Principles of Pharmacotherapy in Chronic Heart Failure .. ....,,
PPhhaarrmm..DD..,, PPhh..DD.. 1. 2. 3. (chronic heart failure)
(acute exacerbation of chronic heart failure decompensated heart
failure)4. (indication) (contraindication) (optimal dosing)
(monitoring) (patient counseling) 5. digoxin digoxin 6. (goals of
care) 7. 2. 2 | pageCardiac output cardiac output (/) stroke volume
/Cardiac output (L/min) = heart rate x stroke volumeStroke volume
stroke volume 1. Preload or Venous return Frank-Starlings law of
the heart (Stroke volume) (venous return) (force of contraction)
(preload or venous return) preload (cardiac myocyte) (stretching)
preload hemodynamic preload left ventricular end-diastolic volume
(LVEDV) left ventricular end-diastolic pressure (LVEDP) stroke
volume preload 12. Cardiac contractility Inotropic state preload (
Frank-Starling) Contractility inotropy state sympathetic nervous
system (SNS), catecholamines , digoxin, dopamine, dobutamine
contractility Contractility stroke volume ventricular function
curve 2. 3. 3 | page3. Afterload (Ventricular wall stress) 3 :a.
(intravenricular size radius ) (Cardiac chamber enlargement)b.
(ventricular wall thickness)c. (intraventricular systolic pressure)
total peripheral vascular resistance afterload Afterload Parameters
Afterload = Intraventricular systolic pressure x radiusEjection
fraction (EF) (eject) systole (left ventricular systolic function)
diastole EF = Stroke volume x 100End-diastolic volume EF
50-60Ventricular wall thickness 1 Frank-Starling Mechanism 2
Cardiac function curve 4. 4 | page (Heart failure) (clinical
presentation) oxygen (dyspnea onexertion) (orthopnea) (peripheral
edema) (interstitium) oxygen 1. 3 a. Systolic heart failure
(contraction or inotropy) (cardiac output) systolic dysfunction
systolic heart failure ejection fraction 40% (EF< 40%) EF 40-60%
mild systolic dysfunctionb. Diastolic heart failure (relaxation or
lusitropy) ( ) (ventricular filling preload) cardiac output
FrankStarling diastolic heart failure normal ejection fraction (EF
> 60%) 1 3 diastolic heart failure systolic heart failurec.
Combination of systolic and diastolic heart failure EF
echocardiography2. (functional classification) New York Heart
Association (NYHA) New York Heart Association Functional
Classification of Heart Failure 4 5. 5 | pagea. NYHA funcional
class I (ordinary physicalactivity) b. NYHA functional class II
(slight limitation) c. NYHA functional class III (no symptoms at
rest)d. NYHA functional class IV (symptoms at rest)3. (staging of
disease progression) American Heart Association (AHA) American
College of Cardiology (ACC) a. Stage A hypertension,
atherosclerotic diseases ( ), diabetes, obesity, metabolic syndrome
cardiomyopathyb. Stage B (structural abnormalities) (left
ventricular hypertrophy) ejection fraction c. Stage C d. Stage D
refractory heart failure ventricular assisted device,chronic
inotropes therapy 6. 6 | page (Causes) 3 1. a. Ischemic heart
disease myocardial infarction systolic heart failure diatolic heart
failureb. (cardiomyopathies) (1) Dilated cardiomyopathy systolic
heartfailure(2) Hypertrophic cardiomyopathy (disarray) diastolic
heart failure.(3) Restrictive cardiomyopathy diastolic heart
failurec. (myocarditis) 2. valvular stenosis regurgitation (aortic,
pulmonic,mitral, tricuspid valve) a. stenosis ( mitral tricuspid
valve stenosis) preload diastolic heart failure ( pulmonicvalve
stenosis) ( aortic valve stenosis) systolic heart failure b.
regurgitation insufficiency ( mitral regurgitation tricuspid
regurgitation), pulmonary artery right ventricle ( pulmonic valve
regurgitation) aorta ( aorticregurgitation) left ventricle (volume
overload) 7. 7 | page(increased preload) (cardiac dilatation)
systolicheart failure3. () (increasedcardiac workload) 2 (pressure
overload) (volume overload) a. (systemic hypertension) heart
failureb. (pulmonary hypertension) c. shunt patent ductus
arteriosus (PDA), atrial septal defect (ASD), ventricular
septaldefect (VSD) 4. a. ventricular fibrillation or tachycardiab.
