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Pharmacological management of
Heart Failure
Dr Naser Ashraf Tadvi
What is heart failure
Pathophysiology of heart failure
Heart failure
↓ FOC ↓ COP
↑ Sympathetic
discharge
↓ Renal perfusion
•Vasoconstriction
•β1 activation
↑ preload
↑ afterload
↑ FOC
↑ HR
↑ Renin
release
↓ GFR
Cardiac
remodelling
Ventricular
dilation
Back pressure
Oedema
Na &
water
retention
(Oedema)
↑ AT-II
↑ AT-1
↑ Aldosterone
Initially ↑CO
Later ↓ CO
Objectives
• List major drug groups used in treatment of heart failure
• Explain mechanism of action of digitalis and its major
effects
• Explain the nature and mechanism of digitalis toxic
effects
• Describe the clinical implications of diuretics,
vasodilators, ACE inhibitors and other drugs that lack
positive inotropic effects in heart failure
• Describe the strategies used in the treatment of heart
failure
Major drug groups used in heart
failure
Chronic Heart Failure
• Diuretics
• Aldosterone receptor
antagonists
• Angiotensin converting
enzyme inhibitors
• Angiotensin receptor
blockers
• Beta blockers
• Cardiac glycosides
• Vasodilators
Acute Heart failure
• Diuretics
• Vasodilators
• Oxygen
• Morphine
• Bipyridines
• Beta receptor agonist:
Dobutamine
Drugs used in heart failure
• Diuretics:
– Loop diuretic: Furosemide
– Thiazide diuretic: Hydrochlorthiazide
– Spironolactone: Potassium sparing diuretic and
aldosterone antagonist
• Angiotensin converting enzyme inhibitors
– Enalapril, lisinopril, captopril
• Angiotensin receptor blockers
– Losartan, telmisartan
• Beta blockers
– Bisoprolol, Carvedilol, Metoprolol, Nebivolol
• Vasodilators
– Hydralazine, Isosorbide dinitrate, Nesiritide
• Drugs which increase cardiac contractility:
(Ionotropic drugs)
– Cardiac glycosides: Digoxin
– Beta agonist: Dobutamine
– Bipyridines (Phosphodiesterase inhibitors) : Milrinone
Drugs used in heart failure
Mechanism of action of Digoxin
CARDIAC
• ↑force of contraction &
Cardiac Output
•  Heart rate
• ↑ Refractory period & 
conduction velocity in AV
node
• Increased automaticity
• ECG: ↑PR interval ,  QT
interval , Flattening or
inversion of T wave
EXTRA CARDIAC
• Kidney:
– Increased renal
perfusion
– Retained salt and water
is gradually excreted
• CNS:
– Nausea, vomiting
Major effects of digoxin
(Pharmacological actions)
Cardiotonic drugs
Uses of Digoxin
• Congestive heart failure
• Atrial fibrillation
• Atrial flutter
• Paroxysmal atrial tachycardia
Digoxin adverse effects (Toxicity)
• Visual changes:(Visual disturbance, disturbance in color
vision, blurring, photophobia)
• Gastrointesinal toxicity: anorexia, nausea, vomiting
• Cardiac adverse effects:
– Bradycardia
– Extrasystoles
– A-V Block
– Paroxysmal atrial Tachycardia
– Sino Atrial arrest
– Ventricular tachycardia
• Miscellaneous toxicity
– Gynaecomastia, Skin Rashes
Contraindication to digoxin
therapy is digoxin toxicity
• Prompt insertion of a temporary cardiac pacemaker &
administration of digitalis antibodies (digoxin immune fab)
• These antibodies recognize cardiac glycosides from many
plants in addition to digoxin. They are extremely useful in
reversing severe intoxication with most glycosides
• Oral or parenteral potassium supplements :
– contraindicated in presence of hyperkalemia
• For ventricular arrhythmias:
– Lidocaine IV drug of choice
• For supraventricular arrhythmia:
– Propranolol may be given IV or orally
• For AV block and bradycardia
– Atropine 0.6 -1.2 mg IM
Treatment of digoxin toxicity
• Amrinone & milrinone : selective phosphodiesterase III
inhibitors
• ↑ cAMP levels
• The PDE III isoenzyme is specific for intracellular degradation of
cAMP in heart, blood vessels and bronchial smooth muscles.
