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Cardiotonic drugs. 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. 2 MAIN TYPES of CHF. SYSTOLIC CHF – insufficiency of output DIASTOLIC CHF - insufficiency of input.
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Inotropic agentsCongestive Heart Failure (CHF) • Heart pumps less blood than it receives, so excess blood pools in the chambers and stretches the walls of the heart
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
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 Causes of Congestive Heart Failure
Pharmacodynamics Cardiac action Extracardiac action
Cardiac action • Positive inotropic • Positive bathmotropic • Negative chronotropic • Negative dromotropic
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
ECG changes under the influence of CG Vvvvvvvvvvvvvvvvvvvvvvvv vvvvvvvvvvvvvvv • Changes which correlate to positive inotropic action Narrowing QRS complex Decreasing ST T-blip – double-phased, negative • Changes which correlate to negative dromotropic action Prolongation of PQ interval • Changes which correlate to negative chronotropic action Increase of RR interval
Extracardiac action of CG • Diuretic • Sedative • Stimulating influence on smooth muscles
The following manifestations testify about therapeutic action of CG1. 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
Drug List Agents for CHF • digoxin (Lanoxicaps, Lanoxin) Antidote for digoxin toxicity: • digoxin immune Fab (Digibind)
digoxin (Lanoxicaps, Lanoxin) • Increases force of contraction • Increases effective refractory period • Affects SA node, causing direct stimulation
“dig toxicity” • Systemic accumulation Happens frequently - 6-23 % Mortality - over 40 % Warning!
Drug List Agents for CHFVasodilators • milrinone (Primacor) • nitroprusside (Nitropress)
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 angiotensineIIdecreases (vasoconstrictor, inductor of aldosterone, norepinephrine, endothelin secretion, myocardium hypertrophy) • Accumulation of bradikinin (inductor of prostacycline and nitrogen oxide synthesis)
ACE Inhibitor Dispensing Issues • Stand slowly to prevent orthostatic hypotension • Avoid salt substitutes • Do not take potassium supplements Warning!
Drug List Agents for CHFACE Inhibitors • benazepril (Lotensin) • captopril (Capoten) • enalapril (Vasotec) • fosinopril (Monopril) • lisinopril (Prinivil, Zestril)
Drug List Agents for CHFACE Inhibitors • moexipril (Univasc) • perindopril (Aceon) • quinapril (Accupril) • ramipril (Altace) • trandolapril (Mavik)
INHIBITORS OF ANGIOTESINE CONVERTING ENZYME (IACE) captopril (capoten), ramipril, enalapril etc.