Dobutamine
Encyclopedia
Dobutamine is a sympathomimetic drug
used in the treatment of heart failure and cardiogenic shock
. Its primary mechanism is direct stimulation of β1 receptors of the sympathetic nervous system
. Dobutamine was developed by a laboratory led by Drs. Ronald Tuttle and Jack Mills at Eli Lilly and Company
, as a structural analogue
of isoprenaline.
or in cases of septic
or cardiogenic shock, on the basis of its positive inotropic
action.
Dobutamine can be used in cases of congestive heart failure
to increase cardiac output. It is indicated when parenteral therapy
is necessary for inotropic support in the short-term treatment of patients with cardiac decompensation
due to depressed contractility
, which could be the result of either organic heart disease or cardiac surgical procedures. It is not useful in ischemic heart disease because it increases heart rate and thus increases myocardial oxygen demand.
The drug is also commonly used in the hospital setting as a pharmacologic stress testing agent to identify coronary artery disease.
, angina
, arrhythmia, and tachycardia
. Used with caution in atrial fibrillation as it has the effect of increasing the atriovenrticular (AV) conduction.
The most dangerous side effect of dobutamine is increased risk of arrhythmia, including fatal arrhythmias. Studies suggest that while this medication can improve symptoms in chronic CHF, it actually shortens a patient's lifespan.
s to induce the release of norepinephrine
(another α1 agonist), dobutamine is less prone to induce hypertension than is dopamine
.
Dobutamine is predominantly a β1-adrenergic agonist, with weak β2 activity, and α1 selective activity, although it is used clinically in cases of cardiogenic shock for its β1 inotropic effect in increasing heart contractility and cardiac output. Dobutamine is administered as a racemic mixture consisting of both (+) and (−) isomer
s; the (+) isomer is a potent β1 agonist and α1 antagonist, while the (−) isomer is an α1 agonist. The administration of the racemate results in the overall β1 agonism responsible for its activity. (+)-Dobutamine also has mild β2 agonist activity, which makes it useful as a vasodilator.
. The methoxyl-protecting groups of this intermediate are cleaved by hydrogen bromide
giving dobutamine.
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
used in the treatment of heart failure and cardiogenic shock
Cardiogenic shock
Cardiogenic shock is based upon an inadequate circulation of blood due to primary failure of the ventricles of the heart to function effectively....
. Its primary mechanism is direct stimulation of β1 receptors of the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
. Dobutamine was developed by a laboratory led by Drs. Ronald Tuttle and Jack Mills at Eli Lilly and Company
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
, as a structural analogue
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of isoprenaline.
Clinical uses
Dobutamine is used to treat acute but potentially reversible heart failure, such as which occurs during cardiac surgeryCardiac surgery
Cardiovascular surgery is surgery on the heart or great vessels performed by cardiac surgeons. Frequently, it is done to treat complications of ischemic heart disease , correct congenital heart disease, or treat valvular heart disease from various causes including endocarditis, rheumatic heart...
or in cases of septic
Septic shock
Septic shock is a medical emergency caused by decreased tissue perfusion and oxygen delivery as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome and death...
or cardiogenic shock, on the basis of its positive inotropic
Inotrope
An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions...
action.
Dobutamine can be used in cases of congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
to increase cardiac output. It is indicated when parenteral therapy
Total parenteral nutrition
Parenteral nutrition is feeding a person intravenously, bypassing the usual process of eating and digestion. The person receives nutritional formulae that contain nutrients such as glucose, amino acids, lipids and added vitamins and dietary minerals...
is necessary for inotropic support in the short-term treatment of patients with cardiac decompensation
Decompensation
In medicine, decompensation is the functional deterioration of a previously working structure or system. Decompensation may occur due to fatigue, stress, illness, or old age. When a system is "compensated," it is able to function despite stressors or defects. Decompensation describes an inability...
due to depressed contractility
Contractility
Myocardial contractility is the intrinsic ability of the heart to contract independent of preload and afterload. Changes in the ability to produce force during contraction result from different degrees of binding between myosin and actin filaments...
, which could be the result of either organic heart disease or cardiac surgical procedures. It is not useful in ischemic heart disease because it increases heart rate and thus increases myocardial oxygen demand.
The drug is also commonly used in the hospital setting as a pharmacologic stress testing agent to identify coronary artery disease.
Adverse effects
Primary side effects include those commonly seen for β1 active sympathomimetics, such as hypertensionHypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, angina
Angina
Angina pectoris, commonly known as angina, is chest pain due to ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries . Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries...
, arrhythmia, and tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
. Used with caution in atrial fibrillation as it has the effect of increasing the atriovenrticular (AV) conduction.
The most dangerous side effect of dobutamine is increased risk of arrhythmia, including fatal arrhythmias. Studies suggest that while this medication can improve symptoms in chronic CHF, it actually shortens a patient's lifespan.
Pharmacology
Dobutamine is a direct-acting agent whose primary activity results from stimulation of the β1-adrenoceptors of the heart, increasing contractility and cardiac output. Since it does not act on dopamine receptorDopamine receptor
Dopamine receptors are a class of metabotropic G protein-coupled receptors that are prominent in the vertebrate central nervous system . The neurotransmitter dopamine is the primary endogenous ligand for dopamine receptors....
s to induce the release of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(another α1 agonist), dobutamine is less prone to induce hypertension than is dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
.
Dobutamine is predominantly a β1-adrenergic agonist, with weak β2 activity, and α1 selective activity, although it is used clinically in cases of cardiogenic shock for its β1 inotropic effect in increasing heart contractility and cardiac output. Dobutamine is administered as a racemic mixture consisting of both (+) and (−) isomer
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
s; the (+) isomer is a potent β1 agonist and α1 antagonist, while the (−) isomer is an α1 agonist. The administration of the racemate results in the overall β1 agonism responsible for its activity. (+)-Dobutamine also has mild β2 agonist activity, which makes it useful as a vasodilator.
Chemistry
It is synthesized by the reaction of 2-(3,4-dimethoxyphenyl)ethanamine and 1-(4-methoxyphenyl)-3-butanone with a simultaneous reduction of formed imineImine
An imine is a functional group or chemical compound containing a carbon–nitrogen double bond, with the nitrogen attached to a hydrogen atom or an organic group. If this group is not a hydrogen atom, then the compound is known as a Schiff base...
. The methoxyl-protecting groups of this intermediate are cleaved by hydrogen bromide
Hydrogen bromide
Hydrogen bromide is the diatomic molecule HBr. HBr is a gas at standard conditions. Hydrobromic acid forms upon dissolving HBr in water. Conversely, HBr can be liberated from hydrobromic acid solutions with the addition of a dehydration agent, but not by distillation. Hydrogen bromide and...
giving dobutamine.
- R. R. Tuttle, J. Mills, (1973).
- J. Mills, R. R. Tuttle, (1976).