Pharm: Congestive Heart Failure

Front 1

What is Congestive Heart Failure?

Back 1

Inability of cardiac muscles to pump sufficient blood to meet the peripheral metabolic demand.
May be caused by impaired ability of cardiac muscle to contract or by an increased workload imposed on cardiac tissue
Results in increased blood volume and interstitial fluid.

Front 2

Depression of ventricular function causes:

Back 2

- coronary artery disease
- hypertension
- dilated cardiomyopathy
- valvular disease
- congenital heart disease

Front 3

What causes restriction of ventricular filling?

Back 3

- Mitral stenosis
- Restrictive cardiomyopathy
- Pericardial disease

Front 4

What are precipitating factors of CHF?

Back 4

- Increased Na+ intake
- Noncompliance with anti-CHF medications
- Acute MI
- Exacerbation of hypertension
- Infections
- Pulmonary embolism
- Infective endocarditis

Front 5

Symptoms of CHF:

Back 5

Decreased exercise tolerance
Shortness of breath
Tachycardia
Pulmonary and peripheral edema
Cardiomegaly (enlargement of the heart)
Fatigue

Front 6

Risk Factors of CHF:

Back 6

Age
Coronary artery disease
Hypertension
Smoking
Alcohol
Thyroid disease
Rheumatic heart disease
Cardiotoxic drugs

Front 7

CHF Compensatory Mechanisms: Increased sympathetic activity

Back 7

Increased sympathetic activity:
activation of β-adrenergic receptors in heart
↓
increase in heart rate and cardiac output
↓
vasoconstriction
↓
enhanced venous return and increased cardiac output

Front 8

CHF Compensatory Mechanisms:
Fluid retention

Back 8

Fluid retention:
Decreased cardiac output
↓
↓ blood flow to kidney (GFR)
↓
↑ Renin, aldosterone & Angiotensin II
↓
↑ Peripheral resistance, retention of Na and water
↓
↑ Blood volume

Front 9

Symptoms of CHF:

Back 9

pic

Front 10

Cycle of CHF:

Back 10

pic

Front 11

Compensatory Mechanisms:
Myocardial Hypertrophy & Cardiac Remodeling

Back 11

Ventricular hypertrophy (adaptive change)
Myocardial structural and functional alterations.
Change in cardiac size, shape and composition

Front 12

Neurohormonal Compensatory Mechanisms:

Back 12

Increase in Angiotensin II levels
Increase in Aldosterone levels
Increase in Norepinephrine levels
Increase in Endothelin levels
Increase in Vasopressin levels

Front 13

Four categories of CHF:

Back 13

pic

Front 14

Decreased Cardiac Output leads to:

Back 14

pic

Front 15

Cardiac failure leads to:

Back 15

pic

Front 16

Blood over fill:

Back 16

pic

Front 17

CHF Heart size:

Back 17

xray

Front 18

Frank-Starling Mechanism

Back 18

pic

Front 19

Therapeutic Goals of CHF:

Back 19

Elimination of precipitating cause of symptoms
Management of heart failure symptoms
Increase cardiac output and enhance tissue/organ perfusion
Modulation of neurohumoral response.

Front 20

CHF Treatment Schedule:

Back 20

Diuretic
β-blocker
Angiotensin Converting Enzyme Inhibitor
Digoxin

Front 21

Diuretics:

Back 21

Thiazides:
Hydrochlorothiazide (Esidrex)
Metolazone (Diulo)
Loop:
Furosemide (Lasix)
Bumetanide (Bumex)
Torsemide (Demadrex)

Front 22

What do Diuretics do?

Back 22

Relieve pulmonary congestion and peripheral edema
Reduction in plasma volume and venous return to heart
Reduction in cardiac workload and oxygen demand
Reduction in afterload and blood pressure
Reduction in fluid retention
Reduction in pulmonary congestion
Decreased edema through reduced preload
Dosage adjustment based on symptomatic improvement and daily body weight

Front 23

Diuretic differential:

Back 23

Agents acting in Loop of Henle are most effective (Furosemide, Bumetanide)
Thiazide diuretics (Hydrochlorothiazide) are less effective, more so in decreased renal perfusion.
Thiazides are better suited in hypertensive patients with mild congestion

Front 24

When are Diuretics indicated?

Back 24

Indicated in both systolic and diastolic heart failure (fluid overload)
Maintenance of euvolemia in symptomatic and Stages C & D of heart failure

Front 25

When is a combination used?

Back 25

A patient in CHF that is resistant to Furosemide.
Combination diuretic therapy may be required in patients not responding after therapy with a loop diuretic
↓
Furosemide + metolazone
or
Furosemide + hydrochlorothiazide
Continuous IV therapy produces greatest diuresis within 2-4h

Front 26

Diuretics Dosage:

Back 26

Initiation of diuretic therapy on low dose.
Dosage adjustment based on symptomatic improvement and daily body weight.
Target weight loss of 2 lb/day (mild to moderate volume overload).
Cautious tapering and withdrawal.

