Core pharmacology

Class Group

NON-ADRENERGIC

Legacy Cicm Level

Level 1

Introduction

selective phosphodiesterase inhibitor

Indications Uses

used in severe refractory heart failure and
for short periods post cardiac surgery

Presentation

is a yellow solution, stored at room temperature, should not be given with HCO3 or frusemide

pKA of 9.67 and pH of 6.35

Main Action

PDEIII Inhibition: Improves myocardial contractility, vasodilation

Mechanism of action

Via selective PDE3 inhibition which causes
decreased cAMP breakdown intracellularly
and hence increased Ca

This improves myocardial contractility and improves cAMP-dependent protein phosphorylation leading to vascular smooth muscle relaxation.

Physiological effects

CVS
- Positive inotrope, leading to increased cardiac output. CI increases 30%
- PCWP decreases 20%, with improved lusotropy
- SVR and MAP decrease
- May increase AV nodal conductance, accelerating arrhythmias in atrial fibrillation or flutter

Resp: Decreased PVR

GU: UO and GFR may increase in response to increased CO

Adverse Effects Toxicity

may be proarrhythmogenic causing SVT and
VT. Have been shown to worsen outcomes
in acute on chronic heart failure

Absorption

IV only

Distribution

small vd

Volume of distribution

0.4 L/kg

Metabolism

minimally hepatic

Excretion

excretion is in the urine, mostly as
unchanged drug, dose adjustment
in renal failure

Half-life

2 hours

Route And Dose

IV
50mcg/kg loading dose over 10min (optional)
0.375mcg/kg/min-0.75mcg/kg/min