atrial fibrillation or tachycardiac. bradycardiad. complete heart
block (Precipitating factors) (compensated state) cardiac output
(acute exacerbation decompensation ) pulmonary hypertension 8. 8 |
page corticosteroids NSAIDs afterload myocardial contractility
beta-blocker propranolol, metoprolol non-dihydropyridine calcium
channel antagonists verapamil, diltiazem(Compensatory mechanisms to
increase cardiac output) cardiac output (compensatory mechanisms)
cardiac output compensated state cardiac output decompensated
stateCompensatory mechanisms cardiac output 1. (heart rate)
(contractility) sympathetic (activation of autonomic
sympatheticnervous system SNS) catecholamines 2. (increased
preload) 2 a. (vasoconstriction) (Non-vital organs) redistribute
preload. neurohormones norepinephrine, angiotensin II,
endothelin-1, B-type natriuretic peptide (BNP) argininevasopressin
preload afterload (total peripheral resistance) b. (increased renal
reabsorption of water andsodium chloride) (renal hypoperfusion)
cardiac output redistribute 9. 9 | page (1) (2) renin
juxtaglomerular cells renin angiotensinogen angiotensin I,
angiotensin I angiotensin II angiotensin converting enzyme
(ACE),angiotensin II aldosterone aldosterone sodium chloride
(increased intravascular volume) (increased preload) Frank-Starling
cardiac output preload cardiac output ( Frank-Starling curve)
preload cardiac output preload stroke volume ( Frank-Starling
curve) leftventricular end-diastolic volume left ventricular
end-diastolic pressure (pulmonary congestion) (systemic venous
congestion) renin SNS renin -1 receptor SNS renin angiotensin II3.
/ (ventricular dilation and/orhypertrophy) preload, afterload
cardiaccontractility / cardiac output neurohormones catecholamines,
angiotensin II, aldosterones sympathetic nervous system ventricular
remodeling hypertrophy angiotensin II ( ACEIs),
(-receptorantagonists), aldosterone ventricular remodeling
hypertrophy - ischemic heart disease oxygen demand - (ventricular
relaxation) diastolic heart failure- ventricular systolic function
10. 10 | page- cardiac arrhythmias Compensatory mechanisms (vicious
cycle) (Continued worsening and downward spiraling of the heart
failure state) (1) (2) 3 (CLINICAL PRESENTATION OF DECOMPENSATED
HEART FAILURE) (right-sided heart failure) cardiac output cardiac
output 11. 11 | page (increased right ventricular end-diastolic
pressure) (venous return) (systemic venous congestion) (liver) :
(peripheral edema) interstitial fluid cardiac output oxygen carbon
dioxide (engorged and elevated neck vein) (hepatomegaly hepatic
enlargement) (jugular vein) (hepatojugular reflux) (anorexia)
(abdominal fullness) (nausea) (left-sided heart failure) cardiac
output cardiac output (increased left atrial and ventricle
end-diastolicpressure) (pulmonary congestion) : (dyspnea)
(orthopnea) (paroxysmal nocturnal dyspnea) (pulmonary edema)
(fatigue) (right-sided heart failure) pulmonary vascular resistance
systemic venous congestion 12. 12 | page (Complications)a. Cardiac
arrhythmia and sudden cardiac deathb. Ischemic heart failurec.
Acute renal failure (Prerenal)d. Thromboembolism1. (medical
history) a. b. c. d. 2. (physical examination)a. b. (fluid
retention status) (peripheral edema) pitting edema ( 1 ) (gut
edema) ( hepatic enlargement, hepatojugular reflux positive) (
jugular venous distention engorged neck vein) (pulmonary edema)
(dyspnea) (tachypnea) 13. 13 | page (crepitation) rales crackles
chest radiography (chest-x-ray) (interstitial infiltrate)c. (tissue
perfusion status) cyanosis (mental confusion) urine output3.
(Echocardiography with Doppler flow study) (systolic diastolic
heart failure) systolic heart failure (myocardialwall motility
during diastole and systole) (ejection fraction)4. electrolytes
B-type natriuretic peptide echocardiography5.