Front 27

Where to the Diuretics work?

Back 27

pic

Front 28

beta-Blockers studies showed:

Back 28

Studies with:
Carvedilol (COREG) and
Metoprolol (LOPRESSOR)
showed a reduction in mortality in patients with stable heart failure. Low dose will reduce effects of epi on heart.

Front 29

What do beta-Blockers do for CHF patients?

Back 29

- Augmented cardiac output
- Reduction in hemodynamic deterioration
- Improved survival.
- Reduction in mortality rates in patients with severe heart failure
- Early use prevents ventricular remodeling and inhibition of inflammatory immune factors

Front 30

What do beta-Blockers do for CHF patients? cont...

Back 30

- Counteraction of adverse hemodynamic changes
- Reduction in heart rate
- Blunting of sympathetic activation
- Anti-ischemic action.
- Used in combination with ACE inhibitors and/or diuretics

Front 31

Dosage schedule:

Back 31

Carvedilol (Coreg)
Metoprolol (Lopressor)

Commence with low dose with gradual increments every 1-2 weeks
Indicated in Class II/III CHF patients

Front 32

CHF - Drug Chart

Back 32

Pic

Front 33

Beta-blockers are indicated when?

Back 33

In all CHF patients that are stable. If not, do not administer beta-Blockers (even stop it abruptly.)

Front 34

Advantages of beta-Blockers:

Back 34

Prevent adverse effects of ... pic

Front 35

ACE Inhibitors MOA:
(The cornerstone of treatment for all heart failures.)

Back 35

↓ Angiotensin II
↓ Bradykinin inactivation
↓Aldosterone secretion
↓ Vascular resistance
↓ Venous tone
↓ blood pressure
⇓
Cardiac Output

Front 36

What does and ACE inhibitor accomplish?

Back 36

Reduce vascular resistance and thereby reduce afterload
Reduce salt and water retention—reduce preload
Reduce SNS activity-decrease NE release
Reduce cardiac remodeling
Increased bradykinin levels → vasodilation
Release of vasodilatory prostaglandins and histamine.
Arterial and venous dilatation
Reduction of preload and afterload
Decrease in myocardial load.

Front 37

ACE inhibitor diagram:

Back 37

pic

Front 38

Indications for ACE Inhibitors:

Back 38

- Indicated as cornerstone of therapy
- Indicated in all patients with LV systolic heart failure
- Indicated in diabetic patients
- Indicated in post-myocardial infarction
- Slows progression of renal disease
- Reduction in mortality rates

Front 39

ACE Inhibitor dosage:

Back 39

- Commence therapy with low doses followed by upward titration
- Initiate therapy with captopril (shorter half-life)
- Switch to longer-acting agent for maintenance (enalapril)
- Evaluate renal function and serum potassium.

Front 40

ACE Inhibitor Contraindications:

Back 40

Contraindicated in angioedema, bilateral renal artery stenosis and pregnancy.

Relative contraindication in unilateral renal artery stenosis, cough, renal insufficiency, hypotension, hyperkalemia (monitor closely!!)

Front 41

ACE Inhibitors:

Back 41

Captopril (Capoten)
Enalapril (Vasotec)
Lisinopril (Zestril)
Quinapril (Accupril)
Ramipril (Altace)
Fosinopril (Monopril)
Trandolapril (Mavik)

Front 42

Angiotensin Receptor Blockers:

Back 42

Candersartan
Losartan
Valsartan

Front 43

What do Angiotensin Receptor Blockers do?

Back 43

- Inhibit binding of angiotensin II
- Reduction in plasma volume
- Vasodilation and reduction in peripheral resistance
- Antiproliferative effects

Front 44

What do Angiotensin Receptor Blockers do? cont...

Back 44

- Reduced incidence of dry cough.
- Used in combination with diuretic and ACE inhibitor.
- Effective replacement for ACE inhibitors in patients who are intolerant or have contraindications

Front 45

Advantages of ACE Inhibitors:

Back 45

pic

Front 46

Aldosterone Antagonists

Back 46

Spironolactone (Aldactone)
Eplerenone (Inspra)

Front 47

Aldosterone Antagonists accomplish:

Back 47

- Prevention of aldosterone binding.
- Neurohormonal inhibition
- Inhibition of Na and fluid retention
- Inhibition of ventricular remodeling
- Reduction in mortality

Front 48

When should a aldosterone antagonist be combined?

Back 48

- Combined with loop diuretic, beta-blocker, digoxin, ACE inhibitor.
- Indicated in advanced heart failure (Class III/IV) patients

Front 49

When should you not use Spironolactone?

Back 49

- If you want to avoid the adverse endocrine effects of spironolactone.
- Eplerenone does not possess adverse endocrine effects of spironolactone.
- Eplerenone is a strong CYP3A4 substrate!!.

