DRUG AFFECTING

CARDIOVASCULAR
FUNCTION
Peter Kabo
Hypertensions
Coronary Artery Disease
Heart failure
Arrhythmia
Anti hypertensive agents
Drugs used for the treatment of myocardial ischemia (anti
angina agents)
Pharmacological treatment of heart failure
Anti arrhythmic drugs
Physiology & pathophysiology of the cardiovascular system
Drug Affecting Cardiovascular Function
Sistem konduksi
Automatisasi
Miokard
Kontraktilitas (hukum starling)
Katup
Ao, pul. Mitral. Trikomidal
Artery Coroner
Lumen
Driving Pressure
Tunika Antima
Vasoaktif sub
Tunika Media
Elastisitas
Jantung
Pembuluh darah
ANATOMI SSO
FAAL SSO
Conservative
Reservation
Parasimpatis
Fight
Flight reaction
Sympathies
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-paru
Otot bronkus + trankea
Kelenjar bronkus
Sel mast

1

1
1
1

1 & 2
2

2
2 / 2
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

Sel lemak
Kelenjar liur

1 & 2
2
1
2

1
1

2
1

1
2
1
1
1, 2

2
2

3
1

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

Hidroksilase

Dekarboksilase

Hidroksilase

Metiltrasferase
Langley (1878)
Reseptor
Obat yang menimbulkan respon
Agonis
Obat yangmenghambat respon yang
ditimbulkan Agonis
Antagonis
Denervasi kurase
Nikotin respon
Asetilkolin
Muskarinik
(M)
Nikotinik
(N)
Noradrenalin
Adrenalin
Isoprenalin



Anti Hypertensive Agents
Diuretics
Sympatholytic drugs
Vasodilators
Ca
++
Channels Blockers
Angiotensin Converting Enzyme Inhibitors (ACE-I)
Angiotensin II Receptor Antogonits
Hydrochlorothiazide (hct) 50 mg, 25 mg/ tab
Chlorthalidone (hygrodone 50 mg/ tab)
Indapamide (Natrilix SR 1,5 mg/ tab)
Thiazides & related agents:
Furosemide (Lasix 20 mg/ amp, 40 mg/ tab)
Bumetanide
Loop diuretics
Spironolactone (Aldactone 25mg, 50 mg, 100 mg)
Amilorita
K sparing diuretics
Diuretics
Hypo kalemia
Hyper uricemia
Hyoerglycemia
Ototokicity (loop diuretics)
LDL, Trigliceride & HDL cholesterol
Gynecomastia (Spironolactone) Hyper K
+

(NSAID, Blocker & ACE-I)
Sexual impotence
Diuresis CO
Na
+
Excretion 1 receptor sensitivity BP
Uric acid excretion
K
+
excretion (except spironolactone)
Pharmacological Effects
Adverse effect
Oedema
Hypertension
Congestive Heart Failure
Therapeutic uses
1Bed Rest
Increase dose
Administration of smaller doses more
frequently
Combination therapy
Diuretic Resistance
Central acting agents (methyldopa, clonidine)
Adrenergic neuron blocking agents
adrenergic antagonists ( blockers)
adrenergic antagonists ( blockers)
Mixed & adrenergic antagonists (Labetolol, Carvedilol)
-methyldopa (Dopamet 250 mg/tab)

