L5 Heart Failure-Dr. Yagub S Saleh

Anbar Medical College Heart Failure Dr.
Yagub S Saleh
Dep. Pharmacology 2023-2024
Heart Failure
The inability of the heart to maintain an adequate cardiac output sufficient to meet the
metabolic demands of the body. Heart failure is the most common reason for
hospitalization in adults >65 years old
Risk Factors for Heart Failure

Other risk factors:
o Coronary artery disease  Obesity
o Hypertension (LVH)  Age
o Valvular heart disease  Smoking
o Alcoholism  High or low hematocrit
o Infection (viral) level
o Diabetes
o Congenital heart defects Symptoms of Heart Failure
Think FACES...
• Fatigue
Compensatory mechanism to maintain COP • Activities limited
• Chest congestion
1. Neurohormonal (extrinsic compensatory mechanism)
• Edema or ankle swelling
involves two major mechanisms: • Shortness of breath
 Increase activities of sympathetic nervous system.

 Increase activities of renin-angiotensin-aldosterone system (RAAS).
2. Myocardial hypertrophy (intrinsic compensatory mechanism), which later can lead to

ischemic changes, impairment of diastolic filling and alterations in ventricular geometry.
Remodeling is the term applied to slow structural changes that occurs in the stressed
myocardium.
Principles of Treatment
•  Preload
•  Afterload
•  Ionotropy
•  Neurohumoral activity
AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 1

Anbar Medical College Heart Failure Dr. Yagub S Saleh
Drug groups commonly used in heart failure
Treatment of Heart Failure

ACE Inhibitors
 Works to inhibit the over stimulation of the RAS that leads to myocardial hypertrophy
and fibrosis
 Causes balanced vasodilation
 Decrease the rate of morbidity & mortality in all patient with systolic heart failure
Angiotensin Converting Enzyme (ACE) Inhibitors:
 Reduction in arterial resistance (afterload)
 Reduction in venous tension (preload)
 Reduction in aldosterone secretion
 Inhibition of cardiac and vascular remodeling
Angiotensin II type 1receptor blockers (ARBs )

Mechanism of action:
 Antagonizing ang II →↓preload and after load

 Block AT1 receptors directed angiotensin II to AT2 receptors→ vasodilation
&Antiproliferative action.
 No increase in bradykinines so no angioedema &cough.

Cardiac Inotropic Drugs

Cardiac Inotropic Drugs (Cardiac Glycocides)
Cardiac glycosides are mainly derived from plant products such as:
 purple foxglove (digitalis purpurea: digitoxin)
 white foxglove (digitalis lanata: digoxin)
 Strophantus gratus: ouabain.
DIGOXIN
1. Inhibits Na/K ATP pump
2. Increases intracellular Ca++
3. Increases contractility
4. Decreases AV conduction velocity
Indications
1. Atrial fibrillation (vagal effect on the AV-node)
2. Paroxysmal supraventricular tachycardia (vagal effect on the SA and AV-nodes)
3. Cardiac failure
Digoxin is used as a first-line drug in patients with congestive heart failure who are in
atrial fibrillation.
Adverse effects
 Abnormal cardiac rhythm (e.g. ventricular ectopic beats, Bradycardia, Heart block)
 GI effects (e.g. anorexia, vomiting, and diarrhoea)
 Visual effects (e.g. disturbances of colour vision, photophobia and blurring)
 Gynaecomastia
 Mental effects (e.g. confusion, agitation, nightmare and acute psychoses)

Treatment of Digitalis Toxicitiy:

1. Stop the responsible drug.
2. KCl syrup or slow release or I.V. with ECG monitoring if plasma potassium is low or
normal.
3. If due to calcium injection give disodium edetate I.V. which is chelating agent for
calcium.
4. Cholestyramine binds to digitalis in gut, thus inhibit absorption and decreases the toxicity
especially of digitoxin.
5. In acute toxicity give specific digitalis antibodies (Fab fragment).
Cautions/contraindications
1. Hypokalaemia
2. Hypercalcaemia
3. AV-block II – III (unless treated with pacemaker)
4. Impaired renal function (age-related)
5. Hypothyroidism
6. Conditions may lead to increased Na-influx (e.g. electrical cardioversion, acute
myocardial infarction) increases contractility and we dont have enough O2 rn
Other Inotropic Drugs

Dopamine
Low doses
It stimulates D1-receptors causing renal, mesenteric and coronary vasodilatation.
Hence, dopamine may lead to an increase in glomerular filtration rate and urine
production.
Higher doses
Dopamine progressively increases heart rate and force by directly stimulating β1-
adrenoceptors and indirectly releasing neuronal noradrenaline, which in turn
activates β 1-adrenoceptors.
Still higher doses

Stimulate α-adrenoceptors, causing a rise in blood pressure with a decrease in
blood flow to vital organs including the kidneys.

