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Chapter: Modern Medical Toxicology: Cardiovascular Poisons: Cardiac Drugs and Lipid Lowering Agents

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Dobutamine - Beta Adrenergic Receptor and Dopaminergic Receptor Agonists

Dobutamine hydrochloride is a synthetic catecholamine struc-turally related to dopamine, and is primarily an inotropic agent with secondary peripheral vasodilating properties.

Dobutamine

Dobutamine hydrochloride is a synthetic catecholamine struc-turally related to dopamine, and is primarily an inotropic agent with secondary peripheral vasodilating properties.

Toxicokinetics

Dobutamine is inactive orally, and is invariably administered intravenously. The duration of action is less than 10 minutes. Apparent volume of distribution varies between 0.20 to 0.08 L/kg in patients with low output cardiac failure. Dobutamine is metabolised in the liver and other tissues, and excreted in the urine. Elimination half life is 2.4 ± 0.7 minutes.

Mode of Action

Dobutamine exerts its cardiovascular action through its beta1-adrenergic agonist activity, and also induces alpha1-adrenoceptor-mediated vasoconstriction as well as beta2-adre-noceptor-mediated vasodilation. It has no action on dopamine receptors.

The usual therapeutic regimen is an intravenous infusion dose of 2.5 to 10 mcg/kg/min up to a maximum of 40 mcg/ kg/min.

Adverse Effects

·              Cardiac arrhythmias, myocardial ischaemia, hypotension, palpitations, headache, dyspnoea, nausea.

·              Extravasation can lead to tissue necrosis at the site.

Drug Interactions

·              Additive effect with nitroprusside.

·              Antagonistic to phentolamine and prazocin.

Toxic (Clinical) Features

·      Hypotension (sometimes hypertension), oliguria, tachyar-rhythmias, myocardial ischaemia, tachypnoea, paraesthe-sias, stuffy nose, mydriasis, and warm and flushed skin.

·              These manifestations usually clear in 2 to 3 hours.

·      In rare cases, the sodium bisulfite component of commercial dobutamine solution can induce allergic-type reactions including anaphylaxis.

·      Local erythema and pruritis are often reported 4 to 12 days subsequent to dobutamine use, at the site of IV administration.

·      Withdrawal of dobutamine therapy sometimes leads to worsening of dyspnoea, hypertension, and renal dysfunction.

Treatment

·      Stop dobutamine administration.

·      Monitor respiration, blood pressure, arterial blood gases, and if possible central venous pressure and pulmonary wedge pressure.

·              Supportive measures.

·              Dobutamine withdrawal manifestations can be treated with 25 mg hydralazine before the first reduction in dobutamine infusion, and every 4 hours subsequently (upto a maximum of 150 mg).

 

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