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.
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.
3.
4.
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.
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.
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.
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
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.
17.
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.
19.
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.
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