This document discusses drugs used to treat congestive heart failure (CHF). CHF occurs when the heart cannot pump enough blood to meet the body's needs. Key drugs mentioned include digitalis glycosides like digoxin, which increase the force of heart contractions; diuretics like furosemide that reduce fluid buildup; ACE inhibitors and ARBs that lower blood pressure and prevent further heart damage; and inotropic drugs like dobutamine that strengthen heart contractions. Adverse effects, mechanisms of action, and guidelines for use are provided for several common CHF medications.

1. DRUGS
FOR
CONGESTIVE HEART FAILURE
(CHF/ CCF)

2. Congestive Heart Failure
 State where the heart cannot maintain an
adequate cardiac output to meet metabolic
demands of the body
 Almost all form of heart disease can lead to
heart failure

3.  Congestive heart failure (CHF) is a chronic
progressive condition that affects the pumping
power of your heart muscles.
 You have four heart chambers. The upper half of
your heart has two atria, and the lower half of your
heart has two ventricles. The ventricles pump
blood to your body’s organs and tissues, and the
atria receive blood from your body as it circulates
back from the rest of your body.
 CHF develops when your ventricles can’t pump
blood in sufficient volume to the body. Eventually,
blood and other fluids can back up inside your:
-lungs -abdomen -liver -lower body

4. New York Heart Association(NYHA) Classification
Drugs for CHF contd. ...……
Class I No symptoms with ordinary physical activity
Class
II
Symptoms with ordinary physical activity but
comfortable at rest
Class
III
Symptoms with less than ordinary physical
activity but comfortable at rest
Class
IV
Cannot carry on any physical activity without
symptoms. Symptoms may be present even at
rest. The symptoms increases with increase
physical activity

5.  Left, right & biventricular heart failure
Drugs for CHF contd. ...……
Left Heart Failure Right Heart Failure
Cardiomegaly
Pulmonary oedema
Raised JVP +/++
Pitting oedema +/++
Pleural effusions
Raised JVP +++
Hepatomegaly
Ascites
Pitting oedema +++

6. Therapy of CHF
Drugs for CHF contd. ...……
Correction of reversible cause
Diet and activity
o Salt restriction
o extremes of temperature & heavy physical
exertion should be avoided.
o Drugs that worsen CHF should be avoided
(including NSAIDs)
o Other
Drugs therapy

7. Drugs for CHF
Drugs for CHF contd. ...……
Inotropic drugs: Digoxin, Dobutamine,
Dopamine, Amrinone,
Milrinone
Diuretics: Furosemide, Bumetanide,
Thiazides, Spironolactone
(Aldosterone antagonist)
Vasodilators: ACE Inhibitors /ARB,
Hydralazine, Prazosin, Sod.
Nitroprusside, Nitrates
β Blocker: Metoprolol, Bisoprolol,
Carvedilol

8. CARDIAC GLYCOSIDES (Digitalis)
Drugs for CHF contd. ...……
 E.g. Digoxin, Digitoxin
 ↑ Force of contraction and CO without ↑ing HR-
Cardiotonic
Chemistry
Glycosides consists
of aglycone ring
attached with one
or more sugar
moites
Source:
Digitalis lanata

9. Digitalis Contd……… Drugs for CHF contd. ...……
Effect in Heart:
 In failing heart; it ↑ force of contraction (Dose
dependent ) → ↑ CO
 Slow AV conduction → bradycardia
 More complete emptying of failing and dilated
ventricles
 SA node and A-V node automaticity is reduced at
therapeutic concentration
 They increase myocardial contractility and output in a
hypodynamic heart without a proportionate increase
in O2 consumption

10. Digitalis Contd……… Drugs for CHF contd. ...……
Mechanism of action:
Increase intracellular Ca2+ by blocking
Na+-K+ATPase

11. Digitalis Contd……… Drugs for CHF contd. ...……
Mechanism of action:
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
3Na+
2K+

12. Mechanism Contd……… Drugs for CHF contd. ...……
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
3Na+
2K+Digoxin 3Na+

13. Digitalis Contd……… Drugs for CHF contd. ...……
Effect in Blood vessels:
 No prominent effect in BP so can be given in
hypertensive patient
Effect CNS:
 Little effect in therapeutic dose
 Higher dose- activate CTZ, hyperapnoea,
central sympathetic stimulation, mental
confusion , disorientation, visual
disturbances

14. Digitalis Contd……… Drugs for CHF contd. ...……
PHARMACOKINETICS:
 Digitoxin: more lipid soluble ; slow & long acting
 Digoxin:
1. Fast and short acting than digitoxin
2. Relatively polar (……….)
3. Bioavailability differ from manufacture to
manufacturer
4. Food delay absorption
5. Concentrate in heart, Skeletal muscle, kidney
and liver : large volume of distribution (6-8 L/Kg)
6. t1/2 in elderly people………..?

