Ephedrine

The physiologic effects of ephedrine were described in 1887 [64], but it was not until the 1920s that the drug was introduced into Western medicine [13] and clinical anesthesia. Ephedrine (Fig. 40.4) is a mixed-acting sympathomimetic: it has both direct and indirect stimulating effects on - and -adrenoceptors. Intravenous administration causes rapid increases in heart rate, cardiac output, and blood pressure that last 1015 minutes; repeat doses have a decreasing effect (tachyphylaxis) [65]. Intramuscular injection has a slower rate of onset (510 minutes), but a longer duration of effect (3545 minutes). Ephedrine has a half-life of 36 hours and is eliminated largely unchanged in the urine. Ephedrine has a stimulatory effect on the CNS, relaxes bronchial smooth muscle, and increases trigone and sphincter muscle tone in the urinary bladder. Uterine and placental artery blood flow is not adversely affected when ephedrine is used to sustain blood pressure during spinal anesthesia for cesarean section [36], and umbilical artery vascular resistance remains unchanged [66,67]

Ephedrine Ephedrine is an indirect-acting (through the stimulation of the endogenous release of norepinephrine) synthetic noncatecholamine that stimulates - and -adrenergic receptors. This drug also evokes pharmacologic effects by direct stimulant effects on adrenergic receptors. Ephedrine is resistant to metabolism by MAO in the gastrointestinal tract (thus it is effective orally). The slow inactivation and excretion of ephedrine are responsible for the prolonged duration of action of this sympathomimetic. Mydriasis accompanies the administration of ephedrine, and CNS stimulation does occur (but less than with amphetamine). Clinical Uses (Table 12-6) Cardiovascular Effects The cardiovascular effects of ephedrine resemble those of epinephrine, but its systemic blood pressure-elevating response is less intense and lasts approximately 10 times longer. The intravenous administration of ephedrine results in increases in systolic and diastolic blood pressure, heart rate, and cardiac output, thus reflecting -receptor mediated peripheral arterial and venous vasoconstriction and increased myocardial contractility due to activation of 1receptors. A second dose of ephedrine produces a less P.306 intense systemic blood pressure response than the first dose (tachyphylaxis). TABLE 12-6. CLINICAL USES OF EPHEDRINE Treat decreased blood pressure (10 to 25 mg IV) due to sympathetic nervous system blockade produced by regional anesthesia or inhaled or injected anesthetics Treat decreased blood pressure in parturients due to spinal or epidural anesthesia (phenylephrine also acceptable) Bronchial asthma (oral administration) Decongestant nasal spray
V Ephedrine
Ephedrine is a naturally occurring alkaloid that can cross the blood-brain barrier and thus exert a strong CNS-stimulating

effect in addition to its peripheral actions.The latter effects are primarily due to its indirect actions and depend largely on the release of norepinephrine. However, ephedrine may cause some direct receptor stimulation, particularly in its bronchodilating effects. Because it resists metabolism by both COMT and MAO, its duration of action is longer than that of norepinephrine. As is the case with all indirectly acting adrenomimetic amines, ephedrine is much less potent than norepinephrine; in addition, tachyphylaxis develops to its peripheral actions. Unlike epinephrine or norepinephrine, however, ephedrine is effective when administered orally.

Pharmacological Actions
Ephedrine increases systolic and diastolic blood pressure; heart rate is generally not increased. Contractile force of the heart and cardiac output are both increased. Ephedrine produces bronchial smooth muscle relaxation of prolonged duration when administered orally. Aside from pupillary dilation, ephedrine has little effect on the eye.

Clinical Uses
Ephedrine is useful in relieving bronchoconstriction and mucosal congestion associated with bronchial asthma, asthmatic bronchitis, chronic bronchitis, and bronchial spasms. It is often used prophylactically to prevent asthmatic attacks and is used as a nasal decongestant, as a mydriatic, and in certain allergic disorders. Although its bronchodilator action is weaker than that of isoproterenol, its oral effectiveness and prolonged duration of action make it valuable in the treatment of these conditions. Because of their oral effectiveness and greater bronchiolar selectivity, terbutaline and albuterol are replacing ephedrine for bronchodilation.

Adverse Effects
Symptoms of overdose are related primarily to cardiac and CNS effects. Tachycardia, premature systoles insomnia, nervousness, nausea, vomiting, and emotional disturbances may develop. Ephedrine should not be used in patients with cardiac disease, hypertension, or hyperthyroidism.