Weiping Zhang, MD, Ph.D., Department of Pharmacology Zhejiang University School of Medicine
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Weiping Zhang, MD, Ph.D., Weiping Zhang, MD, Ph.D., Department of PharmacologyDepartment of PharmacologyZhejiang University School of MedicineZhejiang University School of Medicine
2010.6.28
Part 6 Drugs for Treatment of Congestive Heart Failure
Pharmacology for cardiovascular system
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ContentsContentsI. IntroductionII. Basic Pharmacology of Drugs Used
in Heart Failure
III. Clinical Pharmacology of Drugs Used in Heart Failure
Cardiac glycoside Diuretics and vasodilators ACE inhibitors receptor blockers Others
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1.1. Heart Failure:(1) Systolic failure: the mechanical pumping action (contractility) and the ejection fraction of the heart are reduced.(2) Diastolic failure: stiffening and loss of adequate relaxation plays a major role in reducing cardiac output and ejection fraction may be normal. e.g. Pericarditis 铁甲心(3) High-output failure: can result from hyperthyroidism, beriberi, anemia, and arteriovenous shunts.
I. I. IntroductionIntroduction
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2. New Approach to the Classification of Heart Failure
Marked symptoms at rest despite maximal medical therapy (e.g., those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions)
Refractory end-stage HFD
Known structural heart diseaseShortness of breath and fatigueReduced exercise tolerance
Symptomatic HFC
Previous MILV systolic dysfunctionAsymptomatic valvular disease
Asymptomatic HFB
HypertensionCAD Diabetes mellitusFamily history of cardiomyopathy
High risk for developing heart failure (HF)A
Patient DescriptionStage
Hunt SA et al. J Am Coll Cardiol. 2001;38:2101–2113.
At Risk
Heart Failure
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Myocardial injury Fall in cardiac output
Activation of RAAS, SNS and others
Myocardial toxicityPeripheral vasoconstrictionHemodynamic alterations
Remodeling andprogressive
worsening ofLV function Heart failure symptomsMorbidity and mortality
ANPBNP
Fonarow GC. Rev Cardiovasc Med..2001;2:7–12.
3. Pathophysiology of Heart Failure:
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3. Pathophysiology of Heart Failure:intrinsic compensatory:myocardial hypertrophy: helps maintain cardiac performance at the beginning but can lead to ischemic changes, impairment of diastolic filling, and alterations in ventricular geometry.Remodeling: proliferation of connective tissue cells as well as abnormal myocardial cells with some biochemical characteristics of fetal myocytes.
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Pathophysiologic Effects of Angiotensin IIPathophysiologic Effects of Angiotensin IIand Epinephrine/Norepinephrineand Epinephrine/Norepinephrine
Cardiac Myocyte Fibroblast Peripheral Artery Coronary ArteryHypertrophy
Apoptosis
Increased Wall Stress
Increased O2 Consumption
Cell Sliding
Impaired Relaxation
Collagen Synthesis
Hyperplasia
Decreased ComplianceFibrosis
Vasoconstriction
HypertrophyEndothelial Dysfunction
VasoconstrictionEndothelial DysfunctionAtherosclerosis
ThrombosisRestenosis
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Cardiac failureCardiac failure
Cardiac outputCardiac output
Venous pressureVenous pressure
Venous hyperemiaVenous hyperemia
Pulmonary circulaPulmonary circulation:tion:cough, emptysis, cough, emptysis, dyspneadyspnea
Systemic circulationSystemic circulation hyperemiahyperemia ::jugular vein jugular vein distension, edemadistension, edema
Blood supplyBlood supply
Renal blood flowRenal blood flow
Renin - angiotension ⅡRenin - angiotension ⅡAldosterone Aldosterone
Sodium and waterSodium and waterretentionretention
Changes of hemodynamics in CHFChanges of hemodynamics in CHF
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3. Pathophysiology of Heart Failure:extrinsic compensatory:• Sympathetic nervous system• RAAs
Cardiac output
Sympatheticdischarge
Angiotensin II
Renin release
Renal blood flow
Remodeling
Rate
force
Preload
Afterload
Carotid sinus firing
Cardiac output (via compensation)
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
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Positive inotropic agents, very helpful in acute failure and reduce symptoms in chronic failure. ---act on myocardia.ACEI, -blockers, spironolactone (an aldosterone receptor antagonist) and hydralazine + isosorbide can actually prolong life in patients with chronic heart failure. ---act both cardiac and non-cardiac target, such as kidney, adrenergic system, RAA system. To improve the life qualitity, decrease hospitalization and the mortality.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
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?