Front 50

Advantages of Spironolactone:

Back 50

pic

Front 51

Vasodilators:

Back 51

- Impaired contractile function of heart is exacerbated by compensatory increase in pre-load and afteload.
- Vasodilators reduce excessive preload and afterload

Front 52

What is the best vasodilator for CHF?

Back 52

Although several classes of drugs exhibit vasodilator activity and may improve symptoms in heart failure only hydralazine-isosorbide dinitrate combinations have been shown to improve survival in clinical trials

Front 53

Venous and Arteriolar vasodilators:

Back 53

- Venous vasodilator (nitrates) increase venous capacitance, decrease venous return to the heart and reduce preload

- Arteriolar vasodilator (hydralazine) reduces systemic vascular resistance and therefore afterload-useful in increasing forward cardiac output

Front 54

Vasodilator combination Therapy:

Back 54

Combination therapy is an appropriate substitute for angiotensin II antagonists or ACE inhibitors and add-on therapy for African –American patients
Under no circumstances should you add a vadodilator to an ACE Inhibitor. It is to replace it only.

Front 55

Digoxin MOA:

Back 55

Highly effective in increasing heart contractility by:
- Positive inotropic effect
- Inhibits Na/K ATPase (this inhibition is reversible-membrane bound transporter protein also known as sodium pump)
- Increased intracellular sodium
- Increased cardiac contractility
- Reduced sympathetic activation
- Reduced renin-angiotensin-aldosterone activation

Front 56

Digoxin:

Back 56

Does not decrease mortality. Provides symptomatic relief.

Front 57

Digoxin MOA diagram:

Back 57

Pic

Front 58

CO vs Ventricular end-diastolic pressure:

Back 58

pic

Front 59

Indications of Digoxin:

Back 59

- Indicated in persistently symptomatic patients
- Indicated in atrial fibrillation (slowing of ventricular rate)
- Reduces ventricular size.
- Used in combination with ACE inhibitors, diuretics, β-blocker

Front 60

Digoxin Contraindications:

Back 60

- Narrow theroputic window.
- Half life is quite long. In renal comp patients you can accumulate - Digoxin.
- Elimination half-life for digoxin 36-48 hours
↓
Permits once a day dosing
- Renal elimination through the kidney (most part unchanged)
- Half-life increased to > 4 days in renal failure

Front 61

Digitalization & Maintenance Dose of Digoxin:

Back 61

- Digitalis Glycosides used to restore adequate circulation in patients with CHF or to slow ventricular rate in patients with atrial fibrillation.
↓
- Long term therapy is frequently necessary to maintain therapeutic myocardial concentrations
- Low margin of safety increases critical nature of dosage and administration

Front 62

Target Window for Digoxin:

Back 62

*Test Question!*

- Loading dose administered over 24h followed by maintenance dose based on age, weight, renal function and serum digoxin levels.

- Target plasma levels: 0.5-1 ng/mL.
- Quinidine, verapamil, amiodarone– increases plasma levels of digoxin (by displacing tissue binding sites and depressing renal digoxin clearance)
- Cholestyramine– decreases the absorption of digoxin

Front 63

Toxicology of Digoxin:

Back 63

Lethal dose likely to be only 5-10 times minimal effective dose.

Intoxication is frequently precipitated by depletion of serum K caused by diuretic therapy
↓
May also occur from accumulation of maintenance glycoside doses taken over a long period of time

Front 64

Digoxin Toxicity: cont...

Back 64

Decreased renal function predisposes patients to digitalis toxicity.

Signs of systemic toxicity appears with plasma concentrations > 2ng/mL:
anorexia
nausea, vomiting
headache, delirium
ventricular tachycardia

Front 65

Treatment of Digoxin Toxicity:

Back 65

- Discontinue digoxin
- Maintain serum K concentrations between 4-5 mmol/l
- Treat ventricular arrhythmias with lidocaine
- Treat AV block with atropine
- Antidigoxin antibodies for overdose

Front 66

B-Natriuretic Peptide:

Back 66

- Nesiritide (Natrecor)
- Human recombinant B-type natriuretic peptide.
- Intravenous vasodilator drug for hospitalized patients (decompensated heart failure).
- Rapid vasodilation.
- Increases cardiac output.
- Promotes diuresis
- Antagonizes effects of renin-angiotensin-aldosterone system and endothelin.
- Antagonizes antidiuretic hormone.

Front 67

Staging and Drugs:

Back 67

Pic

Front 68

Diagram

Back 68

pic

Front 69

Goals and Pharmacotheropy Rationale

Back 69

pic

Front 70

ABCDs of Managing Heart Failure:

Back 70

pic

Front 71

A patient in STage III of heart failure, on Furosemide, Captopril and low dose carvedilol now shows significant renal Compromise. The best approach would be?

Back 71

Replace the captopril with hydralazine-isosorbide dinatrate.