(hemodynamicmonitoring) pulmonary artery catheter (atrial
ventricular pressure), (pulmonar capillary wedge pressure)
ventricular end-diastolic pressure ventricular preload,
systemicvascular resistance, central venous pressure cardiac index
6. ECG , myocardial biopsy 14. 14 | page(ACUTE EXACERBATION OF
CHRONIC HEART FAILURE DECOMPENSATED HEART FAILURE)1.
(respiratoryfailure) (cardiogenic shock) (suddencardiac death)2.
(optimization of cardaic contractility and fluid status)
(optimization of cardiac output and preload)1. (non-pharmacological
therapy)a. NSAIDs, corticosteroids, negative inotropic drugs
calcium channel blockers beta-blockers b. sympathetic nervous
systemc. oxygen oxygen d. sodium 2 e. 0.5 1.0 fluid output fluid
input = 0.5 1.0 fluid balance intravascular volume depletion ()
preload tissue hypoperfusion ( volume overload tissue
hypoperfusion) fluid output fluid inputf. ultrafiltrationg. shock
h. (respiratory failure) (mechanical ventilation) respiratory
failure O2 / 15. 15 | page CO2 severe pulmonary edema, 2.
(pharmacological therapy)a. b. (critical care unit) (hemodynamic
monitoring) pulmonary artery catheter c. pulmonary aretery catheter
2 cardiac index ( cardiac output/body surface area)
L/min/m2pulmonary capillary wedge pressure (PCWP) mm Hg left
ventricularend-diastolic pressure preloadd. cardaic index (CI)
tissue perfusion 2.2 L/min/m2 (tissue hypoperfusion) cardiac output
preload Frank Starling PCWP heart failure 8-12 mmHg preload cardiac
output intravascular volumedepletion PCWP 12-20 mmHg intravascular
volume overload pulmonary congestion cardiac output preload PCWP
PCWP 15 18 mmHg e. 1. CI > 2.2 L/min/m2 PCWP 12-20 mmHg cardiac
output ventricular filling pressure (preload) 2. CI > 2.2
L/min/m2 PCWP > 20 mmHg intravascularvolume overload preload
(diuretics vasodilators) sympathetic nervous system
renin-angiotensin-aldosterone system (1) cardiac index (2)
intravascular volume depletion 16. 16 | page3. CI < 2.2 L/min/m2
PCWP > 20 mmHg hypoperfusion intravascular volume overload
preload (diuretics vasodilators) cardiaccontractility vasodilators
afterload cardiac contractility inotropic agent afterload reducer
vasodilator vasodilators cardiac output vasodilators afterload 4.
CI < 2.2 L/min/m2 PCWP 12-20 mmHg hypoperfusion intravascular
volume overload cardiac contractility vasodilators afterload,
vasodilator vasodilators cardiac output vasodilators afterload
preload vasodilators afterload preload ACEIs, IV nitroprusside, IV
nitroglycerin vasodilators IV fluid preload (PCWP 18-20)
hypoperfusion preload cardiac output intravascular volume overload
.f. pulmonary artery catheter cardiac contractility tissue
perfusion narrow pulse presssure hypoperfusion cardiac output
preload volume status (pulmonary congestion) chest radiography
rales, S3, volume overload overload tachycardia intravascular
volumedepletion tachycardia CI PCWP hypoperfusion ( cardiac output)
intravascular volume overload (preload) preload (diuretics
vasodilators) cardiac contractility afterload (3) g. 17. 17 |
page1. preloada. DiureticsDiuretics sodium intravascular volume
preload fluid overload loop diuretics (1) Thiazides thiazide-like
diuretics hydrochlorothiazide, chlorothalidone,metolazone loop
diuretics (creatinine clearance < 30 ml/min) thiazides
loopdiuretics diuretic resistance loop diuretics thiazides loop
diuretics 30 (2) Loop diuretics furosemide, bumetanide, torasemide
thiazide diuretics creatinine clearance ~ 10 ml/min (Henles loop)
heart failure (gut edema) (urine output) 1 furosemide 240 mg/
diuretics hydration intravascular volume hypoperfusion prerenal
acute renal failure intravascular volume depletion baroreceptor
reflex sympathetic nervous system renin-angiotensin-aldosterone
system tachycardia myocardial infarction cardiac arrhythmia b.
