Chapter 14

### INTRODUCTION

Vasoactive agents were recognized in 1895 by H.D. Rollerston, when he described a suprarenal extract as a “powerful vascular tonic.”1 Today, these drugs have an important role in anesthetics and critical care.

Adrenergic receptors are classified into two commonly recognized subtypes, α and β. Many subtypes of these receptors have been described, but the most clinically important subtypes are α1, α2, β1, and β2. α1 receptors are found primarily on smooth muscle in the vasculature where activation leads to vasoconstriction. They are also found in the genitourinary tract, intestine, as well as cardiac and liver tissue. α receptors are found in pancreatic beta cells, nerves, and platelets. They are also present on vascular smooth muscle, although to a lesser extent than α1 receptors. β1 receptors are found primarily in the heart and kidney. In the heart their stimulation leads to an increase in chronotropy, inotropy and atrial-ventricular node conduction velocity. Their activation in the kidney causes renin release. β2 Receptors are prominent in smooth muscle. Activation of β2 receptors in the vasculature results in vasodilation, while activation of the same receptors in the airways leads to bronchodilation.

Dopamine, norepinephrine, and epinephrine are endogenous adrenergic agonists synthesized from the enzymatic alteration of phenylalanine. They are most frequently used for the acute management of hypotension, although epinephrine is also indicated for use in acute bronchoconstriction and anaphylaxis. By causing vasoconstriction, these agents will alter perfusion and oxygen delivery to different organs. The clinical significance of this altered blood flow varies dramatically between patients but sometimes results in organ ischemia or ischemia of the distal extremities necessitating amputation. Tachycardia and increased myocardial oxygen consumption can lead to dysrhythmias if cardiac oxygen delivery is inadequate. Cerebral hemorrhage can occur if vasoconstriction leads to severe systemic hypertension.

#### Epinephrine

Epinephrine is the prototypical sympathomimetic drug and is active at both α and β receptors. At very low doses the vasodilatory effects of β2 activation can be most prevalent, but as the dose increases the β2 and α1 effects dominate. Its vasoconstriction and bronchodilation properties make it an excellent drug for the treatment of anaphylaxis and it may be administered intramuscularly (IM) for the treatment of bronchoconstriction or anaphylaxis. Typical IM dosing is 300 mcg for adults and 150 mcg in children. When given IM, peak effects are seen within 15 minutes.2 Intravenous (IV) bolus dosing effects are seen within seconds after reaching the circulation, and these effects typically last less than 5 minutes. Inhaled epinephrine can cause bronchodilation within 1 minute, but tachycardia and other systemic effects may be seen at high doses. Epinephrine is primarily eliminated by hepatic metabolism. Epinephrine causes a rise in blood glucose levels by increasing hepatic gluconeogenesis and decreasing pancreatic insulin secretion.

#### Norepinephrine

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