Download Management of Heart Failure

Heart failure drugs
Prepared By
Dr Rasol M Hasan
Drugs Used for Management of
Heart Failure
Compensatory physiological responses in CHF
Decompensated heart failure
 If these mechanisms adequately restore cardiac output, the
heart failure is said to be compensated.
 However, these compensations increase the work of the
heart and contribute to further decline in cardiac
performance.
 If the adaptive mechanisms fail to maintain cardiac output,
the heart failure is termed decompensated.
Drugs commonly used in management of HF
1. Angiotensin-Converting Enzyme (ACE) Inhibitors: Captopril
2. Angiotensin II receptor blockers: Losartan, candesartan, irbesartan
3. Diuretics: Thiazides (eg, hydrochlorothiazide) and furosemide
4. Inotropic-cardiotonic drugs: Digoxin, amrinone and Nesiritide
5. Aldosterone Antagonist: Spironolactone
6. Vasodialators: Nitrates, hydralazine and isosorbide dinitrate
7. Beta adrenergic blocking agents: carvedilol
8. Adrenergics : Dopamine or dobutamine
Drugs used for management of CHF
In CHF, compensatory mechanisms increase both
preload and afterload.
Preload is the volume of blood that fills the
ventricle during diastole.
Elevated preload causes overfilling of the heart,
which increases the workload.
Afterload is the pressure that must be overcome
for the heart to pump blood into the arterial system.
Elevated afterload causes the heart to work harder
to pump blood into the arterial system.
Vasodilators are useful in reducing excessive
preload and afterload.
1. Vasodilators: Dilation of venous blood vessels
increases venous capacitance
leading to a decrease in cardiac
preload
Arterial dilatation reduces systemic
arteriolar resistance and decrease
afterload.
2. Diuretics
: Decrease blood volume thus
decreasing pre- and afterload and
decreasing oedema
Mechanism of action of ACE -I
Angiotensin Converting Enzyme Inhibitors (ACE-I)
Clinical Uses
2. Hypertension
Relatively weak anti-hypertensive effect when administered alone .
Synergistic when administered with diuretics or vasodilators.
First-line agents in those with concomitant heart failure or type I diabetes
3. Diabetes
Reduce proteinuria and slow the progression of nephropathy in diabetes
Used as first-line therapy in diabetics with hypertension
Increasingly as first-line therapy in diabetics with early renal disease
who are normotensive
4. Myocardial Infarction
ACE inhibitors improve survival after MI in those with left ventricular failure
(even if transient) - Study - 26% reduction in mortality
Angiotensin Converting Enzyme Inhibitors (ACE-I)
Adverse Effects
• First dose hypotension -more likely if RAS activated i.e. elderly, sodium
and water depletion, diuretic use, renal artery stenosis.
• Initiate therapy with a test dose .
• Exacerbation of hypotension
• Renal failure - 0.5-1%
• Cough -20%
• Rash, taste disturbance, neutropenia
• Angioedema - rare but life-threatening
• Reproductive effects -oligohydramnios, delayed fetal growth and decreased
fetal survival
Angiotensin Converting Enzyme Inhibitors (ACE-I)
DRUG INTERACTIONS
• Potassium-sparing diuretics - Severe hyperkalaemia may result if these
drugs are used in combination with potassium sparing diuretics
(eg amiloride) especially if the patient has some pre-existing degree of
renal insufficiency.
• Beta-blockers : because beta blockers suppress renin release, they
reduce sensitivity to the effect of ACE-inhibitors.
• Diuretics : potentiate the hypotensive activity of ACE inhibitors.
Angiotesin II Receptor Blockers
Clinical uses
• Hypertension
• Similar efficacy to ACE inhibitors and beta-blockers
• Reduces blood pressure without any change in heart rate
• Synergistic with thiazides
• Alternative to those who have ACE inhibitor intolerance
• CHF, post-MI, diabetic nephropathy - studies ongoing
Adverse Effects
Similar to ACE inhibitors but cough less frequent
Avoid during pregnancy
Drugs commonly used in management of HF
2. Diuretics
• Diuretics are used in treating both acute and chronic HF.
• Thiazides (eg, hydrochlorothiazide) can be used for mild
diuresis in clients with normal renal function;
• loop diuretics (eg, furosemide) should be used in clients who
need strong diuresis or who have impaired renal function.
What are cardiotonic-inotropic drugs?
Inotropics and cardiotonics are medications that increase the strength
of the muscle contractions that pump blood from the heart.
They are mainly used for treatment for heart failure .
What are the different classes of inotropics?
1. Digitalis glycosides (Mainly Digoxin)
2. Phosphodiestrase inhibitors e.g amrinone (Inocor), and milrinone IV
(Primacor)
3. Human Natriuretic Peptide B-type e.g Nesiritide (Natrecor)
4. Endothelin Receptor Antagonists( Bosentan) pul.HT.
A. Digoxin (Lanoxin)
Pharmacology of digoxin on CVS:
•
•
•
•
Positive inotropic action - inhibits Na+/K+ ATPase
Suppression of sympathetic nervous system activity
Increase of parasympathetic activity .
Negative chronotropic effect
Actions in Heart Failure
• In HF, digoxin exerts a cardiotonic or positive inotropic effect that improves
the pumping ability of the heart.
• Increased myocardial contractility allows the ventricles to empty more
completely with each heartbeat.