vasodilatorsVasodilators acute heart failure ACEIs (PO IV), IV
nitroglycerin, IV sodiumnitroprusside, nitrates PO isosorbide
dinitrate, hydralazine PO or IV(1) ACEIs preload afterload IV
enalaprilat active metabolite enalapril acute renal failure ACEIs
18. 18 | page(2) Sodium nitroprusside preload afterload sodium
nitroprusside cyanide (cyanide toxicity) cyanide lactic acidosis
thiocyanate cyanide thiosulfate thiocyanate thiocyanate 24-48
thiocyanate IV nitroglycerin(3) IV nitroglycerin Nitrates preload
afterload IV nitroglycerin vasodilator of choice intravascular
volumeoverload (4) Hydralazine afterload preload reflex tachycardia
vasodilators :(1) IV decompensation (2) preload vasodilators
cardiac output cardiac output intravascular volume preload reflex
tachycardia cardiac output afterload 2 tissue hypoperfusion
diuretics preload reducer 2. cardiac contractility (positive
inotropic agents) positive inotropic agents (myocardial infarction)
myocardial oxygen demand ventriculartachycardia 19. 19 | pagea.
Digoxin Na-K ATPase calcium ion myocardial contractility loading
dose maintenance dose positive inotropic b. Catecholamines dopamine
dobutamine norepinephrine epinephrine systemic vascular resistance
afterload (1) Dopamine 5 mcg/kg/min dopamine-1 receptor renal
perfusion 5-10mcg/kg/min beta-1 receptor cardiac contractility
heart rate cardiacoutput 10 mcg/kg/min alpha-1 receptor blood
pressure afterload cardiac output renal ischemia dopamine renal
perfusion 10 mcg/kg/min cardiac contractility (2) Dobutamine beta-1
alpha-1 beta-2 cardiac contractility heart rate sympathetic nervous
system 1-10 mcg/kg/min tachycardia hypotensionc. Phosphodiesterase
inhibitors phosphodiesterase isozyme III cAMP cardiac contractility
cardiac output contractility afterload amrinone milrinone cardiac
contractility dopamine dobutamine ventricular tachycardia
beta-blockers dobutamine dopamine phosphodiesterase inhibitors d.
Nesiritide 20. 20 | page 1 55 2 PMH: Chronic heart failure x 5
Chronic stable angina x 5 Hypertension x 10 All: NKDAMeds: Aspirin
80 mg PO AMCarvedilol 6.25 PO BIDIsosorbide mononitrate 60 mg PO
AMEnalapril 10 mg PO BIDFurosemide 20 mg PO AMPE: BP 180/100 mmHg ,
P 100 , RR 22, T 38.6, wt 65 kg, ht 174 cmalert & oriented,
anxious, dyspneic man(+) neck vein engorgement(+) S1 S2, (+) S3 ,
no systolic murmur(+) crepitation bilaterally(+) hepatojuxgular
reflux, (-) bowel sound(+) pitting edema 4+CXR: interstitial
infiltration both lungLabs: Na 136 K 4.8 Cl 98 CO2 24 BUN 20 Scr
1.2 Ca 9.7 Mg 2.1 Alb 4.1WBC 11 HGB 15 HCT 44 PLT 347UA: (+) WBC ,
(+) bacteria, (-) protein, (-) glucose acute exacerbation of
chronic heart failure (CHRONIC SYSTOLIC HEART FAILURE)1. 2. 21. 21
| page chronic heart failure1. Non-pharmacologic therapya. coronary
artery bypass graft myocardial contractility b. afterload, c.
