Transcript Inotropic Agents

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
•
•
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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
Cardiac 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)
- blockades
- combined disorders of rhythm
Intoxication with CG
Extracardiac symptoms
Gastro-intestinal (40-50 %)
Neurological and psychical (25 %)
Eye symptoms (65 %)
Worsening of kidneys function
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
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benazepril (Lotensin)
captopril (Capoten)
enalapril (Vasotec)
fosinopril (Monopril)
lisinopril (Prinivil, Zestril)
Drug List
Agents for CHF
ACE Inhibitors
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•
•
•
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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