DOBUTAMINE HCL

Chemistry - Dobutamine HCl is a synthetic inotropic agent related structurally to dopamine. Itoccurs as a white, to off-white, crystalline powder with a pKa of 9.4. Dobutamine is sparinglysoluble in water and alcohol.

Storage, Stability, Compatibility

Dobutamine injection should be stored at room temperature(15-30°C). It must be further diluted before administration (see Preparation of Solution below);diluted solutions should be used within 24 hours.
Dobutamine is compatible with the usually used IV solutions (D5W, sodium chloride 0.45% &0.9%, dextrose-saline combinations, lactated Ringer's) and is reported to be compatible with thefollowing drugs: amiodarone HCl, atropine sulfate, dopamine HCl, epinephrine HCl, hydralazine
HCl, isoproterenol HCl, lidocaine HCl, meperidine HCl, metaraminol bitartrate, morphine sulfate, nitroglycerin, norepinephrine (levarterenol) bitartrate, phentolamine mesylate, phenylephrine HCl, procainamide HCl, propranolol HCl, and verapamil HCl.
Dobutamine may be incompatible with the following agents: aminophylline, bretylium tosylate, bumetamide, calcium chloride or gluconate, diazepam, digoxin, furosemide, heparin (inconsistentresults), regular insulin, magnesium sulfate, phenytoin sodium, potassium chloride (at highconcentrations only - 160 mEq/l), potassium phosphate, and sodium bicarbonate.

Pharmacology - DOBUTAMINE HCL

Dobutamine is considered a direct beta1-adrenergic agonist. It also has mildbeta2- and alpha1-adrenergic effects at therapeutic doses. These effects tend to balance one anotherand cause little direct effect on the systemic vasculature. In contrast to dopamine, dobutamine doesnot cause the release of norepinephrine. It has relatively mild chronotropic, arrhythmogenic, andvasodilative effects.
Increased myocardial contractility and stroke volumes result in increased cardiac output.
Decreases in left ventricular filling pressures (wedge pressures) and total peripheral resistanceoccur in patients with a failing heart. Blood pressure and cardiac rate generally are unaltered orslightly increased because of increased cardiac output. Increased myocardial contractility mayincrease myocardial oxygen demand and coronary blood flow.

Uses, Indications

Dobutamine is used as a rapid-acting injectable positive inotropic agent forshort term treatment of heart failure.

Pharmacokinetics - DOBUTAMINE HCL

Because it is rapidly metabolized in the GI tract and is not available after oraladministration, dobutamine is only administered intravenously (as a constant infusion). Afterintravenous administration, the onset of action generally occurs within 2 minutes and peaks after 10minutes.
Dobutamine is metabolized rapidly in the liver and other tissues and has a plasma half-life ofapproximately 2 minutes in humans. The drug's effects diminish rapidly after cessation of therapy.
Pharmacokinetic data for domestic animals is apparently unavailable. It is unknown if dobutaminecrosses the placenta or into milk.
Contraindications/Precautions - Dobutamine is contraindicated in patients with known hypersensitivity to the drug or with idiopathic hypertropic subaortic stenosis (IHSS). The injectable formulation contains sodium bisulfite as a preservative which has been documented to cause allergic-type reactions in some human patients. Hypovolemic states must be corrected before administering dobutamine. Because it may increase myocardial oxygen demand and increase infarct size, dobutamine should be used very cautiously after myocardial infarction. Dobutamine can enhance atrioventricular conduction, animals with atrial fibrillation should be digitalized prior to receiving dobutamine.

Adverse Effects, Warnings

The most commonly reported adverse effects in humans are: ectopicbeats, increased heart rate, increased blood pressure, chest pain, and palpitations. Similar adverseeffects could be expected for veterinary patients. At usual doses these effects are generally mild andwill not necessitate halting therapy, but dosage reductions should be performed. Other, more rareadverse effects reported include: nausea, headache, vomiting, leg cramps, paresthesias, and dyspnea.
Overdosage - Symptoms reported with excessive dosage include tachycardias, increased bloodpressure, nervousness, and fatigue. Because of the drug's short duration of action, temporarilyhalting therapy is usually all that is required to reverse these effects.

Drug Interactions

beta-Blockers (e.g., propranolol) may antagonize the cardiac effects ofdobutamine, and result in a preponderance of alpha adrenergic effects and increased total peripheralresistance.
Use of halothane or cyclopropane with dobutamine may result in increased incidences of ventricular arrhythmias.
Synergistic effects (increased cardiac output and reduced wedge pressure) may result if dobutamine is used with nitroprusside.
Insulin requirements may increase in diabetic patients receiving dobutamine.
Oxytocic drugs may induce severe hypertension when used with dobutamine in obstetric patients.