DRUGS USED IN HEART FAILURE

I Wayan SumardikaPharmacology DepartmentFaculty 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

Compensation response:

* Tachycardia

* Increase of peripheral resistention

* Salt and water retention

* Cardiomegali

Affected by: Neuro-simpatic system Renin-angiotensin aldosteron system

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 FailureClass I—ordinary activity does not cause

S/SClass 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 New classification of heart failurefailure Stage A: Asymptomatic with no heart Stage A: Asymptomatic with no heart

damage but have risk factors for heart failuredamage but have risk factors for heart failure Stage B: Asymptomatic but have signs of Stage B: Asymptomatic but have signs of

structural heart damagestructural heart damage Stage C: Have symptoms and heart damageStage C: Have symptoms and heart damage Stage D: End stage diseaseStage D: End stage disease

ACC/AHA guidelines, 2001ACC/AHA guidelines, 2001

THERAPY

LIFE STYLE MODIFICATION

PHARMACOLOGICTREATMENT

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

DIURETICSDiuretics

inhibition of tubular Na+ reabsorption

diuresis (Na+ and water loss)

body water volume - blood

blood pressure

heart work load

preload

DIURETICS(especially longterm use of thiazide)

inhibition of tubular Na+ reabsorption

intracellular Na+

intracellular Ca2+

vasodilatation

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

ToleranceLack of oral efficacyArrhytmogenic 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 SumardikaPharmacology DepartmentFaculty of Medicine, Udayana University

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)

Angina pectoris

Therapy of ANGINA PECTORIS

increase coronary blood flow

coronary vasodilators

decrease myocardial oxygen demand decrease heart contraction (-blockers and Ca Channel Blocker.)

antithrombus aspirin, heparin (for unstable angina)

Nitrate dan nitrite (amilnitrite, nitroglyserine, isosorbide dinitrate)

Calcium antagonists (verapamil,diltiaze, nifedipin)

Beta-blockers (acebutolol, atenolol, propranolol)

NITRATES

Nitroglycerine First-pass effect----90% Mechanism of Action

Nitrates are 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

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