Congestive heart failure

Congestive Heart Failure
Presented By
Shubham Sharma
M.Pharmacy
Deptt. Pharmacology

Congestive heart failure (CHF) is a common clinical disorder
that results in pulmonary vascular congestion and reduced
cardiac output . Heart failure is characterized by the heart’s
inability to pump an adequate supply of blood to the body.
Heart Failure may primarily be due to systolic dysfunction or
diastolic dysfunction.
Systolic dysfunction: The ventricles are dilated and unable to
develop sufficient wall tension to eject adequate quantity of
blood.
Diastolic dysfunction: The ventricular wall is thickened and
unable to relax properly during diastole , ventricular filling is
impaired because of which output is low. It occurs in sustained
hypertension , congenital heart disease.

• Heart failure can affect the right or left side of your heart, or both at the
same time. It can be either an acute (short time) or chronic ( ongoing )
condition.
• In acute heart failure, the symptoms appear suddenly but go away fairly
quickly. This condition often occurs after a heart attack.
• In chronic heart failure , however symptoms are continuous and don’t
improve over time.
• About 5.7 million Americans have heart failure.
The symptoms of heart failure may include:
•Excessive Fatigue
•Sudden weight gain
•A loss of appetite
•Persistent coughing
•Irregular pulse
•Heart palpitations
•Shortness of breath

Etiology of heart failure:
•The most common cause of heart failure is coronary artery disease
(CAD). A disorder that causes narrowing of the arteries that supply
blood and oxygen to the heart.
•Cardiomyopathy, a disorder of the heart muscle that causes the heart
to become weak.
•A congenital heart defect
•A heart attack
•Certain types of arrhythmias
•High blood pressure
•Diabetes
•HIV
•Severe forms of anemia
•Certain cancer treatments, such as chemotherapy
•Drug or alcohol misuse

Systolic heart failure Diastolic heart failure
(Contraction) (Relaxation)
Blood in lungs
Congestion in lungs
Congestive heart failure
Coronary artery disease Hypertension
(Fatty plaque formation) (Increased afterload)
Atherosclerosis Increased Blood Pressure

Coronary artery disease Hypertension
(Fatty plaque formation) (Increased afterload)
Atherosclerosis Increased Blood Pressure
Decrease Stroke Volume
Decrease Cardiac output
Structural changes attempt Increase Heart rate Kidney
to Increase Stroke volume
• Dilated Cardiomyopathy RAAS
• Hypertropic Cardiomyopathy

1. Inotropic drugs:
• Cardiac glycosides : Digoxin, Digitoxin, Ouabain
• Sympathomimetics : Dobutamine, Dopamine
• Phosphodiesterase ш Inhibitors : Amrinone
2. Diuretics :
• High ceiling diuretics : Furosemide, Bumetanide
• Thiazide like diuretics :Hydrochlorothiazide, Metolazone
3. Aldosterone antagonist : Spironolactone
4. Inhibitors of Renin – angiotensin system :
• ACE- inhibitors : Enalapril, Ramipril
• Angiotensin (AT receptor) antagonists : Losartan

• Vasodilators :
• Venodilators : Glyceryl trinitrate
• Arteriolar dilator : Hydralazine
• Arteriolar + Venodilator : Sodium Nitroprusside
6. ß- adrengeric blockers : Metoprolol, Bisoprolol
7. Others :
• Metabolic cardioprotectives : Trimetazidine
• Calcium sensitizers : Levosimendan
• Levocarnitine

IN VITRO METHODS :
• Isolated Hamster cardiomyopathic heart
• Isolated Cat Papillary Muscle (catell and Gold)
• Quabain binding
IN VIVO METHODS :
 Rat models :
• Rat coronary ligation model
• Rat aortic banding model
• Dhal salt sensitive rats model
• Spontaneous hypertensive rat model

 Dog Models :
• Chronic rapid pacing model
• Volume overload
• Coronary artery ligation and microembolization
 Rabbit Models :
• Volume and pressure overload
• Tachycardia pacing model
• Doxorubicin cardiomyopathy model
 Guinea Pig Models :
• Cardiac insufficiency model
 Syrian Hamster Models :
• Cardiomyopathic Hamster
 Transgenic Mice

Tail Cuff Instrument used to check blood pressure in rat

Recent advanced treatment of congestive
heart failure:
Two new heart drugs can also help lower your chances of hospital visits
because of your heart failure.
Ivabradine (Corlanor) : This medication slows your heart rate.
It may also cut your time in the hospital.
Sacubitril/Valsartan (Entresto) : Lowes says combination of two
heart drugs can shorten your time in the hospital.
Implantable cardioverter defibrillator : This gives your heart an
electric shock, When it senses a life-threatening change in rythum.
Cardiac resynchronization therapy : A type of pacemaker, this
tiny, implanted device helps your heart beat in regular rythum.
Implantable monitor : It lets doctor monitor your heart and
adjust your treatment .It measures the pressure on your arteries
and your heart rate.It about a size of small paper clip, and it’s
inserted into an artery without the needs for batteries or wires.
Left ventricular assist device (LVAD) : LVAD’s also pump blood
continuously. which makes more efficient than other older options.

