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 CGIntoxication with CG

Happens frequently -

6-23 %

Mortality -

over 40 %

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)

INHIBITORS OF ANGIOTESINE INHIBITORS OF ANGIOTESINE CONVERTING ENZYMECONVERTING ENZYME ( (IACEIACE))

• Increase duration and improve quality of Increase duration and improve quality of life of patients with CHFlife 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 Brake development of myocardium hypertrophy 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 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

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 NONGLYCOSIDE CARDIOTONIC DRUGSDRUGS

• DobutaminDobutamin – beta1-adrenomimetic - in case of acute and chronic CHF – intravenously dropping – 2,5-5-10 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