PCOL LEC - Drugs against Congestive Heart Failure

Heart Failure

the progressive inability of the heart to supply adequate blood flow to vital organs

Heart Failure

A phenomenon wherein the heart cannot meet the metabolic requirements of the peripheral systems

Mechanical Abnormalities; Coronary Artery Disease; Arrhythmias; Diabetes; Toxic Injury

Causes of Heart Failure (5)

Pericardial Tamponade

Mechanical Abnormalities, such as ______________ can cause Heart Failure

Ischemia

CADs, such as myocardial failure (aka ____________) can also cause heart failure

Cardiomyopathy, Inflammation

Ischemia may cause these two phenomena

Dyspnea; Edema; Fatigue

Cardinal Symptoms of Heart Failure (3)

Ejection fraction

It is the ratio of the amount of blood pumped out of the ventricle (Stroke Volume) and the total amount of blood in the ventricle (End-Diastolic Volume)

Stroke volume

It represents the amount of blood ejected by the heart with each beat.

55-70%

[Ejection Fraction Measurement] Normal

40-55%

[Ejection Fraction Measurement] Below Normal

Less than 40%

[Ejection Fraction Measurement] May confirm diagnosis of heart failure

[Ejection Fraction Measurement] Patient may be at risk of life-threatening irregular heartbeats

Diastolic heart failure

Type of heart failure that occurs when the heart contracts normally, but the ventricles do not relax properly or are stiff and less blood enters the heart during normal filling

Systolic Heart Failure

A type of heart failure wherein the left ventricle heart muscle doesn't contract with enough force

Systolic Failure

[Types of Heart Failure] Reduced mechanical pumping (contractility)

Systolic Failure

[Types of Heart Failure] Reduced ejection fraction (

Diastolic Failure

[Types of Heart Failure] Clinical Manifestations include: Hypertrophy; Stiffening; Loss of adequate relaxation necessary in reducing filling and CO; Normal ejection fraction; Significantly reduced stroke volume

High-output Cardiac Failure

A rare form of cardiac failure; Causes of such hyperthyroidism, beri-beri; anemia; arteriovenous shunts

RAAS (Angiotensin II); Endothelin release; Sympathetic stimulation (NE, EPI); Natriuretic peptides (Brain Natriuretic Peptide)

Compensatory Mechanisms During Heart Failure (4)

Hypertrophy

Enlargement of myocardial cells due to death of some cardiac muscles caused by ischemia (MI) and release of caspases

Remodeling

Dilation and other structural changes that occur in the stressed myocardium

Dilated Cardiac Myopathy

Cardiac remodeling example

Preload

Pressure required to achieve a particular EDV

Preload

Represented by sarcomere stretching prior to contraction

Myocardium

In the concept of Preload, increased blood volume and venous tone increases fiber length or filling pressure, and increases oxygen demand in the _____________

diuretics and venodilators

Preload can be reduced by _______ and ________

Afterload

It is the resistance against which the heart must pump blood

Endothelin

a potent vasoconstrictor peptide

Baroreceptor Reflex activation, RAAS activation, and endothelin release

In the concept of Afterload, decreased CO in chronic failure results to reflex increase in Systemic Vascular Resistance (SVR) mediated by _________ (3)

Arteriolar tone

Afterload can be reduced by drugs that reduces _____________

Contractility

Reduction in the velocity of muscle shortening, rate of intraventricular pressure development, and stroke output is the result of decreased ________________

Inotropic drugs

This type of drugs increase contractility

Heart rate

It is the major determinant of cardiac output

Beta adrenoceptors

Increase in HR through sympathetic activation of __________ adrenoceptors is the first compensatory mechanism that comes into play to maintain CO

Reducing symptoms; Slowing progression as much as possible during relatively stable periods; Prevent hospitalization through managing acute episodes of decompensated (functional deterioration) failure; Patient education; Prevent mortality

Goals in the Treatment of Heart Failure (5) (wag niyo na sagutan basta basahin niyu nalang dami eh wahhahaha)

Vasopressor

Treatment for decreased renal perfusion (1)

Beta-blockers, ACE inhibitors, ARBs (ATII blockers)

Treatment for neurohumoral activation (3)

Diuretics and vasodilators

Treatment for water and salt Retention, and vasoconstriction (2)

Diuretics

Treatment for lung congestion (1)

Inotropes

Treatment for decreased cardiac output (1)

Class I

[NYHA Classification] Includes patients with cardiac disease BUT WITHOUT limitations of physical activity. Ordinary activity DOES NOT CAUSE undue fatigue, dyspnea, or palpitations.

