OBAT

ANTIHIPERTENSI
DIAGNOSIS
based on repeated, reproducible measurements of
elevated blood pressure
 ETIOLOGI
SPESIFIK
secondary hypertension
renal artery constriction, coarctation of
the aorta, pheochromocytoma,
Cushing’s disease, and primary
aldosteronism.
established in only 10–15% of patients.
NON SPESIFIK
essential or primary hypertension
Abnormality autonomic nervous system
function, baroreceptor reflexes, the renin-
angiotensin-aldosterone system, and the
kidney
Mutasi Gen :
angiotensinogen, ACE, beta 2
adrenoceptor, alpha adducin
(a cytoskeletal protein)
The heritability → 30%.
psychological stress, and
environmental and dietary factors
(increased salt and decreased potassium or
calcium intake)
PATOFISIOLOGI NORMAL REGULATION OF BLOOD PRESSURE
Baroreflexes, mediated by autonomic nerves, act in combination with
humoral mechanisms, including the reninangiotensin-aldosterone
system, to coordinate function at these four control sites and to
BP = CO X PVR maintain normal blood pressure

PVR : peripheral vascular resistance

CO : cardiac output

three anatomic sites :

1. arterioles,
2. postcapillary venules (capacitance vessels),
3. heart

CO = HR X SV

4. the kidney, contributes to maintenance of blood

pressure by regulating the volume of intravascular fluid
 BARORECEPTOR REFLEX
Baroreflexes are responsible
for rapid, moment-to-moment
adjustments in blood
pressure, such as in
transition from a reclining to
an upright posture
Renal Response to Decreased Blood Pressure
A reduction in renal perfusion pressure

• intrarenal redistribution of blood flow

• increased reabsorption of salt and water
• decreased pressure in renal arterioles
• Sympathetic neural activity (via beta-
adrenoceptors)

Stimulasi RENIN

Increase production of ANGIOTENSIN II

(1) direct constriction of (2) stimulation of aldosterone synthesis in

resistance vessels the adrenal cortex
which increases renal sodium
absorption and intravascular blood volume.
 AGEN
ANTIHIPERTENSI
DRUGS THAT ALTER VASODILATORS
SODIUM &
WATER BALANCE

AGEN
ANTIHIPERTENSI

DRUGS THAT ALTER

SYMPATHETIC INHIBITORS OF
NERVOUS SYSTEM FUNCTION
ANGIOTENSIN
 DRUGS THAT ALTER
SODIUM &
WATER BALANCE

DIURETIC
 CENTRALLY ACTING
SYMPATHOPLEGIC
DRUGS

DRUGS THAT ALTER

SYMPATHETIC
NERVOUS SYSTEM
FUNCTION

ADRENERGIC NEURON– ADRENOCEPTOR

BLOCKING ANTAGONISTS
AGENTS
 CENTRALLY ACTING
SYMPATHOPLEGIC
DRUGS

Activate Alpha 2 adrenoceptors

Reduce central sympathetic

outflow reduce norepinephrine release
from noradrenergic nerve endings
ADRENERGIC NEURON–
BLOCKING
AGENTS

Interferes with amine release

and replaces norepinephrine in
vesicles
Reduce all sympathetic effects, especially
cardiovascular, and reduce blood pressure

Blocks vesicular amine

transporter in noradrenergic
nerves and depletes transmitter
stores
ADRENOCEPTOR
ANTAGONISTS BETA BLOCKER

ALFA BLOCKER
Prazosin, Terazosin, Doxazosin

BLOCK ALPHA 1 ADRENORESEPTOR

Prevent sympathetic vasoconstriction

reduce prostatic smooth muscle tone

Hipertensi
BPH (Benign Prostatic Hyperplasia)
ADRENOCEPTOR ALFA BLOCKER
ANTAGONISTS Prazosin, Terazosin, Doxazosin

