G7i / 20B15: Compare and contrast the pharmacology of dobutamine and levosimendan

20B15: Exam Report

Compare and contrast the pharmacology of dobutamine and levosimendan.

41% of candidates passed this question.

The objective of this question was that candidates relay a detailed knowledge of both drugs with respect to their individual pharmacology highlighting the important clinical aspects of each drug (e.g., mechanism of action, metabolism, duration of effect). Then an integration of this knowledge was in the contrast section where the better candidates highlighted features of the drug that would influence when or why one may use it with respect to the second agent. Tabular answers of the pharmacology of each drug without any integration or comparison scored less well. A detailed knowledge of both agents was expected to score well.

G7i / 20B15: Compare and contrast the pharmacology of dobutamine and levosimendan

Chemical

Dobutamine

Synthetic catecholamine, predominate b1 activity

Levosimendan

A Calcium sensitizer inotropic agent

Comments

Dobutamine is adrenergic whereas Levo is not

Use

Dobutamine

Inotrope in low CO states

Levosimendan

Inodilator

Comments

Levo can be used when there are high PAPs to dually increase Force of contraction and reduce the RV afterload

Presentation

Dobutamine

250mg/20ml

Clear, colourless solution

Racemixture of 2 isomers

Dextro (+) = potent b1 agonist & a1 antagonist

Levo (-) = potent a1 agonist

(alpha effects neutralised)

Levosimendan

Clear, yellow solution 2.5mg/ml in 5 and 10ml ampoules

Comments

Dose

Dobutamine

Infusion

1-20mcg/kg/min

Levosimendan

Infusion

Load: 6-12mcg/kg over 10min

Infusion 0.1-0.2mcg/kg/min

Comments

Levo requires a load first – requires caution in pts w low BP, esp in cases of hypovolaemia

Route

Dobutamine

Levosimendan

Comments

Onset

Dobutamine

Immediate

Levosimendan

1hr

Comments

Very different time profiles; D has rapid onset & offset, whereas it takes days for Levo requires an hour for peak effect and days to offset

DoA

Dobutamine

T1/2 2mins

Levosimendan

Peak plasma concentration in 48-7hrs

Comments

Very different time profiles; D has rapid onset & offset, whereas it takes days for Levo requires an hour for peak effect and days to offset

MoA

Dobutamine

Selective B1 agonist

B1 – Gs – increase cAMP – increase Ca2+

Small effect at b2 – may VD vessels

Levosimendan

INOTROPY

Increases affinity of TnC for Ca
Directly stabilises TnC-Ca conformation
Magnifies the effect when Ca binds TnC

VASODILATION

Large Conductance vessels and Resistance vessels via manipulation of K channels

Comments

PD

Dobutamine

CVS

Increase FoC

Increase HR

Increase Myocardial O2 consumption

Increase BP

Levosimendan

CVS

Increased myocardial contractility without increasing Myocardial O2 consumption

Increase CO

Coronary & Peripheral dilatation

Comments

Levo has a more favourable profile for myocardial BF & consumption

PK

Dobutamine

D – 0.2L/kg

M – rapidly by COMT

E – metabolites conjugated & renally excreted

Levosimendan

D – high PPB 97% Vd 0.2L/kg

M – liver by conjugation to cysteine conjugates and intestinal reduction to active metabolites OR-1855 & OR-1896

E- renal & fecal excretion

T1/2b 3hrs

Comments

Levo has well documented active metabolites with very long half lives (70-80hrs)

A/E

Dobutamine

Arrythmias

Increased ventricular response due to increased AV conduction

C/I w outflow obstruction

Tachyphylaxis

Levosimendan

Hypotension

Headache, dizziness

N+V

Arrythmias

Expense

Comments

Levo requires approval secondary to its huge cost

Both prone to arrythmias but a more profound hypotension w Levo, need to ensure pt well filled