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What is the MOA of digitalis?

inhibition of 3Na/2K pump

What changes are seen on an ECG of a patient taking digitalis?

↑ PR interval, ↓ QRS duration, ↓ QT, and ↓ ST segment, flattened inverted T wave

What does inhibition of the 3Na/2K pump result in physiologically?

↑ free intracellular Ca²⁺, ↑ # of troponin C molecules to bind Ca²⁺, ↑ intensity of actin-myosin interaction

How does digitalis effect action potential at therapeutic concentrations?

↓ action potential duration

How does digitalis effect action potential at toxic concentrations?

↑ slope of phase 4, less negative maximal diastolic membrane potential

The negative chronotropic action of digitalis results from?

stimulation of vagal nucleus and direct depressive action upon SA and AV nodes

How large is the therapeutic index of digitalis?

very narrow
toxic effects at 2-3x normal dose

What can be given to treat ventricular tachycardia caused by digitalis?

lidocaine or phenytoin

What therapy is extremely effective in the case of life-threatening digoxin overdose?

Digoxin immune Fab

What are the most common arrhythmias caused by digitalis?

ventricular extrasystoles, 2nd or 3rd AV block

What are the common electrolyte disturbances that can alter digitalis effects?

hyper or hypokalemia

What are the major contraindications of digitalis?

hypertrophic cardiomyopathy
diastolic dysfunction
chronic cor pulmonale (hypoxia increases sensitivity of digoxin), COPD

What are the therapeutic uses of digitalis?

acute and chronic systolic heart failure, atrial fib, atrial flutter, nodal tachycardia

What receptors does dopamine activate at different dose levels?

low: D1
med: D1, β1, β2
high:D1, D2, β1, β2, α1

What is the therapeutic use of dopamine?

Acute decompensated heart failure
cardiogenic, neurogenic, septic shock
(especially for poor renal perfusion)
the clinical picture)

What are the main mechanisms by which β1 agonist increase cardiac contractility?

↑ phosphorylation of troponin C, and ↑ opening of voltage gated Ca²⁺ channels

What are the therapeutic uses of dobutamine?

acute decompensated heart failure, or cardiogenic shock when the left ventricular function is severely depressed

What drugs are phosphodiesterase inhibitors?

milrinone, inamrinone, enoximone

How do phosphodiesterase inhibitors work?

Inhibition of phosphodiesterase isozyme 3 → ↑ cAMP
→ ↑ free intracellular Ca²⁺ in myocardium
→ ↓ phosphorylation of myosin light chain in smooth muscle

What are the therapeutic uses of phosphodiesterase inhibitors?

acute decompensated heart failure, or cardiogenic shock when pts don't respond to other therapies OR are on beta blockers

What are the mechanisms by which ACE inhibitors improve chronic heart failure?

reducing preload and afterload

What drug is a recombinant brain natriuretic peptide?


What is the MOA of nesirtide?

activation of guanylyl cyclase and ↑ synthesis of cGMP

What disorder increases the risk of digitalis toxicity?


What is the treatment for digoxin overdose?

digoxin antibodies

What do broad spectrum antibiotics do to the bioavailability of digoxin?

↑ bioavailabilty
(less GI bugs to metabolize digoxin)

What are the adverse effects of combining digoxin with loop or thiazide diuretics?

hypokalemia and hypomagnesemia

What effect does spironolactone have on the serum concentration of digoxin?

increases the serum concentration by 30% (can lead to toxicity)

In what stage of chronic failure do you start using digoxin?

Stage C
(selected patients)

In what stage of chronic failure do you start using ionotropes?

Stage D

What classes of drugs are used in all stages of heart failure?

ACE inhibitors and Angiotensin receptor antagonists

In what stage of chronic failure do you start using β blockers?

Stage B

What vasodilatory drug have the greatest impact on both preload and afterload?

nitrates (nitroprusside)

Not all β blockers are useful in the tx of heart failure, which ones are?

metoprolol, bisoprolol, carvedilol

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