BETA BLOCKER
NON SELEKTIF
SELEKTIF Propanolol,
Metoprolol, Nadolol, Carteolol, Betaxolol, & Bisoprolol
Atenolol, esmolol Labetalol, Carvedilol, & Nebivolol
Pindolol, Acebutolol, & Penbutolol

Prevent sympathetic cardiac stimulation

reduce renin secretion

HIPERTENSI
HEART FAILURE
 SODIUM
FENOLDOPAM NITROPRUSSIDE
HYDRALAZINE

VASODILATORS MINOXIDIL
DIAZOXIDE
amlodipine, felodipine, isradipine,
nicardipine, nifedipine,
dihydropyridine and nisoldipine
CALCIUM
CHANNEL
BLOCKERS NONdihydropyridine Verapamil, diltiazem
ANGIOTENSIN-CONVERTING ENZYME
(ACE) INHIBITORS

INHIBITORS OF
ANGIOTENSIN

ANGIOTENSIN RECEPTOR–BLOCKING
AGENTS

RENIN INHIBITOR
ANGIOTENSIN-CONVERTING ENZYME
(ACE) INHIBITORS

Captopril inhibit the converting enzyme peptidyl dipeptidase that

Lisinopril hydrolyzes angiotensin I to angiotensin II and (under the
name plasma kininase) inactivates bradykinin, a potent
Enalapril vasodilator, which works at least in part by stimulating
release of nitric oxide and prostacyclin.
Ramipril
Benazepril
fosinopril
perindopril
quinapril
The hypotensive activity of captopril
results both from an inhibitory
action on the renin-angiotensin
system and a stimulating action on
the kallikrein-kinin system
 ANGIOTENSIN RECEPTOR–BLOCKING
AGENTS

valsartan • no effect on bradykinin metabolism

• more selective blockers of angiotensin effects than ACE inhibitors.
• benefits similar to those of ACE inhibitors in patients with HF and
Losartan CKD
• adverse effects are similar to those described for ACE inhibitors,
candesartan including the hazard of use during pregnancy
• Cough and angioedema can occur but are less common with ARB
than with ACEI
eprosartan
olmesartan
telmisartan
irbesartan
DIRECT RENIN INHIBITOR

ALISKIREN
 VASODILATOR DAN
PENGOBATAN ANGINA
PEKTORIS
 PATOFISIOLOGI ANGINA

The primary cause of angina pectoris is an imbalance between the

oxygen requirement of the heart and the oxygen supplied
to it via the coronary vessels.

decreasing
increasing delivery
oxygen demand
Determinants of Myocardial Oxygen Demand

The myocardial oxygen requirement

increases when there is an increase in
heart rate, contractility, arterial pressure,
or ventricular volume.
 Determinants of Coronary Blood Flow & Myocardial
Oxygen Supply

Coronary blood flow is directly related to the perfusion pressure (aortic diastolic pressure) and the
duration of diastole.

Coronary blood flow is inversely proportional to coronary vascular bed resistance.

Resistance is determined mainly by intrinsic factors—including metabolic Products and autonomic activity—
and by various pharmacologic agents

Damage to the endothelium of coronary vessels has been shown to alter their ability to dilate and to
increase coronary vascular resistance.
DRUG IN ANGINA Nitroglycerin isosorbide dinitrate

NITRATES & NITRITES

Amyl nitrite
isosorbide mononitrate.
Propranolol

BETA BLOCKERS
Atenolol, metoprolol Ranolazine

NEWER ANTIANGINAL DRUGS

ivabradine

Verapamil, diltiazem

CALCIUM CHANNEL BLOCKERS Nifedipine

Amlodipine
NITRATES & NITRITES
Nitroglycerin relaxes all types of smooth muscle

1. Vascular smooth muscle  All segments of the vascular

system from large arteries through large veins relax in response
to nitroglycerin.

