Dobutamine

Dobutamine is an Antihypertensive agent belonging to Adrenergic agonist / Inotropic agents.

Dobutamine is a beta-1 agonist used to treat cardiac decompensation in patients with organic heart disease or from cardiac surgery.

Inactivated when given orally. Dobutamine is hepatically metabolized, and it converted to 3-O-methyldobutamine by COMT and via conjugation by glucuronic acid. It is mainly excreted via urine and faeces (small amounts). The elimination half-life is approximately 2 min.

Dobutamine shows common side effects like Increased heart rate, Chest pain, Changes in blood pressure, Irregular heartbeat, Headache, Shortness of breath, Increased urination frequency, Nausea, Skin Rash, Fever, Swelling and redness at the injection site.

Dobutamine is available in the form of Injectable solution.

Dobutamine is available in India, US, UK, Canada, Africa, Singapore, Japan and Australia.

Dobutamine belonging to the Adrenergic agonist / Inotropic agents, acts as an Antihypertensive agent.

Dobutamine, a racemic mixture, stimulates myocardial beta₁-adrenergic receptors primarily by the (+) enantiomer and some alpha₁ receptor agonism by the (-) enantiomer, resulting in increased contractility and heart rate, and stimulates both beta₂- and alpha₁-receptors in the vasculature. Although beta₂ and alpha₁ adrenergic receptors are also activated, the effects of beta₂ receptor activation may equally offset or be slightly greater than the effects of alpha₁ stimulation, resulting in some vasodilation in addition to the inotropic and chronotropic actions.

The onset of action of Dobutamine is about 1-10 minutes.

The Duration of Action for Dobutamine in the body is not clinically established.

The Tmax of Dobutamine was found within 10-20 minute.

Dobutamine is available in the form of Injectable solution.

Dobutamine Injectable solution is given via intravenous route.

Dobutamine is used for the short-term treatment of heart failure (a condition in which your heart is unable to pump enough blood) caused due to a weakened heart muscle. It works by improving the blood flow through stimulation of the heart muscles.

Dobutamine is an Antihypertensive agent belonging to Adrenergic agonist / Inotropic agents.

Dobutamine directly stimulates beta-1 receptors of the heart to increase myocardial contractility and stroke volume, resulting in increased cardiac output.

Dobutamine is approved for use in the following clinical indications

Adult indication

• Acute decompensated heart failure

Dobutamine is a beta-1 agonist used to treat cardiac decompensation in patients with organic heart disease or from cardiac surgery.

Although not approved, there have been certain off-label indications. These include

• Inotropic support
• Stress echocardiography, routine
• Stress echocardiography, viability assessment

Pediatric indication

• Hemodynamic support

Adult Dose

• Acute decompensated heart failure

Continuous infusion: IV: Initial: 2 to 5 mcg/kg/minute; titrate based on clinical end point (eg, BP, end-organ perfusion); usual dosage range: 2 to 10 mcg/kg/minute; maximum dose: 20 mcg/kg/minute.

• Inotropic support

Continuous infusion: IV: Initial: 2 to 5 mcg/kg/minute; titrate based on clinical end point (eg, BP, end-organ perfusion); usual dosage range: 2 to 10 mcg/kg/minute; however, doses as low as 0.5 mcg/kg/min have been used in less severe cardiac decompensation; maximum dose: 20 mcg/kg/minute.

• Stress echocardiography, routine

Continuous infusion: IV: Initial: 5 mcg/kg/minute; increase at 3-minute intervals to 10 mcg/kg/minute, then 20 mcg/kg/minute, then 30 mcg/kg/minute, and then 40 mcg/kg/minute. May coadminister atropine in patients who do not achieve target heart rate.

• Stress echocardiography, viability assessment

Continuous infusion: IV: Initial: 2.5 mcg/kg/minute; increase at 5-minute intervals in 2.5 mcg/kg/minute increments until contractile response is noted, up to a maximum dose of 10 mcg/kg/minute.

Pediatric Dose

• Hemodynamic support

Infants, Children, and Adolescents

Continuous IV or intraosseous infusion: Initial: 0.5 to 1 mcg/kg/minute; titrate gradually every few minutes until desired response achieved; usual range: 2 to 20 mcg/kg/minute.

Dobutamine is available in various strengths as 12.5 mg/mL; 1 mg/mL-D5%; 2 mg/mL-D5%; 4 mg/mL-D5%; 500 mcg/mL-D5%.

Dobutamine is available in the form of Injectable solution.

Dobutamine is contraindicated in patients with

• In patients with idiopathic hypertrophic subaortic stenosis.
• In patients who have shown previous manifestations of hypersensitivity to dobutamine injection.

• Increase In Heart Rate or Blood Pressure

Dobutamine may cause a marked increase in heart rate or blood pressure, especially systolic pressure. Approximately 10% of patients in clinical studies have had rate increases of 30 beats/minute or more, and about 7.5% have had a 50 mm Hg or greater increase in systolic pressure. Usually, reduction of dosage promptly reverses these effects. Because dobutamine facilitates atrioventricular conduction, patients with atrial fibrillation are at risk of developing rapid ventricular response. Patients with preexisting hypertension appear to face an increased risk of developing an exaggerated pressor response.

