{ Heart Failure }

Prepared By:
Shara Fuad Nissan Kamaran
Mihraban Omer Asma Khidhir
Heart Failure :is a complex progressive disorders in which the heart is
unable to pump sufficetient blood to meet needs of body and impaired ability of
heart to fill with and push blood. And HF leads to activation of the renin
angiotensin aldosterone system via these mechanism.
HF

diastolic systolic

Diastolic HF is the Systolic HF is with

impaired ability of the reduced ejection
ventricles to relax and fraction(HFrEF) and is
accept blood by the result of the ventricle
structural changes e.g being unable to pump
Hepertrophy. effectively.
Causes of HF include : Atriosclerotic heart disease , MI, hypertensive heart disease
valvular heart disease ,dilated cardiomyopathy and congenital heart disease.

Treatment : 7 classes of drugs have been shown to be effective:

Angiotensin- converting enzyme inhibitors (ACE inhibitor)
Angiotensin receptor blocker (ARB inhibitor)
B- BLOCKER
Aldosterone antagonist
Diuretics Direct vas- and venodilators
Inotropic agents
 ACE inhibitors :are standard treatment in patients with reduced systolic left
ventricular function, patients who have had an MI, and patients with diabetes
who are also hypertensive or nephropathic.

Examples of Angiotensin-converting enzyme inhibitor (ACE inhibitors) drugs

include: Benazepril , Captopril (Capoten), Enalapril/Enalaprilat , Fosinopril ,
Lisinopril, Moexipril, Perindopril, Quinapril, Ramipril , and Trandolapril .
Mechanism of action of ACE inhibitors :
captopril:used in CHF :
• HP

• Left ventricular dysfunction aftera an MI

• And diabetic nephropathy

• Administrated on an empty stomach .

• For full effect it requires weeks .

• Onset:in 15-30 min it produce initial response and in 60-90 it reaches peak response.

• Drug interactions same as benezapril.

• In pregnants it should be discontinued ,and also it enters breast milk.

• Half life 2 hrs ,and has a 70-75% bioavailibilty.

• Contra indicated in: hx of ACEI-induced angioedema.

• Side effects may include :hyperkalemia >10% , hypersensitivity rxns >4-7% ,skin rashes.

Doses: 25mg - 50mg , 3 times daily.

Enalapril: Taken once or twice daily and 1st dose before bedtime cause it cause dizziness.
Indications: HF and chronic hypertrnsion.also its used hypertensive emergency and
urgency.
Available in forms of tab, injectable solution, powder for powder solution (Epaned), IV.
Tablets are available in 2.5mg ,5mg, 10mg,or 20mg strength

Benazepril :it works by prevening blood vessel constricting and relaxes it

. And this lowers blood
pressure and increases the blood supply and
oxygen to heart.
• Available as tablets (orally).
• Duration of action 24 hrs, and reaches peak plasma in 0.5-1 hr.
• Half life 12-11 hrs and excreted primarily in urine and low percentage in bile.
• Drug interaction: aliskiren, valsartan
• Use drug cautiously when using : aluminum hydroxide cause it decrease effects of
beznazepril by unspecified mechanism.and also aspirin.
 ARBS
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 for ACE inhibitors in those patients with severe cough or
angioedema, which are thought to be mediated by elevated bradykinin levels

Examples of angiotensin II receptor blockers include:

• Azilsartan
• Candesartan
• Eprosartan
• Irbesartan
• Losartan
• Olmesartan
• Telmisartan
• Valsartan
ARB inhibitors
• All the drugs are orally active and a re dosed once-daily, with the exception of valsartan which is
twice a day

• Losartan , the prototype of the class,

• differs in that it undergoes extensive first-pass hepatic metabolism, including conversion to its
active metabolite
• Interactes with ACE-I
• Use with caution in patient with liver problem such cirrhosis cause effects may increase due to
slower removal from body.

• Side Effects:
headache ,,fainting ,dizziness ,fatigue respiratory symptoms high potassium level.
difficult breathing. dizziness, faintness, or lightheadedness when getting up suddenly from a lying
or sitting position. fast or irregular heartbeat. ARBs have a lower incidence of cough and
angioedema.