sodium 3 intravascular volume overloadd. decompensation 4 American
Heart Association/American College ofcardiology 2009 22. 22 |
page2. Pharmacologic therapya. Vasodilators preload / afterload
cardiac output(1) angiotensin-converting enzyme inhibitors (ACEIs)
captopril, enalapril, lisinopril preload afterload sympathetic
nervous system angiotensin II ventricular hypertrophy ACEIs AHA/ACC
stage A (JNC7 thiazides ) stage B, C D ACEIs ACEIs hypoperfusion
preload cardiac output tissue hypoperfusion hypotension serum
creatinine serum potassium ACEIs perfusion pressure glomerular
filtration acute renal failure intravascular volumedepletion
diuretics ( diuretics ACEIs diuretics volume depletion) GFR < 30
ml/min/1.73 m2, NSAIDs, atherosclerosis renal artery stenosis (2)
Angiotensin receptor blockers (ARBs) losartan, valsartan,
candesartan ACEIs angioneurotic edema ACEIs ARBs ACEIs ARBs chronic
heart failure stage C ACEIs, diuretics beta-blockers ARBs ARBs
ACEIs hyperkalemia worsening renal function
rennin-angiotensin-aldosterone system serum creatinineAHA/ACC ARBs
ACEIs aldosterone antagonist ( 3 ) hyperkalemia (3) Hydralazine
oral nitrate hydralazine oral nitrates ACEIs ACEIs hydralazine
nitrate combination hydralazine +oral nitrate ACEIs hydralazine
oral nitrate clinical trials hydralazine oral nitrates ARBs 23. 23
| pagehydralazine + oral nitrate clinical trial 2 regimens ARBs
ACEIs ARBs ACEIs hypertension, prevention of systolic dysfunction
post-MI,prevention of coronary heart disease in high risk patients
heart failure hydralazine nitrate stage C ACEIs, beta-blocker
diuretics (adherence) b. Diuretics preload diuretics diuretics
intravascular volume depletion tissuehypoperfusion, prerenal renal
failure, reflex tachycardia myocardial infarction ACEIs
beta-blocker stable thiazide loop diuretics (thiazides creatinine
clearance < 30 ml/min)c. Beta-blockers sympathetic nervous
system renin-angiotensin-aldosterone system ejection fraction
carvedilol, metoprololsuccinate SR bisoprolol AHA carvedilol 3.125
mg BID metoprolol 12.5 mg BID hypotension , beta-blockers
(decompensatedheart failure) myocardial contractility
decompensation blood pressure, heart rate, worsening heart
failured. Digoxin cardiac contractility sympathetic system preload
digoxin stage C ACEIs diuretics beta-blocker narrow therapeutic
index 24. 24 | pagee. Spironolactone Eplerenone aldosterone
antagonist aldosterone ventricular wall remodeling heart failure (
stage C NYHA functional class III-IV) EF 2.5 mg/dL >2.0 mg/dL )
hyperkalemia (serum potassium > 5.0mEq/L) potassium ventricular
tachycardia fibrillation f. Calcium channel blockers systolic heart
failure calcium channel antagonist heart failure sympathetic
nervous system stimulation ischemic heart disease calcium channel
antagonists systolic heart failure amlodipine systolic heart
failure ischemic heart disease diastolic heart failure
non-dihydropyridines verapamil diltiazem 2 heart rate ventricular
filling time preload ( diastolicheart failure beta-blocker calcium
channel antagonist cardiac contractility) 2 62 8/1/xyHPI: 2-3 2
PMH: Chronic heart failureOsteoarthritis x 5 Type 2 Diabetes x 5
Hypertension x 10 Meds: 8/1/xy Diltiazem 180 mg AM PO AJ8/1/xy
Glibenclamide 5 mg BID PO AJ8/1/xy Aspirin 80 mg AM PO AJ 25. 25 |
page8/1/xy Furosemide 20 mg AM PO AJ8/1/xy Glucosamine sulfate
sachet 1884 mg AM PO AJ8/1/xy Amoxicillin 500 mg TID PO AJ8/1/xy
Triprolidine/Pseudoedrine 2.5mg/60mgTID PO AJ10/12/xx Diltiazem 180
mg AM PO AJ10/12/xx Glibenclamide 5 mg BID PO AJ10/12/xx Aspirin 80
mg AM PO AJ10/12/xx HCTZ 25 mg AM PO AJ10/12/xx Glucosamine sulfate
sachet 1884 mg AM PO AJ13/11/xx Glibenclamide 2.5 mg BID PO
GG13/11/xx Aspirin 80 mg AM PO GG13/11/xx HCTZ 25 mg AM PO
GG13/11/xx Glucosamine sulfate sachet 1884 mg AM PO GG17/10/xx
Enalapril 10 mg BID PO TB17/10/xx Glibenclamide 2.5 mg BID PO
TB17/10/xx Aspirin 80 mg AM PO TB17/10/xx HCTZ 25 mg AM PO TBLABs:
Na 144 K 4.2 Cl 98 CO2 24 BUN 19 Scr 1.4 FBS 128 digoxinTherapeutic
uses digoxinDigoxin digitalis glycoside Digitalis digoxin 1.
