Cardiotonic drugs

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

• 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

CHF

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

DRUGS FOR СONGESTIVE HEART FAILURE (CHF)

CARDIAC GLYCOSIDES

Strophantus

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

• 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

ECG changes under the influence of CGchanges under the influence of CGVvvvvvvvvvvvvvvvvvvvvvvv

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Extracardiac action of CG

• Diuretic • Sedative

• Stimulating influence on smooth muscles

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

• “dig toxicity”– Systemic accumulation

Happens frequently -

6-23 %

Mortality -

over 40 %

Warning!

Intoxication with CGIntoxication with CGCardiac symptomsCardiac symptoms

Worsening of contractive function of Worsening of contractive function of myocardiummyocardium, , increasing of circulation increasing of circulation insufficiencyinsufficiency ((1818--26 %)26 %)Disturbance of heart rhythmDisturbance of heart rhythm(90(90--95 %, 65 % 95 %, 65 % -- single symptom of single symptom of intoxicationintoxication))

-- tachyarrhythmiatachyarrhythmia ((increasing of automatismincreasing of automatism))-- blockadesblockades-- combined disorders of rhythmcombined disorders of rhythm

Intoxication with CGIntoxication with CG

ExtracardiacExtracardiac symptomssymptoms

GastroGastro--intestinalintestinal (40(40--50 %)50 %)

Neurological and psychical Neurological and psychical (25 %)(25 %)

Eye symptomsEye symptoms (65 %)(65 %)

Worsening of kidneys functionWorsening of kidneys function

Agents for CHFVasodilators

• 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 INHIBITORS OF ANGIOTENSINE CONVERTING ENZYMECONVERTING ENZYME ( (IACE)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)

captopril (capoten), ramipril, enalapril etc.

ACE Inhibitor Dispensing Issues

• Stand slowly to prevent orthostatic hypotension

• Avoid salt substitutes

• Do not take potassium supplements

Warning!

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)

Drug List

INHIBITORS OF ANGIOTESINE CONVERTING ENZYME

(IACE) captopril (capoten), ramipril, enalapril etc.