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

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

DiscussionWhy 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 outputDIASTOLIC CHF - insufficiency of input

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

Causes of Congestive Heart FailurePrimary causes:CardiomyopathyCoronary artery diseaseHypertensionSecondary causes:High salt intakeNoncompliance with treatment

Side effects of drug therapyKidney failureStressInfection and inflammationCigarette smokingObesity

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 inside the cell - Stimulate exit of from sarcoplasmic reticulum - Block , Na-TP-ase (braking repolarization)Improve usage of macroergic substances by cells, decrease myocardium need in oxygenIncrease tone of sympathetic nervous system

Extracardiac action of CG

Diuretic Sedative Stimulating influence on smooth muscles

MODE of ACTION of CG IN CASE OF CHFIncreasing 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 organismElimination 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 CHFdigoxin (Lanoxicaps, Lanoxin) Antidote for digoxin toxicity: digoxin immune Fab (Digibind)Drug List

digoxin (Lanoxicaps, Lanoxin)Increases force of contractionIncreases effective refractory periodAffects SA node, causing direct stimulation

digoxin Dispensing Issuesdig toxicitySystemic accumulation

Warning!

Intoxication with CGHappens frequently - 6-23 %

Mortality - over 40 %

Intoxication with CGCardiac symptoms Worsening of contractive function of myocardium, increasing of circulation insufficiency (18-26 %) Disturbance of heart rhythm (90-95 %, 65 % - single symptom of intoxication)tachyarrhythmia (increasing of automatism)blockadescombined disorders of rhythm

Intoxication with CG

Extracardiac symptoms

Gastro-intestinal (40-50 %)

Neurological and psychical (25 %)

Eye symptoms (65 %)

Worsening of kidneys function

Agents for CHFVasodilatorsmilrinone (Primacor)nitroprusside (Nitropress)Drug List

ACE InhibitorsInhibits conversion of angiotensin I to angiotensin IILowers 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 tolerance towards physical loadsDecrease risk of recurring MIBrake development of myocardium hypertrophy

ACE Inhibitors Side EffectsDry, nonproductive coughDizziness during first few days

ACE Inhibitor Dispensing IssuesStand slowly to prevent orthostatic hypotensionAvoid salt substitutesDo not take potassium supplements

Warning!

Agents for CHFACE Inhibitorsbenazepril (Lotensin)captopril (Capoten)enalapril (Vasotec)fosinopril (Monopril)lisinopril (Prinivil, Zestril)Drug List

Agents for CHFACE Inhibitorsmoexipril (Univasc)perindopril (Aceon)quinapril (Accupril)ramipril (Altace)trandolapril (Mavik)Drug List

Angiotensin II-Receptor AntagonistsBlocks the action of angiotensin IIWorks as well as ACE inhibitors with less coughing and better toleration

Angiotensin II-Receptor Antagonist Dispensing IssuesLook-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

Dobutamin 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 arrhythmiasAmrinon, milrinon inhibitors of phosphodiesterase for temporary improvement of patients condition in terminal stages of CHF