• Improved cardiac output leads to decrease in all the following:
heart size, heart rate, end-systolic and end-diastolic
pressures, vasoconstriction, sympathetic nerve
stimulation, and venous congestion.
Mechanism of action of digoxin in arrhythmia
In atrial dysrhythmias, digoxin slows the rate of ventricular contraction
(negative chronotropic effect). This effect is caused by several factors:
1. First, digoxin has a direct depressant effect on cardiac conduction
tissues, especially the atrioventricular node. This action decreases
the number of electrical impulses allowed to reach the ventricles from
supraventricular sources.
2. Second, digoxin indirectly stimulates the vagus nerve.
3. Third, increased efficiency of myocardial contraction and vagal stimulation
decrease compensatory tachycardia that results from the sympathetic
nervous system in response to inadequate circulation.
Digoxin Dosages
• Oral or intravenous
• Loading dose for rapid "digitalization" only if patient can be monitored
closely for toxicity .
• Steady-state plasma levels take about 7 days to achieve due to slow
elimination, longer if renal impairment .
• Usual maintenance dose 0.125-0.25 mg/day
• Trough plasma levels to monitor for toxicity
Therapeutic Uses of Digoxin
• Management of HF,
• Atrial fibrillation, and atrial flutter.
Contraindications to Digoxin use
Digoxin is contraindicated in:
Severe myocarditis, ventricular tachycardia, or ventricular fibrillation and
must be used cautiously in clients with acute myocardial infarction, heart
block, Wolff-Parkinson-White syndrome (risk of fatal dysrhythmias),
electrolyte imbalances
(hypokalemia, hypomagnesemia, hypercalcemia), and renal impairment
Administration and Digitalization
• Digoxin is given orally or intravenously (IV).
• I.M route is not recommended because pain and muscle necrosis may occur
at injection sites.
• When given orally, onset of action occurs in 30 minutes to 2 hrs, and peak
effects occur in approximately 6 hrs.
• When given IV, the onset of action occurs within 10 to 30 minutes, and peak
effects occur in 1 to 5 hours.
• In the heart, maximum drug effect occurs when a steady-state tissue
concentration has been achieved. This occurs in approximately 1 week
unless loading doses are given for more rapid effects.
• Traditionally, a loading dose is called a digitalizing dose.
Administration and Digitalization
• Traditionally, a loading dose is called a digitalizing dose.
• Digitalization (administration of an amount sufficient to produce therapeutic
effects) may be accomplished rapidly by giving a total dose of 0.75 to 1.5 mg
of digoxin in divided doses, 6 to 8 hours apart, over a 24-hour period.
• When digoxin is discontinued, the drug is eliminated from the body in
approximately 1 week.
Digoxin Toxicity
• Narrow therapeutic range 0.8-2.0 ng/ml
• Risk of toxic effects at levels above 2.0 ng/ml
• Severe toxicity at levels above 3.5 ng/ml
• GIT and CNS S/E are commonest and include anorexia, nausea, vomiting,
diarrhoea, abdominal cramps, visual disturbance, disorientation,
hallucinations and convulsions
• Cardiac toxicity includes bradycardia, heart block and ventricular
tachyarrhythmias
• Others - gynaecomastia, allergic skin reactions
Management of Toxicity
Mild to moderate toxicity without serious arrhythmia
• Withdrawal of digoxin
• Correction of electrolyte disturbance
Moderate to severe toxicity with arrhythmia
• Withdrawal of digoxin
• Correction of electrolyte disturbance (K+, Ca++ and Mg++)
• Cardiac pacing for bradyarrhythmias
• Antiarrthymic drugs, lidocaine, phenytoin and propranolol
• Digoxin antibodies (Digibind)
B. Phosphodiesterase Inhibitors
amrinone (Inocor), and milrinone IV (Primacor)
Cardiotonic-inotropic agents used in short-term management of acute, severe
HF that is not controlled by digoxin, diuretics, and vasodilators.
Mechanism of action
- The drugs increase levels of cyclic adenosine monophosphate (cAMP) in
myocardial cells by inhibiting phosphodiesterase, the enzyme that
normally metabolizes cAMP.
- They also relax vascular smooth muscle to produce vasodilation and
decrease preload and afterload.
Drugs commonly used in management of HF
Adrenergics : Dopamine or dobutamine may be used in acute, severe
heart failure (HF) when circulatory support is required, usually in a critical
care unit.
Aldosterone Antagonist
Increasingly, spironolactone is also being added for clients with moderate to
severe HF.
Spironolactone is an aldosterone antagonist that reduces the aldosteroneinduced retention of sodium and water and impaired vascular function.
Although ACE inhibitors also decrease aldosterone initially, this effect is
transient.
Spironolactone is given in a daily dose of 12.5 to 25 mg, along with standard
doses of an ACE inhibitor, a loop diuretic, and usually digoxin.
Drugs commonly used in management of HF
Vasodilators
Vasodilators are essential components of treatment regimens
for HF, and the beneficial effects of ACE inhibitors and angiotensin
receptor antagonists stem significantly from their vasodilating effects .
Other vasodilators may also be used.
Venous dilators (eg, nitrates) decrease preload
Arterial dilators (eg, hydralazine) decrease afterload.
Isosorbide dinitrate and hydralazine may be combined to decrease both
preload and afterload. The combination has similar effects to those of an ACE
inhibitor or an ARB, but may not be as well tolerated by clients.
Oral vasodilators usually are used in clients with chronic HF and parenteral
agents are reserved for those who have severe HF or are unable to take oral
medications.