1.
Drugs Used In the Treatment of
Congestive heart failure
Dr. Hiwa K. SaaedDr. Hiwa K. Saaed,,
PhD PharmacologyPhD Pharmacology
School of Pharmacy, University of SulaimaniSchool of Pharmacy, University of Sulaimani

2.
Congestive Heart Failure (CHF)
• Heart failure (HF) is a complex, progressive disorder in which
the heart is unable to pump sufficient blood to meet the
needs of the body.
• Chronic CHF: the clinical condition in which an individual
expels less than 40% of the blood from the left ventricle per
heartbeat (ejection fraction [EF] 40%).
• A normal individual expels about 55 to 65% of the blood from
the left ventricle per heart- beat (EF 55–65%).
• HF is due to an impaired ability of the heart to adequately fill
(diastolic failure) with and/or eject blood (Systolic failure).
• It is often accompanied by abnormal increases in blood
volume and interstitial fluid, hence the term congestive HF.

3.
• Can involve the heart: left side (usually), right side, or both
side
• Its cardinal symptoms are: Dyspnea, Fatigue, and Fluid
retention.
• symptoms include dyspnea from pulmonary congestion in left
HF, and peripheral edema in right HF.
• Underlying causes of HF include:
– arteriosclerotic heart disease,
– Myocardial Infarction,
– hypertensive heart disease,
– valvular heart disease,
– dilated cardiomyopathy,
– and congenital heart disease.
Congestive Heart Failure (CHF)

4.
The pathophysiology
Reduce Cardiac output:
 low renal perfusion   renin production  
angiotensin 
1- stimulation of aldosterne  Na+
and fluid retention  in venous return 
 in preload
2- peripheral vasoconstriction (  in after load and preload)
 low carotid sinus flow   in the sympathetic activity to
maintain ventricular contractility  tachycardia and in
TPR.

5.
In CHF, the impaired contractile function of the heart is exacerbated
by compensatory increase in preload and afterload

6.
Physiology of cardiac muscle contraction
The myocardium,
•like smooth and skeletal muscle, responds to stimulation
by depolarization of the membrane.
•However, the cardiac muscle cells are interconnected in
groups that respond to stimuli as a unit, contracting
together whenever a single cell is stimulated.
•unlike skeletal muscle, which shows graded contractions
depending on the number of muscle cells that are
stimulated,

7.
Ion movements during the contraction of cardiac muscle.
ATPase

8.
Ion fluxes in cardiac cells

9.
Therapeutic strategies in HF
Chronic HF is typically managed by:
• a reduction in physical activity,
• fluid limitations (less than 1.5 to 2 L daily);
• low dietary intake of sodium (<1500 mg/day),
• treatment of comorbid conditions, and judicious use of:
– diuretics,
– inhibitors of the renin-angiotensin system,
– and inotropic agents.
Avoid Drugs that may precipitate or exacerbate
HF, such as:
• NSAIDs (nonsteroidal anti-inflammatory drugs),
• alcohol,
• Nondihydropyridine calcium-channel blockers,
• some antiarrhythmic drugs, should be avoided if possible.

10.
The therapeutic goal for CHF
Increase cardiac output, relieve the symptoms of cardiac
insufficiency, Slow disease progression, and improve
survival do not reverse the underlying pathologic condition.
1.inhibitors of the renin-angiotensin system (RAS).
2.β-adrenoreceptor blockers.
3.diuretics; decease extracellular fluid volume,
4.inotropic agents; increase the strength of contraction of
cardiac muscle
5.direct vasodilators; reduce the load on the myocardium.
6.aldosterone antagonists

11.
Angiotensin converting enzyme (ACE) inhibitors
ex : captopril, lisinopril, enalapril
ACE inhibitors decrease:
1. vascular resistance,
2. venous tone,
3. blood pressure,
resulting in an increased cardiac output
Adverse effects
postural hypotension
renal insufficiency
persistent dry cough
should not be used in pregnant women

12.
Effects of (ACE) inhibitors.

13.
Angiotensin receptor blockers (ARBs):
Ex: losartan, valsartan, etc
are nonpeptide, orally active compounds that are
extremely potent competitive antagonists of the AT1
receptor.
ARBs have the advantage of more complete blockade of
angiotensin action, because ACE inhibitors inhibit only
one enzyme responsible for the production of
angiotensin II.

