Compare and contrast the pharmacology of dobutamine and levosimendan

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College Answer

LEVOSIMENDAN

DOBUTAMINE

Class

Calcium sensitiser

Synthetic catecholamine

Pharmacokinetics

Slower onset of action
(requires loading dose)
t1/2 of parent compound 1 h Metabolised by conjugation and acetylation
Active metabolite with t1/2 
80-96 h (Effects persist once
infusion ceased for up to 7-
10 days)

Onset of action in 1 – 2 min
t1/2 < 3min
Metabolised by methylation and
conjugation 
Excreted in urine and bile
Inactive metabolites

Mechanism of
action

Increases myocyte sensitivity
to calcium by binding to troponin C
Opens ATP-dependant K+ channels in vascular smooth muscle

Selective beta-1 and beta-2
receptor agonist

Therapeutic 
effects

Increased cardiac
contractility 
Coronary, systemic and pulmonary vasodilation Reduced preload and afterload without impairing diastolic relaxation

Increased cardiac contractility
Mild peripheral vasodilation

LEVOSIMENDAN

DOBUTAMINE

Adverse effects

Hypotension 
Headache

Drug-induced myocardial
ischaemia 
Rate/ rhythm disturbances
Hypotension Hypertension in XS dose Tachyphylaxis

Contraindications

Hypersensitivity to
levosimendan 
LV outflow tract obstruction Severe renal or hepatic failure
Severe hypotension and tachycardia
History of torsade de pointes

Hypersensitivity to dobutamine
LV outflow tract obstruction

Discussion

With such a detailed and comprehensive college answer, one can do nothing more than to rewrite the table with less information, so as to render the information it contains more memorable.

Features

Dobutamine

Levosimendan

Class of drug

Synthetic catecholamine

Calcium sensitizer

Administration

IV infusion 5-15mcg/kg/min

IV infusion 0.05-0.2mcg/kg/min

Pharmacokinetics

Rapidly metabolised by COMT; 
Half-life ~ 5 minutes
No active metabolites

Excreted into the small intestine
Slowly eliminated metabolites (half life ~ 80 hours)

 

Mechanism of action

Activates beta-1 adrencoeptors and increases heart rate and contractility by increasing the intracellular levels of cAMP, thus increasing the availablility of intracellular calcium.

Enhances the affinity of contractile proteins (partiularly cardiac troponin C) for calcium, thereby increasing contractility without incurring additional ATP cost

Clinical effects

Increased inotoropy
Increased chronotropy
Peripheral vasodilation (beta-2 effect of one of the enantimers)

Increased inotropy
Increased chronotropy
Increased lusitropy
Pulmonary vasodilation
Peripheral vasodilation (by action on ATP-sensitive potassium channels in vascular smooth muscle)

Adverse effects

Arrhythmia
Hypotension
Increased cardiac metabolic demand, thus potentially exacerbating ischaemia                 

Arrhythmia
Hypotension


 

References

Antila, Saila, Stig Sundberg, and Lasse A. Lehtonen. "Clinical pharmacology of levosimendan." Clinical pharmacokinetics 46.7 (2007): 535-552.

Papp, Zoltán, et al. "Pharmacological mechanisms contributing to the clinical efficacy of levosimendan." Cardiovascular drug reviews 23.1 (2005): 71-98.