• Inodilator action: Inotropic effect with vasodilation
• IV administration for short term treatment of severe heart
failure
• Common adverse effect of amrinone is thrombocytopenia
• Milrinone is more potent & doesn’t cause thrombocytopenia
Phosphodiesterase inhibitors in heart failure
• Diuretics, especially furosemide, are drugs of
choice in heart failure
• Almost all symptomatic Patients treated with a
diuretic
• High ceiling diuretics (loop diuretics) preferred
– Low dose therapy for maintenance
• They increase salt and water excretion & reduce
blood volume
– Reduce preload & venous pressure
– Improve cardiac performance & relieve edema
Role of diuretics in heart failure
Role of spironolactone in heart failure
• Aldosterone antagonist & potassium sparing
diuretic
• ↓ mortality by 30% when added to in patients
receiving ACE inhibitors and other standard
therapy.
• Possible mechanism for this benefit is prevention
of aldosterone induced myocardial and vascular
fibrosis and baroreceptor dysfunction in addition
to its renal effects.
• ↓ peripheral resistance (↓ afterload)
• ↓reduce salt and water retention by ↓
aldosterone secretion (↓ preload).
• ↓ long-term remodeling of the heart and
vessels an effect that may be responsible for
the observed reduction in mortality and
morbidity
• Drug of first choice in left ventricular
dysfunction without edema
ACE Inhibitors in heart failure
• Losartan , telmisartan
• Block AT1 receptor on the heart, peripheral
vasculature and kidney
• Produce beneficial hemodynamic effects
similar to those of ACE inhibitors.
• large clinical trials suggest that angiotensin
receptor blockers are best reserved for
patients who cannot tolerate ACE inhibitors
(usually because of cough)
Angiotensin receptor blockers in heart failure
Role of vasodilators in heart failure
• The combination of hydralazine and
isosorbide dinitrate should be used if
intolerant of ACE-i and ARBS as it reduces
mortality.
• It also reduces mortality when added to
standard therapy.
Role of Beta blockers in heart failure
• Not all β blockers have proved useful, but
bisoprolol, carvedilol, metoprolol, and nebivolol
have been shown to reduce mortality.
• The beneficial effect may be due attenuation (↓)
of adverse effects of activated sympathetic drive
• Useful even though they have negative inotrophic
action
Approach to the Patient with Heart Failure
Assessment of LV function (echocardiogram)
EF < 40%
Assessment of
volume status
Signs and symptoms of
fluid retention
No signs and symptoms of
fluid retention
Diuretic
(titrate to euvolemic state)
ACE Inhibitor
b-blocker
Digoxin
Management of acute LVF with
pulmonary edema
• Semi-upright posture
• Oxygen : 6-8 litres/min
• Furosemide: 40-80 mg IV
• Morphine
• Aminophylline: if associated bronchospasm
• Sublingual nitroglycerine
• Digoxin IV in patients with Atrial fibrillation/SVT/
Heart failure
• Continued management of heart failure /heart
disease after resolution of acute heart failure
Newer drugs for heart failure
• Vasopeptidase inhibitors:
– Omapatrilat
– Nesiritide
• Omecamtiv mecarbil: selective cardiac myosin
activator
Summary
Reduce the number of
sacks on the wagon
Limit the speed, thus saving
energy
Like the carrot placed in
front
Increase the efficiency
Inotrops
Vasodilators
b blockers
Diuretics, ACE inhibitors
KATZUNGS BASIC AND CLINICAL
PHARMACOLOGY 13TH EDITION
references

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pharmacologicalmanagementofheartfailure-171027075756.pdf

  • 1. Pharmacological management of Heart Failure Dr Naser Ashraf Tadvi
  • 2. What is heart failure
  • 3. Pathophysiology of heart failure Heart failure ↓ FOC ↓ COP ↑ Sympathetic discharge ↓ Renal perfusion •Vasoconstriction •β1 activation ↑ preload ↑ afterload ↑ FOC ↑ HR ↑ Renin release ↓ GFR Cardiac remodelling Ventricular dilation Back pressure Oedema Na & water retention (Oedema) ↑ AT-II ↑ AT-1 ↑ Aldosterone Initially ↑CO Later ↓ CO
  • 4. Objectives • List major drug groups used in treatment of heart failure • Explain mechanism of action of digitalis and its major effects • Explain the nature and mechanism of digitalis toxic effects • Describe the clinical implications of diuretics, vasodilators, ACE inhibitors and other drugs that lack positive inotropic effects in heart failure • Describe the strategies used in the treatment of heart failure
  • 5. Major drug groups used in heart failure Chronic Heart Failure • Diuretics • Aldosterone receptor antagonists • Angiotensin converting enzyme inhibitors • Angiotensin receptor blockers • Beta blockers • Cardiac glycosides • Vasodilators Acute Heart failure • Diuretics • Vasodilators • Oxygen • Morphine • Bipyridines • Beta receptor agonist: Dobutamine
  • 6. Drugs used in heart failure • Diuretics: – Loop diuretic: Furosemide – Thiazide diuretic: Hydrochlorthiazide – Spironolactone: Potassium sparing diuretic and aldosterone antagonist • Angiotensin converting enzyme inhibitors – Enalapril, lisinopril, captopril • Angiotensin receptor blockers – Losartan, telmisartan
  • 7. • Beta blockers – Bisoprolol, Carvedilol, Metoprolol, Nebivolol • Vasodilators – Hydralazine, Isosorbide dinitrate, Nesiritide • Drugs which increase cardiac contractility: (Ionotropic drugs) – Cardiac glycosides: Digoxin – Beta agonist: Dobutamine – Bipyridines (Phosphodiesterase inhibitors) : Milrinone Drugs used in heart failure
  • 8. Mechanism of action of Digoxin
  • 9. CARDIAC • ↑force of contraction & Cardiac Output •  Heart rate • ↑ Refractory period &  conduction velocity in AV node • Increased automaticity • ECG: ↑PR interval ,  QT interval , Flattening or inversion of T wave EXTRA CARDIAC • Kidney: – Increased renal perfusion – Retained salt and water is gradually excreted • CNS: – Nausea, vomiting Major effects of digoxin (Pharmacological actions) Cardiotonic drugs Uses of Digoxin • Congestive heart failure • Atrial fibrillation • Atrial flutter • Paroxysmal atrial tachycardia
  • 10. Digoxin adverse effects (Toxicity) • Visual changes:(Visual disturbance, disturbance in color vision, blurring, photophobia) • Gastrointesinal toxicity: anorexia, nausea, vomiting • Cardiac adverse effects: – Bradycardia – Extrasystoles – A-V Block – Paroxysmal atrial Tachycardia – Sino Atrial arrest – Ventricular tachycardia • Miscellaneous toxicity – Gynaecomastia, Skin Rashes Contraindication to digoxin therapy is digoxin toxicity
  • 11. • Prompt insertion of a temporary cardiac pacemaker & administration of digitalis antibodies (digoxin immune fab) • These antibodies recognize cardiac glycosides from many plants in addition to digoxin. They are extremely useful in reversing severe intoxication with most glycosides • Oral or parenteral potassium supplements : – contraindicated in presence of hyperkalemia • For ventricular arrhythmias: – Lidocaine IV drug of choice • For supraventricular arrhythmia: – Propranolol may be given IV or orally • For AV block and bradycardia – Atropine 0.6 -1.2 mg IM Treatment of digoxin toxicity
  • 12. • Amrinone & milrinone : selective phosphodiesterase III inhibitors • ↑ cAMP levels • The PDE III isoenzyme is specific for intracellular degradation of cAMP in heart, blood vessels and bronchial smooth muscles. • Inodilator action: Inotropic effect with vasodilation • IV administration for short term treatment of severe heart failure • Common adverse effect of amrinone is thrombocytopenia • Milrinone is more potent & doesn’t cause thrombocytopenia Phosphodiesterase inhibitors in heart failure
  • 13. • Diuretics, especially furosemide, are drugs of choice in heart failure • Almost all symptomatic Patients treated with a diuretic • High ceiling diuretics (loop diuretics) preferred – Low dose therapy for maintenance • They increase salt and water excretion & reduce blood volume – Reduce preload & venous pressure – Improve cardiac performance & relieve edema Role of diuretics in heart failure
  • 14. Role of spironolactone in heart failure • Aldosterone antagonist & potassium sparing diuretic • ↓ mortality by 30% when added to in patients receiving ACE inhibitors and other standard therapy. • Possible mechanism for this benefit is prevention of aldosterone induced myocardial and vascular fibrosis and baroreceptor dysfunction in addition to its renal effects.
  • 15. • ↓ peripheral resistance (↓ afterload) • ↓reduce salt and water retention by ↓ aldosterone secretion (↓ preload). • ↓ long-term remodeling of the heart and vessels an effect that may be responsible for the observed reduction in mortality and morbidity • Drug of first choice in left ventricular dysfunction without edema ACE Inhibitors in heart failure
  • 16. • Losartan , telmisartan • Block AT1 receptor on the heart, peripheral vasculature and kidney • Produce beneficial hemodynamic effects similar to those of ACE inhibitors. • large clinical trials suggest that angiotensin receptor blockers are best reserved for patients who cannot tolerate ACE inhibitors (usually because of cough) Angiotensin receptor blockers in heart failure
  • 17. Role of vasodilators in heart failure • The combination of hydralazine and isosorbide dinitrate should be used if intolerant of ACE-i and ARBS as it reduces mortality. • It also reduces mortality when added to standard therapy.
  • 18. Role of Beta blockers in heart failure • Not all β blockers have proved useful, but bisoprolol, carvedilol, metoprolol, and nebivolol have been shown to reduce mortality. • The beneficial effect may be due attenuation (↓) of adverse effects of activated sympathetic drive • Useful even though they have negative inotrophic action
  • 19. Approach to the Patient with Heart Failure Assessment of LV function (echocardiogram) EF < 40% Assessment of volume status Signs and symptoms of fluid retention No signs and symptoms of fluid retention Diuretic (titrate to euvolemic state) ACE Inhibitor b-blocker Digoxin
  • 20. Management of acute LVF with pulmonary edema • Semi-upright posture • Oxygen : 6-8 litres/min • Furosemide: 40-80 mg IV • Morphine • Aminophylline: if associated bronchospasm • Sublingual nitroglycerine • Digoxin IV in patients with Atrial fibrillation/SVT/ Heart failure • Continued management of heart failure /heart disease after resolution of acute heart failure
  • 21. Newer drugs for heart failure • Vasopeptidase inhibitors: – Omapatrilat – Nesiritide • Omecamtiv mecarbil: selective cardiac myosin activator
  • 22. Summary Reduce the number of sacks on the wagon Limit the speed, thus saving energy Like the carrot placed in front Increase the efficiency Inotrops Vasodilators b blockers Diuretics, ACE inhibitors
  • 23. KATZUNGS BASIC AND CLINICAL PHARMACOLOGY 13TH EDITION references