II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Positive Inotropic Drugs• Digitalis• Beta Adrenoceptor Stimulants• Dopamine2. Diuretics3. RAAS inhibitors• ACEI• ARB• Adolsterone antagonists4. Vasodilators5. Beta blockers6. rhBNP
Whether they can decrease the mortality
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Stage C patients Stage D patients
2009 guideline2009 guideline
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Positive Inotropic Drugs• Digitalis Adrenoceptor Stimulants• Dopamine2. Diuretics3. RAAS inhibitors• ACEI• ARB• Adolsterone antagonists4. Vasodilators5. Beta blockers6. rhBNP
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis:Digitalis is the genus name for the family of plants that provide most of the medically useful cardiac glycosides, eg, digoxin.
Aglycone (genin)
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Pharmacokinetics• Absorption and Distribution
1Ouabain and digitoxin are no longer in use in the USA.
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Pharmacokinetics• Metabolism and Excretion
Almost 2/3 of digoxin is excreted unchanged by the kidneys.Digitoxin is metabolized in the liver and excreted into the gut via the bile. The enterohepatic circulation of digitoxin contributes to the very long half-life.Ouabain must be given parenterally and is excreted, mostly unchanged, in the urine.
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Pharmacoligical mechanism
XX
Hypokalemia Hyperkalemia
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Pharmacoligical mechanismACTIONS( 1 ) Positive inotropic action - inhibitor of Na+-K+ATPase( 2 ) Negative chronotropic action - inhibits sympathetic activities - improves vagal activities ( 3 ) Actions on cardiac electrophysiology - decreases automaticity of sinoatrial node slow conduction - increases automaticity of Pukinje fibres - shortens ERP of fast reaction cells
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Pharmacoligical mechanismACTIONS( 4 ) Actions on nervous system - autonomic nervous system - central nervous system ( D2 receptor )( 5 ) Actions on neuroendocrine system - inhibits RAAS - increases ANP (心房钠尿肽) ( 6 ) Actions on kidney ( diuretic effect ) - increases blood supply of kidney - decreases Na+ resorption (inhibition of Na+-K+ ATP ase)
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Cardiac failureCardiac failure
Cardiac outputCardiac output
Venous pressureVenous pressure
Venous hyperemiaVenous hyperemia
Pulmonary circulaPulmonary circulation:tion:cough, emptysis, cough, emptysis, dyspneadyspnea
Systemic circulationSystemic circulation hyperemiahyperemia ::jugular vein jugular vein distension, edemadistension, edema
Blood supplyBlood supply
Renal blood flowRenal blood flow
Renin - angiotension ⅡRenin - angiotension ⅡAldosterone Aldosterone
Sodium and waterSodium and waterretentionretention
Changes of hemodynamics in CHFChanges of hemodynamics in CHF
DigoxinDigoxin
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Cardiac output
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Clinical usage and toxicity
Therapeutic uses :( 1 ) CHF Especially associated with atrial fibrillation and ventricular tachycardia( 2 ) Some arrhythmias - atrial fibrillation - atrial flutter - paroxysmal surpraventricular tachycardia
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Administration & Dosage
II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Clinical usage and toxicity
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Toxicity and prevention
1) Cardiac toxicity Tachyarrhythmia : various Bradyarrhythmia : atrial ventricular block, sinus brad
ycardia. Atropine, isoprenaline,. Digoxin immune fab
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Toxicity and prevention
2) GI responseAnorexia, nausea, vomit, diarrhea. Should be distinguish wit
h heart failure.
3) CNS response and visual disturbance• Dizzy, headache, fatigue, xanthopsia, chloropsia etc
4) The symptoms to stop digitalis administration : Severe vomit 、 chromatopsia, Ventricular premature, He
art rate < 60 times/min
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Serum digitalis and K+ levels and the ECG should be monitored during therapy of significant digitalis toxicity. Of the available antiarrhythmic agents, lidocaine is favored.Digitalis antibodies (digoxin immune fab) are clinically used for severe toxic patients.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Digitalis Toxicity and prevention
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• Hypokalemia increase the risk of serious digitalis-induced cardiac arrhythmias• Quinidine displaces digoxin from tissue binding sites (a minor effect) and depresses renal digoxin clearance (a major effect) .• Antibiotics that alter gastrointestinal flora may increase digoxin bioavailability.• Agents that release catecholamines may sensitize the myocardium to digitalis induced arrhythmias.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
Interactions1. Digitalis Toxicity and prevention
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Effect of Digoxin on Mortality in Heart Effect of Digoxin on Mortality in Heart FailureFailure: The Digitalis Investigation Group
DIG (Digitalis Investigation Group): 6,800 patients with LVEF 45% randomized to digoxin (n=3,403) or placebo (n=3,397) in addition to therapy with diuretics and ACEI followed for 37 months.The DIGITALIS Investigation Group. N Engl J Med. 1997;336:525–532.
