RX412: Gulsevin Chemistry of Positive Inotropes

What are the structural motifs that form digoxin?

3 sugar residues attached to a steroid group

What is the MOA of Digoxin?

Binds on the extracellular side of Na+/K+ ATPASE and blocks potassium binding site non-competitively

What is the result of Digoxin binding to its target?

Indirect increase in intracellular calcium levels

What is the caution with dosing Digoxin?

Therapeutic serum range is close to toxic range

Where is Digoxin excreted?

Kidney

What is the impact of renal impairment on Digoxin?

Increases the risk of toxicity

What is this structure?

Digoxin

What is the half life of Digoxin?

36-48 hours

What is the antidote for acute digoxin toxicity?

Ovine digoxin immune Fab (DigiFab)

Why can’t you give verapamil and some macrolipids with Digoxin?

They inhibit P-Glycoprotein

What is the main mechanism of clearing Digoxin out of the body

P-glycoprotein (ATP dependent)

What can reduce digoxin absorption?

E.lenta (Bacteria found in the gut)

What is the issue with digoxin absorption?

Disruption from the gut flora can increase digoxin absorption, so it is hard to predict amount of drug absorbed.

What drug is this?

Milrinone

What type of drug is milrinone?

Positive inotrope and vasodilator (Inodilator)

What does milrinone act on?

PDE3 in different cell types

Where is milrinone metabolized?

Kidney and some liver

What drug is this?

Dobutamine

What is the MOA of Dobutamine?

Selectively stimulate beta 1 adrenergic receptors to increase intracellular levels of cAMP

What is the result of Digoxin’s activity?

Increase calcium influx into cardiac myocytes → increased myocardial contractility

What is the half-life of dobutamine?

2 minutes

What is the route of administration of dobutamine?

IV or continuous infusion

What is Dobutamine’s main metabolite?

3-O-methyldobutamine. It is inactive for the most part

What type of solution is Dobutamine injected in?

Acidic to increase solubility

What drug is this?

Levosimendan

What does Levosimendan do?

Calcium sensitizer

What is the MOAs of this drug?

Sensitizes troponin C to calcium dependent of calcium concentration