15. Digitalis Contd……… Drugs for CHF contd. ...……
ADVERSE EFFECTS:
 Toxicity is high
 Margin of safety is low (therapeutic index 1.5-3)
 Extracardiac:
1. Initially: Anorexia, nausea, vomiting, diarrhoea
and abdominal pain
2. Fatigue, malaise, headache, mental confusion,
restlessness, hyperapnoea, disorientation,
psychosis, visual disturbances
3. Skin rashes and gynaecomastia rarely
 Cardiac:
Bradycardia, A-V block, any type of arrhythmias

16. Digitalis Contd……… Drugs for CHF contd. ...……
TREATMENT OF DIGITALISTOXICITY:
 Stop digitalis on earliest sign of toxicity
 Pot. Chloride administration (if toxicity is due to
chronic use/ use of diuretics ) which is guided by
serum pot. measurement
 Treatment of arrhythmias (if required)
a. Ventricular arrhythmias: Lignocaine i.v.
b. Supraventricular arrhythmias: Propranolol (oral/ i.v.)
c. A-V block & bradycardia: Atropine (i.m.)
 Digoxin antibody- very effective Orphan drug.
NOT used in our part

17. Digitalis Contd……… Drugs for CHF contd. ...……
CONTRAINDICATIONS:
 Hypokalemia
 Elderly, renal or severe hepatic disease (pt. more
sensitive)
 Hypothyroidism (low elimination, cumulation)
 Ventricular tachycardia
 Partial A-V Block

18. Digitalis Contd……… Drugs for CHF contd. ...……
Interactions:
Loop diuretics
Thiazide diuretics
Corticosteroids
Hypokalemia
Amiodarone
Verapamil
Erythromycin
Displace digitalis
from protein
binding site
Enhance digitalis
Cardiotoxicity
Catecholamines
Succinylcholine
Cause arrhythmias
Calcium

19. Digitalis Contd……… Drugs for CHF contd. ...……
Interactions:
Antacids
Sucralfate
Neomycin
Decrease
absorption of
digoxin
Enzyme inducers
Phenytoin
Phenobarbitone
Increase
metabolism of
digoxin
Decreased
digitalis Effect

20. Digitalis Contd……… Drugs for CHF contd. ...……
USES:
1. Congestive Heart Failure:
 Not commonly used because:
a. Have low margin of safety
b. Inable to reverse/ retard the disease progression
 Drug of choice in CHF patient:
a) With dilated heart and low ejection fraction
b) With atrial fibrillation
c) Not controlled by other drugs (resistant case)
 Prescribe in dose that provides plasma
concentration (0.8 -1.2ng/dl)- digitalization
 Stable clinical state for 2-3 months, withdrawal of
digitalis therapy can be attempted

21. Digitalis Contd………
Drugs for CHF contd. ...……
2. Cardiac arrhythmias:
 Atrial fibrillation (AF)
 Atrial flutter (AFl)
 Paroxysmal supraventricular tachycardia (PSVT)

22.  Atrial flutter and atrial fibrillation are
both abnormal heart rhythms.
 In atrial fibrillation, the atria beat irregularly. In
atrial flutter, the atria beat regularly, but faster
than usual and more often than the ventricles
 Dose: 0.125-0.25 mg PO/IV

23. DIURETICS Drugs for CHF contd. ...……
 High ceiling diuretics are preferred, but thiazide /
spironolactone can be added to overcome
resistance
 Mechanism:
a. ↑ Na+ & water excretion →↓ ECF volume →
↓ preload & improve ventricular efficacy
b. Remove oedema and congestion
 i.v furosemide increase venous capacitance
 Give quick symptomatic relief but DONOT influence
the disease process
 Intermittently used when required at low dose

24. Diuretics contd………… Drugs for CHF contd. ...……
 Spironolactone (aldesterone antagonist) –
decrease morbidity and mortality in patient
with severe heart failure
 Spironolactone is used in low dose (12.5-
25mg/day) as add on therapy with ACEIs
 Beneficial effect of spironolactone is slow
 Spironolactone is contraindicated in renal
insufficiency patient & pt. with hyperkalemia

25. Drugs for CHF contd. ...……
ACE Inhibitors/ ARBs:
 Orally active medium efficacy mixed dilator
 Vein dilation: ↓venous return → ↓ ventricular end
diastolic pressure & volume → reduce ventricle size
→ improve systole (Laplace law)
 Arteriolar dilation: ↓ afterload → weaker ventricular
contraction can pump more blood
 ↓ aldosterone release
 Recommended for all grades of CHF especially for
patient with left ventricular dysfunction but no
edema
 Advantages with ACEI:
a. Afford symptomatic relief
b. Retard/ reverse ventricular hypertrophy, myocardial
cell apoptosis and remodeling

26. Drugs for CHF contd. ...……
ROLE OF OTHERVASODILATORS:
Nitrates:Venodilator
Hydralazine, Minoxidil: Arteriolar dilators
Prazosin, Nitroprusside: Mixed dilators
 Hydralazine preferred in renal insufficiency patient

27. Drugs for CHF contd. ...……
Sympathomimetic inotropic drugs:
DOBUTAMINE:
 Selective β1 agonist given i.v.
 NOT commonly used b/c of potential to
produce angina or arrhythmias
 Preferred in acute HF accompaning MI,
cardiac surgery

28. Drugs for CHF contd. ...……
Phosphodiesterase III inhibitors:
AMRINONE (Inamrinone)
 Increase myocardial cAMP & influx of Ca2+
 Inodilator: (+ve inotropic and vasodilator)
 Given i.v.- action within 5 min & last for 2-3 hours
 Adverse effects: Thrombocytopenia (dose
related, transient & asymptomatic), nausea,
diarrhoea, abdominal pain, liver damage, fever
and arrhythmias
 Uses: Severe and refractory CHF (Short term i.v.
use along with other drugs)

29. Drugs for CHF contd. ...……
MILRINONE:
 More selective, more potent and short
acting than amrinone
 Thrombocytopenia – NOT significant
 Preferred over amrinone for short term use