Inotropic agents

Congestive Heart Failure (CHF) Heart pumps less blood than it receives, so excess blood pools in the chambers and stretches the walls of the heart

Discussion Why is it dangerous for blood to pool in the chambers of the heart?

Discussion Why is it dangerous for blood to pool in the chambers of the heart? Answer: decreased oxygen supply to tissues; risk of blood clot formation and movement throughout the body

2 MAIN TYPES of CHF SYSTOLIC CHF – insufficiency of output DIASTOLIC CHF - insufficiency of input

CHF Occurs in 10% of the population over 75 Can result in death through progressive heart damage or sudden death Overworking of the heart leads to cardiomegaly and myocardial hypertrophy

Causes of Congestive Heart Failure Primary causes: –Cardiomyopathy –Coronary artery disease –Hypertension Secondary causes: –High salt intake –Noncompliance with treatment –Side effects of drug therapy –Kidney failure –Stress –Infection and inflammation –Cigarette smoking –Obesity

CARDIAC GLYCOSIDES

Purple Foxglove

Foxglove

Lily of the valley

Lychnis

Chemical structure of cardiac glycosides

Pharmacodynamics Cardiac action Extracardiac action

Cardiac action Positive inotropic Positive bathmotropic Negative chronotropic Negative dromotropic

Cardiac Glycosides

MECHANISM OF CARDIOTONIC (POSITIVE INOTROPIC) ACTION Of CG Promote increasing of Calcium ions concentration in myocardiocytes cytoplasm - Transport of Са inside the cell - Stimulate exit of Са from sarcoplasmic reticulum - Block К, Na-АTP-ase (braking repolarization) Improve usage of macroergic substances by cells, decrease myocardium need in oxygen Increase tone of sympathetic nervous system

Extracardiac action of CG Diuretic Sedative Stimulating influence on smooth muscles

MODE of ACTION of CG IN CASE OF CHF Increasing of systolic and minute volumes of heart activity (enhancing cardiac muscle contractility, thus increasing output) Improving of circulation in lungs and peripheral organs, decreasing volume of blood circulation, excretion of surplus liquid from the organism Elimination of hypoxia and metabolic acidosis in tissues

The following manifestations testify about therapeutic action of CG 1. Improving of general state of the patient (decreasing of weakness, short breath, sleep normalization, disappearing of edema, cyanosis, etc.) 2. Tachycardia transforms into normo (brady)cardia 3. Increasing of diuresis 4. Typical changes in ECG

Agents for CHF digoxin (Lanoxicaps, Lanoxin) Antidote for digoxin toxicity: digoxin immune Fab (Digibind) Drug List

digoxin (Lanoxicaps, Lanoxin) Increases force of contraction Increases effective refractory period Affects SA node, causing direct stimulation

digoxin Dispensing Issues “dig toxicity” –Systemic accumulation Warning!

Intoxication with CG Happens frequently % Mortality - over 40 %

Intoxication with CG Intoxication with CG

Agents for CHF Vasodilators milrinone (Primacor) nitroprusside (Nitropress) Drug List

ACE Inhibitors Inhibits conversion of angiotensin I to angiotensin II Lowers blood pressure and lowers the stress on the heart

INHIBITORS OF ANGIOTENSINE CONVERTING ENZYME (IACE) In case of CHF they brake pathological consequences of activation of renin-angiotesine system by inhibiting ACE: production of angiotensine II decreases (vasoconstrictor, inductor of aldosterone, norepinephrine, endothelin secretion, myocardium hypertrophy) Accumulation of bradikinin (inductor of prostacycline and nitrogen oxide synthesis)

INHIBITORS OF ANGIOTESINE CONVERTING ENZYME (IACE) Increase duration and improve quality of life of patients with CHFIncrease duration and improve quality of life of patients with CHF Increase tolerance towards physical loadsIncrease tolerance towards physical loads Decrease risk of recurring MIDecrease risk of recurring MI Brake development of myocardium hypertrophyBrake development of myocardium hypertrophy

ACE Inhibitor’s Side Effects Dry, nonproductive cough Dizziness during first few days

ACE Inhibitor Dispensing Issues Stand slowly to prevent orthostatic hypotension Avoid salt substitutes Do not take potassium supplements Warning!

Agents for CHF ACE Inhibitors benazepril (Lotensin) captopril (Capoten) enalapril (Vasotec) fosinopril (Monopril) lisinopril (Prinivil, Zestril) Drug List

Agents for CHF ACE Inhibitors moexipril (Univasc) perindopril (Aceon) quinapril (Accupril) ramipril (Altace) trandolapril (Mavik) Drug List

Angiotensin II-Receptor Antagonists Blocks the action of angiotensin II Works as well as ACE inhibitors with less coughing and better toleration

Angiotensin II-Receptor Antagonist Dispensing Issues Look-alike and Sound-alike Drugs: –losartan (Cozaar) –valsartan (Diovan) Warning!

Agents for CHF Angiotensin II-Receptor Antagonists Human B-type Natriuretic Peptide (hBNP) nesiritide (Natrecor) Drug List

NONGLYCOSIDE CARDIOTONIC DRUGS DobutaminDobutamin – beta 1 -adrenomimetic - in case of acute and chronic CHF – intravenously dropping – 2, mcg/(kg.min); in case of constant infusion tolerance develops after 3-4 days; in case of increasing of dose – heart arrhythmias Amrinon, milrinonAmrinon, milrinon – inhibitors of phosphodiesterase – for temporary improvement of patient’s condition in terminal stages of CHF