[PCOL2-MID-01-PT3] DRUGS FOR HEART FAILURE

THIS SET OF FLASH CARDS IS ABOUT CARDIOVASCULAR DRUGS.

Cardiac Glycosides

These drugs has the ability to increase the force of myocardial contraction (positive inotropic action).

• Results in increased cardiac output, decreased heart size, venous pressure, and blood volume.

• Digoxin

• Digitoxin

What are the two (2) drugs under cardiac glycosides?

Hint: Digitalis

• Digitalis lanata

• White foxglove

Digoxin is derived from the plant?

• Digitalis purpurea

• Purple foxglove

Digitoxin is derived from the plant?

No longer used (obsolete) because of its long pharmacokinetic profile; matagal ma-eliminiate aka toxic.

Cardiac Myocytes

Cardiac Glycosides: MOA

Digoxin inhibits Na⁺K⁺-ATPase Pump in the?

• Cardiac

• Extracardiac

• Interactions with K, Ca, and Mg

What are the three (3) Effects of Digoxin?

Hint: CEI

• Mechanical Effects

• Electrophysiological Effects

What are the two (2) Cardiac Effects of Digoxin?

Hint: ME Effects

Mechanical Effects of Digoxin

Identify the Cardiac Effect of Digoxin:

Increase contraction of cardiac sarcomere by increasing the free intracellular calcium concentration.

• Increase intracellular sodium (Na⁺K⁺ ATPase inhibition)

• Reduction of calcium expulsion from the cell (Na⁺Ca⁺ exchanger)

1. Cytoplasmic calcium

2. SERCA

Mechanical Cardiac Effect of Digoxin:

Increased (1)_____ calcium is sequestered by (2)_____ in the SR for later release (whenever a trigger calcium enters in the cardiac cell).

• Papasok pabalic sa SERCA

• Mag-bind sa troponin

• Lumabas sa cell

What are the three (3) fates of Calcium?

Info

The electrophysiological effects of digoxin is dose-dependent.

Atrium

Kapag tama ang dose ng Digoxin, it targets the?

• Stimulates vagus centrally

• Decreases sympathetic tone

Anong nangyayari kapag targeted yung atrium?

Info

“Anong nangyayari kapag therapeutic ang dose?”

• Increased parasympathetic activity (bradycardia; slow HR)

• “Malakas (+ inotropy) yung tibok ng puso pero mabagal (- chronotropy)”

Narrow Therapeutic Index (NTI)

Digoxin is a drug that has a narrow?

Therapeutic Drug Monitoring (TDM)

When the drug has a narrow therapeutic index, it needs?

1. Ventricles

2. Tachycardia (+ chronotropy)

At higher doses, digoxin targets the (1)____ causing (2)_____.

“Malakas at mabilis”

That is why digoxin sometimes causes ventricular tachycardia.

Lidocaine (IV)

When a person develops ventricular tachycardia associated with digoxin toxicity, the treatment is?

Info

Autonomic Actions of Digoxin:

Higher Doses

• Stimulates vagus centrally

• Enhanced automaticity

0.5-1.5 ng/mL

What is the therapeutic plasma concentration of digoxin?

>2 ng/mL

What is the toxic plasma concentration of digoxin?

0.25 (0.125-0.5) mg

What is the daily dose (slow loading or maintenance) of digoxin?

0.5-0.75 mg every 8 hours for three doses

What is the rapid digitalizing dose (rarely used) of digoxin?

GIT Effects (Anorexia, N&V, Diarrhea)

What is the common extracardiac effects of digoxin?

Info

Most common and deadly effect:

1. Cardiac: Ventricular Tachycardia

2. Extracardiac: GIT Effect

• Visual disturbances (yellow-green discoloration)

• Gynecomastia (among men)

What are the other two (2) extracardiac effects of digoxin?

Info

Potassium and Digoxin competes for the same binding site on the pump (Na⁺K⁺ATPase).

Hyperkalemia

Digoxin’s interactions with Potassium (K⁺):

Reduces enzyme-inhibiting actions of cardiac glycosides and inhibit abnormal cardiac automaticity.

Decreased activity of Digoxin.

Hypokalemia

Digoxin’s interactions with Potassium (K⁺):

Facilitates enzyme-inhibiting actions of cardiac glycosides.

Delikado; increases the activity of digoxin; can cause ventricular tachycardia.

• Thiazides

• Loop Diuretics

Recall: What are the diuretics that causes hypokalemia?

Info

Mas lalala ang effect ng digoxin kapag nag-take ka pa ng thiazides or loop diuretics.

Spironolactone

What drug is safe to take because it doesn’t have strong hypokalemia effect?

Hypercalcemia

Digoxin’s interactions with Calcium (Ca²⁺):

Facilitates toxic actions of cardiac glycosides by accelerating the overloading of intracellular Ca²⁺-digitalis induces abnormal automaticity.

Mataas yung Ca²⁺ sa extracellular space.

Magnesium

This is referred to as a natural calcium-channel blocker; effects appear to be opposite those of calcium.

Hypomagnesemia

Digoxin’s interactions with Magnesium (Mg²⁺):

Increases the risk of a digitalis-induces arrythmia.

Decreased Mg²⁺ = Increased Ca²⁺ and vice versa.

Info

Delikado ang hypokalemia, hypercalcemia, at hypomagnesemia kasi pwede nilang pataasin ang risk ng ventricular tachycardia.

• Verapamil

• Erythromycin

• Tetracycline

• Amiodarone

• Quinidine

These (4) drugs increases the digitalis concentration that may occur during concurrent therapy.

Hint: VETA-Q

“Paano nila napapataas ang digoxin sa dugo?”

• Pinapababa nila ang digoxin clearance.

Cimetidine

This drug is an enzyme inhibitor; yung enzyme na nag-me-metabolize kay digoxin pwedeng i-stop ng drug na ito.

Effect: Increased digoxin concentration; potential cardiotoxicity — ventricular tachycardia.

• Corticosteroids

• Thiazide diuretics

• Loop diuretics

These (3) drugs can decrease the level of blood potassium causing hypokalemia; could also lead to cardiotoxicity, ventricular tachycardia (greatest risk of digitalis toxicity).

Hint: CTL

• Withdrawal of Drugs

• Correction of Electrolyte Imbalances

• Magnesium Replacement

What are the three (3) Treatments of Digitalis Toxicity?

Withdrawal of Drugs

Treatment of Digitalis Toxicity:

Discontinued the use of cardiac glycosides and K⁺ depleting diuretics.

Correction of Electrolyte Imbalances

Treatment of Digitalis Toxicity:

Oral or by slow IV infusion of KCl.

• If hypokalemia is present

• Do not give K⁺, if there is severe A-V block or if serum K⁺ levels are high

Magnesium Replacement

Treatment of Digitalis Toxicity:

Because hypomagnesemia may accompany hypokalemia.

Antiarrhythmics

At higher doses, this is administered.

Phenytoin

This antiarrhythmic is for ventricular and atrial arrythmias.

• Lidocaine

• Procainamide

These antiarrhythmics is for ventricular tachyarrhythmias.

Propranolol

This antiarrhythmic is for ventricular and supraventricular tachycardia but not in the presence of A-V block.

Atropine

This antiarrhythmic is for sinus bradycardia and various degrees of A-V block.

Digoxin-binding Antibodies (DIGIBIND)

This antibody is administered when the condition is life-threatening digoxin or digoxin overdosage; patients exhibiting shock or cardiac arrest, ventricular arrhythmias, progressive bradyarrhythmia, or severe hyperkalemia.

• DigiFab

• Digibind

What are the two (2) brands of DIGIBIND?