7. CONGESTIVE HEART
FAILURE
• Congestive : buildup/accumulation of fluids
It is a complex , progressive disorder in which the heart is unable to
pump sufficient blood to meet the body need.
In CHF the heart do not stop working completely but lessen in its
working due to multiple reasons.
8. GENERAL CAUSES
• Impaired ability of heart to fill and eject the blood.
• Abnormal increase in blood volume and interstitial fluid
• Atherosclerotic heart disease
• Myocardial infarction
• Hypertensive heart disease
• Valvular heart disease
• Congenital heart disease
9. CLASSIFICATION
Heart failure often only affects the left or right side of the heart, but can
affect both. Doctors differentiate between three types of heart failure,
accordingly:
Left-sided heart failure:
The left ventricle of the heart no longer pumps enough blood around the
body. As a result, blood builds up in the pulmonary veins (the blood vessels
that carry blood away from the lungs). This causes shortness of breath,
trouble breathing or coughing – especially during physical activity. Left-
sided heart failure is the most common type.
10. Right-sided heart failure:
•Here the right ventricle of the heart is too weak to pump enough blood to the lungs. This
causes blood to build up in the veins (the blood vessels that carry blood from the organs and
tissue back to the heart). The increased pressure inside the veins can push fluid out of the veins
into surrounding tissue. This leads to a build-up of fluid in the legs, or less commonly in the
genital area, organs or the abdomen (belly).
Biventricular heart failure:
•In biventricular heart failure, both sides of the heart are affected. This can cause the same
symptoms as both left-sided and right-sided heart failure, such as shortness of breath and a
build-up of fluid.
11. Classification based on pumping
ability
• Heart failure with reduced pumping ability: The heart muscle has become weaker, and
no longer pumps enough blood around the body when it contracts (squeezes). As a result,
the organs in the body don’t get enough oxygen. The medical term for this is “heart failure
with reduced ejection fraction.”
• Heart failure with preserved pumping ability: Although the heart muscle is still strong,
it can no longer relax and widen enough after it has squeezed blood out, so it doesn’t fill
up with blood properly. Despite pumping strongly enough, not enough blood is pumped
out into the body as a result, especially during physically strenuous activities. Doctors call
this “heart failure with preserved ejection fraction.”
Heart failure with reduced pumping ability is sometimes referred to as “systolic” heart
failure, and heart failure with preserved pumping ability is also known as “diastolic” heart
failure. The systolic phase of the cardiac cycle is the phase when the heart contracts
(squeezes), and the diastolic phase is when the heart relaxes and widens.
12.
13. Role of physiologic compensatory
mechanisms in progression of
Heart Failure
• Chronic activation of sympathetic nervous system
• Renin angiotensin-aldosterone system(RAAS)
Remodeling of cardiac tissue , loss of monocytes , hypertrophy and fibrosis
14. pharmacological
intervention in HF
• Goals of treatment are to alleviate symptoms, slow disease
progression, and improve survival. The following classes of drugs have
been shown to be effective:
• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin receptor blockers
• Aldosterone antagonists
• β-blockers
• Diuretics
• Direct vasodilators
• Inotropic agents
15. enzyme (ACE)
inhibitors
• The compensatory activation of the RAAS in HF leads to increased workload on the
heart and a resultant decline in cardiac function. Therefore, inhibition of the RAAS is
an important pharmacological target in the management of HF.
• Angiotensin-converting enzyme (ACE) inhibitors are a part of standard
pharmacotherapy in HFrEF. These drugs block the enzyme that cleaves angiotensin I
to form the potent vasoconstrictor angiotensin II. They also diminish the inactivation
of bradykinin.
16. Actions:
ACE inhibitors decrease vascular resistance (afterload) and venous tone (preload),
resulting in increased cardiac output.
Therapeutic use :
ACE inhibitors may be considered for patients with asymptomatic and symptomatic
HFrEF. Importantly, ACE inhibitors are indicated for patients with all stages of left
ventricular failure.
ACE inhibitors are also used in the treatment of hypertension.
Pharmacokinetics:
ACE inhibitors are adequately absorbed following oral administration. Food may
decrease the absorption of captopril [KAP-toe-pril], so it should be taken on an
empty stomach. Except for captopril and injectable enalaprilat [en-AL-a-pril-at],
ACE inhibitors are prodrugs that require activation by hydrolysis via hepatic
enzymes.
17. Adverse Effects
• Postural Hypotension
• Renal Insufficiency
• Hyperkalemia
• Persistent Dry Cough
• Angioedema (rare)
• ACE inhibitors are teratogenic and should not be used in pregnant
women.
20. Actions
Although ARBs have a different mechanism of action than ACE inhibitors, their actions on preload and afterload are similar.
Their use in HF is mainly as a substitute in patients who cannot tolerate ACE inhibitors due to cough or angioedema.
Pharmacokinetics
ARBs are orally active and are dosed once daily, with the exception of valsartan [val-SAR-tan], which is dosed twice daily.
They are highly plasma protein bound. Losartan [loe-SAR-tan] differs in that it undergoes extensive first-pass hepatic
metabolism, including conversion to an active metabolite. The other drugs have inactive metabolites. Elimination of
metabolites and parent compounds occurs in urine and feces.
Adverse effects
ARBs have an adverse effect and drug interaction profile similar to that of ACE inhibitors. However, the ARBs have a lower
incidence of cough and angioedema. Like ACE inhibitors, ARBs are contraindicated in pregnancy.
21. β-Adrenoreceptor
Blockers
• Improve systolic function and reverse cardiac remodeling in patients
receiving β-blockers and decrease the chronic activation of the
sympathetic nervous system.
