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 – Side effects of drug
– Coronary artery therapy
disease – Kidney failure
– Hypertension – Stress
• Secondary causes: – Infection and
inflammation
– High salt intake
– Cigarette smoking
– Noncompliance with
– Obesity
treatment
 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
 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
 digoxin Dispensing Issues

Warning!
• “dig toxicity”
– Systemic accumulation
Intoxication with CG

Happens frequently -
6-23 %

Mortality -
over 40 %
Intoxication with CG
 Drug List
Agents for CHF
Vasodilators
• 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 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 CHF
• Increase tolerance towards physical
loads
• Decrease risk of recurring MI
• Brake development of myocardium
hypertrophy
 ACE Inhibitor’s Side Effects

• Dry, nonproductive cough

• Dizziness during first few days
 ACE Inhibitor Dispensing
Issues
Warning!
• Stand slowly to prevent orthostatic
hypotension
• Avoid salt substitutes
• Do not take potassium supplements
 Drug List
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)
 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
Warning!
• Look-alike and Sound-alike Drugs:
– losartan (Cozaar)
– valsartan (Diovan)
 Drug List
Agents for CHF

Angiotensin II-Receptor Antagonists

Human B-type Natriuretic Peptide (hBNP)
• nesiritide (Natrecor)
 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 arrhythmias
• Amrinon, milrinon – inhibitors of
phosphodiesterase – for temporary improvement
of patient’s condition in terminal stages of CHF