There are two distinct goals of drug therapy in CHF. Relief of congestion/ low cardiac output symptoms and restoration of cardiac performance. Ionotropic agents, Vasodilators, Diuretics, BETA Blockers. Arrest/reversal of disease progression and prolongation of survival. ACE inhibitors, ARBs, Beta Blockers, Aldosterone Antagonists.

1. Prepare
By
Nida Sehar Noman
MBA(Finance) & MS (Pharmacology)
nidasehar19@yahoo.com

2. • There are two distinct goals of drug therapy in CHF.
• Relief of congestion/ low cardiac output symptoms and
restoration of cardiac performance.
• Ionotropic agents, Vasodilators, Diuretics, BETA
Blockers.
• Arrest/reversal of disease progression and prolongation
of survival.
• ACE inhibitors, ARBs, Beta Blockers, Aldosterone
Antagonists.

5. • Aldosterone is produced in excess in the adrenal gland
in edematous states.
• It is not simply a biomarker of disease activity, but a
potent mediator of ventricular and vascular remodeling
and disease progression.
• In HF major triggers of aldosterone release include
angiotensin II, serum potassium concentration, and
corticotropin.

7. • Heart
 Myocyte hypertrophy
 Interstitial fibrosis
 Coronary atherosclerosis
 Decreased natriuretic peptide synthesis
 Reduced norepinephrine uptake
• Kidney
 Sodium and water retention
 Potassium and magnesium wasting
 Glomerulosclerosis
 Tubulointerstitial fibrosis
 Podocyte apoptosis and proteinuria
• Vasculature
 Endothelial cell hypertrophy
 Vascular smooth muscle cell hypertrophy
 Atherosclerosis
 Reduced nitric oxide bioavailability
 Vasomotor dysfunction

9. • Block enzyme responsible for converting angiotensin I to
angiotensin II and for degrading various kinins.
• Chronic use can result in development of resistance for
at least 2 reasons.
 Increased renin levels, resulting in higher levels of
angiotensin I, and II.
 Production of angiotensin II through non-ACE enzyme
systems.
• Side effects, including cough, angioedema, azotemia,
hypotension, worsening renal function, and
hyperkalemia.

10. Generic Name Trade Name Initial dose Target dose
Captopril Capoten 6.25 mg Tid 50 mg Tid
Enalapril Vasotec 2.5 mg Bid 10 mg Bid
Fosinopril Monopril 5-10 mg Qd 80 mg Qd
Lisinopril Zestril 2.5-5 mg Qd 20 mg Qd

11. • Block the effects of angiotensin II on the ATI receptor, independent of
the source of angiotensin II production.
• The addition of ARBs to ACE inhibitors in patients with chronic HF
might provide additional blockade of the RAAS and greater
therapeutic benefit.
• Used in ACE inhibitor intolerant patients with chronic HF and LVEF
less than 40%.
• Used instead of ACE inhibitors primarily in patients who are
intolerant of ACE inhibitors because of intractable cough or
angioedema.
• Common side effects include hypotension, worsening renal function,
and hyperkalemia.

12. Generic Name Trade Name Initial daily Dose Target Dose
Candasartan Atacand 4-8 mg Qd 32 mg Qd
Losartan Cozaar 12.5-25 mg Qd 150 mg Qd
Valsartan Diovan 40 mg Bid 160 mg Qd

13. • They act by competitively inhibiting aldosterone at the
mineralocorticoid receptor sites.
• Two agents currently available are spironolactone and eplerenone.
• They differ in tolerability rather than clinical efficacy.
• Spironolactone is a nonselective MRA structurally similar to
progesterone.
• It also inhibits the effects ofdihydrotestosterone at the receptor site
and increases the peripheral conversion of testosterone into
estradiol.
• Associated with antiandrogenic and progestogenic activity.
• Adverse effects including gynecomastia, impotence and menstrual
irregularities.
• Eplerenone is a selective MRA.
• 100- to 1000-fold lower affinity for androgen, glucocorticoid, and
progesterone receptors than spironolactone.
• Not associated with the antiandrogenic side effects

14. Generic Name Trade Name Initial Dose Target Dose
Spironolactone Aldactone 12.5-25 mg Qd 25 mg Qd
Eplerenone Inspra 25 mg Qd 50 mg Qd

