulin ↓
Pankreas α2 Sekresi insulin ↓
Sel β β2
Lipolisis ↑ ↑
Sel lemak β3 Sekresi ↑
Kelenjar liur α1 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 kurase
Nikotin respon
Anti Hypertensive Agents
Diuretics
Pharmacological Effects Therapeutic uses

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

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 Takikardi Gagal jantung


(-) kronotropik Takiaritmia Bradikardi
↓ resistensi perifer Hipertensiangina pektoris
(non-selektif) Infark miokard
↓ sekresi renin Turunkan TD HOCM
↓ cardiak output Feokromasitoma
↓ resistensi perifer Tirotoksikosis
(pengguna kronis) Glaukoma

Saluran nafas Bronkokonstriksi Bronkospasme

Efek metabolik ↓ Asam lemak Hipertrigliserid


↓ Trigliserida Hipoglikemi
↓ HDL !! Putus obat
↓glikogenolisis
Penghambat saraf adrenergik

Clonidine

Methyl Dopa

Negative Feed back mechanism


Calcium Channel Blockers (CCB)

Relative Cardiovascular Effects


Vasodilatasi Supression of
Contractility Automaticity Conduction
Nifedipin 5 1 1 0
Diltiazem 3 2 5 4
Verapamil 4 4 5 5
ANGIOTENSIN CONVERTING ENZYME (ACE) - INHIBITORS

Pharmacodynamic
Adverse effect

Bradikinin system Angiotensin system


Kinino gen Angitensinogen

Endothelium

Bradykinine Angiotensin I

Prostaglandin ACE-I
NO
Inactive Angiotensin II
peptide
Va
so
di n
la tio
ta i c
tio st r
n on
AT
s oc
1 Va
G Angiotensin receptor antagonists
PLC
AT AT1 - antagonists
2

DAG IP3

Proteinkinase C

Contraction
PENGHAMBAT ACE & ANGIOTENSIN RECEPTOR ANTAGONIST

Sel
Angitensoinogen
juxtaglomerolus
Renin
Bradikinin
AI
Non - ACE-I
ACE
AI ACE
Peptide maktif

Vasokinstriksi ↑ Aldosteron

Mekanisme Kerja ACE-I 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
in
res
T bi p
h -H P o m aso
ad ac G AD Tr V
n
B
M S P T V
Nitrat 2

Endotel

EDRF
NO?)
GS

P
GMP
Toleransi - SH
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 Metab Eks Indikasi Efek samping
puncak
KINIDIN + + 3 X 200 mg 60 – 90’ H G/H AF, SVT
PROKAINAMID + + 3X (250000 – 45 – 70’ H G VES, SVT Lupus like syndrome,
500) mg leukopeni

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


konstipasi,
penglihatan kabur
LIDOKAIN - + 1 MG/ KG bb H VT (pasca miokard hipotensi
=1mg/ jam infark)

PROPAFENON + + 3 x(150 -300) 60 – 180’ VES


mg

Cinchonism

• Demam
• Tinitus
• Penglihatn kabur
• Diplopia
• Sakit kepala
• Delirium
• Prikosis
• Gangguan GIT
Amiodaron
Farmakokinetik indikasi Efek samping

O P T1/2 Dosis VT, AF Pro aritmik,


Hipotensi, gangguan fungsi: hati, tiroid,
+ + 25 – 60 jam Loading 600 s/d paru & mata
800 mg/ hari
Maintenance
300mg/ hari

Sotalol
Farmakokinetik indikasi Efek samping

O P T1/2 Dosis SVT, VT Gagal jantung

+ - 11 jam 800 s/d 320


mg/hari
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

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