Digoxin
Placebo
00 4 8 12 16 20 24 28 32 36 40 44 48 52
10
20
30
40
50
Relative Risk 0.9995% CI 0.91–1.07
P=.80
All-cause mortality rates: Placebo 35.1%; Digoxin 34.8%
Mor
talit
y Fr
om A
ny C
ause
(%)
MonthsNumber of patients at risk:Placebo 3,403 3,239 3,105 2,976 2,868 2,758 2,652 2,551 2,205 1,881 1,506 1,168
734 339Digoxin 3,397 3,269 3,144 3,019 2,882 2,759 2,644 2,531 2,184 1,840 1,475 1,156
737 335
CV Mortality 0%
HF Hospitalizations 28%
Total Hospitalizations 6%
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Adrenoceptor Stimulants, e.g. dobutamineResult in cardiac output and ventricular filling pressure.There is potential for producing angina or arrhythmias in patients with coronary artery disease.Side effects: angina, arrhythmias and tachyphylaxis etc
II. II. Basic Pharmacology of Drugs Used in Heart Failure
2. Other Positive Inotropic Drugs Used in Heart Failure(略)
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Dopamine has also been used in acute heart failure and may be particularly helpful if there is a need to raise blood pressure.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
2. Other Positive Inotropic Drugs Used in Heart Failure(略)
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Positive Inotropic Drugs• Digitalis• Beta Adrenoceptor Stimulants• Dopamine2. Diuretics3. RAAS inhibitors• ACEI• ARB• Adolsterone antagonists4. Vasodilators5. Beta blockers6. rhBNP
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Diuretics
To reduce venous pressure and ventricular preload. The results are reduction of edema and its symptoms and reduction of cardiac size, which leads to improved pump efficiency.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
3. Drugs Without Positive Inotropic Effects Used in Heart Failure
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Therapeutic effects of Therapeutic effects of diuretics in CHFdiuretics in CHF
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Positive Inotropic Drugs• Digitalis• Beta Adrenoceptor Stimulants• Dopamine2. Diuretics3. RAAS inhibitors• ACEI• ARB• Adolsterone antagonists4. Vascular dilators5. Beta inhibitors6. rhBNP
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Angiotensinogen
A IRenin
A II
• Antiproliferation• Antifibrotic• NO Release• Differentiation• Vasodilation
• Hypertrophy/proliferation• Vasoconstriction• Sympathetic stimulation• Aldosterone release• Vasopressin
AT1 receptor AT2 receptor
ACE
Degradation products
Bradykinin
RAASt-PACathepsin GToninCAGE
Cathepsin GChymase
Vasodilatation Vascular perm Prostaglandins Inhibits Na/H20
reabsorption
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RAAS inhibitorsReduce peripheral resistance and thereby reduce afterload;Reduce salt and water retention (by reducing aldosterone secretion) and in that way reduce preload.Reduces sympathetic activity.Reduce the long-term remodeling of the heart and vessels.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
3. Drugs Without Positive Inotropic Effects Used in Heart Failure
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Angiotensinogen
A IRenin
A II
• Antiproliferation• Antifibrotic• NO Release• Differentiation• Vasodilation
• Hypertrophy/proliferation• Vasoconstriction• Sympathetic stimulation• Aldosterone release• Vasopressin
AT1 receptor AT2 receptor
ACE
Degradation products
Bradykinin
RAASt-PACathepsin GTonin
CAGECathepsin GChymase
Vasodilatation Vascular perm Prostaglandins Inhibits Na/H20
reabsorption
X
X X
X
ACEI
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CV Risk, reduction in future cardiovascular events; DN, diabetic nephropathy; H, hypertension; HF, heart failure; Post MI, reduction in heart failure or other cardiac events following myocardial infarction.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
3. Drugs Without Positive Inotropic Effects Used in Heart Failure
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Angiotensinogen
A IRenin
A II
• Antiproliferation• Antifibrotic• NO Release• Differentiation• Vasodilation
• Hypertrophy/proliferation• Vasoconstriction• Sympathetic stimulation• Aldosterone release• Vasopressin
AT1 receptor AT2 receptor
ACE
Degradation products
Bradykinin
RAASt-PACathepsin GToninCAGE
Cathepsin GChymase
xARB
x
Vasodilatation Vascular perm Prostaglandins Inhibits Na/H20
reabsorptionx ARB
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CV Risk, reduction in future cardiovascular events; DN, diabetic nephropathy; H, hypertension; HF, heart failure; Post MI, reduction in heart failure or other cardiac events following myocardial infarction.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