22. Action:
Beta-blockers primarily antagonize the beta-adrenergic receptors (β1 and β2
receptors), reducing the effects of sympathetic nervous system activation on the
heart.
Reduction of heart rate by blocking β1 receptors in the heart thereby decreasing
myocardial oxygen demand and improving cardiac efficiency.
Beta-blockers reduce myocardial contractility, which can help in CHF by reducing
the workload on the heart.
Therapeutic Use:
Beta-blockers have been shown to improve left ventricular ejection fraction,
reverse ventricular remodeling, and reduce myocardial hypertrophy in patients
with CHF.
Three β-blockers have shown benefit in HFrEF: bisoprolol , carvedilol , and long-acting
metoprolol succinate. Carvedilol is a nonselective β-adrenoreceptor antagonist that also
blocks α-adrenoreceptors, whereas bisoprolol and metoprolol succinate are β1 -selective
antagonists. β-Blockade is recommended for all patients with chronic, stable HFrEF.
23. Pharmacokinetics
• Beta-blockers are well absorbed after oral administration, with
varying degrees of bioavailability depending on the specific drug.
• They are distributed widely throughout the body, including the heart
and peripheral tissues.
• Beta-blockers undergo hepatic metabolism via various cytochrome
P450 enzymes, leading to the formation of active and inactive
metabolites. Most beta-blockers and their metabolites are excreted
renally, although some undergo biliary excretion.
Adverse Effects
Bradycardia
Hypotension
Bronchospasm
25. Action
Relieve pulmonary congestion and peripheral edema.
Reduce symptoms of volume overload.
Decrease plasma volume and venous return (preload) to heart.
Decrease cardiac work load and decease oxygen demand.
Decrease plasma volume=decrease afterload=decrease BP.
It increase salt & water elimination=decrease blood volume=decrease venous pressure
Note
Loop diuretic are most commonly used diuretics in CHF.
Therapeutic Use
Diuretics are used to reduce fluid retention and relieve symptoms of congestion in
patients with CHF, including dyspnea, orthopnea, and peripheral edema.
Diuretics are often administered in acute decompensated heart failure (ADHF) to
achieve rapid fluid removal and alleviate respiratory distress.
In chronic stable CHF, diuretics are frequently used as maintenance therapy to prevent
fluid accumulation and symptom exacerbation.
26. Pharmacokinetics
Most diuretics are well-absorbed after oral administration, with varying onset and
duration of action.
They distribute throughout the body, with some acting primarily in the kidney tubules
(loop and thiazide diuretics) and others exerting systemic effects (potassium-sparing
diuretics).
Metabolism varies among different diuretics, with some undergoing hepatic
metabolism and others being primarily excreted unchanged.
Diuretics are predominantly eliminated renally, with renal impairment affecting their
clearance and necessitating dose adjustments.
Adverse Effect
Electrolytes imbalance
Dehydration
Ototoxicity
Hyperuricemia
27. Inotropic Drugs
Positive inotropic agents enhance cardiac contractility and, thus, increase
cardiac output. Although these drugs act by different mechanisms, the
inotropic action is the result of an increased cytoplasmic calcium
concentration that enhances the contractility of cardiac muscle. All
positive inotropes in HFrEF that increase intracellular calcium
concentration have been associated with reduced survival, especially in
patients with HFrEF. For this reason, these agents, with the exception of
digoxin, are only used for a short period mainly in the inpatient setting.
Digitalis glycosides
The cardiac glycosides are often called digitalis or digitalis glycosides,
because most of the drugs come from the digitalis (foxglove) plant. They
are a group of chemically similar compounds that can increase the
contractility of the heart muscle and, therefore, are used in treating HF.
The digitalis glycosides have a low therapeutic index, with only a small
difference between a therapeutic dose and doses that are toxic or even
fatal. The only available agent is digoxin [di-JOX-in].
29. • Digoxin inhibits Na+/K+ exchange by Na+/K+ -ATPase.
• The concentration of intracellular Na+ increases , and the concentration
gradient across the membrane decreases.
• Increased Na+ decreases the driving force for the Na+/Ca2+ into the
extracellular space
This ultimately results in small but physiologically important increase in free
Ca2+ thereby leading to increased cardiac contractility.
30. Therapeutic use
Digoxin therapy is indicated in patients with HFrEF who are symptomatic on optimal HF
pharmacotherapy. A low serum drug concentration of digoxin (0.5 to 0.8 ng/mL) is beneficial
in HFrEF.
Pharmacokinetics
Digoxin is available in oral and injectable formulations. It has a large volume of distribution,
because it accumulates in muscle. The dosage is based on lean body weight. In acute
situations, such as symptomatic atrial fibrillation, a loading dose regimen is used. Digoxin has
a long half-life of 30 to 40 hours. It is mainly eliminated intact by the kidney, requiring dose
adjustment in renal dysfunction.
31. Adverse effects
At low serum drug concentrations, digoxin is well tolerated. However, it has a
very narrow therapeutic index. Anorexia, nausea, vomiting, blurred vision, or
yellowish vision may be initial indicators of toxicity.
Digoxin should also be used with caution with other drugs that slow AV
conduction, such as β-blockers, verapamil, and diltiazem.
• Cardiac effect: Arrhythmia (Tachycardia and
bradycardia),hypokalemia.
• GIT Effect: Anorexia, nausea, vomiting , diarrhea
• CNS Effect: Headache , Fatigue , blurred vision ,
yellowish vision , confusion.