Chronic heart failure digoxin Na-K ATPase (myocyte) calcium ion
sarcoplasmic reticulum myocytes calcium ion myocardialcontractility
(positive inotropic effects)2. Control of ventricular rate in
supraventricular tachycardia (e.g. atrial fibrillation) digoxin
acetylcholine vagus nerve atrioventricular node (AV node)
refractory period digoxin atrial fibrillation 26. 26 | page digoxin
digoxin digoxin (1) narrow therapeutic index (2) digoxin renal
impairment, drug interactions, (3) digoxin ventricular tachycardia
digoxin (Absorption)Digoxin passive non-saturable diffusion (dosage
forms) 1 (Tmax) 10 digoxin tablet bioavailability 70-80% (F=
0.7-0.8), digoxin elixir F = 0.75-0.85 F = 1 (Distribution) digoxin
2-compartment model 6 digoxin ATPase digoxin 70 digoxin digoxin
lean bodyweight total body weight 20-30 digoxin digoxin 27. 27 |
page (Volume of distribution; Vd) digoxin 6-7 1 (L/kg) hemodialysis
5-6 L/kg hemodialysis 4-5 L/kg extracellular fluid, hyperkalemia,
Na-K ATPase activity digoxin ( ), , 20 Na-K ATPase activity digoxin
digoxin (Metabolism) digoxin (metabolism) metabolites enterohepatic
recycling digoxin metabolites chronic heart failure digoxin (drug
clearance) heart failure (Excretion) digoxin glomerular filtration
active tubularsecretion digoxin creatinine clearance digoxin
digoxin 38 creatinine clearance digoxin 106 digoxin heart failure
digoxin digoxin 0.8 2.0 ng/mL (g/L) digoxin digoxin 0.8-1.2 ng/mL
atrial fibrillation ventricular response 28. 28 | page -blockers
non-dihydropyridines calcium channel blockers digoxin
atrialfibrillation digoxin therapeutic range digoxin premature
ventricular contractions, atrioventricular nodalblock, , , , , , ,
, , 6 (troughlevel) (steady-state) 7-14 digoxin digoxin 1. 2. 3.
digoxin 4. (therapeuticrange) digoxin 1. aluminium magnesium
digoxin 252. Cholestyramine digoxin 20-353. penicillins,
tetracyclines digoxin digoxin 4. Amiodarone digoxin 70-100 1-7
amiodarone digoxin digoxin 30-50 29. 29 | page digoxin digoxin 7
digoxin loading dose (maintenance dose)Jeliffe Method1. ideal lean
body weight (LBW)2. creatinine clearance Cockroft Gault3. loading
dose (LD) LD = 10 g/kg x LBW(kg) = total body store (TBS)F
bioavailability 0.7-0.8 total body store 10 g/kg LD 3 6 1/4 1/4 6
(1/2 + 1/4 + 1/4)4. (% daily loss) creatinine clearance % Daily
loss = 14 + CrCl (ml/min) 14 CrCl/5 (% daily loss digoxin clearance
)5. maintenance dose(MD)MD = TBS x % daily loss Jeliffe method 50
chronic heart failure 175 cm. 80 kg Scr 1.1mg/dL LD MD digoxin
Jeliffe method1. LBWLBW = 50 + (2.3 x 10) = 73 kg2. CrClF5 30. 30 |
pageCrCl = (140-50) x 73 = 83 ml/min72 x 1.13. LDLD = 10 g/kg x 73
= 913 g ~ 1 mg LD 0.5 mg 0.25 mg 6 0.25 mg 6 1 mg4. % daily loss%
daily loss = 14 + 83/5 = 30.6% ~ 31% TBS5. MDMD = 0.913 mg x 0.31 =
0.27 mg digoxin tablet 0.25 mg Volume-Clearance Method Jeliffe
method volume of distribution (Vd) (Vd digoxin uremictoxin )
volume-clearance method 1. LBW2. CrCl ml/min/70 kg 140 ( x 0.85 )3.