-methyl dopamine

-methyl Noradrenaline

Sympathetic tone
Cardiac output
Peripheral resistance
Myocardial contractility
Heart rate
Renin secretion
Sympatholytic agents (Anti Adrenergic)
Pharmacological Effects:
Prazosin (Minipress, 1 & 2 mg/tab)
Terazosin (Hytrin, 1 & 2 mg/tab)
Doxazosin (Cardura, 1 & 2 mg/tab)
Vasodilatation
Arterial resistence
Venous capaetance
Triglyceride
LDL Cholesterol
HDL Cholesterol
Resistance in trigone muscle BPH of
bladder and urethra
Pharmacological Effects
Hypertension
Vasospastic disorders
Indication
First dose effect
Postural hypotension
Adverse Effects
Isprenalin
Propanolol
Atenolol
Metoprolol
Bisoprolol
Timolol
Pindolol
Kardioselektif ISA
Bio
Availibilita
s Oral (%)
Metabolis
me 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
Takikardi
Takiaritmia
Hipertensiangina
pektoris
Infark miokard
HOCM
Feokromasitoma
Tirotoksikosis
Glaukoma
Gagal jantung
Bradikardi
Saluran nafas Bronkokonstriksi Bronkospasme
Efek metabolik Asam lemak
Trigliserida
HDL
glikogenolisis
Hipertrigliserid
Hipoglikemi
!! Putus obat
Mekanisme kerja
Mongosongkan katekolamin di ujung saraf adrenergik
Farmakodinamik
Cardiac output
Resistensi perifer
Indikasi
Hipertensi
Efek samping
Depresi psikotik
Penghambat saraf adrenergik
Clonidine
Methyl Dopa
Negative Feed back mechanism
Relative Cardiovascular Effects
Vasodilatasi Supression of
Contractility Automaticity Conduction
Nifedipin
Diltiazem
Verapamil
5
3
4
1
2
4
1
5
5
0
4
5
Golongan Dihidropiridin
Nifedipin
Amlodipin
Felodipin
Nikardipin
Nimodopin
Benzodtiazepin
Diltiazem
Difenalkilamin
Verapamil
Calcium Channel Blockers (CCB)
Kinino gen
Bradykinine
Angitensinogen
Angiotensin I
Angiotensin II
Inactive
peptide
Endothelium
Prostaglandin
NO
ACE-I
Bradikinin system Angiotensin system
Contraction
AT
2
G
PLC
DAG
IP3
Proteinkinase C
Na+ reabsorbsion
Sympathetic activity
Growth (cardiac remodeling
vascular hyperthrophy)
Antigrowth
Apoptosin
Vasodilatory
Pharmacodynamic
ANGIOTENSIN CONVERTING ENZYME (ACE) - INHIBITORS
Cough
Angioedema
Hyper K++
Prelipitating renal failure
Applets anemia
Dysgensia
Adverse effect
Losartan
Valsartan
Irbesartan
Candesartan
Angiotensin receptor antagonists
AT1 - antagonists
aktivitas sistem simpatis
AII
Sekresi Aldosteron
Atrial Natriuric Factor
Prostaglandin
Batuk kering
Udem Angioneurotik
First dose hipotensi
Hiper K
++

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
Captopril (Capoten) 25 mg/ tab
Enalapril (Inoprilat) 5 mg/ tab
Lisinopril (Zestril) 5 mg/ tab
Perindopril (Prexum) 4 mg/ tab
Ramipril (Triatec) 5 mg/ tab
Losartan
Valsartan (Diovan)
Preparat
Kegunaan
:
Hipertensi ringan s/d sedang
(+) gagal jantung
LVH
DM
Angiotensin antagonis:
ACE - Inhibitors
Captopril
Zefenoprilat
Sulfhydryl Containing:
Enalaprilat Benazeprilat
Lisinopril Cilaprilat
Perindoprilat Delaprilat
Quinaprilat Spiraprilat
Ramiprilat Trandolaprilat
Non- Sulfhydryl Containing:
Fosinoprilat
Phophoryl containing:
Lipid solubility
Cone max
T
T max
AUC
Pharmacokinetic:
Diabetes (+ protein urea)
ACE-I
Heart Failure
ACE-I, Diuretics
Isolated systolic HT
Diuretics, Ca++ antagonists
Myocardial infarction
-blockers, ACE-I
Angina Pectoris
-blockers, Ca++ antagonists
Dyslipidemia
blockers
Hyperthyroidism
-blockers
Osteoporosis
Thiazide
Essential tremor
-blockers (non-selective)
Benign Prostate hypertrophy
blockers
Renal insufficiency
ACE-I
First line:
1. Diuretics
2. blocker
Pharmacological Treatment of Hypertension
Compelling indication & drug of choice (except contraindication)
VASODILATOR
S
Arterial (Hydrolazine, Minoxidile)
Arterial & Venous (Na
+
- Nitroprusside)
Arnil nitrat
Nitro gliserin
(Gliseril trinitrat = GTN)
Isosorbid Di-Nitrat
(ISDN)
Isosorbid 5 Mononitrat
Penta Eritritol Tetranitrat
Eritritil Tetranitrat
ANGINA PECTORIS
Mekanisme kerja
B
2
M S P T V
EDRF NO?)
GS
CGMP
Relaksasi
Toleransi
Endotel
Nitrat
GMP
- SH
Relaksasi otot polos pembuluh darah Supply
preload Wall
stress
Hipotensi
Sakit kepala
Refleks Takikardi
Koroner
+
sistemik
Angina Pektoris
Miokard Infark
Gagal Jantung Kongestif
Rebound fenomena
Kontraindikasi: Syok &Hipersensitif
Farmakokinetik :
Farmakodinamik :
Reabsorbsi
SL
Oral
Topikal
IV
Sirkulasi
Hati
Metabolit di
Ginjal
Indikasi
William Withering (1789) Digitalis lanata (foxglove putih)
Digitalis purpura (foxglove ungu)
Farmakokinetik
Kardenolit : Inti steroid lipofilik
Inti lakton hidrofilik
Absorbsi (40 75%)
tergantung jenis
Metabolit usus (reabsorbsi) sirkulasi & lerohepatis
(t )
Metabolisme : Hati
Distribusi : Seluruh tubuh
terutama di jantung
Eliminasi : tanpa
perubahan melalui ginjal
Cardiac Glicoside
Farmakokinetik
0.75 1.5 mg (oral)
0.5 1.0 mg (I.V.)
Dosis (beban) digitalisasi
(loading dose)
0.125 0.5 mg (oral)
0.25 mg (I.V.)
Dosis pemeliharaan/ hari
(maintenance dose)
1.5 3 jam (oral)
5 30 menit (I.V.)
Mula kerja
4 6 jam (oral)
1.5 3 jam (I.V.)
Efek maksimal
75% Absorbsi intestinal
1.6 hari T
0.5 2.0 mg/ml Kadar terapi
Ginjal Eliminasi
Sign & Symptoms of Cardiac Glycoside Toxicity
Arterial + ventricular Ectopic
SA & AV node conduction
disturbances
(bradyarrhytmias)
Cardiac
Anorexia, Nausea, vomiting,
Abdominal pain Gastrointestinal
Blurred or yellow vision,
halos
Visual
Delirium, fatigue, malaise,
confusion, abnormal
dreams, dizziness
Psychiatric
drug
Cholestyramine,
Kaolin peptin,
Neomylin,
Sulfazolazin, Bram
Antacid, Albuterol,
Thyroxim
Propafenone,
Pecinidine,
Amiodarone,
Verapamil,
Diltiazem,
Nifedipine,
Captopril,
Cyclosporin
Change in
digoxin level