• Ectopic Activity

Dobutamine may precipitate or exacerbate ventricular ectopic activity, but it rarely has caused ventricular tachycardia.

• Hypersensitivity

Reactions suggestive of hypersensitivity associated with administration of dobutamine injection, including skin rash, fever, eosinophilia, and bronchospasm, have been reported occasionally. Dobutamine injection contains sodium met bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes, in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when dobutamine hydrochloride is administered to a nursing woman. If a mother requires dobutamine treatment, breast-feeding should be discontinued for the duration of the treatment.

Dobutamine should not be used as a diagnostic agent for stress testing during pregnancy; use should be avoided when other options are available. Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant female. Appropriate medications should not be withheld due to concerns of fetal teratogenicity. Dobutamine use during the post-resuscitation phase may be considered; however, the effects of inotropic support on the fetus should also be considered.

Common Adverse effects

• Increased heart rate, systolic blood pressure, ventricular premature contractions, angina pectoris, chest pain, palpitations, Headache, Nausea, Dyspnea.

Rare Adverse effects

• Hypotension, ventricular ectopy, Decreased serum potassium, Cardiomyopathy, eosinophilia, hypersensitivity reaction, localized phlebitis.

• Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics.
• Beta-Blockers: May diminish the therapeutic effect of Dobutamine.
• Calcium Salts: May diminish the therapeutic effect of Dobutamine.
• Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics.
• Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use.
• COMT Inhibitors: May increase the serum concentration of COMT Substrates.
• Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline.
• Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics.
• Kratom: May enhance the adverse/toxic effect of Sympathomimetics.
• Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available.
• Ozanimod: May enhance the hypertensive effect of Sympathomimetics.
• Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol.
• Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics.
• Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics.

The common side effects of Dobutamine include the following

Common

● Increased heart rate, Chest pain, Changes in blood pressure, Irregular heartbeat, Headache, Shortness of breath, Increased urination frequency, Nausea, Skin Rash, Fever, Swelling and redness at the injection site.

Rare

● Anxiety, Low blood potassium.

• Pregnancy

Pregnancy Category B

Reproduction studies performed in rats and rabbits have revealed no evidence of harm to the fetus due to dobutamine. The drug, however, has not been administered to pregnant women and should be used only when the expected benefits clearly outweigh the potential risks to the fetus.

• Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when dobutamine hydrochloride is administered to a nursing woman. If a mother requires dobutamine treatment, breast-feeding should be discontinued for the duration of the treatment.

• Pediatric Use

Dobutamine has been shown to increase cardiac output and systemic pressure in pediatric patients of every age group. In premature neonates, however, dobutamine is less effective than dopamine in raising systemic blood pressure without causing undue tachycardia, and dobutamine has not been shown to provide any added benefit when given to such infants already receiving optimal infusions of dopamine.

• Geriatric Use

Clinical studies of dobutamine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.

Signs and Symptoms: Toxicity from dobutamine hydrochloride is usually due to excessive cardiac β-receptor stimulation. The duration of action of dobutamine hydrochloride is generally short (T½ = 2 minutes) because it is rapidly metabolized by catechol-O-methyltransferase. The symptoms of toxicity may include anorexia, nausea, vomiting, tremor, anxiety, palpitations, headache, shortness of breath, and anginal and nonspecific chest pain. The positive inotropic and chronotropic effects of dobutamine on the myocardium may cause hypertension, tachyarrhythmias, myocardial ischemia, and ventricular fibrillation. Hypotension may result from vasodilation. If the product is ingested, unpredictable absorption may occur from the mouth and the gastrointestinal tract.

Treatment: To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. Telephone numbers of certified poison control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient. The initial actions to be taken in a dobutamine hydrochloride overdose are discontinuing administration, establishing an airway, and ensuring oxygenation and ventilation. Resuscitative measures should be initiated promptly. Severe ventricular tachyarrhythmias may be successfully treated with propranolol or lidocaine. Hypertension usually responds to a reduction in dose or discontinuation of therapy. Protect the patient's airway and support ventilation and perfusion. If needed, meticulously monitor, and maintain, within acceptable limits, the patient's vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten the elimination of some drugs that have been absorbed. Safeguard the patient's airway when employing gastric emptying or charcoal. Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion have not been established as beneficial for an overdose of dobutamine hydrochloride.

Pharmacodynamic

Dobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the beta-adrenoceptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects. Dobutamine acts primarily on beta-1 adrenergic receptors, with negligible effects on beta-2 or alpha receptors. It does not cause the release of endogenous norepinephrine, as does dopamine.

Pharmacokinetics

• Absorption

Inactivated when given orally.

• Distribution

Information is not available.

• Metabolism and Excretion

Dobutamine is hepatically metabolized, and it converted to 3-O-methyldobutamine by COMT and via conjugation by glucuronic acid. It is mainly excreted via urine and faeces (small amounts). The elimination half-life is approximately 2 min.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020255s016lbl.pdf
• https://www.rxlist.com/dobutamine-drug.htm
• https://reference.medscape.com/drug/dobutamine-342434
• https://www.mims.com/india/drug/info/dobutamine?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00841
• https://www.drugs.com/mtm/dobutamine.html#:~:text=What is dobutamine?,have been tried without success.
• https://www.uptodate.com/contents/dobutamine-drug-information