Dobutamine Injection - Clinical Pharmacology
Dobutamine hydrochloride is a direct-acting inotropic agent whose primary activity results from stimulation of the β receptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects. It does not cause the release of endogenous norepinephrine, as does dopamine. In animal studies, dobutamine hydrochloride produces less increase in heart rate and less decrease in peripheral vascular resistance for a given inotropic effect than does isoproterenol.
In patients with depressed cardiac function, both dobutamine hydrochloride and isoproterenol increase the cardiac output to a similar degree. In the case of dobutamine hydrochloride, this increase is usually not accompanied by marked increases in heart rate (although tachycardia is occasionally observed), and the cardiac stroke volume is usually increased. In contrast, isoproterenol increases the cardiac index primarily by increasing the heart rate while stroke volume changes little or declines.
Facilitation of atrioventricular conduction has been observed in human electrophysiologic studies and in patients with atrial fibrillation.
Systemic vascular resistance is usually decreased with administration of dobutamine hydrochloride. Occasionally, minimum vasoconstriction has been observed.
Most clinical experience with dobutamine hydrochloride is short-term − not more than several hours in duration. In the limited number of patients who were studied for 24, 48, and 72 hours, a persistent increase in cardiac output occurred in some, whereas output returned toward baseline values in others.
The onset of action of dobutamine is within 1 to 2 minutes; however, as much as 10 minutes may be required to obtain the peak effect of a particular infusion rate.
The plasma half-life of dobutamine hydrochloride in humans is 2 minutes. The principal routes of metabolism are methylation of the catechol and conjugation. In human urine, the major excretion products are the conjugates of dobutamine and 3-O-methyl dobutamine. The 3-O-methyl derivative of dobutamine is inactive.
Alteration of synaptic concentrations of catecholamines with either reserpine or tricyclic antidepressants does not alter the actions of dobutamine in animals, which indicates that the actions of dobutamine hydrochloride are not dependent on presynaptic mechanisms.
Indications and Usage for Dobutamine Injection
Dobutamine Injection, USP is indicated when parenteral therapy is necessary for inotropic support in the short-term treatment of adults with cardiac decompensation due to depressed contractility resulting either from organic heart disease or from cardiac surgical procedures.
In patients who have atrial fibrillation with rapid ventricular response, a digitalis preparation should be used prior to institution of therapy with dobutamine hydrochloride.
*************************
Advertisement
1. Mechanism
1. Synthetic Sympathomimetic amine
2. Overall effect similar to Dopamine with Nitroprusside
3. Selective for Beta Adrenergic Receptors
1. Beta 1 Adrenergic Receptor
1. Increased cardiac contractility and Heart Rate
2. Beta 2 Adrenergic Receptor
1. Mild increase in vasodilation
2. Does not directly affect renal or splanchnic flow
4. Relatively mild Alpha 1 Adrenergic Receptor effect
1. Vasoconstriction countered by more potent beta effect
5. Minimal effects on myocardial oxygen demand
1. Favorable balance between oxygen supply and demand
1. Preferred in Cardiogenic Shock over Dopamine
2. Increased perfusion balances inotropic strain
3. Benefit lost if not titrated to avoid tachycardia
2. Does not increase infarct size
3. Does not elicit arrhythmia
2. Pharmacokinetics
1. Short half-life
1. Only effective by infusion
3. Indications
1. Cardiogenic Shock (Severe Congestive Heart Failure)
1. Pulmonary congestion or Hypotension
2. Right ventricular infarction
1. Use with fluid Resuscitation
3. Often used in combination with Dopamine
1. Moderate dosages of each (7.5 ug/kg/min)
2. Maintains critical organ perfusion
3. Less pulmonary congestion than with Dopamine alone
4. Not shown to alter mortality
5. May alter secondary organ injury outcomes
2. Septic Shock
1. May be useful in enhancing left ventricular function
2. Epinephrine is preferred agent in Septic Shock
3. Not usually indicated in non-Cardiogenic Shock
1. Other Catecholamines preferred in other shock types
4. Pediatric Infusion (Same as Dopamine preparation)
1. Preparation
1. Draw up "x" mg of Dobutamine
2. Where "x" = 6 x Weight in Kilograms
3. Add enough D5W or NS to Dobutamine for 100 ml total
4. At this dilution
1. Infusion rate of 1 ml/h provides 1.0 ug/kg/min
2. Start Dose: 5-10 ug/kg/min or 5-10 ml/hour
3. Titrate to clinical response (usually <20 ug/kg/min)
5. Adult Infusion
1. Preparation
1. Start with 2-4 ampules Dobutamine (250 mg each)
2. Dissolve 500-1000 mg Dobutamine in 250 ml D5W or NS
3. Final Concentration: 2000-4000 ug/ml
2. Start Dose: 0.5 to 2.0 ug/kg/min
3. Titrate: 2-20 ug/kg/min to clinical response
1. Perfusion
2. Urine output
3. Blood Pressure
4. Avoid increasing Heart Rate 10% over baseline
6. Adverse Effects
1. Tachycardia
2. Arrhythmia
3. Ectopic beats
4. Provokes Myocardial Ischemia if tachycardia occurs
5. Headache
6. Nausea
7. Tremor
8. Hypokalemia
الأحد أبريل 22, 2012 10:22 pm