Vd CrCl ( ml/min/70 kg) Vd 70kg LBW Vd/70 kg = 226 + 298 x CrCl
CrCl ml/min/70 kg Vd Vd 70 kg4. LDLD = Cp x Vd Cp digoxin g/L
(ng/mL)Vd volume of distribution LBW (4) ( Vd/70 kg)F
bioavailabilityScr29 + CrClF0.8 31. 31 | page5. Clearance/70 kg
digoxin CrCl/70 kg non-renalclearance (Clnon-renal) Clnon-renal
chronic heart failure Clnon-renal = 41 ml/min/70 kg CHFClnon-renal
= 20 ml/min/70kg CHFClearance digoxin/70 kg (Cldigoxin/70 kg) =
(1.303 x CrCl) + Clnon-renal6. MD MD = Cp x Cldigoxin x LBW x MD
maintenance dose mgCp digoxin ng/mLCldigoxin clearance digoxin (5)
mL/min/kg ( 70 kg)LBW lean body weight kg (dosing interval) 1440 1
F bioavailability 106 ng mg volume-clearance method 50 chronic
heart failure 170 cm 73 kg Scr 3.7 mg/dL LD MD volume-clearance
method1. LBWLBW = 45.5 + (2.3 x 8) = 63.9 kg2. CrClCrCl = (140-50)
X 0.85 = 20.7 ml/min/70 kg3. Vd digoxin CrCl Vd/70 kg = 226 + 298 x
20.7 = 349.9 L/70 kg = 5.0 L/kg Vd = 5.0 x 63.9 = 319 L4. LD106x
F3.729 + 20.7 32. 32 | pageLD = 1.5 g/L X 319 L = 598 g = 0.598 mg
~ 0.625 mg () 0.25 mg 6 0.25 mg 6 0.125 mg5. clearance digoxin
(Cldigoxin) creatinine clearance chronic heart failureCldigoxin /70
kg = (1.303 x 20.7) + 20 = 47.0 ml/min/70 kg= 0.671 ml/min/kg6.
MDMD = 1.5 ng/mL x 0.671 ml/min/kg x 63.4 kg x 1440 min= 0.115 mg
0.125 mg 1 (steady-state) digoxin linear pharmacokinetics
steady-state Dose 1 = Dose 2 steady-state digoxin 0.125 mg
steady-state 0.8 ng/mL 1. 6 ng/mL 0.125 mg = Dose 2Dose 2 = 0.25 mg
0.25 mg 0.8106x 0.8Cp1 Cp20 .8 ng/mL 1.6 ng/mL 33. 33 | page 31.
systolic heart failure diastolic heart failure 1. Ejection
fraction2. cardiac output3. . 1 . 1 2 . 2 3 . 1, 2 32.
(compensatory mechanisms) cardiac output 1. renin 2.
catecholamines3. myocardial contractility. 1 . 1 2 . 2 3 . 1, 2 33.
tissue hypoperfusion 1. Pulmonary edema: chest X-ray 2. Mental
confusion: 3. Decreased urine output: . 1 . 1 2 . 2 3 . 1, 2 34.
(acute heart failure) pulmonary artery catheter PCWP = 8, HR = 110,
BP = 100/80 . IV Furosemide. IV nitroglycerin5. (acute heart
failure) pulmonary artery catheter PCWP = 28 , HR = 100, BP =
156/100 . IV Furosemide. IV nitroglycerin6. . digoxin .
Spironolactone . carvedilol . enalapril 34. 7. ACEIs 1. ACEIs
preload afterload 2. ACEIs tissue hypoperfusion acute renal failure
, hypotension potassium hypokalemia 3. ACEIs hydralazine oral
nitrates angiotensin II receptor antagonists. 1 . 1 2 . 2 3 . 1, 2
38. Beta-blockers 1. sympathetic nervous system heart rate
myocardialcontractility renin 2. asthma chronic obstructive
pulmonary disease bronchospasm 3. , heart rate, . 1. . 1 2 . 2 3 .
1, 2 39. Spironolactone 1. aldosterone antagonists 2. hyperkalemia
3. 100 mg 1 . 1 . 1 2 . 2 3 . 1, 2 310. Diuretics 1. preload sodium
(salt and water retention)2. intravascular volume depletion
reflextachycardia renal hypoperfusion3. loop diuretics creatinine
clearance 30ml/min. 1 . 1 2 . 2 3 . 1, 2 3 35. 11. 65 hypertension,
DM, chronic heart failure , CXR: pulmonary edema , BP 160/100, HR =
110, Pulmonary artery catheter CI = 2.5 L/min/m2, PCWP = 28 . IV
furosemide . IV dopamine . IV dobutamine . IV digoxin12.
