Exam #02 Cardiac Glycosides and Positive Inotropes to Treat HF Flashcards
Digoxin
Cardiac Glycoside
SOA:
contractile cells in atrial and ventricular myocardium
MOA:
directly increases intracellular [Ca+2] by blocking Na+/K+ ATPase pump on cardiac plasma membrane
Major Therapeutic Use:
treat HF by increasing CO
Basic MOA of Cardiac Glycosides and Direct Effects on Cardiovascular System
- cardia glycosides block the Na+/K+ ATPase
- Na is not being pumped out of the cell and accumulates inside the cell
- potential energy from Na+ concentration gradient is lost and less energy is available to drive out Ca+2 at the Na+/Ca+2 exchanger
- decreased exchange leads to increased cytosolic [Ca+2]
- increased [Ca+2]: increases contractility, increases stroke volume, and increases CO
Indirect Effects of Cardiac Glycosides on Cardiovascular System
Cardiac glycosides increase parasympathetic output from the ANS, stimulating vagus nerve which increases release of ACh at SA node which decreases HR and decreases SA node activity (automaticity)
Describe the effect of K+ on Cardiac Glycosides binding to the Na+/K+ pump
Hyperkalemia: low affinity
Hypokalemia: high affinity
During hyperkalemia, pump spends greater time in dephosphorylated state b/c greater amount of K+ being transported through pump promoting dephosphorylation and cardiac glycosides bind with low affinity
During hypokalemia, not a lot of K+ around so the pump remains phosphorylated and cardiac glycosides bind with high affinity
Inamrinone
PDE-3 Inhibitor
MOA:
Prevents hydrolysis of cAMP producing an increase level of intracellular cAMP. The increased [cAMP] activates PKA which phosphorylates voltage-sensitive Ca+2 channels leading to influx of and elevated intracellular levels of Ca+2
Major Therapeutic Use:
Given IV along with beta-1 agonist for acute episodes of HF
AE:
liver and bone marrow toxicity
N, V
can produce arrythmias on their own
Milrinone
PDE-3 Inhibitor
MOA:
Prevents hydrolysis of cAMP producing an increase level of intracellular cAMP. The increased [cAMP] activates PKA which phosphorylates voltage-sensitive Ca+2 channels leading to influx of and elevated intracellular levels of Ca+2
Major Therapeutic Use:
Given IV along with beta-1 agonist for acute episodes of HF
AE:
liver and bone marrow toxicity
N, V
can produce arrythmias on their own
Hydralazine
Direct acting vasodilator
SOA:
arterioles
MOA:
increases cGMP by activating guanylyl cyclase to produce vasodilation and decrease peripheral resistance
Major Therapeutic Use:
used to treat HF by reducing BP (anti-hypertensive)
AE:
lupus-like syndrome
Minoxidil
Direct acting vasodilator
Brand Name:
Rogaine
SOA:
arterioles
MOA:
activates K+ channels to cause plasma membrane hyperpolarization and reduce Ca+2 influx
Major Therapeutic Use:
used more for hypertension, but can be used to treat HF by reducing BP
AE:
inhibits insulin release
facial hair
Diazoxide
Direct acting vasodilator
SOA:
arterioles
MOA:
activates K+ channels to cause plasma membrane hyperpolarization and reduce Ca+2 influx
Major Therapeutic Use:
used to treat HF by reducing BP (anti-hypertensive)
AE:
inhibits insulin release
Nitroprusside
Direct acting vasodilator
SOA:
arterioles and veins
MOA:
prodrug that releases NO. NO then activates guanylyl cyclase and increases cGMP
Major Therapeutic Use:
used to treat HF by reducing BP (anti-hypertensive)
usually given IV in hospital where patients can be monitored
AE:
inhibits insulin release
Fenoldopam
Direct acting vasodilator
SOA:
arterioles
MOA:
activation of peripheral dopamine D1 receptors
Major Therapeutic Use:
used more for hypertension, but can be used to treat HF by reducing BP
Isosorbide Dinitrate + Hydralazine
Direct acting vasodilators
Brand Name:
BiDil
Indications:
specifically for African Americans with CHF
Isosorbide Dinitrate is a vasodilator while hydralazine is an anti-hypertensive