2. Other smooth muscle organs Relaxation of smooth muscle of the

bronchi, gastrointestinal tract (including biliary system), And genitourinary
tract

3. Action on platelets  The increase in cGMP that results is responsible for

a decrease in platelet aggregation

4. Other effects  nitrite ion reacts with hemoglobin (which contains ferrous
iron) to produce methemoglobin (which contains ferric iron) 
pseudocyanosis, tissue hypoxia, and death.
 Toxicity & Tolerance
A. Acute Adverse Effects  are direct extensions of therapeutic vasodilation: orthostatic
hypotension, tachycardia, and throbbing headache.
B. Tolerance  With continuous exposure to nitrates, isolated smooth muscle may develop complete
tolerance (tachyphylaxis)

Beneficial and deleterious effects of nitrates in the treatment of

angina.
CALCIUM CHANNEL-BLOCKING DRUGS
 Organ system effects
1. Smooth muscle

2. Cardiac muscle

3. Skeletal muscle

4. Cerebral vasospasm and infarct following subarachnoid hemorrhage

5. Other effects
Mechanisms of Clinical Effects
Calcium channel blockers decrease myocardial contractile force, which reduces myocardial oxygen
requirements
BETA-BLOCKING DRUGS
Although they are not vasodilators (with the possible exception of nebivolol), ß-blocking drugs are
extremely useful in the management of effort angina

hemodynamic effects

decreased heart rate, blood pressure, and contractility

decrease myocardial oxygen requirements at rest and during exercise.

PENGOBATAN
PADA GAGAL
JANTUNG
 systolic failure,reduced mechanical pumping action (contractility) and
reduced ejection fraction

HF
Diastolic failure,  stiffening and loss of adequate relaxation playing a
major role in reducing filling and cardiac output
CONTROL OF NORMAL CONTRACTILITY

contraction of heart muscle is determined by

several processes that lead to the movement of
actin and myosin filaments in the cardiac
sarcomere.
Ultimately, contraction results from the
interaction of calcium (during systole) with the
actin-troponin-tropomyosin system, thereby
releasing the actin-myosin interaction.

This calcium is released from the sarcoplasmic

reticulum (SR).
A. Sensitivity of the Contractile Proteins to Calcium  Levosimendan increases calcium
sensitivity

B. Amount of Calcium Released from the Sarcoplasmic Reticulum Ryanodine is

a potent negative inotropic plant alkaloid that interferes with the release of calcium through cardiac SR
channels.

C. Amount of Calcium Stored in the Sarcoplasmic Reticulum The SR membrane

contains a very efficient calcium uptake transporter, known as the sarcoplasmic endoplasmic reticulum
Ca2+ ATPase (SERCA)

D. Amount of Trigger Calcium  The amount of trigger calcium that enters the cell depends
on the availability of membrane calcium channels (primarily the L type) and the duration of their opening
 CCB reduce this influx and depress contractility.

E. Activity of the Sodium-Calcium Exchanger

F. Intracellular Sodium Concentration and Activity of Na+K+ ATPase removing

intracellular sodium, is the major determinant of sodium concentration in the cell
 Pathophysiology of Heart Failure

Systolic dysfunction, with reduced cardiac output and

significantly reduced ejection fraction (< 45%), is typical of acute failure,
especially that resulting from myocardial infarction.

Diastolic dysfunction often occurs as a result of hypertrophy

and stiffening of the myocardium, and although cardiac output is
reduced, ejection fraction may be normal.