15. • It is a combination of angiotensin receptor blocker
Valsartan and neprilysin inhibitor Sacubitril. (Entresto)
• Valsartan blocks the AT1 receptor for Angiotensin II
resulting in vasodilation and reduction of ECF volume.
• Sacubitril is a prodrug activated to Sacubitrilat which
inhibits the enzyme neprilysin, a neutral endopeptidase
that degrades vasoactive peptides including bradykinin,
natriuretic peptides and adrenomedullin.
• Increases level of peptides results in vasodilation and
reduction of ECF volume via Na excretion.
• Side effects include cough, hyperkalemia (which can be
caused by valsartan), kidney dysfunction and
hypotension.

16. • The wholesale cost for a year of valsartan/sacubitril is
$4,560 per person . Similar class generic drugs without
sacubitril, such as valsartan alone, cost approximately
$48 a year.
• Dose:
 Initial dose 49 mg/ 51 mg PO BID
 Target maintenance dose after 2-4 weeks 97 mg/103 mg
PO BID as tolerated.
 Adjustment required in severe renal and moderate
hepatic impairment.
 Contraindicated in severe hepatic impairment.

18. • Their key role is due to their effect on kidney which is the
main target of hemodynamic, hormonal and autonomic
nervous system changes that are a result of failing
myocardium .
• The overall effect is retention of salt and water and
expansion of extracellular volume.
• These help to mantain cardiac output and tissue
perfusion by improving ventricular performance.

20. • They are considered first line diuretic therapy in CHF.
• They act by blocking Na K Cl co transporter in
ascending limb of loop of Henle.
• Their response depends upon drug bioavailability
(increase on an empty stomach) and nutritional level (as
proteins re required for transportation to kidney)
• Have significant role in reducing symptoms of edema
and dyspnea.
• Frequent administration result in resistance development
(fluid retention and congestion).

21. • They act by inhibiting sodium reabsorption by inhibiting
Na Cl co transporters in distal convulated tubules.
• Used if loop diuretics do not produce desired effect .T
• Generally administered thirty minutes before loop
diuretics.
• Combination therapy should be monitored for
hypovolemia, hypokalemia, hypomagnesia and
hyponatremia.

22. • They act by interfering with Na reabsorption in distal
tubules thereby decreasing K secretion.
• Weak diuretic and antihypertensive effect and should be
used in combination with loop diuretics.
• Contraindicated in patients with hyperkalemia and renal
failure.

24. BLOCKE
RS

25. • Decreased CO in chronic heart failure leads to activation
of multiple neurohormonal symptoms to maintain
circulation.
• One of these is increased circulating levels of nor
epinephrine which is considered a poor prognosis
marker.
• Our body becomes desensitized to agonist stimulation.
Leading to cardiac hypertrophy, fibrosis, necrosis and
apoptosis.
• Continuous stimulation ultimately leads to progressive
loss of ventricular function such as ventricular dilation
with reduced LVEF.

26. • Beta blocker therapy is appropriate in patients with NYHA
class II or class III symptoms resulting from left
ventricular systolic dysfunction.
• Unless contraindicated, beta blockers should be
considered a mainstay of therapy in these patients to
improve symptoms and mortality and to decrease
hospitalizations.
• However they should be considered disease-modifying
agents rather than “rescue” agents (as they do not
provide immediate symptomatic relief.)
• Thus, patients should be hemodynamically stable when
beta-blocker therapy is initiated.

27. • They act by inhibiting sympathetic nervous system and alpha
1 induced vasoconstriction.
• They offer moderate afterload reduction and slight preload
reduction.
• Side effects include dizziness and postural hypotension.
• Examples: Carvedilol
Dose
• Immediate release
• 3.125 mg PO Q12hr gradually increased upto 25 mg PO twice
daily
• Extended release
• 10 mg/day PO; maintained for 1-2 weeks if tolerated increased
upto 80 mg/day PO if necessary

28. • They are selective only in blocking Beta 1 adrenoceptors.
• Generally used for reduction of blood pressure and heart
rate.
• Examples: Metoprolol and Bisoprolol.
• Dose
• Initial dose: 25 mg QD ( XL formulation) for two weeks (
NYHA class II heart failure) and 12.5 mg QD (XL
formulation) ( more severe heart failure).
Maintenance dose: Based on tolerability can be
increased upto 200 mg