3. Drugs Without Positive Inotropic Effects Used in Heart Failure
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Aldosterone antagonistsAldosterone antagonists
Spironolactone and Eplerenone get additional functio
n to decrease morbidity and mortality in patients with
severe heart failure who are also receiving ACE inhib
itors and other standard therapy.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
3. Drugs Without Positive Inotropic Effects Used in Heart Failure
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Cardiac Myocyte Fibroblast Peripheral Artery KidneyHypertrophy
Norepinephrine Release Collagen Synthesis
Hyperplasia
Decreased ComplianceFibrosis
Vasoconstriction
HypertrophyEndothelial Dysfunction
Potassium LossSodium Retention
Effects of AldosteroneEffects of Aldosterone
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RALES: Aldosterone Antagonist Reduces All-Cause Mortality in Chronic HF
*Ejection fraction ≤35% Class III or IV symptoms at some point in prior 2 months.
Spironolactone (25 mg) + standard care (n = 822)Placebo + standard care (n = 841)
Prob
abili
ty o
f Sur
viva
l (%
)
1.000.950.900.850.800.750.700.650.600.550.50
03 6 912 15 18 21 24 27
Months
HR = 0.70 (95% CI, 0.60 to 0.82)
0
0.45
30 33 36
P<.001
Pitt B et al. N Engl J Med. 1999;341:709-717.
HR = hazard ratio; RR = risk reduction.
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EPHESUS Co-Primary Endpoint:Total Mortality
Adapted from Pitt B et al. N Engl J Med. 2003;348:1309-1321.
Eplerenone + standard care (n = 3319)
Placebo + standard care (n = 3313)
Cum
ulat
ive
Inci
denc
e (%
)
22201816141210
86420
3 6 912 15 18 21 24 27
Months Since Randomization
HR = 0.85 (95% CI, 0.75 to 0.96)P = .008
0
(16.7%)
(14.4%)
HR = hazard ratio.
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Positive Inotropic Drugs• Digitalis• Beta Adrenoceptor Stimulants• Dopamine2. Diuretics3. RAAS inhibitors• ACEI• ARB• Adolsterone antagonists4. Vasodilators5. Beta blockers6. rhBNP
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VasodilatorsReduction in preload (through venous dilation), or reduction in afterload (through arteriolar dilation), or both.Long-term use of hydralazine and isosorbide dinitrate can also reduce damaging remodeling of the heart.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
3. Drugs Without Positive Inotropic Effects Used in Heart Failure
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JCardiacFail 2007;13:331-339
I/H meanes isosorbide dinitrate and hydralazineI/H meanes isosorbide dinitrate and hydralazine
Survival
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JCardiacFail 2007;13:331-339
Survival
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AmJCardiol2007;100:684(R)C689
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II. II. Basic Pharmacology of Drugs Used in Heart Failure
1. Positive Inotropic Drugs• Digitalis• Beta Adrenoceptor Stimulants• Dopamine2. Diuretics3. RAAS inhibitors• ACEI• ARB• Adolsterone antagonists4. Vasodilators5. blockers6. rhBNP
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Effect of Carvedilol in Heart FailureEffect of Carvedilol in Heart FailureUS Carvedilol Heart Failure Trials Program
1094 Class II-IV CHF pts on triple therapy (ACEI, digoxin, diuretics)Carvedilol 6.25 bid test 2 weeks, then 12.5 bid, then 25 bid vs placeboPacker NEJM 1996;334:1349-55
0 50 100 150 200 250 300 350 400Follow-up (days)
50
60
70
80
90
100Survival Proportion
CarvedilolPlacebo
P<0.001
65%
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Effect of Metoprolol CR/XL in Heart FailureEffect of Metoprolol CR/XL in Heart FailureMERIT-HF
3991 pts with CHF Class II-IV, ave age 64 and LVEF 0.28 Randomized to Metoprolol CR/XL 12.5 mg or 25 mg PO qd, target dose 200 mg qdLancet 1999;353:2001-07
0 3 6 9 12 15 18 21Follow-up (months)
80
85
90
95
100Survival Proportion
Metoprolol CR/XLPlacebo
RR 0.66 (0.53-0.81)P=0.0062
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The Use of Beta Adrenergic Blocking Agents in Heart Failure
0 6 12 18 24
Time (weeks)
0
5
10
15
-5
-10
LVE
F %
cha
nge
Initial hemodynamic deterioration followed by reverse remodeling (decrease in EDV and ESV) with improved ventricular function over time (increased LVEF )
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Early Benefits and Early Safety of Carvedilol in Severe HF: COPERNICUS
Packer M. N Engl J Med. 2001;344:1651–1658. Krum H. JAMA. 2003;289:712–718.
