Dobutamine

Dobutamine

Clinical data
Drug class	Synthetic catecholamine
Uses	Low cardiac output, pharmacologic cardiac stress echocardiography
Contraindications	Corn hypersensitivity, idiopathic hypertrophic subaortic stenosis
Routes of administration	IV
Dosage
Pharmacodynamics
Mechanism of action	beta-1 agonism (primary), beta-2 agonism and alpha-1 agonism (secondary)
Adverse effects	Hypertension, hypotension, arrhythmia, hypokalemia, nausea, headache, chest pain
Pharmacokinetics
Onset of action	1-2 minutes
Metabolism	Liver metabolism by catechol-O-methyltransferase and glucuronidation to inactive metabolites
Clearance	90 mL/kg/min
Physical and chemical data
Formula	C18H23NO3
Molar mass	301.38
Article quality
Editor rating	Comprehensive
User likes	0

Dobutamine is a direct-acting sympathomimetic with preferential activation of beta-1 adrenergic receptors accounting for most of its ionotropic and chronotropic effects. It is also active at beta-2 and alpha-1 adrenergic receptors. Its primary indication is the treatment of low cardiac output secondary to CHF, cardiogenic shock, septic shock, or following cardiac surgery; Dobutamine is also the preferred agent for pharmacologic cardiac stress testing in patients who cannot tolerate an exercise stress test.

Uses

• Low cardiac output secondary to congestive heart failure, cardiogenic shock, septic shock, or following cardiac surgery

• Stress echocardiography, preferred alternative test for evaluation of myocardial ischemia if the patient is unable to exercise, though this use is off-label

Contraindications

Absolute contraindications

• Corn hypersensitivity, as premixed bags contain dextrose

• Idiopathic hypertrophic subaortic stenosis

Precautions

• Acute myocardial infarction and coronary artery disease, as dobutamine may worsen myocardial ischemia
• Atrial fibrillation, ventricular arrhythmias, as dobutamine increases AV conduction and can precipitate or worsen ectopic activity
• Hypertension
• Hypotension and hypovolemia
• Renal failure,  as continuous infusions may result in myoclonia
• Premature neonates, as dobutamine has been shown to be less effective than dopamine in this population
• Geriatric patients
• Pregnancy and breast feeding
• Sulfite hypersensitivity, as some preparations include sulfites

Pharmacology

Pharmacodynamics

Mechanism of action

Dobutamine is a direct-acting synthetic catecholamine. It is formulated as a racemic mixture of 2 enantiomers, the positive enantiomer is predominantly a beta-agonist (beta-1 greater than beta-2), while the negative enantiomer has partial alpha-1 agonist effects. Dobutamine binding to beta-1 adrenergic receptors enhances voltage-gated calcium channel expression on cardiac myocytes and increases myocardial contractility, leading to larger stroke volumes and increased cardiac output. This increased cardiac output activates baroreceptors, which decrease systemic vascular resistance, resulting in minimal change to arterial blood pressure. Dobutamine also has minor beta-2 and alpha-1 adrenergic stimulatory effects.

Adverse effects

• Hypertension
• Hypotension due to decreased systemic vascular resistance
• Tachycardia
• Rapid ventricular response or premature ventricular contractions
• Hypokalemia
• Nausea
• Headaches
• Chest pain
• Palpitations
• Shortness of breath

Pharmacokinetics

• Onset of action: 1-2 minutes, though peak effect can take up to 10 minutes
• Plasma half-life: 2 minutes
• Metabolized in the liver catechol-O-methyltransferase and by glucuronidation to inactive metabolites, excretion of metabolites via the kidneys

History

Dobutamine was developed by Drs. Tuttle and Mills in 1975, after they modified the structure of isoprenaline.