Dobutamine
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Dobutamine is a medication used in the treatment of cardiogenic shock (as a result of inadequate tissue perfusion) and severe
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an
injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutri ...
or
intraosseous Intraosseous infusion (IO) is the process of injecting medications, fluids, or blood products directly into the marrow of a bone; this provides a non-collapsible entry point into the systemic venous system. The intraosseous infusion technique i ...
as a continuous infusion. The amount of medication needs to be adjusted to the desired effect. Onset of effects is generally seen within 2 minutes. It has a half-life of two minutes. This drug is generally only administered short term, although it may be used for longer periods to relieve symptoms of
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
in patients awaiting heart transplantation. Common side effects include a
fast heart rate Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
, an irregular heart beat, and inflammation at the site of injection. Use is not recommended in those with idiopathic hypertrophic subaortic stenosis. It primarily works by direct stimulation of β1 receptors, which increases the strength of the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
's contractions, leading to a positive ionotrophic effect. Generally it has little effect on a person's
heart rate Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions (beats) of the heart per minute (bpm). The heart rate can vary according to the body's physical needs, including the need to absorb oxygen and excr ...
. Dobutamine was approved for medical use in the United States in 1978. It is available as a
generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
. It was initially made from
isoproterenol Isoprenaline, or isoproterenol (brand name: Isoprenaline Macure), is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropyla ...
.


Medical uses

Dobutamine is used to treat acute but potentially reversible
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, such as which occurs during
cardiac surgery Cardiac surgery, or cardiovascular surgery, is surgery on the heart or great vessels performed by cardiac surgeons. It is often used to treat complications of ischemic heart disease (for example, with coronary artery bypass grafting); to corr ...
or in cases of septic or cardiogenic shock, on the basis of its positive
inotropic An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction. The term ''inotro ...
action. Dobutamine can be used in cases of
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
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 In medicine, decompensation is the functional deterioration of a structure or system that had been previously working with the help of compensation. Decompensation may occur due to fatigue, stress, illness, or old age. When a system is "compensate ...
due to depressed
contractility Contractility refers to the ability for self-contraction, especially of the muscles or similar active biological tissue *Contractile ring in cytokinesis *Contractile vacuole *Muscle contraction **Myocardial contractility *See contractile cell for ...
, which could be the result of either organic heart disease or cardiac surgical procedures. Higher doses are not useful with history of recent 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
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
,
angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typical ...
,
arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
, and
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
. Used with caution in atrial fibrillation as it has the effect of increasing the atrioventricular (AV) conduction. The most dangerous side effect of dobutamine is increased risk of arrhythmia, including fatal arrhythmias. Overall, dobutamine tends to produce less tachycardia and peripheral vascular effects than agents such as epinephrine and isoproterenol.


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 receptor Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system (CNS). Dopamine receptors activate different effectors through not only G-protein coupling, but also signaling through diffe ...
s to inhibit the release of
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
(another α1 agonist), dobutamine is less prone to induce hypertension than is
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
. 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 An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction. The term ''inotro ...
effect in increasing heart contractility and cardiac output. Dobutamine is administered as a
racemic mixture In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
consisting of both (+) and (−)
isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...
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.


History

It was developed in the 1970s by Drs. Ronald Tuttle and Jack Mills at
Eli Lilly and Company Eli Lilly and Company is an American pharmaceutical company headquartered in Indianapolis, Indiana, with offices in 18 countries. Its products are sold in approximately 125 countries. The company was founded in 1876 by, and named after, Colonel ...
, as a
structural analogue A structural analog (analogue in modern traditional English; Commonwealth English), also known as a chemical analog or simply an analog, is a compound having a structure similar to that of another compound, but differing from it in respect to a ce ...
of
isoprenaline Isoprenaline, or isoproterenol (brand name: Isoprenaline Macure), is a medication used for the treatment of bradycardia (slow heart rate), heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropyla ...
.


References


External links

* {{Portal bar , Medicine Beta1-adrenergic agonists Inotropic agents Wikipedia medicine articles ready to translate Eli Lilly and Company brands