Pimobendan review

Question 1

How is pimo classified?

Answer 1

non-sympathomimetic, nonglycoside inotropic drug

Question 2

What is pimo MOA?

Answer 2

dual MOA:
- Ca2+ sensitization
- PDE3 inhibition

Question 3

What is the prominant inotropic effect of pimo in heart failure?

Answer 3

Ca2+ sensitization -> increases the affinity of cardiac troponin C (TnC) regulatory site for Ca2+ -> binding of Ca2+ to TnC activates myofibrillar protein interaction -> miocardial contraction

Question 4

T/F: the strenght of cardiac contraction is directly correlated to the quantity of free cytosolic Ca2+

Answer 4

T. + the binding affinity of Ca2+ to TnC

Question 5

How does PDE3 inhibition affect cardiac myocytes?

Answer 5

increase cAMP-> activates protein kinase-> phosphorilation of substrates (of which phospholamban)= increase Ca2+ influx and release by sarcoplasmic reticulum during systole

Question 6

What is the role of pimo’s active metabolite (UD-CG 212 Cl)?

Answer 6

Competitive antagonist for A1 adenosine rec -> cAMP synthesis and positive inotropy.

Question 7

Why is pimo considered safer than digitalis and cathecolamines as inotropic agent?

Answer 7

other agents increase cytosolic Ca+ while pimo mainly increases Ca2+ sensitization, reducing risk of Ca2+ overload, increased myocardial O2 consumption and arrhythmias

Question 8

T/F pimo causes venodilation and concurrent arterioconstriction

Answer 8

F. both arterial and venodilation via inhibition of PDE in vascular smooth mm= increases cAMP and cGMP-> facilitates Ca2+ uptake by intracell storage sites, decreasing Ca2+ available for contraction.

Question 9

List all the effects of pimo.

Answer 9

• Ca2+ sensitization
• PDE3 inhibition
• arterial and veno-dilation
• inhibition of pro-inflamm cytokines/immunomodulation
• reduce cathecolamine synthesis and secretion
• antithrombotic (=inhibits platelets aggregation)
• insulinotropic

Question 10

What is the peak onset of action of pimo?

Answer 10

<1h

Question 11

How much of pimo and its metabolite is found bound to proteins?

Answer 11

> 90%

Question 12

What is the half life?

Answer 12

30min for pimo, 2h for its metabolite. But pharmacodynamic effects are >8h in people

Question 13

T/F: pimo is recommended starting from MMVD stage B1

Answer 13

F. B1= cardiac remodelling but asymptomatic. It is recommended starting from stage B2 (symptomatic)

Question 14

How is pimo pharmacokinetic different in cats compared to dogs?

Answer 14

C max more than 4x higher compared to dogs + elimination half-life 3x longer