14.
β-blockers
Carvedilol, metoprolol and bisprolol
• The benefit of β-blockers is attributed, in part, to their
ability to prevent the changes that occur because of the
chronic activation of the sympathetic nervous system,
including decreasing the heart rate and inhibiting the
release of renin.
• In addition, β -blockers also prevent the direct
deleterious effects of norepinephrine on the cardiac
muscle fibers, decreasing remodeling, hypertrophy and
cell death.

15.
Diuretics
bumetanide, furosemide, hydrochlorothiazide
Thiazide diuretics are relatively mild diuretics and lose
efficacy if patient creatinine clearance is less than 50
ml/min. Loop diuretics are used in patients with renal
insufficiency
Diuretics:
•relieve pulmonary congestion and peripheral edema
•useful in reducing the symptoms of volume overload
including orthopnea and nocturnal dyspnea
•↓ plasma volume: ↓preload→↓ cardiac work & O2
demand
• ↓aftereload→ ↓ BP

16.
Direct vasodilators
Vasodilators are useful in reducing excessive preload and
afterload as follow
• venodilator→↓preload
• arterial dilators →↓afterload
• Nitrates are commonly employed venodilator in
CHF
• CCBs should be avoided

17.
Inotropic agents
• positive inotropic agents
• enhance cardiac muscle contractility
• increase cardiac output
• although these drugs act by different mechanisms ,in
each case the inotropic action is the result of an
increased cytoplasmic calcium concentration that
enhances the contractility of the cardiac muscle

18.
Cardiac glycosides
(Digitalis: foxglove) digoxin & digitoxin
digoxin (lanoxin) is the most widely used agent
Mechanism of action: Inhibit Na-K-ATPase

19.
Therapeutic uses
• digoxin is indicated in patients with severe left ventricular
systolic dysfunction after initiation of diuretic and
vasodilation therapy
• NOT indicated in patient with diastolic or right sided heart
failure
• patients with mild to moderate heart failure will often
respond to treatment with ACE inhibitors and diuretics
and do not require digoxin
N.B. The digitalis glycosides have low therapeutic index

20.
Adverse effects
• Cardiac effects: is arrhythmia (common), characterized by
slowing of AV conduction associated with atrial arrhythmias.
hypokalemia is the primary predisposing factor in these effects.
Caused by thiazide or loop diuretics and prevented by use
of a K sparing diuretics or supplementation with KCl
• GIT effects: Anorexia, nausea, and vomiting.
• CNS effects: headache, fatigue, confusion, blurred vision,
alteration of color perception, and halos on dark objects.

21.
Factors predisposing to digitalis toxicity
a) Electrolytic disturbances
– hypokalemia can preciptate serious
arrhythmia
– hypercalcemia and hypomagnesemia
also predispose to digitalis toxicity.
B) drugs:
– Quinidine, verapamil, amiodarone:
displacing digoxin from protein binding
and by competing with digoxin for renal
excretion
– Erythromycin and tetracycline
– Thiazide and loop diuretics
C) Disease: hypothyroidism, hypoxia,
renal failure, myocarditis

22.
Another inotropic agent: β1-AGONISTS
• ex : dobutamine →↑cAMP→ activation of protein
kinase → slow Ca+2
channel phosphorylation → Ca+2
entry → enhancing contraction
• improves cardiac performance by both
positive inotropic effects and vasodilation
• must be given by I.V. infusion and is primarily used in
the treatment of acute heart failure in hospital setting

23.
Phosphodiesterase inhibitors:
Inamrinone and milrenone →↑cAMP →
↑ intracellular Ca+2
→ contraction

24.
Spirolactone (Aldosterone antagonists)
Patients with advanced heart disease have elevated
levels of aldosterone due to:
– angiotensin II stimulation
– reduced hepatic clearance of the hormone.
Adverse effects include
•gastric disturbances, such as gastritis and peptic ulcer
•CNS effects, such as lethargy and confusion
•endocrine abnormalities, such as
– gynecomastia,
– decreased libido,
– menstrual irregularities.

25.
Ventricular function curves in the normal heart, in heart
failure (HF), and in HF treated with digitalis.

26.
Treatment options for various stages of heart failure.
Stage D (refractory symptoms requiring special interventions) is not shown.