DRUGS USED IN

HEART FAILURE

I Wayan Sumardika
Pharmacology Department
Faculty of Medicine, Udayana University
 HEART FAILURE

 heart cannot pump enough blood to meet

tissue needs for oxygen and nutrients

defect in myocardial contraction

myocardial abnormality
coronary atherosceloris
congenital, valvular, hypertensive
HEMODYNAMIC OVERLOAD
HOMEOSTATIC RESPONSE
Affected by:
 Neuro-simpatic system
Renin-angiotensin aldosteron system

 Compensation response:
* Tachycardia
* Increase of peripheral resistention
* Salt and water retention
* Cardiomegali
COMPENSATION RESPONSE
Cardiac output

Carotid sinus firing Renal blood flow

Symphatetic discharge Renin release

Force
Rate
Preload Afterload Remodelling

Cardiac output
(via compensation)
Classification of Heart Failure
 Class I—ordinary activity does not cause
S/S
 Class II—slight limitations, asymptomatic
at rest. Activity does result in fatigue,
palpitations, dyspnea or anginal pain
 Class III-marked limitation of physical
activity. Less than ordinary activity causes
fatigue, palpitations, dyspnea or angina
 Class IV—any physical activity results in
discomfort, s/s at rest.
New classification of heart
failure
 Stage A: Asymptomatic with no heart
damage but have risk factors for heart failure
 Stage B: Asymptomatic but have signs of
structural heart damage
 Stage C: Have symptoms and heart damage
 Stage D: End stage disease

ACC/AHA guidelines, 2001

 LIFE STYLE MODIFICATION

THERAPY

PHARMACOLOGIC
TREATMENT
 DRUGS USED IN HEART FAILURE

Positive inotropic drugs Vasodilators Chronic failure

Cardiac glycosides Nitroprusside Loop diuretics Beta-blockers

Beta agonists Nitrates ACE inhibitors Spironolactone
PDE Inhibitors Hydralazine Thiazides
CARDIAC GLYCOSIDES
 Digitalis (Digitalis purpura or
Digitalis lanata)
 digoxin
 digitoxin
 lanatoside A, B, C (cedilanid D)
 Has a narrow therapeutic window
 Clinical Uses:
 Congestive heart Failure
 Atrial fibrilation
CARDIAC GLYCOSIDES
 Mechanism of Action
 inhibits Na+K+-ATP-ase
 Na+ pump
(Na+K+Ca++ exchange)
 Ca++ intracellular
heart contraction
 heart contraction : efficient
CARDIAC GLYCOSIDES
CARDIAC GLYCOSIDES
 strengthen of heart muscle contraction
(positive inotropic effect)
 decrease of the rate of heart contraction

(negative chronotropic effect)

heart contraction : efficient
Drugs Interaction:
 Quinidine digoxin clearance
 CARDIAC GLYCOSIDES
 Side effect/Toxicity:
 nausea, vomitus, diarrhoea
 disturbance of color vision
 cardiac arrhythmias
 heart block, extrasystole

 Treatment:
 Correction of potassium or
magnesium
 Antiarrhytmic drugs
 Digoxin antibodies
DIURETICS
1. Carbonic Anhidrase Inhibitors (acetazolamide)
2. Loop Diuretic (Furosemide, Bumetanide,
Torsemide)
3. Thiazide (HCT)
4. Potassium-Sparing Diuretics (Spironolactone,
Triamterene, Amiloride)
5. Osmotic Diuretic (Mannitol, Glycerin)
6. ADH Antagonist
DIURETICS
 Used in acute and chronic heart failure.
 Loop diuretics when degree of renal insufficiency
present.
 Decrease plasma volume and increase excretion of
sodium and water.
 Decreases preload.
 Will also need meds to enhance cardiac contractility and
vasodilatation.
 Cautious administration and monitoring of potassium
DIUTERTICS
DIURETICS
Diuretics

inhibition of tubular Na+ reabsorption

diuresis
(Na+ and water loss)

body water volume - blood

blood pressure

heart work load

DIURETICS
(especially longterm use of thiazide)

inhibition of tubular Na+ reabsorption

intracellular Na+

intracellular Ca2+

vasodilatation  preload

blood pressure

heart workload
DIURETICS
(especially furosemide and thiazide)

inhibition of tubular Na+ reabsorption

diuresis
(Na+ and water loss)