Class II

[NYHA Classification] Includes patients with cardiac disease that results in SLIGHT LIMITATIONS of physical activity. Ordinary activity RESULTS in fatigue, palpitations, dyspnea, or angina.

Class III

[NYHA Classification] Includes patients with cardiac disease that results in MARKED LIMITATIONS of physical activity. Although patients are comfortable at rest, LESS THAN ORDINARY ACTIVITY WILL LEAD TO SYMPTOMS.

Class IV

[NYHA Classification] Includes patients with cardiac disease that results in AN INABILITY TO CARRY ON PHYSICAL ACTIVITY WITHOUT DISCOMFORT. Symptoms of heart failure are present EVEN AT REST.

Amrinone

Inamrinone is formerly called as ________

Cardiac glycosides, Bipyridines, Beta-receptor stimulants

[Drugs for CHF] Positive inotropes (3)

Diuretics; ACE Inhibitors, ARBs and related agents; Vasodilators; Beta blockers

[Drugs for CHF] Drugs that does not have inotropic effects

Digoxin

[Drugs for CHF] Cardiac glycoside example (1)

Inamrinone, Milrinone

[Drugs for CHF] Bipyridines examples (2)

Dobutamine

[Drugs for CHF] Beta-receptor stimulants example (1)

Istaroxime, Levosimendan

[Drugs for CHF] Other positive inotropic drugs (2)

Istaroxime

Investigational steroid derivative; inhibit Na+ /K+ /ATPase and facilitates sequestration of Ca2+ by the SR

Levosimendan

sensitizes the troponin system to calcium and inhibit phosphodiesterase

Digitalis lanata

Digoxin is extracted from white foxglove or __________

Digitalis purpurea

Digitoxin is extracted from purple foxglove or ____________

Cardiac Glycosides

This class of drugs has the ability to increase the force of myocardial contraction (positive inotropic action); Results in increased CO, decreased heart size, venous pressure and blood volume

Inhibits (or slows) Na+/K+ ATPase, which results to increase in intracellular Na. Due to increased intracellular Na, Na+/Ca2+ Exchanger is also slowed down, which results to reduced intracellular Ca2+ removal, therefore increasing TN-C Ca2+ binding and increasing inotropy

MOA of Digoxin

Stimulates vagus centrally; Decreases Sympathetic Tone

Negative chronotropic effect of digoxin (2)

Increases

[Digoxin Negative Chronotropic Effects] Digoxin stimulates vagus centrally, and thus (increases/decreases) refractoriness of AV node

Decreases

[Digoxin Negative Chronotropic Effects] Digoxin stimulates vagus centrally, and thus (increases/decreases) ventricular response to atrial rate

Atrial fibrillation

[Digoxin Negative Chronotropic Effects] Digoxin stimulates vagus centrally, and thus controls heart rate in ______________

Decreases, decreases

[Digoxin Negative Chronotropic Effects] Digoxin slows depolarization rate of SA node, and thus (increases/decreases) sinus rate and (increases/decreases) heart rate in Sinus Tachycardia

Baroreceptor stimulation

[Digoxin Negative Chronotropic Effects] Digoxin decreases sympathetic tone, and thus resulting to _______________

Both (parasympathetic and sympathetic) systems

[Autonomic Actions of Digoxin] It involves (parasympathetic/sympathetic/both) systems

Parasympathomimetic

[Autonomic Actions of Digoxin] At lower dose range, cardioselective (parasympathomimetic/parasympatholytic) effects predominate

Cholinergic

[Autonomic Actions of Digoxin] (Adrenergic/Cholinergic) innervation is much richer in the atria (affects atrial and AV nodal function more than Purkinje or ventricular function)

Increased

[Autonomic Actions of Digoxin] At toxic levels, sympathetic outflow is (increased/decreased)

Digoxin

It is the first-line drug in patients with congestive heart failure who are in atrial fibrillation

Decrease

Digoxin increase the refractoriness of AV node thus (increase/decrease) ventricular response to atrial rate.