Highest-Risk Subgroup
15
10
All Patients
6.45.1
11.4
8.8
Placebo
Carvedilol
Lower Risk for Worsening CHF
(n=1,133) (n=1,156) (n=316) (n=308)
5
0
Early Mortality Reduction
3
2
1
00 2 4 6 8
Weeks After Randomization
Patie
nts
With
Eve
nt (%
) Placebo(n=1,133)
Carvedilol(n=1,156)
Risk Reduction 25%
(35%–59%)
Event rates: Placebo 2.3%; Carvedilol 1.7%
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Effects of SympatheticEffects of SympatheticActivation in Heart FailureActivation in Heart Failure
1-receptors
Cardiac sympathetic activity Sympathetic activity to kidneys+ blood vessels
2-receptors
1-receptors
Activationof RAS
VasoconstrictionSodium retention
Myocyte deathIncreased arrhythmias
Disease progression
1- 1-
CNS sympathetic outflow
Bristow MR. Circulation. 2000;101:558-569.
CompensationCompensationDe-compensationDe-compensation
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-Blockers Differ in Their Long-Term Effects on Mortality in HF
Bisoprolol1
Bucindolol2
Carvedilol3-5
Metoprolol tartrate6
Metoprolol succinate7
Nebivolol8
Xamoterol9
Beneficial No effectBeneficialNot well studiedBeneficialNo effectHarmful
1CIBIS II Investigators and Committees. Lancet. 1999;353:9-13. 2The BEST Investigators. N Engl J Med 2001; 344:1659-1667. 3Colucci WS, et al. Circulation 1996;94:2800-2806. 4Packer M, et al. N Engl J Med 2001;344:1651-1658. 5The CAPRICORN Investigators. Lancet. 2001;357:1385-1390. 6Waagstein F, et al. Lancet. 1993;342:1441-1446. 7MERIT-HF Study Group. Lancet. 1999;353:2001-2007. 8SENIORS Study Group. Eur Heart J. 2005; 26:215-225. 9The Xamoterol in Severe heart Failure Study Group. Lancet. 1990;336:1-6.
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H, hypertension; HF, heart failure; Post MI, reduction in heart failure or other cardiac events following myocardial infarction.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
3. Drugs Without Positive Inotropic Effects Used in Heart Failure
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Therapeutic effects of Therapeutic effects of ββ receptor antagonists on receptor antagonists on cardiac function in heart failure patientscardiac function in heart failure patients
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Drugs Used in Heart Failure1. Positive Inotropic Drugs• Digitalis• Beta Adrenoceptor Stimulants• Dopamine2. Diuretics3. RAAS inhibitors• ACEI• ARB• Adolsterone antagonists4. Vasodilators5. Beta blockers6. rhBNP
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rhBNP
Nesititide: proved in 2001
1. Publication Committee for the VMAC Investigators. Intravenous nesiritide vs nitroglycerin for treatment of de-compensated congestive heart failure: a randomized controlled trial. JAMA , 2002,287(12):1531-1540.
2. Yancy CW, Saltzberg MT , Berkowitz RL,et al. Safety and feasibility of using serial infusions of nesiritide for heart failure in an outpatient setting (from the FUSION I trial). Am J Cardiol,2004,94(5): 595-601.
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rhBNP
The clinical trials after 2005 showed controversial results
1. Sackner2Bernstein JD, Skop icki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely de-compensated heart failure. Circulation, 2005, 111 (12) : 1487-1491.
2. Sackner2Bernstein JD, KowalskiM, FoxM, et al. Short-term risk of death after treatment with nesiritide for de-compensated heart failure: a pooled analysis of randomized controlled trials. JAMA, 2005, 293 (15) : 1900-1905
Risk of kidney damage and short –term of death
Also some results showed no effects ??
