Miscellaneous Effects

Epi rapidly increases the number of circulating polymorphonuclear leukocytes, likely due to b receptor—mediated demargination of these cells. Epi accelerates blood coagulation and promotes fibrinolysis. The effects of Epi on secretory glands are not marked; in most glands, secretion is inhibited, partly owing to the reduced blood flow caused by vasoconstriction. Epi stimulates lacrimation and a scanty mucus secretion from salivary glands. Sweating and pilomo-tor activity are minimal after systemic administration of Epi, but occur after intradermal injection of dilute solutions of either Epi or NE; such effects are inhibited by a receptor antagonists.

Mydriasis is readily seen during physiological sympathetic stimulation but not when Epi is instilled into the conjunctival sac of normal eyes. Epi usually lowers intraocular pressure (see Chapter 63).

Epi facilitates neuromuscular transmission, particularly that following prolonged rapid stimulation of motor nerves; stimulation of a receptors promotes transmitter release from the somatic motor neuron, perhaps as a result of enhanced influx of Ca2+. These responses likely are mediated by at receptors and may explain in part the ability of intra-arterial Epi to briefly increase strength in patients with myasthenia gravis. Epi also acts directly on white, fast-twitch muscle fibers to prolong the active state, thereby increasing peak tension. Of greater physiological and clinical importance is the capacity of Epi and selective b2 agonists to increase physiological tremor, at least in part due to b receptor—mediated enhancement of discharge of muscle spindles.

Via activation of b2 receptors, Epi promotes a fall in plasma K+, largely due to stimulation of K+ uptake into cells, particularly skeletal muscle. This is associated with decreased renal K+ excretion.

ABSORPTION, FATE, AND EXCRETION Epi is ineffective after oral administration because it is rapidly metabolized in the GI mucosa and liver. Absorption from subcutaneous tissues occurs relatively slowly because of local vasoconstriction, and the rate may be further decreased by systemic hypotension (e.g., in shock). Absorption is more rapid after intramuscular injection. In emergencies, it may be necessary to administer Epi intravenously. When relatively concentrated solutions (1%) are nebulized and inhaled, the actions of the drug largely are restricted to the respiratory tract; however, systemic reactions such as arrhythmias may occur, particularly if larger amounts are used.

Epi is rapidly inactivated, especially by the liver, which is rich in COMT and MAO (see Figure 6-6 and Table 6-5).

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