hypertension, DM, chronic heart failure aspirin, furosemide,
isosorbide dinitrate enalapril (angioneurotic edema) 140/90 mm Hg,
HR 70 bpm . digoxin . valsartan . diltiazem . hydralazine13. 58
hypertension, dyslipidemia, s/p MI, chronic heart failure NYHA
class II furosemide 40 mg PO AM, simvastatin 20 mg POHS, enalapril
20 mg PO BID, aspirin 81 mg PO AM 140/86 mm Hg . . metoprolol.
hydralazine nitrate . spironolactone14. 64 hypertension, ischemic
heart disease, DM, chronic heart failure atenolol, furosemide,
aspirin, glibenclamide, digoxin, SLnitrate BUN 24 Scr 1.5 140/90,
HR 70 bpm, . . amlodipine. verapamil . lisinopril15. 68
hypertension, DM, chronic heart failure NYHA class III aspirin 325
mg PO AM, furosemide 40 mg PO AM, digoxin 0.125mg PO AM,
glimepiride 4 mg PO AM, lisinopril 40 mg PO AM, carvedilol 25 mg PO
BID BUN 34 Scr 1.9 140/90, HR 80 bpm . isosorbide dinitrate .
spironolactone. hydralazine . metolazone16. Case: 60 PMH: Chronic
heart failure x 2 Hypertension x 12 IHD, s/p MI x 2 36. Meds PTA:
Nifedipine sustained-release 60 mg PO ODAspirin 325 mg PO ODISDN 5
mg SL PRN for chest painIndomethacin 50 mg PO TID for back pain
(from drugstore near pts home)PE: P 110 , BP 145/100, RR 25, Temp
37.6Confused, Drowsy(+) S3(+) Dyspnea, (+) crackles in lung(+)
hepatojugular reflux(-) bowel sound3+ pitting edemaskin cold and
moist ()Labs: Na 135 K 4.0 Cl 102 CO2 24 BUN 18 Scr 1.2Other labs
are within normal limitTnI: negativeCXR (chest x-ray): suggests
pulmonary edema, mild cardiomegalyECG: tachycardia, normal
rhythmEcho: EF ~ 30% (1 )Impression: acute exacerbation of heart
failureMDs order:1. Admit2. Monitor vital sign q 1 h till stable
then q 4 h , notify MD if HR 110 OR SBP 1503. O2 by nasal cannula
to keep O2 sat >90%4. IV D-5-S/2 to keep vein open5. Draw lipid
profile in AM16.1 problem list SOAP 16.2 36 PE: (-) dyspnea, (-)
crackles, 1+ pitting edemaCXR: (-) for pulmonary edemaVS: BP 136/86
, HR 80, RR 20, Temp 37.6LABs: All are WNL except Cho 210 LDL 170
TG 130Current meds: IV nitroglycerin 20 mcg/min (on titrate-down
schedule)IV furosemide 20 mg IVP OD AMAspirin 150 mg OD AMa. SOAP
37. b. digoxin loading dose maintenance dose Jeliffe
volume-clearance16.3 3 16.4 Guideline & Review ArticlesACCF/AHA
Task Force on Practice Guidelines. 2009 focused update incorporated
into the ACC/AHA 2005guidelines for the diagnosis and management of
chronic heart failure in the adult. Circulation 2009;
119:e391-e479.Lindenfeld J, et al. on behalf of the Heart Failure
Society of America. Executive Summary: HFSA 2010Comprehensive Heart
Failure Practice Guideline. J Card Fail 2010; 16: 475-539.Dickstein
K, et al. ESC Guidelines for the diagnosis and treatment of acute
and chronic heart failure2008. Eur Heart J 2008; 29: 23882442.Mc
Murray J, et al. Practical recommendations for the use of ACE
inhibitors, beta-blockers, aldosteroneantagonists and angiotensin
receptor blockers in heart failure: Putting guidelines into
practice. TheEuropean. J Heart Fail 2005; 7: 710 721. 60 SOB,
fatique, orthopnea at nightPMH: CHF x 2 HTN x 12 IHD, s/p MI x 2
Current Meds: Enalapril 20 mg PO BIDAspirin 160 mg PO AMISDN 5 mg
SL PRN for chest painSpironolactone 12.5 mg PO AMFurosemide 20 mg
PO AMLabs: all are WNL