NARROW (NAMALI AKO NUNG UNA NILAGAY KO WIDE GAIS NAEDIT Q NA HUHU SORRY)

[Adverse effects of Cardiac Glycosides] Therapeutic dose ratios are (wide/narrow)

Hypokalemia

[Adverse effects of Cardiac Glycosides] May promote cardiac K+ loss and __________ which precipitate life-threatening arrhythmias when used with diuretics

Hypokalemia

[Adverse effects of Cardiac Glycosides] This adverse effect facilitates enzyme-inhibiting actions of cardiac glycosides

emesis, anorexia, nausea, diarrhea

[Adverse effects of Cardiac Glycosides] Cardiac glycosides cause Abdominal discomfort such as _______________ (4)

Green-yellow halos

[Adverse effects of Cardiac Glycosides] Cardiac glycosides cause visual disturbance, which causes __________ halos around bright objects

0.5-1.5 ng/mL

Digoxin Therapeutic plasma concentration

Hyperkalemia

This condition reduces enzyme-inhibiting actions of cardiac glycosides and inhibit abnormal cardiac automaticity

Hypercalcemia

This condition facilitates toxic actions of cardiac glycosides by accelerating the overloading of intracellular Ca2+

Digitalis induced abnormal automaticity

Digoxin treatment while having hypercalcemia can cause ___________

Hypomagnesemia

This condition increases the risk of a digitalis-induced arrhythmia

Magnesium

During digoxin treatment, the effects of this mineral appear to be opposite those of calcium

Withdrawal of drugs, Correction of electrolyte imbalances, Administration of antiarrhythmias, Administration of Digoxin-specific antibody fragment (DIGIBIND)

Treatment of digitalis toxicity (4)

Potassium chloride (KCl)

[Treatment of Digitalis Toxicity] If hypokalemia is present during digoxin treatment, digitalis toxicity can be treated with oral or by slow IV infusion of ______

If there is severe A-V block or if serum K+ levels are high

[Treatment of Digitalis Toxicity] In what situation or instance should KCl administration not be considered or stopped in treating digitalis toxicity

Magnesium replacement

[Treatment of Digitalis Toxicity] This procedure can also be done to treat digitalis toxicity since hypomagnesemia may accompany hypokalemia

Phenytoin

[Treatment of Digitalis Toxicity] Anti-arrhythmia for ventricular and atrial arrhythmias

Lidocaine and procainamide

[Treatment of Digitalis Toxicity] Anti-arrhythmia for Ventricular tachyarrhythmias

Propranolol

[Treatment of Digitalis Toxicity] Anti-arrhythmia for Ventricular and supraventricular tachycardia but not in the presence of A-V block

Atropine

[Treatment of Digitalis Toxicity] Anti-arrhythmia for Sinus bradycardia and various degrees of A-V block

Administration of Digoxin-specific antibody fragment - DIGIBIND

[Treatment of Digitalis Toxicity] Treatment for life-threatening digoxin or digitoxin overdosage

Administration of Digoxin-specific antibody fragment - DIGIBIND

[Treatment of Digitalis Toxicity] Treatment for patients exhibiting shock or cardiac arrest, ventricular arrhythmias, progressive bradyarrhythmias, or severe hyperkalemia

Phosphodiesterase III Inhibitors (PDE3 Inhibitors)

Bipyridines are also known as __________

Increase contractility, promote vasodilation

Bipyridines increase __________ and promote ____________

Intravenously

Bipyridines are only administered ______________

acute heart failure; chronic heart failure

Bipyridines are used only for ___________ or severe exacerbation of ______________

Arrhythmias; Hypotension; Abdominal pain; Fever; Dizziness; Nausea and vomiting; Hepatotoxicity; Thrombocytopenia

Adverse Effects of PDE3 inhibitors (8)

Dobutamine

Selective beta-1 agonist (parenteral); Increase CO with a decrease in ventricular filling pressure

Dobutamine

A drug with chronotropic, arrhythmogenic, and vasodilative effects; Widely used in heart failure

Diuretics; ACE inhibitors; Angiotensin receptor antagonists (ARB's); Aldosterone antagonists; Beta blockers

Drugs without positive inotropic effects used in CHF (5)

Reduce venous pressure and ventricular preload

Major mechanism of action of Diuretics in CHF