Fraksi Ejeksi (EF) : Jumlah darah yang dipompa keluar dari ventrikel selama setiap detak jantung
Pathophysiology of Cardiac Performance
Preload (Beban awal) : beban yang diterima ventrikel kiri saat akhir diastole
(volume akhir diastolic ventrikel kiri)  dipengaruhi jumlah darah yang kembali dr
system vena  atrium kanan  ventrikel kanan  paru-paru  atrium kiri  ventrikel
kiri

HF  preload ↑ because of increased blood volume and venous tone

Afterload (Beban akhir) : Beban yang dihadapi otot jantung saat berkontraksi memompa
darah keluar dr ventrike kiri menuju aorta
HF  CO ↓  reflex increase in systemic vascular resistance occurs

Contractility

Heart rate
CO = HR X SV
Preload ↑, afterload ↓, kontraktilitas ↑  Stroke Volume ↑
The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure 
baroreceptor sensory input to the vasomotor center is reduced even at normal pressures 
sympathetic outflow is increased tachycardia, increased cardiac contractility, and increased
vascular tone  increased by angiotensin II and endothelin  a potent vasoconstrictor released
by vascular endothelial cells  Vasoconstriction increases afterload  reduces ejection fraction
and cardiac output
 The most important intrinsic compensatory mechanism is myocardial hypertrophy

This increase in muscle mass helps maintain cardiac performance

hypertrophy can lead to ischemic changes, impairment of diastolic filling, and alterations in ventricular geometry

Remodeling
proliferation of connective tissue cells

myocytes in the failing heart die at an accelerated rate through apoptosis

ETIOLOGY GAGAL JANTUNG

KEGAGALAN KONTRAKTILITAS  pada infark miokardium, hipertensi, kardiomiopati

HIPERTENSI

PENYAKIT JANTUNG KORONER

ARITMIA  TAKIKARDI
DRUG USE IN HF
 DIGITALIS digoxi
n

POSITIVE
INOTROPIC BETA-ADRENOCEPTOR STIMULANTS
EFFECTS
BIPYRIDINES

ACEI , ARB, & RELATED AGENTS

NON POSITIVE DIURETICS

INOTROPIC
EFFECTS VASODILATORS

BETA-ADRENOCEPTOR BLOCKERS
Menghambat Na+K+ATPase ↑ sodium intracellular 
↓ calcium expulsion from the cell by the sodium-calcium
exchanger

DIGOXIN
 increase contraction
Mechanical effects
of the cardiac sarcomere by increasing the free calcium
concentration

Electrical effects

EFEK DIGOXIN

Effects on Other Organs anorexia, nausea, vomiting, and diarrhea

Interactions with Potassium, Calcium, and Magnesium

 BETA-ADRENOCEPTOR STIMULANTS

DOPAMIN
Dopamine receptor agonist  Increases renal blood flow  Acute decompensated heart failure
higher doses activate α and β adrenoceptors  higher doses increase cardiac force and blood pressure shock

DOBUTAMIN
Beta1–selective agonist increases cAMP synthesis ↑ cardiac
contractility ↑ CO
Acute decompensated heart failure, intermittent therapy in chronic failurereduces symptoms

Toxicity: Arrhythmias.
Interactions: Additive with other sympathomimetics
 BIPYRIDINES

Inamrinone
nausea and inhibit phosphodiesterase isozyme 3 (PDE-3)
vomiting;arrhythmias, increase in cAMP and the increase in
thrombocytopenia, and liver
enzyme contractility and vasodilation.

milrinone Inamrinone and milrinone are now used only intravenously

and only for acute heart failure or severe exacerbation
of chronic heart failure.
less likely to cause bone
marrow and liver toxicity
thaninamrinone, but it does
cause arrhythmias
DRUGS WITHOUT POSITIVE
INOTROPIC EFFECTS USED
IN HEART FAILURE

the first-line therapies for chronic heart failure

DIURETICS
Furosemide
Loop diuretic: Decreases NaCl and
KCl reabsorption in thick
ascending limb of the loop of
Henle in the nephron
Hydrochlorothiazide
Decreases NaCl
reabsorption in the distal
convoluted tubule
• Acute and chronic heart failure Hypovolemia,
• severe hypertension hypokalemia, orthostatic
• edematous conditions hypotension, ototoxicity,
sulfonamide allergy
• Increased excretion of salt and
water
• reduces cardiac preload and
afterload
• Reduces pulmonary and
peripheral edema
Hyponatremia,
• Mild chronic failure
hypokalemia,
hyperglycemia,
• mild-moderate hypertension hyperuricemia,
• hypercalciuria hyperlipidemia,
sulfonamide allergy
ALDOSTERONE ANTAGONISTS
Spironolactone
Block cytoplasmic aldosterone
receptors in collecting tubules
of nephron
• Increased salt and
water excretion
• reduces remodeling
• reduces mortality