• Valsartan:
it relaxes blood vessels and lowers BP. Indications :in congestive heart failure its available in a
combinations
drug sacubitril/valsartan (Entresto) this has shown to be effective.
 Aldosteron antagonist
Aldosterone makes your kidneys hold on to salt and water, which raises your
blood pressure. Aldosterone is one of the ways your body adjusts blood
pressure naturally in your blood vessels.
When you take an aldosterone blocker, your kidneys are able to release excess
water and salt from your blood. The extra water and salt come out in your pee.
• Patients with advanced heart disease have elevated levels of aldosterone due
to angiotensin II stimulation and reduced hepatic clearance of the hormone
so aldosterone antagonist prevent aldosterone hormone
Aldosterone antagonists are indicated in patients with more severe stages of Heart
failure and recent myocardial infarction .

Spironolactone : Tablet or liquid you swallow once a day with or without food
Spironolactone is also available in combination with hydrochlorothiazide, a
diuretic.should not use in renal failure.

Eplerenone : Tablet you swallow once or twice a day with or without food.
Eplerenone is an alternative aldosterone receptor antagonist that is less likely to
produce sexual side effects such as gynaecomastia, breast pain or menstrual
irregularities.
• What is the action of eplerenone?
Eplerenone may increase the hypotensive activities of Acebutolol. The risk or severity of
renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is
combined with Eplerenone.
Pharmacological differences between spironolactone and eplerenone include lower
affinity of eplerenone for progesterone, androgen, and glucocorticoid receptors
What side effects may I notice from receiving this medication?

Side effects that you should report to your care team as soon as possible:
• Allergic reactions: skin rash, itching, hives, swelling of the face, lips, tongue, or throat
• Dehydration: increased thirst, dry mouth, feeling faint or lightheaded, headache, dark
yellow or brown urine.
• High potassium level: muscle weakness, fast or irregular heartbeat
• Kidney injury: decrease in the amount of urine, swelling of the ankles, hands, or feet
• Low blood pressure: dizziness, feeling faint or lightheaded, blurry vision
• Low sodium level: muscle weakness, fatigue, dizziness, headache, confusion
• Upper gastrointestinal side effects

Aldosterone antagonists are used to treat:

• Congestive heart failure
• High blood pressure
• Ascites (abdomen swelling caused by fluid accumulation) due to cirrhosis and portal
hypertension (increase in pressure of portal vein which carries blood from the digestive organs)
• Hypokalemia (low potassium level)
Off-label use includes hirsutism (unwanted male-pattern hair growth on a woman's face, chest
and back) and acne.
 Beta blockers:
The benefit of β-blockers is attributed, in part, to their ability to prevent the
changes that occur because of chronic activation of the sympathetic nervous
system. These agents decrease heart rate and inhibit release of renin in the
kidneys. In addition, β-blockers prevent the deleterious effects of
norepinephrine on the cardiac muscle fibers, decreasing remodeling,
hypertrophy, and cell death

• Three β-blockers have shown benefit in HF: bisoprolol , carvedilol , and long-
acting metoprolol succinate.
• Carvedilol is a nonselective β-adrenoreceptor antagonist that also blocks α-
adrenoreceptors.
• not take carvedilol if have asthma, bronchitis, emphysema, severe liver
disease.
• whereas bisoprolol and metoprolol succinate are β1-selective antagonists.
Treatment should be started at low doses and gradually titrated to target doses
based on patient tolerance and vital signs

β-Blockers should also be used with caution with other drugs that slow AV
conduction, such as amiodarone, verapamil, and diltiazem.

Side effects of beta blockers:

• feeling tired, dizzy or lightheaded (these can be signs of a slow heart rate)
• cold fingers or toes (beta blockers may affect the blood supply to your hands
and feet)
• difficulties sleeping or nightmares.
• difficulty getting an erection or other difficulties with sex.
• feeling sick.
 Diuretics, also called water pills, are medications designed to increase the
amount of water and salt expelled from the body as urine.

