ADHF Agent MOA and PK points

Which ADHF drug is a prodrug?

Nitroglycerin

What activates nitroglycerin?

Aldehyde dehydrogenase (ALDH)

What does nitroglycerin affect?

• Nitric oxide — increases

• cGMP — increases

Nitroprusside chemical components

Complex of iron with cyanide (CN) groups and one isocyanide group attached

What does nitroprusside affect?

• Nitric oxide — increases

Nitroprusside mechanism of toxicity

• May gain an additional electron and be converted to cyanide

• Cyanide binds to tissue oxidases and leads to toxicity

Nitroprusside toxicity antidote

Thiosulfate

ADHF agent most associated with methemoglobinemia?

Nitroprusside

Which ADHF agent reduces afterload?

Nitroprusside

What does dobutamine affect?

• Beta-1 agonist

• Beta-2 agonist

What does milrinone affect?

• cAMP — increases

• Nitric oxide — increases

What does dopamine affect?

• <5 mcg/kg/min: dopamine receptor stimulation

  • Dopamine receptors located on vessels in kidneys, GI tract, brain, and coronary vessels

• 5-10 mcg/kg/min: beta-1 stimulation

  • Increases inotropy/contractility

  • Increased heart rate

  • Increased cardiac output

• >10 mcg/kg/min: alpha-1 stimulation 

  • Vasoconstriction