Download Drugs for Heart Failure

Heart failure
 Congestive heart failure (CHF)= chronic heart failure
 Occurs when the heart is unable to pump sufficiently to maintain
blood flow to meet the body's needs
 There are two main types of heart failure:
 heart failure due to left ventricular dysfunction
 heart failure with normal ejection fraction
 Heart failure is a common, costly, and potentially fatal condition
 In the year after diagnosis the risk of death is about 35% after which
it decreases to below 10% each year
Terminology
 The term "acute" is used to
mean rapid onset, and
"chronic" refers to long
duration.
 Chronic heart failure is a
long term condition, usually
kept stable by the treatment
of symptoms.
 Acute decompensated
heart failure is a worsening
of chronic heart failure
symptoms
Management of heart failure
 Treatment focuses on improving the symptoms and preventing
the progression of the disease.
 Treatments include lifestyle and pharmacological modalities.
Acute decompensated heart failure
 In acute decompensated heart failure, the immediate goal is to
re-establish adequate perfusion and oxygen delivery to end
organs. This entails ensuring that airway, breathing, and
circulation are adequate.
Chronic management
 The goals of treatment for people with chronic heart failure are
the prolongation of life, the prevention of acute decompensation
and the reduction of symptoms, allowing for greater activity.
Treatment strategies provide significant improvement in the relief of
symptoms, exercise tolerance, and a decrease in the likelihood of
hospitalization or death.
Two distinct goals of drug therapy
(a) Relief of congestive/low output symptoms:
 ACE inhibitors
 Vasodilators— nitrate, nitroprusside,hydralazine
 β blocker—Nebivolol, Carvedilol, Metoprolol, bisoprolol
 Diuretics—Furosemide, thiazides
 Inotropic drugs—Digoxin, dobutamine
(b) Arrest/reversal of disease progression and
prolongation of survival:
 ACE inhibitors,
 β blockers
 Aldosterone antagonist—Spironolactone, eplerenone
The vicious cycle in CHF: compensatory mechanisms evoked in response to reduced
cardiac output themselves perpetuate failure and contribute to remodeling
responsible for disease progression. The parameter which is improved by different
therapeutic measures is indicated
First-line therapy
 ACE inhibitors
 Vasodilators
 β blocker
Second-line
therapy
 Diuretics
 Inotropic drugs
ACE inhibitors
 First-line therapy for people with heart failure should
include:
 angiotensin-converting enzyme (ACE) inhibitors
 angiotensin receptor blockers (ARBs) if the person
develops a long term cough as a side effect of the ACEinhibitors
!They are recommended for all grades of CHF!
 Use of medicines from this class are associated with
improved survival and quality of life in people with
heart failure by causing:

vasodilatation,

retarding/preventing ventricular hypertrophy,
fibrosis and remodeling.
Beta-adrenergic blocking agents
 A large number of trials have demonstrated subjective,
objective, prognostic and mortality benefits of the β1
blockers and the αβ-blocker (carvedilol) in mild to
moderate CHF treated.
 There is no place for β blockers in decompensated
patients. β blockers should be stopped during an
episode of acute heart failure.
Vasodilators
 Preload reduction:
 Nitrates cause pooling of blood
in systemic capacitance vessels to
reduce ventricular end-diastolic
pressure and volume.
 It is indicated when the central
venous pressure is raised and in
dilated cardiomyopathy.
 Afterload reduction
 Hydralazine dilates resistance
arteries so that even weaker
ventricular contraction is able to
pump more blood
 Calcium channel blockers (DHP)arteriolar dilators (nifedipine,
felodipine, amlodipine)
Pre- and after load reduction
 Sod. Nitroprusside is a high efficacy i.v. dilator with
equal action on the two types of vessels.
 The action is very fast and brief.
 For symptomatic treatment of acute heart failure
Diuretics
 High ceiling diuretics ( furosemide, bumetanide) are
the diuretics of choice for mobilizing edema fluid
 Thiazides are used in CHF.
Diuretics:
 Decrease preload and improve ventricular efficiency
by reducing circulating volume.
 Remove peripheral edema and pulmonary
congestion.
 Furosemide –rapid symptomatic relief in acute left
ventricular failure.
Inotropic drugs
 Drugs with β adrenergic agonistic actions have positive
inotropic and (at low doses) vasodilator properties
which may be utilized to combat emergency pump
failure.
 Dobutamine a selective β1 agonist with prominent
inotropic action
 i.v. in acute heart failure or advanced decompensated
CHF.
 Due to development of tolerance and cardiotoxic
potential when used regularly- no use in the longterm management of CHF.
CARDIAC GLYCOSIDES
 They increase myocardial contractility and output in a
hypodynamic heart without a proportionate increase
in O2 consumption.
 Thus, efficiency of failing heart is increased.
 In contrast, ‘cardiac stimulants’ (Adr, theophylline)
increase O2 consumption rather disproportionately
and tend to decrease myocardial efficiency.
Digitalis
 Cardiac glycosides are found in
several plants.
 Digitalis lanata is the source of
Digoxin, the only glycoside that is
currently in use.
 Others like Digitoxin and
strophanthin, etc. are no longer
clinically used.
 By convention the term, ‘Digitalis’
has come to mean ‘a cardiac
glycoside’.
PHARMACOLOGICAL ACTIONS
1. Heart
 Digitalis has direct effects on myocardial
contractility and electrophysiological
properties.
Force of contraction
 Increase in force of contraction
 Systole is shortened, diastole is prolonged
Heart rate
 Is decreased by:
 Vagal action - Vagal tone is increased
reflexly by sensitization of baroreceptors, as
well as by stimulation of vagal centre.
 Extravagal action- A direct depressant
action on SA and A-V nodes. This component
of bradycardia is not reversed by atropine.
Conduction
 A-V conduction is demonstrably
depressed
Mechanism of positive inotropic action of cardiac
glycosides.
PHARMACOLOGICAL ACTIONS
2. Blood vessels
Digitalis has mild direct vasoconstrictor
Digitalis has no prominent effect on BP: systolic BP may
increase and diastolic may fall in CHF patients—pulse
pressure increases. Hypertension is no contraindication to
the use of digitalis.
3. Kidney
Diuresis occurs promptly in CHF patients, secondary to
improvement in circulation and renal perfusion.
No diuresis occurs in normal Individuals
4. CNS
 High doses produce central sympathetic stimulation,
mental confusion, disorientation and visual disturbances.
PHARMACOKINETICS
 Route of administration- Oral, i.v.
 Bioavailability of digoxin - 60–80%
 It is concentrated in the heart (~20 times than plasma)
 Plasma t½ - 40 hrs ( Its t½ is prolonged in elderly
patients and in those with renal insufficiency: dose has
to be reduced).
 Digoxin is a cumulative drug!!!
Medical use
Heart failure
 Digoxin is no longer the first choice for CHF
Only for :
 Acute heart failure
 Decompensated CHF
Cardiac arrhythmias
 Atrial fibrillation
 Atrial flutter
 The arrhythmia itself is not affected, but the pumping
function of the heart improves, owing to improved filling.
 B-blockers or calcium channel blockers are a better first
choice
ADVERSE EFFECTS
Toxicity of digitalis is high (2/3 patients) !!!!
Cardiac ADR
 Almost every type of
arrhythmia can be
produced by digitalis:
atrial and ventricular
extrasystoles, ventricular
tachycardia, terminally
ventricular fibrillation.
 A-V block
 Severe bradycardia
Extracardiac ADR
 GIT: Anorexia, nausea,
vomiting and abdominal pain
are usually reported first
 Mesenteric vasoconstriction
 CNS: mental confusion,
restlessness, disorientation,
acute psychosis, drowsiness,
dizziness, insomnia,
nightmares, agitation,
depression, amnesia,
convulsions
 Visual disturbances (yellowgreen visual perception) xanthopsia
Treatment of ADR
 Further doses of digoxins must be stopped at the earliest sign of toxicity
 Attempts to enhance the elimination of digoxin by diuretics or haemodialysis are not very
effective.
For tachyarrhythmias
 KCl - K+ tends to antagonize digitalis induced enhanced automaticity. K+ is
contraindicated if higher degree of A-V block is present, because complete A-V block and
ventricular asystole may be precipitated.
For ventricular arrhythmias
 Lidocaine i.v. repeated as required is the drug of choice.
For supraventricular arrhythmias
 b-blokers may be given i.v. or orally depending on the urgency.
For A-V block and bradycardia
 Atropine may help; otherwise cardiac pacing is recommended.
Digoxin antibody
 Digoxin specific antibody is effective in treating toxicity - DIGIBIND
 Given by i.v. infusion it has markedly improved the survival of seriously digitalis
intoxicated patients.
INTERACTIONS
 1. Diuretics:
 cause hypokalemia which increases the risk of digitalis





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arrhythmias; potassium supplements should be given
prophylactically.
2. Calcium: synergises with digitalis → precipitates toxicity.
3. Verapamil, diltiazem, captopril, propafenone and amiodarone
increase plasma concentration of digoxin → plasma concentration
of digoxin is doubled → toxicity can occur.
4. Adrenergic drugs: can induce arrhythmias (both increase ectopic
automaticity).
5. Digoxin absorption is increased by atropinic drugs.
6. Propranolol, verapamil, diltiazem and disopyramide: may
additively depress A-V conduction and oppose positive inotropic
action.
7. Succinylcholine: can induce arrhythmias in digitalized patients.