Na+ and K+ loss

hypokalemia

the risk of cardiac arrhytmia

ANGIOTENSIN ANTAGONIST
 ACEI (Captopril) and Receptor blocker
(Losartan)
 Reduce morbidity and mortality
 Reduce aldosteron secretion, salt and
water retention, and vascular resistance
 With diuretic, first line drugs for chronic
heart failure
PHOSPHODIESTERASE INHIBITORS
 Short term use in acute, severe heart failure that is
not controlled by digoxin, diuretics and vasodilators
 Increase cAMP by inhibiting phosphodiesterase
(metabolizes cAMP)
 Relax vascular smooth muscle so decrease
preload and afterload
 Amrinone and Milranone
 Milranone long half-life, more potent than Amrinone
and has fewer side effects.
 Side effects include: tachycardia, dysrhythmias,
hypotension.
 BETA1-SELECTIVE
ADRENOCEPTOR AGONIST
 Dobutamine and Dopamine
 Acute heart failure (Systolic function is
depressed)
 Not appropriate for chronic failure
 Tolerance
 Lack of oral efficacy
 Arrhytmogenic effect
 BETA-ADRENOCEPTOR
ANTAGONIST
 Carvedilol, Labetalol, Metoprolol
 Reduce progression of chronic heart
failure
 Not effective for Acute failure
 VASODILATORS
 Mechanism of Action
 Release of nitric oxide: Hydralazine, Nitroprusside
 Opening of potassium channels: Minoxidil, Diazoxide
 Reduction of calcium influx: Verapamil, Diltiazem,
Nifedipine
VASODILATORS

vasodilator

Release of nitric oxide, opening potassium channel, blockade of

calcium channels
vasodilatation of arteriolae, capiler and venulae

peripheral vascular resistance venous return

cardiac work load

 DRUGS USED IN
ANGINA PECTORIS

I Wayan Sumardika
Pharmacology Department
Faculty of Medicine, Udayana University
 Angina pectoris
1. Acute angina pectoris (exercise, spasm, emboli)
2. Stable angina pectoris
(exercise - atheroma predictable)

3. Unstable angina pectoris

(resting embolus myocardian infarction)

4. Varian – Prinzmetal angina pectoris

(coronary spasm)
Therapy of ANGINA PECTORIS
 increase coronary blood  Nitrate dan nitrite
flow (amilnitrite,
coronary
nitroglyserine,
vasodilators
isosorbide dinitrate)
 decrease myocardial
oxygen demand  Calcium antagonists
decrease heart (verapamil,diltiaze,
contraction (-blockers nifedipin)
and Ca Channel Blocker.)
 Beta-blockers
 antithrombus aspirin,
heparin (for unstable
(acebutolol, atenolol,
angina) propranolol)
NITRATES
 Nitroglycerine
 First-pass effect----90%
 Mechanism of Action
 Nitratesare converted to nitric oxide in
vascular smooth muscle. Activates guanylate
cyclase affecting cAMP. Decreases calcium
levels in smooth muscle thus decreased
contraction of smooth muscle. End result:
vasodilation.
NITRATES
NITRATES
 Contraindications
are: Increased ICP,
males taking
phosphodiesterase
enzyme type 5
inhibitors
CALCIUM CHANNEL-BLOCKING
DRUGS
 Nifedipine, Dihydropiridine, Diltiazem, Verapamil
 Block voltage-gated “L-type” calcium channels
(most important in cardiac and smooth muscle)
 For profilactic therapy of effort and vasospastic
angina
 Nifedipine used to abort acute anginal attack
 Atherosclerotic angina, combined with nitrate
 SE: constipation, pretibial edema, nausea,
flushing, and dizzines
 Improve blood supply to myocardium by dilating
coronary arteries
 Decrease workload of heart by dilating peripheral
arteries
 Reduce coronary vasospasm
 Slow rate of ventricular response in atrial
fibrillation, flutter and supraventricular
tachydysrhythmias
 Lower blood pressure by dilating peripheral arteries
BETA-BLOCKING DRUGS
 Effective in the prophylactic therapy of
atherosclerotic angina, not for acute attack
 Beneficial effect:
 Decreased heart rate, cardiac force, blood pressure
 Detrimental effect:
 Increased heart size, longer ejection period.
 Tachycardia and increased cardiac force
because of Nitrate can be reduced by Beta
Blockers
 Block beta 1 receptors which increase heart
rate and force of myocardial contraction, so
increase MVO2 consumption.
 Reduce heart rate and contractility. Enhance
blood flow.
 Block response to sympathetic
neurotransmitters
 Caution in asthmatics and those with COPD
 Inderal (propranolol) is prototype.
Metabolized by liver.Need greater doses
po due to liver metabolism.
 Tenormin (Atenolol), Lopressor
(metoprolol )and Corgard (nadolol)—long
half lives so given once daily.
 Usually end in -ol
 Aspirin
 Antilipidemics—statins
 antihypertensives
THANK YOU