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Drugs Used in Heart Failure
2009 guideline
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In the past prescription of a diuretic plus digitalis.
At present diuretics, ACE inhibitors, and -blockers
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
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Management of Chronic Heart Failure
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
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1) Sodium Removal: by dietary salt restriction or a diureticIn mild failure, it is reasonable to start with a thiazide diuretic, switching to more powerful agents as required.Hypokalemia can be treated with potassium supplementation or through the addition of a potassium-sparing diuretic such as spironolactone.
Management of Chronic Heart Failure
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
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2) ACEI & ARBIn patients with left ventricular dysfunction but no edema, an ACE inhibitor should be used first.Additional studies suggest that ACE inhibitors are also valuable in asymptomatic patients with ventricular dysfunction.The angiotensin II receptor antagonists (eg, losartan, valsartan, etc) produce beneficial hemodynamic effects similar to those of the ACE inhibitors.
Management of Chronic Heart Failure
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
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3) VasodilatorsVasodilators include arteriolar dilators, venous dilators, and drugs with nonselective vasodilatory effects.The choice of agent should be based on the patient's signs and symptoms and hemodynamic measurements.high filling pressures--------venous dilatorslow left ventricular output------arteriolar dilatorchronic failure that responds poorly to other therapy-----both
Management of Chronic Heart Failure
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
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4) Blockers blockers such as bisoprolol, carvedilol, and metoprololare beneficial to heart failure, which based on the hypothesis that excessive tachycardia and adverse effects of high catecholamine levels on the heart.BUT SHOULD BE VERY CAREFUL.
Management of Chronic Heart Failure
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
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5) DigitalisDigoxin is indicated in patients with heart failure and atrial fibrillation or in patients with a dilated heart and third heart sound.Digoxin is reduced hospitalization and deaths from progressive heart failure. But there is an increase in sudden death, especially with serum digoxin concentrations of digoxin levels greater than 1.5 ng/mL.
The characteristics of digoxin is long half life and the close of between the therapeutic plasma concentration and the toxic plasma concentration.
Management of Chronic Heart Failure
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
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Treatment of patients with predominantly diastolic dysfunction heart failure has not been well studied
Direct vasodilators are not indicated
Diuretics should be used cautiously, at low dose initially, recognizing that the stiff heart is highly
dependent on adequate preload
ACE inhibitors, calcium channel blockers, and beta blockers have favorable effects upon hemodynamics
Recommend: ACE inhibitors, beta blockers, aldosterone antagonists
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart FailureManagement of Chronic Heart Failure with normal systolic function
constrictive peicarditis
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Acute heart failure occurs frequently in patients with chronic failure. Such episodes are usually associated with increased exertion, emotion, salt in the diet, noncompliance with medical therapy, or increased metabolic demand occasioned by fever, anemia, and acute myocardial infarction, etc
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
Management of Acute Heart Failure
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• Patients with acute myocardial infarction are best treated with emergency revascularization with either coronary angioplasty and a stent or a thrombolytic agent. • Measurements of arterial pressure, cardiac output, stroke work index, and pulmonary capillary wedge pressure are particularly useful in patients with acute myocardial infarction and acute heart failure.
II. II. Basic Pharmacology of Drugs Used in Heart Failure
4. Clinical Pharmacology of Drugs Used in Heart Failure
Management of Acute Heart Failure
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Important Comorbidities inHeart Failure
Cardiovascular Hypertension Coronary artery disease Peripheral vascular
disease Cerebral vascular
disease Hyperlipidemia Atrial fibrillation
Horwich and Fonarow, Chapter 40: Impact and Treatment of Comorbidities in Heart Failure
Non-Cardiovascular Obesity Diabetes Anemia Chronic kidney disease Thyroid disease COPD / Asthma Smoking Sleep disordered
breathing Liver disease Arthritis Cancer Depression
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Evidence-Based Treatment Across the Contineum of LVD and HF
Control VolumeReduce Mortality
Salt Restriction*Diuretics*
Digoxin*
-BlockerACEIor ARB
AldosteroneAntagonist
Treat Residual SymptomsCRT
an ICD* Hyd/ISDN*
*For select indicated patients.
ICD*
Treat Comorbidities
Aspirin*Warfarin*
Statin*
Enhance Adherence
EducationDisease Management
Performance Improvement Systems
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References
Golan DE, et al. Principles of Pharmacology. Lippincott Williams & Wilkins. 2004.
Murphy JE. Clinical Pharmacokinetics, 4th edition. 2006.
ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult.
2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults.