Lecture presentation for B Pharmacy 2nd year

1. Heart Failure
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical Pharmacology
Maharajganj Medical Campus, Kathmandu
8 June 2020 (26 Jestha 2077), Monday

2. By the end of this discussion, B. Pharm
2nd year students will be able to:
 Define the term Heart failure
 List the factors involved in the development of
heart failure
 Explain the pathophysiology of heart failure
 Outline the clinical features of heart failure
 Elaborate the therapeutic objectives and options
for heart failure
 Justify the pharmacotherapy of heart failure

3. Introduction
 Heart Failure:
 A complex clinical syndrome that results from structural or
functional impairment of ventricular filling or ejection of blood,
which in turn leads to the cardinal clinical symptoms of dyspnea
and fatigue and signs of HF, namely edema and rales.
 Includes:
 Heart failure with reduced Ejection fraction (HFrEF)- systolic HF
 Heart failure with preserved Ejection fraction (HFpEF)- diastolic
HF
 Acute decompensated heart failure
 Advanced heart failure

4. Etiology
 Systolic dysfunction (decreased
contractility)
 Reduction in muscle mass (e.g.,
myocardial infarction)
 Dilated cardiomyopathies
 Ventricular hypertrophy
 Pressure overload (e.g.,
systemic or pulmonary
hypertension, and aortic or
pulmonic valve stenosis)
 Volume overload (e.g.,
valvular regurgitation, shunts,
and high-output states)
 Diastolic dysfunction (restriction in
ventricular filling)
 Increased ventricular stiffness
 Ventricular hypertrophy
 Infiltrative myocardial diseases
(e.g., amyloidosis, sarcoidosis,
and endomyocardial fibrosis)
 Myocardial ischemia and
infarction
 Mitral or tricuspid valve stenosis
 Pericardial disease (e.g.,
pericarditis and pericardial
tamponade)

5. Pathophysiology

6. Clinical Features

7. Investigations
 To establish the nature and severity of the underlying
heart disease and detect any complications:
 Serum urea, creatinine and electrolytes, haemoglobin,
thyroid function, ECG, chest X-ray
 Brain natriuretic peptide (BNP): risk assessment
 Echocardiography:
 Determine the aetiology
 Detect unsuspected valvular heart disease
 Identify patients who will benefit from long-term drug
therapy, e.g. ACE inhibitors (see below)

8. Therapeutic Objectives
 To improve symptoms
 To prolong survival

9. Therapeutic Options
 General Information and advice
 Non-pharmacologic therapy
 Pharmacologic therapy
 Referral
• Education
• Explanation of nature of disease,
treatment and self-help strategies
• Diet
• Cessation of alcohol and smoking
• Regular moderate aerobic exercise within
limits of symptoms
• Enhanced External Counterpulsation
• Vaccination
• Consider influenza and pneumococcal
vaccination

10. Therapeutic Options
 General Information and advice
 Non-pharmacologic therapy
 Pharmacologic therapy
 Referral
• Implantable cardiac defibrillators and
resynchronization therapy
• Coronary revascularization
• Heart Transplantation
• Ventricular Assist Devices

11. Therapeutic Options
 General Information and advice
 Non-pharmacologic therapy
 Pharmacologic therapy
 Referral
• Renocentric Therapy model
• Diuretics
• Haemodynamic Therapy model
• Vasodilators (arteriolar, venous)
• Digoxin
• Inotropes
• Disease modifying therapy
• Renin-Angiotensin Aldosterone System
Blockers

12. Pharmacotherapy of Heart Failure
Relief of congestive/low output
symptoms
Arrest/reversal of disease progression
and prolongation of survival
Inotropic drugs: Angiotensin Converting Enzyme
inhibitors (ACE-inhibitors), Angiotensin
Receptor Blockers (ARBs)
Digoxin, Dobutamine, Dopamine,
Amrinone/Milrinone
Diuretics:
Furosemide, Thiazides β- blockers
RAS inhibitors:
ACE inhibitors, ARBs Aldosterone Antagonists:
Vasodilators: Spironolactone, Eplerenone
Hydralazine, Nitrate, Nitroprusside
β- blockers:
Metoprolol, Bisoprolol, Carvedilol,

