Myocardial Inotropic Agents I and II Flashcards
By what mechanism do all FDA approved inotropes act?
by increasing intracellular calcium and cAMP
How does beta receptor modulation affect calcium levels in myocytes?
agonist activity at beta receptor can increase cAMP which increases calcium via PKA-mediated phosphorylation of phospholamban
How does PDE modulation affect calcium levels in myocytes?
PDE-3 inhibitors block degradation of cAMP to AMP allowing for greater PKA-mediated phosphorylation of phospholamban to increase calcium stores
What does addition of an inotrope do the starling curve (stroke volume vs. EDV/preload)?
moves curve up and to the left (improves contractility)
What does addition of a vasodilator do the starling curve (stroke volume vs. EDV/preload)?
moves curve up and to the left (improves contractility by reducing afterload)
What does addition of a vasodilator and inotrope do the starling curve (stroke volume vs. EDV/preload)?
moves curve up and to the left b/c of synergistic contractility improving effects of both drugs
What does addition of a diuretic do the starling curve (stroke volume vs. EDV/preload)?
shift along curve to left b/c reducing volume
What is the most commonly prescribed heart failure medicine and how does it work?
digoxin –> binds to Na/K atpase –> increases intracellular Na –> increased action by Na/Ca exchanger –> increased intracellular calcium causing increased inotropy without increasing HR
*upward and left shift of starling curve)
What do normal levels of extracellular potassium do to efficacy of digoxin?
reduces –> competitively decreases digoxin binding and may be protective in digoxin toxicity
What does hypokalemia do to efficacy of digoxin?
unlike at higher levels/normal potassium which is protective, hypokalemia may increase both effect and toxicity of digoxin
What is the concern with desensitization/tolerance of digoxin?
none –> it’s pretty unique in that you don’t get desensitized
How do low doses of digoxin affect mortality risk?
does not at LOW doses
How is digoxin administered and how is it cleared?
oral administration, renal elimination
What is the therapeutic level of digoxin?
.5-1 (some textbooks say up to 2 but that is dangerous) –> keep levels low!
Hemodynamic effects of digoxin
increased cardiac output, increased LV ejection fraction, increased exercise tolerance, increased natriuresis
decreased LVEDP/preload, decreased neurohormonal activation (reduce norepi, RAAS activity, increased vagal tone/normalization of baroreceptors)
Adverse effects of digoxin
- increased vagal tone reducing AV node automatcity leading to bradycardia and heart block
- at toxic doses, increase sympathetic tone and directly increase automaticity and delayed after polarizations leading to ventricular tachycardia and fibrillation
What was the main lesson from the dig trial?
you have to control digoxin dose for body surface area or you end up with lots of toxic side effects
Clinical uses of digoxin
a-fib with rapid ventricular response, CHF symptoms despite medical therapy
Why must we exercise caution when using digoxin with a beta blocker?
risk of bradycardia and heart block
Does the factor predispose or protect against digoxin toxicity? hypokalemia
predispose
Does the factor predispose or protect against digoxin toxicity? hypokalemia
predispose
Does the factor predispose or protect against digoxin toxicity? hyperkalemia
predispose
Does the factor predispose or protect against digoxin toxicity? hypomagnesia
predispose
Does the factor predispose or protect against digoxin toxicity? hyperkalemia
protect
