9. Positive Inotropic Agents Flashcards
When might acute HF occur?
after MI
Acute HF or chronic HF: peripheral edema
chronic
Acute HF or chronic HF: weight gain
chronic
Acute HF or chronic HF: cardiomegaly
chronic
Acute HF or chronic HF: most severe symptoms
acute
What are the positive inotropic agents?
- Digoxin
- Dopamine
- Dobutamine
- Phosphodiesterase inhibitors
What is the MOA of digoxin?
inhibits Na/K ATPase which increases the availability of intracellular Ca
What are the therapeutic effects of digoxin?
positive inotropic effect due to increased availability of cytostolic Ca during systole
Therapeutic doses of digoxin do not increase HR. (T/F)
True
Without HF, _________ signals dominate.
parasympathetic
With HF, ________ signals dominate.
sympathetic
Therapeutic doses of digoxin __ (↑/↓) SNS activity.
decrease ↓
Therapeutic doses of digoxin __ (↑/↓) PNS activity.
increase ↑
Digoxin decreases SNS activity by regulating what?
baroreceptor sensitivity
How does digoxin increase PNS activity?
- direct stimulation of vagal nuclei in brain
- decreasing conduction velocity of the heart and prolongs refractory period of pacemaker cells
Excessive doses of digoxin produce toxicity by altering _________ ____.
peripheral NS
What are the toxic effects of excessive digoxin on the peripheral nervous system?
- ↑ SNS activity
- ↑ PNS activity: bradycardia and heart block
How do excessive doses of digoxin affect the heart?
Arrhythmias: high intracellular Ca in pacemaker cells leads to ventricular tachycardia or fibrillation
What is the antidote to digoxin?
digoxin immune therapy: Digibind
Dopamine is the endogenous precursor to what?
norepinephrine
Low doses of dopamine stimulate primarily ___ and ___ receptors.
D1 and D2
What is the physiologic response to low doses of dopamine?
dilation of renal vessels: ↑ GFR = diuresis
Positive inotropic effects of dopamine occur at doses of ________.
higher doses: 3-10 mcg/kg/min
The positive inotropic effects of dopamine are mediated by what?
β1 receptors in the heart
What occurs at doses of dopamine > 10 mcg/kg/min?
- increased TPR
- excessive increase in HR
What adrenergic receptors does dobutamine stimulate?
β1, β2, α
In the heart, the primary effect of dobutamine is due to stimulation of what receptor?
β1
At lower doses of dobutamine, there is a minimal increase in HR. (T/F)
True
In the vasculature, α agonism due to dobutamine is significant and causes ADRs. (T/F)
False: a weak α agonist effect is negated by vasodilation from β2 activation
Dobutamine does not activate dopaminergic receptors at any dose. (T/F)
True
What is the MOA of phosphodiesterase inhibitors?
inhibits phosphodiesterase type III: intracellular enzyme that breaks down cAMP
Increased cAMP levels increase intracellular Ca. (T/F)
True
What is the effect of increased cAMP on smooth muscle cells?
vasodilation
Phosphodiesterase inhibitors are much more potent inotropes than adrenergic agents. (T/F)
False: weaker inotrope
What are the inotropic phosphodiesterase inhibitor agents?
Milrinone
What is the route of administration of milrinone?
IV
What is the primary ADR of phosphodiesterase inhibitors?
arrhythmias
What is the agent currently under investigation to be used as positive inotrope in HF?
Levosimendan
What is the MOA of levosimendan?
sensitizes troponin-C in myofilaments to intracelular Ca
How does levosimendan alter intracellular Ca levels?
it does not
Acute or chronic HF?
Presents as anatomical abnormalities that develop gradually or following survival of cardiac event
Chronic HF
Acute or chronic HF?
Adaptive mechanisms to improve cardiac performance
Chronic HF