Pathophysiology of Congestive heart failure

1. Inotropic drugs:
• Cardiac glycosides : Digoxin, Digitoxin, Ouabain
• Sympathomimetics : Dobutamine, Dopamine
• Phosphodiesterase ш Inhibitors : Amrinone
2. Diuretics :
• High ceiling diuretics : Furosemide, Bumetanide
• Thiazide like diuretics : Hydrochlorothiazide, Metolazone
3. Aldosterone antagonist : Spironolactone
4. Inhibitors of Renin – angiotensin system :
• ACE- inhibitors : Enalapril, Ramipril
• Angiotensin (AT receptor) antagonists : Losartan

Digoxin increases the force of contraction of the muscle of the heart
by inhibiting the activity of enzyme (ATPase) that controls
movement of calcium, sodium and potassium into heart muscle.
Calcium controls the force of contraction.

Effect on heart : Digitalis causes a dose dependent increase in
force of contraction of heart. A positive inotropic action.
Effect on blood vessels: Digitalis has mild direct vasoconstrictor
action- peripheral resistance is increased in normal individuals.
Digitalis has no prominent effect on blood pressure.
Systolic blood pressure may increase and diastolic may fall in
CHF patients- pulse pressure increases.
Effect on kidney : Diuresis occurs in CHF patients, No diuresis
Occurs in normal individuals or in patients with edema due to
other causes.
Effect on central nervous system : Higher dose causes CTZ
activation- nausea and vomiting. Still higher doses produce
hyperapnoea, central sympathetic stimulation, mental confusion
and visual disturbances.

• Presence of food in stomach delays absorption of digoxin.
• The volume of distribution of digoxin is large (6-8L/Kg).
• It is concentrated in the heart (~20 times than plasma) , skeletal
muscle, liver and kidney.
• Digoxin is primarily excreted unchanged by the kidney : mainly
by glomerular filtration; rate of excretion is altered parallel to
creatinine clearance.
• It t1/2 is prolonged in elderly patients and in those with renal
insufficiency : dose has to be reduced. i.e. 6-7 days.
Adverse effect :
• Loss of appetite
• Nausea
• Bradycardia
• Ventricular extrasystoles

• Furosemide is a prototype drug.
• Furosermide works by blocking the absorption of sodium, chloride,
and water from the filtered fluid in the kidney tubules, causing a
profound increase in the output of urine.
•High ceiling loop diuretics are preferred in CHF for rapid
mobilization of edema fluid.
Pharmacokinetics : Furosemide is rapidly absorbed orally but
bioavailability is about 60%.
• In severe CHF oral bioavailability may be markedly reduced
necessitating parenteral administration.
• Lipid solubility is low, and it is highly bound to plasma proteins.
• It is partly conjugated with glucuronic acid and mainly excreted
unchanged by glomerular filtration as well as tubular secretion.
• Plasma T1/2 averages 1-2 hours but is prolonged in patients with
pulmonary edema,renal and hepatic insufficiency.

• ACE inhibitors produce vasodilation by inhibiting the formation
of angiotension ᴨ .
• It is converted to angiotensin ᴨ by angiotensin converting
enzyme.
• ACE also breaks down bradykinin (a vasodilator substance).
Cardiorenal effects of ACE inhibitors :
• Vasodilation
•Decrease blood volume
•Depress sympathetic activity
•Inhibit cardiac and vascular hypertrophy

• Propranolol is a non selective beta receptor antagonist.
• It have negative chronotropic and negative inotropic effects on
heart.
• It decreases oxygen consumption; cardiac work and aortic
pressure.
• It decreases nor adrenaline and renin releases. It decreases central
sympathetic out flow.
• It increases oxygen supply and exercise tolerance in angina
patients.
• It decrease automaticity and abbreviates refractory period of
myocardial fibers and decreases rate of depolarization in SA node,
Purkinje fibers, and other ectoptic foci.
• The drug decreases BP in hypertensive individuals.

Pharmacokinetics :
• Absorption: well absorbed orally, bioavailabity is increased by
administering along with food.
• Distribution: Widely distributed in a plasma protein bound form.
• Metabolism: Metabolized in liver.
• Excretion: Excreted through urine Half life of propanolol 4 hours.
Side effects :
1.Congestive heart failure is precipitated or aggravated
2.Decreases coronary blood flow
3.Forgetfulness
4.Nightmares
5.Decreases exercise capacity
6.Decreases carbohydrate tolerance
7.Decrease insulin release

Metabolic cardioprotectives : Trimetazidine

Calcium sensitizers : Levosimendan

Two new heart drugs can also help lower your chances of
hospital visits because of your heart failure.
Ivabradine (Corlanor) : This medication slows your heart rate. It
may also cut your time in the hospital.
Sacubitril/Valsartan (Entresto) : Lowes says combination of two
heart drugs can shorten your time in the hospital.
Implantable cardioverter defibrillator : This gives your heart an
electric shock, When it senses a life-threatening change in rythum.
Cardiac resynchronization therapy : A type of pacemaker, this tiny,
implanted device helps your heart beat in regular rythum.
Implantable monitor : It lets doctor monitor your heart and adjust
your treatment .It measures the pressure on your arteries and your
heart rate.It about a size of small paper clip, and it’s inserted into an
artery without the needs for batteries or wires.
Left ventricular assist device (LVAD) : LVAD’s also pump blood
continuously. which makes more efficient than other older options.

Precautions and Contraindications
• Wear appropriate clothing and shoes for your chosen activity.
• Wait one hour after a light meal to exercise.
• Avoid activities or exercising outdoors when it is older than 40F
or warmer than 80F or on high smog days.

Congestive heart failure

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