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Drugs for CHF


  • Heart failure occurs when cardiac output is inadequate to provide the oxygen needed by the body. It is a highly lethal condition. Two major types of failure may be distinguished.
  • Approximately 50% of younger patients have systolic failure, with reduced mechanical pumping action (contractility) and reduced ejection fraction.
  • The remaining group has diastolic failure, with stiffening and loss of adequate relaxation playing a major role in reducing filling and cardiac output; ejection fraction may be normal even though stroke volume is significantly reduced.

Treatment is therefore directed at two somewhat different goals:


(1) Reducing symptoms and slowing progression as much as possible during relatively stable periods and


(2) Managing acute episodes of decompensated failure.


  • Extensive trials have shown that ACE inhibitors, angiotensin receptor blockers, βeta blockers, aldosterone receptor antagonists, and combined hydralazine-nitrate therapy (BIDIL) are the only agents in current use that actually prolong life in patients with chronic heart failure.
  • Positive inotropic drugs, on the other hand, are helpful mainly in acute systolic failure. Positive inotropic drugs have consistently reduced survival in chronic failure, and their use is discouraged.

Features Of CHF:

  1. Cardiac output is low            
  2. Preload is high     
  3. Afterload is high                  
  4. Salt & water retention
  5. Contractility decreases                    
  6. Compensatory tachycardia


  1. Initially, myocardial dysfunction and the attendant reduction of forward cardiac output lead to expansion of intravascular volume and activation of neuro-humoral systems, particularly the sympathetic nervous system and the renin-angiotensin system. These compensatory responses maintain perfusion to vital organs by increasing left ventricular preload, stimulating myocardial contractility, and increasing arterial tone. Acutely, these mechanisms help to sustain cardiac output by allowing the heart to operate at higher end-diastolic volumes, leading to increased stroke volume; concomitant peripheral vasoconstriction allows for regional redistribution of the cardiac output to critical organs.
  2. Unfortunately, each of these compensatory responses will also promote disease progression. Expansion of the intravascular volume and elevated ventricular chamber volumes lead to increased diastolic and systolic wall stress; these changes in turn impair myocardial energetics and induce hypertrophic remodeling.
  3. Neuro-humoral activation leads to arterial and venous constriction; the former increases left ventricular afterload (thereby compromising left ventricular stroke volume) and the latter increases preload, thereby exacerbating both diastolic and systolic wall stress. In addition, the neurohumoral effectors (such as nor-epinephrine [NE] and angiotensin II [AngII]) may act directly on the myocardium to promote unfavorable remodeling by causing myocyte apoptosis, abnormal gene expression, and alterations in the extracellular matrix.


  1. Digitalis
  • Any cardiac glycoside
  1. Digoxin        
  2. Digitoxin        
  3. Stropanthin        
  4. Oubain        
  5. Latanocide C

What is digoxin?

  • Cardiac glycoside
  1. Cardenolide nucleus (Increases force)
  2. Glycoside part (Pharmacokinetic activity)
  3. Obtained from Digitalis Lanata (Main), Digitalis purpura
  4. William Withering described use of Foxglove (D. Purpura) in 1785  
  • MAO
  1. Inhibits sodium-potassium ATPase (Na+K+ATPase) in a non covalent manner, there by increase in CO (direct action)
  2. Decreases HR (indirect action): - Vagomimetic, AV nodal blocker, anti-adrenergic property
  3. Stimulates ectopic pacemakers-arrhythmias-INCREASES MORTALITY
  • P/K


  1. 70% absorption
  2. Absorption is reduced by bacteria in gut
    1. So increased by broad spectrum antibiotics
    2. Dose of drug needs to be reduced if given with antiobiotics.
  3. Half life=24 hours; elimination is renal (glomerular filtration, tubular secretion)-C/I-renal failure
  4. Vd=6L/kg
  5. Protein binding=30%


