Adrenergic Agonists

Adrenergic Agonists

Adrenergic agonists can be categorized as direct or indirect. Direct agonists bind to the receptor, whereas indirect agonists increase endogenous neurotransmitter activity. Mechanisms of indirect action include increased release or decreased reuptake of norepinephrine. The differentiation between direct and indirect mechanisms of action is particularly important in patients who have abnormal endogenous norepinephrine stores, as may occur with use of some antihypertensive medications or monoamine oxidase inhibitors. Intraoperative hypotension in these patients should be treated with direct agonists, as their response to indirect agonists will be altered.

Phenylephrine

Predominantly direct α1-agonist activity (high doses may stimulate α 2- and β-receptors). The primary effect of phenylephrine is peripheral vasoconstriction with a concomitant rise in systemic vascular resistance and arterial blood pressure. Reflex bradycardia can reduce cardiac output. Coronary blood flow increases because any direct vasoconstrictive effect of phenylephrine on the coronary arteries is overridden by vasodilation induced by the release of metabolic factors. Site of clearance is liver.

Dose: Small intravenous boluses of 50-100 μg (0.5-1 μg/kg) of phenylephrine rapidly reverse reductions in blood pressure caused by peripheral vasodilation (eg, spinal anesthesia). A continuous infusion (100μ g/mL at a rate of 0.25-1μ g/kg/min) will maintain arterial blood pressure but at the expense of renal blood flow. Tachyphylaxis (an effect of drug which becomes less on repeated dose) occurs with phenylephrine infusions requiring upward titration of the infusion. Phenylephrine must be diluted from a 1% solution (10 mg/1-mL ampoule), usually to a 100 μg/mL solution.

Alpha-2 Agonist

  • Clonidine is a α2-agonist that is now commonly used for its antihypertensive (decreased systemic vascular resistance) and negative chronotropic effects. Clonidine appears to decrease anesthetic and analgesic requirements (decreases MAC) and to provide sedation and anxiolysis. During general anesthesia, clonidine reportedly enhances intraoperative circulatory stability by reducing catecholamine levels. Other possible benefits include decreased postoperative shivering, inhibition of opioid-induced muscle rigidity, attenuation of opioid withdrawal symptoms, and the treatment of some chronic pain syndromes. Side effects include bradycardia, hypotension, sedation, respiratory depression, and dry mouth. Sites of clearance are liver and kidneys.

Methyldopa is a centrally acting antihypertensive agent. It is thought to activate central α2 receptors and lower blood pressure in a manner similar to that of clonidine. A fall in peripheral vascular resistance is responsible for a drop in arterial blood pressure (peak effect within 4 h). Renal blood flow is maintained or increased. The usual initial dose of methyldopa is 250 mg twice daily, and there is little additional effect with doses above 2 g per day. Sites of clearance are liver and kidneys.

Epinephrine

Direct stimulation of β1-receptors by epinephrine raises cardiac output and myocardial oxygen demand by increasing contractility and heart rate. Systolic blood pressure rises, although β2-mediated vasodilation in skeletal muscle may lower diastolic pressure. β2 stimulation also relaxes bronchial smooth muscle. In emergency situations (eg, shock and allergic reactions), epinephrine is administered as an intravenous bolus of 0.05-1 mg depending on the severity of cardiovascular compromise. Clearance from the site of action is in the form of enzymatic transformation, catechol-Omethyltransferase (COMT) is responsible for the biotransformation of catecholamine.

Administration of epinephrine is the principal pharmacological treatment for anaphylaxis and can be used to treat ventricular fibrillation. Complications include cerebral hemorrhage, coronary ischemia, and ventricular dysrhythmia. Volatile anesthetics, particularly halothane, potentiate the dysrhythmic effects of epinephrine.

Ephedrine

The cardiovascular effects of ephedrine are similar to those of epinephrine: increase in blood pressure, heart rate, contractility, and cardiac output. Likewise, ephedrine is also a bronchodilator. The indirect agonist properties of ephedrine may be due to central stimulation, peripheral postsynaptic norepinephrine release, or inhibition of norepinephrine reuptake. Site of clearance is the liver

Ephedrine is commonly used as a vasopressor during anesthesia. As such, its administration should be viewed as a temporizing measure while the cause of hypotension is determined and remedied. Unlike direct-acting α1-agonists, ephedrine does not decrease uterine blood flow. This makes it the preferred vasopressor for most obstetric uses. Ephedrine has also been reported to possess antiemetic properties, particularly in association with hypotension following spinal anesthesia. The usual dose is 2.5 to 25 mg given intravenously or 25 to 50 mg administered intramuscularly.

Dopamine

The clinical effects of dopamine, a nonselective direct and indirect adrenergic agonist, vary markedly with the dose. Small doses (≤2 μg/kg/min) of dopamine have minimal adrenergic effects but activate dopaminergic receptors. Stimulation of these noradrenergic receptors vasodilates the renal vasculature and promotes diuresis. At moderate doses (2-10 μg/kg/min); β1-stimulation increases myocardial contractility, heart rate, and cardiac output. α1-effects become prominent at higher doses (10-20 μg/kg/min), causing an increase in peripheral vascular resistance and a fall in renal blood flow. Dopamine is commonly used in the treatment of shock to improve cardiac output, support blood pressure, and maintain renal function. It is administered as a continuous infusion (400 mg in 1000 mL D5W; 400μg/mL) at a rate of 1-20 μg/kg/min. Site of clearance is hepatic enzymatic transformation.

Beta 2-Agonists

Are used to treat reactive airway disease. With large doses the β2-receptor selectivity can be lost, and severe side effects related to β1-adrenergic stimulation are possible. Commonly used agents include albuterol.

Last modified: Wednesday, 16 November 2016, 4:04 PM