• Thiazide diuretics
Thiazides are the most commonly prescribed diuretics. They’re most often used
to treat high blood pressure.
Examples of thiazides include:
• chlorthalidone
• hydrochlorothiazide (Microzide)
• metolazone
• indapamide
• Loop diuretics:
Loop diuretics are often used to treat heart failure.
Examples of these drugs include:
• torsemide (Demadex)
• furosemide (Lasix)
• bumetanide

• Potassium-sparing diuretics:
Potassium-sparing diuretics reduce fluid levels in your body without causing
you to lose potassium.
Examples of potassium-sparing diuretics include:
• amiloride
• triamterene (Dyrenium)
• spironolactone (Aldactone)
• eplerenone (Inspra)
The more common side effects of diuretics include:
• too little potassium in the blood
• too much potassium in the blood (for potassium-sparing diuretics)
• low sodium levels
• headache
• dizziness
• thirst
• increased blood sugar
• muscle cramps
• increased cholesterol
• skin rash
• gout
• diarrhea

Some medications that might interact with a diuretic include:

• cyclosporine (Restasis)
• antidepressants such as fluoxetine (Prozac) and venlafaxine (Effexor XR)
• lithium
• digoxin (Digox)
• other drugs for high blood pressure
 VASO- AND VENODILATORS :
Dilation of venous blood vessels leads to a decrease in cardiac preload by
increasing venous capacitance. Nitrates are commonly used venous
dilators to reduce preload for patients with chronic HF.

hydralazine reduce systemic arteriolar resistance and decrease afterload.

If the patient is intolerant of ACE inhibitors or β-blockers, or if additional
vasodilator response is required, a combination of hydralazine and
isosorbide dinitrate may be used.

Headache, hypotension, and tachycardia are common adverse effects with

this combination.
Hydralazine is generally used in combination with an oral nitrate
preparation. It is employed in patients who remain symptomatic
from heart failure following optimization of ACE inhibitors, ARBs,
diuretics, and beta-blockers

Mechanism of action: reduce peripheral resistance directly by

relaxing the smooth muscle cell layer in arterial vessels.

Contraindications: Hypersensitivity to hydralazine; coronary

artery disease; mitral valvular rheumatic heart disease are
contraindications for its use.
 Inotropic agent
Positive inotropic agents enhance cardiac contractility and, thus, increase
cardiac output. Although these drugs act by different mecha- nisms, the
inotropic action is the result of an increased cytoplasmic calcium
concentration that enhances the contractility of cardiac muscle.

• Digitalis glycosides
Often called digitalis or digitalis glycosides , because most of the drugs come
from the digitalis(foxglove) plant. They are also increase contractility of heart , so
used in treating HF.
The most widely used agent is digoxin. Digitoxin is seldom used due to its
considerable duration of action.
Mechanism of action:
Therapeutic uses: Digoxin therapy is indicated in patients with severe HFrEF
after initiation of ACE inhibitor, β-blocker, and diuretic therapy. A low serum
drug concentration of digoxin (0.5 to 0.8 ng/ mL) is beneficial in HFrEF. At this
level, patients may see a reduction in HF admissions, along with improved
survival.

Digoxin is not indicated in patients with diastolic or right sided HF unless the
patient has concomitant atrial fibrillation or flutter.

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.
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.
Adverse effects: it has a very narrow therapeutic index, and digoxin toxicity
is one of the most common adverse drug reactions leading to hospitalization.
Anorexia, nausea, and vomiting may be initial indicators of toxicity. Patients
may also experience blurred vision, yellowish vision (xanthopsia), and various
cardiac arrhythmias, Hypokalemia predispose a patient to digoxin
toxicity,severe toxicity resulting in ventricular tachycardia .
 β-Adrenergic agonists :

β-Adrenergic agonists, such as dobutamine and dopamine, improve cardiac

performance by causing positive inotropic effects and vasodilation.

• Dobutamine is the most commonly used inotropic agent other than digoxin.

Mechanism of action :-
β-Adrenergic agonists lead to an increase in intracellular cyclic adenosine
monophosphate (cAMP), which results in the activation of protein kinase.
Protein kinase then phosphorylates slow calcium channels, thereby increasing
entry of calcium ions into the myocardial cells and enhancing contraction.

Both class drugs must be given by intravenous infusion and are primarily used
in the short-term treat- ment of acute HF in the hospital setting.
 Phosphodiesterase inhibitors :
Milrinone is a phosphodiesterase inhibitor that increases the intracellular
concentration of cAMP.

Mechanism of action:-
increases the intracellular concentration of cAMP results in an increase of
intracellu- lar calcium and, therefore, cardiac contractility.
short-term use of intravenous milrinone is not associated with increased
mortality in patients without a history of coronary artery disease, and some
symptomatic benefit may be obtained in patients with refractory HF.
Thank you