  1. Longer acting (half life=165 hours), less potent, more protein bound (90%)
  2. Eliminated by bile
  3. Safe in renal failure
  4. More lipid soluble
  5. Used for maintenance purposes
  • Side effects of Digitalis like Drugs
  1. MC-nausea                        
  2. Earliest-anorexia        
  3. Delirium       
  4. Yellow vision (xanthopsia)            
  5. Gynecomastia (DISC) 
  6. Arrhythmias
    1. MC-Non-paroxysmal supra ventricular tachycardia
    2. Most characteristic-paroxysmal atrial tachycardia
    3. Others: AV junctional rhythm, ectopic beats, partial heart block, bigeminy, trigeminy, quadrigeminy
    4. Convert atrial flutter to fibrillation
    5. But does not cause atrial fibrillation
    6. Arrhythmias can even occur at therapeutic dose 
  • Toxicity

At therapeutic dose

  1. Toxic level=>1.5ng/ml        
  2. Toxicity precipitated by low potassium
  3. T/t- lidocaine

At overdose

Overdose toxicty 

  • Rx-Digibind
  1. Fab fragment of IgG1 molecule
  2. K+ levels are already high
  3. No use of giving potassium
  4. No use of cardioversion (increases mortality)
  5. Haemodialysis does not work
  • Drug interactions
  1. Quinidine reduces renal clearance-increases toxicity
  2. Many other drugs reduce CL of digoxin-1a, Class-III, ACE inhibitors (except enalapril)
  3. Calcium increases toxicity
  4. Hypomagnesaemia increases toxicity
  5. Hypokalemia increases toxicity  
  • C/I
  1. HOCM                                                  
  2. Partial heart block (safe in full heart block)  
  3. VT (because drug reduces ERP of ectopic tissues)                  
  4. High output failure       
  5. Diastolic failure                                            
  6. Constrictive pericarditis
  7. Cardiac temponade                                              
  8. Myocarditis          
  9. Thyrotoxicosis                                               
  10. Myxedema           
  11. Renal failure
  1. Nesiritide
    1. BNP analogue
    2. MOA-same as nitrates-NO-cGMP pathway
    3. Short acting (half life-10 mins)
    4. No oral absorption
    5. Given IV as infusion
    6. Reduces preload, afterload, natriuresis
    7. S/e-hypotension, nephrotoxic
    8. No value in chronic heart failure
      1. Ularetide            
      2. Carperetide (ANP analogue)                
      3. Under development
  2. Dobutamine
    1. Short term use in CHF
    2. Intermittent use is better due to development of tolerance
      1. Given as IV infusion
      2. Half life: 2 minutes
    3. Used in Refractory heart failure
  3. Bipyridines:
    Inamrinone, Milrinone
  • MOA: Phosphodiesterase type3 inhibitors • decrease cAMP breakdown
  • EFFECTS: Vasodilators; lower peripheral vascular resistance • also increase cardiac contractility
  • USES: Acute decompensated heart failure • increase mortality in chronic failure
  • Toxicity: Arrhythmias • Interactions: Additive with other arrhythmogenic agents

Treatment Of Heart Failure:








No symptoms but risk factors present

Treat obesity, hypertension, diabetes, hyperlipidemia, etc.



Symptoms with severe exercise


ACE Inhibitors/ARB, Beta blocker, Diuretic



Symptoms with marked (class II) or mild (class III) exercise


Add Aldosterone antagonist, Digoxin (IONOTROPES); Hydralazine/ nitrate

Cardiac Resynchronization Therapy,



Severe symptoms at rest

Transplant, Left Ventricular Assist Device

American College of Cardiology/American Heart Association classification. ** New York Heart Association classification


Recent Advances:

Istaroxime: it is a new drug which has same mechanism of action as digoxin i.e. it acts by inhibiting sodium potassium ATPase, in addition to this mechanism istaroxime also increases sequestration of calcium in sarcoplasmic reticulum which decreases side effects like arrhythmias on long term treatment.


Levosimendan: New drug which is phophodiesterase inhibitor as well as increases sensitivity of troponin system of heart towards calcium. Because of these two actions, levosimendan used as an ionotropic agent.


Omecantiv mecarbil: Alters the rate of transition of myosin from a low-actin-binding state to a strongly actin-bound force- generating state. Still under-trial.


Aliskiren, Remikiren: Renin antagonist used in CHF, prevents disease progression and remodeling.


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