13. Diuretics in Heart Failure
 Chronic heart failure:
 Loop diuretics (Furosemide); Thiazide in mild cases
To control symptomatic oedema and dyspnoea in patients
with heart failure
 Spironolactone improves survival in patients with cardiac
failure and counters diuretic-induced hypokalaemia
Monitor for hyperkalaemia
 Acute heart failure:
 Intravenous furosemide ( repeated boluses or infusion)
To correct acute pulmonary oedema

14. Angiotensin Converting Enzyme
Inhibitors in HF
 Patients with HF have overactive RAAS system
 Consequently most likely to benefit from an ACEI in the
long term
 Improves survival
 Start with small bedtime dose
 Gradually increased to one that improves symptoms
(and survival)
 Better response in Caucasian patients
 Preferred due to greater experience and cost
considerations

15. Angiotensin Receptor Blockers in HF
 Similar to those of ACEI apart from a lower
incidence of some adverse effects, including,
particularly, dry cough
 Possibly have additive effect when combined with
ACEI

16. Beta blockers in Heart Failure
 Bisoprolol, Metoprolol, Carvedilol
 Beta-blockers are negative inotropes
 Helps by antagonizing counterregulatory
sympathetic activation and improved survival
 Start with low dose and up-titrate the dose as
tolerated

17. Vasodilators in Heart failure
 Hydralazine and a long-acting nitrate
Hydralazine reduces afterload
Nitrate reduces preload
 Improves survival in African-American patients

18. Digoxin in Heart Failure
 A cardiac glycoside; source: Digitalis lanata
 Digitoxin (D. purpurea); Ouabain (Strophanthus gratus)
 Pharmacological Actions:
 Direct effect on myocardial contractility, electrophysiological properties
 Other effects: Vagomimetic action, altered sympathetic activity (due to
direct CNS effects), reflex effects (altered haemodynamics)
 Myocardial contractility:
 Increased force of contraction
 Decreased Heart Rate
 Addition of digoxin to diuretics and ACEI reduces hospitalization and improves
symptoms, without prolonging life

19. Digoxin: Mechanism of Action
→ Selectively binds to extracellular
face of the membrane associated
Na+K+ ATPase of myocardial fibres
and inhibits it
→ Progressive accumulation of Na+
intracellularly
→ Accumulation of Ca++ intracellularly
→ Taken up by Sarcoplasmic Reticulum
→ Augumented subsequent Ca++
transients
→ Increased force of contraction
Slow and gradual response

20. Digoxin: Adverse Effects
 Extra-cardiac:
 GIT: nausea, vomiting, abdominal pain (gastric irritation,
mesenteric vasoconstriction, CTZ stimulation)
 CNS: fatigue, malaise, headache, mental confusion, restlessness,
hyperapnoea, disorientation, psychosis, visual disturbances
 Skin: rashes
 Endocrine: gynaecomastia
 Cardiac:
 Arrhythmias: all types
 Partial to complete A-V block

21. Digoxin: Adverse Effects
 Treatment:
 Stop further doses
 Extra-cardiac side effects (S/E): nothing more needed
 For tachy-arrhythmias: K+ supplementation for chronic use
associated toxicity; K+ monitoring directed supplementation for
acute ingestion
 For ventricular arrhythmias: Lidocaine
 For supraventricular arrhythmia: Propanolol
 For A-V block and bradycardia: atropine, cardiac pacing
 Digoxin antibody

22. Digoxin: Additional Points
 Precautions and Contraindications
 Hypokalemia
 Elderly, renal insufficiency, hepatic disease
 Myocardial ischaemia
 Thyrotoxicosis
 Myxoedema
 Ventricular tachycardia
 Partial A-V block
 Acute Myocarditis
 Wolff-Parkinson-White syndrome

23. Digoxin: Additional Points
Interactions
 Diuretics
 Calcium
 Quinidine
 Adrenergic drugs
 Metoclopramide, sucralfate, antacids, neomycin,
sulfasalazine: decreased absorption
 Atropinic drugs, TCA: increased absorption
 Propanolol, verapamil, diltiazem, disopyramide
 Succinylcholine

24. Digoxin: Uses
 Congestive Heart Failure
 Standard treatment: ACE inhibitors, ARBs, β- blockers and
diuretics
 Most effective in patients with dilated heart and low ejection
fraction
 Stable clinical state: withdrawal can be attempted
 CHF with AF in need of ventricular rate control: continuous digoxin
 Cardiac arrhythmias:
 Atrial Fibrillation
 Atrial Flutter
 Paroxysmal Supraventricular Tachycardia (PSVT)

25. Thank you!