Drug interaction with Digoxin
Pharmacodynamic
Cardiac contractile state
SA AV conduction
-blockers,
Verapamil, Diltiazem,
Flecainide,
Disopyramide
Automaticity
Kaluretic, Diuretics,
Sympathomimetic
drug
Antidigoxin immunotherapy (fab fragments)
K+
Lidocamil/ Phenytoin
Management of Digoxin toxicity
Menghambat Na+/K+ - ATP ASE
(+) inotropik Indikasi Gagal
Jantung
Efek mekanik
Potensial aksi dini
resistensi membrean diikuti
Arterial Fibrilasi ( indikasi)
Potensial aksi fase plateas
Arterial Fluter (indikasi)
resistensi membran indikasi SVT
tonus vagus
Efek listrik
Semua organ eksitase termasuk otot polos & saraf
GIT
SSP
Ginekomastik (perangsangan estrogen)
Efek pada organ lain
Efek pada Jantung
Anti Arrhytmic drugs
Mechanism of anti arrhythmias drug action
Decreased phase 4 slope
blocker
Increased threshold
Na+ channel blocker
Ca++ channel blocker
Increased max diastolic potential
Adenosine
Acetylcholine
Increased action potential duration
K+ channel blocker
Ant arrhythmic drugs can cause arrhythmias
Some arrhythmias should not be treated
Classification of anti arrhythmia drugs
Sodium channel blocker
Sodium channel (++)
Diisopyramide, Quinidine, Procainamide
Blocks K+ Efflux (+)
Lidocaine, Mexiletine, Tocainide
Sodium channel (+++)
Flecainide, Encainide, Propafenone
Anti adrenergic
blocker
K+ channel Efflux blockers also Na+ blockers
Amiodarone
Sotalol
Ca++ channel blockers
Verapamil & Diltiazem
Autonomic Effects
Vagus stimulation
Digoxin
Adenosine receptor activation
Adenosine
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
Kardiovaskular
QRS Interval
Long QT
Hipotensi / Sinkop
SA block
AV block
Torsades de Poentes
ventrikuler rate (efek
anti kolinergik)
Cinchonism
Demam
Tinitus
Penglihatn kabur
Diplopia
Sakit kepala
Delirium
Prikosis
Gangguan GIT
Farmakokinetik
Amiodaron
Farmakokinetik 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/
hari
Maintenance
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 Block
1. Atropine (I.V.)
2. Temporary Pacemaker
3. Permanent Pacemaker

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