• Chronic heart failure

• aldosteronism
(cirrhosis,adrenal
tumor) • Hyperkalemia
• hypertension • Antiandrogen actions

Eplerenone
Similar to spironolactone; more selective antialdosterone
effect; no significant antiandrogen action
ANGIOTENSIN ANTAGONISTS
Angiotensin-converting enzyme
(ACE) inhibitors:
Angiotensin receptor blockers
(ARBs):
• Arteriolar and venous dilation
• Reduces aldosterone
secretion
• increases cardiac output
• reduces cardiac remodeling

Chronic heart failure hypertension

diabetic renal disease

Cough, hyperkalemia,angioneurotic
edema
BETA BLOCKERS
Competitively blocks β1 receptors
• Slows heart rate
• reduces blood pressure
• reduces heart failure mortality

Chronic heart failure: To slow

progression • reduce mortality in
moderate and severe heart failure

Toxicity: Bronchospasm,
bradycardia,
atrioventricular block, acute
cardiac decompensation
VASODILATORS
– PENGOBATAN PADA ARITMIA JANTUNG
–
ELECTROPHYSIOLOGY OF NORMAL CARDIAC RHYTHM
ANTIARRHYTHMIC
AGENTS
 IA Procainamide Disopyramide Quinidine

CLASS 1 IB Lidocaine Mexiletine

SODIUM CHANNEL-BLOCKING Flecainide Propafenone Moricizine
DRUGS
IC
Propranolol
CLASS 2 Esmolol
BETA-ADRENOCEPTOR–
Amiodarone BLOCKING DRUGS
CLASS 3 Dofetilide
DRUGS THAT PROLONG
EFFECTIVE REFRACTORY
PERIOD BY PROLONGING THE Ibutilide Verapami
ACTION POTENTIAL
CLASS 4
CALCIUM CHANNEL-
BLOCKING
Diltiazem
DRUGS

MISCELLANEOUS : Adenosine, Magnesium, Potassium

 IA
CLASS 1
SODIUM CHANNEL-BLOCKING
DRUGS

INa (primary) and Ikr (secondary)

blockade

• Slows conduction velocity and pacemaker rate

• Prolongs action potential duration and dissociates from Ina
channel with intermediate kinetic
• direct depressant effects on sinoatrial (SA) and atrioventricular
(AV) nodes

• Most atrial and ventricular arrhythmias

• 2nd choice ventricular arrhythmias with IMA
 IB
CLASS 1
SODIUM CHANNEL-BLOCKING
DRUGS

Sodium channel (INa) blockade

• Blocks activated and inactivated channels with

fast kinetics
• does not prolong and may shorten action
potential

• Terminate ventricular tachycardias

• prevent ventricular fibrillation after
cardioversion
 IC
CLASS 1
SODIUM CHANNEL-BLOCKING
DRUGS

Sodium channel (INa) blockade

• Dissociates from channel with slow kinetics

• No change in action potential duration

• Supraventricular arrhythmias in patients with

normal heart
• do not use in ischemic conditions (post
myocardial infarction)
CLASS 2
BETA-ADRENOCEPTOR–
BLOCKING DRUGS
CLASS 3
DRUGS THAT PROLONG
EFFECTIVE REFRACTORY
PERIOD BY PROLONGING THE
ACTION POTENTIAL
CLASS 4
CALCIUM CHANNEL-
BLOCKING
DRUGS
MISCELLANEOUS : Adenosine, Magnesium, Potassium