Isoprenaline
Potent non-selective β-receptor agonist with no or little α-receptor actions
 It reduces peripheral resistance, mean and diastolic blood pressure

 systolic blood pressure and renal blood flow may rise due to increased cardiac
output.
Dobutamine (synthetic drug)
 β1-receptor agonist showing greater inotropic than chronotropic effects on the heart.
 Has some α-receptor activity (but less than that with dopamine).
 It may be useful in shock and in low output heart failure (in the absence of severe
hypertension).
Dopexamine (synthetic catecholamine)

 Positive inotropic action (being a cardiac β-receptor agonist).
 Some d1-receptor agonistic activity (thus, renal vasodilatation).
 Inhibitory activity on noradrenaline reuptake, hence, increasing the synaptic
availability of noradrenaline and thus, the stimulation of cardiac β1-receptor.
BIPYRIDINE DERIVATIVES
(PHOSPHODIESTERASE INHIBITORS)
Milrinone and Inamrinone (formerly known as amrinone, name change, 2000)
They produce their inotropic activity by selectively inhibiting phosphodiesterase III
(cAMP phosphodiesterase) resulting in an increase in tissue cAMP and presumably not
cGMP.
Catecholamines and xanthine derivatives [caffeine, theophylline ethylenediamine

(aminophylline)], however, enhance the availability of both cAMP and cGMP.
Bipyridine derivatives appear to have a superior feature that they produce smaller
positive chronotropic effects compared to catecholamines and xanthine derivatives
and hence lower potential to cause arrhythmias.

Vasodilators (see vasoactive drugs lecture)

Diuretics (see diuretics lecture)
Beta blockers
 Acts primarily by inhibiting the sympathetic
nervous system.
 Increases beta receptor sensitivity (up regulation).
 Anti-arrhythmic properties.
 Anti-oxidant properties.
Beta blockers for CCF:

o Start at low dose and monitor for bradycardia
o Carvedilol, bisoprolol and Metoprolol are the
most commonly used for CCF among beta
blockers
Natriuretic peptide
Nesiritide
o Produced by recombinant DNA technology
o Approved for clinical use by the FDA in August 2001.
o Nesiritide stimulates soluble guanylate cyclase and increases vascular levels of cyclic
GMP
o Causes venous and arterial vasodilation (balanced vasodilator)
o Unlike the nitrates, tolerance does not develop with this drug.
o Given by intravenous administration.
o No benefit as an outpatient basis
o The major side effect is deleterious effect on renal function & prolonged hypotension.

Angiotensin Receptor–Neprilysin Inhibitor given if ACE or ARB arent working
Sacubitril/valsartan
Neprilysin is the enzyme responsible for breaking down vasoactive peptides, such as
angiotensin I, II, bradykinin, and natriuretic peptides. Inhibition of neprilysin augments
the activity of the vasoactive peptides.
To maximize the effect of natriuretic peptides, stimulation of the RAAS must be offset
without further increase in bradykinin. Therefore an ARB, instead of an ACE inhibitor, is
combined with a neprilysin inhibitor to reduce the incidence of angioedema

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Anbar Medical College Heart Failure Dr.

Risk Factors for Heart Failure

 Increase activities of sympathetic nervous system.

2. Myocardial hypertrophy (intrinsic compensatory mechanism), which later can lead to

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 1

Drug groups commonly used in heart failure

Treatment of Heart Failure

 Causes balanced vasodilation

Angiotensin Converting Enzyme (ACE) Inhibitors:

 Reduction in arterial resistance (afterload)

 Reduction in venous tension (preload)

 Reduction in aldosterone secretion

 Inhibition of cardiac and vascular remodeling

Angiotensin II type 1receptor blockers (ARBs )

 Antagonizing ang II →↓preload and after load

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 2

Cardiac Inotropic Drugs

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 3

Treatment of Digitalis Toxicitiy:

Other Inotropic Drugs

Still higher doses

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 4

 It reduces peripheral resistance, mean and diastolic blood pressure

Dopexamine (synthetic catecholamine)

Catecholamines and xanthine derivatives [caffeine, theophylline ethylenediamine

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 5

Vasodilators (see vasoactive drugs lecture)

Beta blockers for CCF:

o Causes venous and arterial vasodilation (balanced vasodilator)

o Given by intravenous administration.

o No benefit as an outpatient basis

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 6

Angiotensin Receptor–Neprilysin Inhibitor given if ACE or ARB arent working

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 7

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