ephedrine

ephedrine hydrochloride

ephedrine sulfate
Pretz-D

Available forms
Available with and without a prescription
Capsules: 25 mg, 50 mg
Injection: 25 mg/ml, 50 mg/ml (parenteral)
Nasal spray: 0.25%

Indications and dosages
 To correct hypotensive states. Adults: 25 to 50 mg I.M. or S.C. Or, 10 to 25 mg via slow I.V. bolus. If needed, a second I.M. dose of 50 mg or I.V. dose of 25 mg may be administered. Additional I.V. doses may be given in 5 to 10 minutes. Maximum dose is 150 mg daily.
Children: 3 mg/kg or 100 mg/m² S.C. or I.V. daily, divided into four to six doses.
 Orthostatic hypotension. Adults: 25 mg P.O. once daily to q.i.d.
Children: 3 mg/kg P.O. daily, divided into four to six doses.
 Bronchodilator or nasal decongestant. Adults and children older than age 12: 12.5 to 50 mg P.O. q 3 to 4 hours, p.r.n., not to exceed 150 mg in 24 hours. As nasal decongestant: 2 to 3 sprays in each nostril not more often than q 4 hours.
Children ages 6 to 12: 6.25 to 12.5 mg P.O. q 4 hours, not to exceed 75 mg in 24 hours. As nasal decongestant: 1 to 2 sprays in each nostril, not more often than q 4 hours.
Alternatively, children age 2 and older: 2 to 3 mg/kg or 100 mg/m² P.O. daily in four to six divided doses.
 Severe, acute bronchospasm. Adults: 12.5 to 25 mg I.M., S.C., or I.V.
 Enuresis. Adults: 25 to 50 mg P.O. h.s.
 Myasthenia gravis. Adults: 25 mg P.O. t.i.d. or q.i.d.

Pharmacodynamics
Direct- and indirect-acting sympathomimetic action: Ephedrine stimulates alpha- and beta-adrenergic receptors. Release of norepinephrine from its storage sites is one of its indirect effects. In therapeutic doses, ephedrine relaxes bronchial smooth muscle and produces cardiac stimulation with increased systolic and diastolic blood pressure when norepinephrine stores aren’t depleted.
Bronchodilator action: Ephedrine relaxes bronchial smooth muscle by stimulating beta₂-adrenergic receptors, resulting in increased vital capacity, relief of mild bronchospasm, improved air exchange, and decreased residual volume.
Vasopressor action: Drug produces positive inotropic effects with low doses by action on beta₁-receptors in the heart. Vasodilation results from its effect on beta₂-adrenergic receptors; vasoconstriction results from its alpha-adrenergic effects. Pressor effects may result from vasoconstriction or cardiac stimulation; however, when peripheral vascular resistance is decreased, blood pressure elevation results from increased cardiac output.
Nasal decongestant action: Ephedrine stimulates alpha-adrenergic receptors in blood vessels of nasal mucosa, producing vasoconstriction and nasal decongestion.

Pharmacokinetics
Absorption: Rapidly and completely absorbed after oral, S.C., or I.M. administration.
Distribution: Widely distributed throughout the body.
Metabolism: Slowly metabolized in the liver by oxidative deamination, demethylation, aromatic hydroxylation, and conjugation.
Excretion: Dose is mostly excreted unchanged in urine; rate of excretion depends on urine pH.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and other sympathomimetics; in those with porphyria, severe coronary artery disease, arrhythmias, angle-closure glaucoma, psychoneurosis, angina pectoris, substantial organic heart disease, or CV disease; and in those taking MAO inhibitors.
 Nasal solution is contraindicated in patients with angle-closure glaucoma, psychoneurosis, angina pectoris, substantial organic heart disease, CV disease, and hypersensitivity to drug or other sympathomimetics.
 Use extremely cautiously in elderly men and in patients with hypertension, hyperthyroidism, nervous or excitable states, diabetes, and prostatic hyperplasia. Use nasal solution cautiously in patients with hyperthyroidism, hypertension, diabetes mellitus, or prostatic hyperplasia.

Interactions
Drug-drug. Acetazolamide: May increase serum ephedrine levels. Monitor patient for toxicity.
Alpha blockers: Causes unopposed beta-adrenergic effects, resulting in hypotension. Avoid use together.
Antihypertensives: Decreases antihypertensive effects. Monitor blood pressure.
Atropine: Blocks reflex bradycardia and enhances pressor effects. Monitor patient carefully.
Beta blockers: Causes unopposed alpha-adrenergic effects, resulting in hypertension. Monitor blood pressure.
Cardiac glycosides, general anesthetics (especially cyclopropane, halothane): May sensitize myocardium to effects of ephedrine, causing arrhythmias. Monitor patient closely.
Diuretics, methyldopa, reserpine: Decrease pressor effects of ephedrine. Monitor patient carefully.
Ergot alkaloids: May enhance vasoconstrictor activity. Monitor patient cautiously.
Guanadrel, guanethidine: Enhance pressor effects of ephedrine. Monitor patient and blood pressure closely.
Levodopa: Enhances risk of ventricular arrhythmias. Monitor patient closely.
MAO inhibitors, tricyclic antidepressants: Enhances pressor effects; may cause hypertensive crisis. Allow 14 days after stopping MAO inhibitor before using ephedrine.
Sympathomimetics: Increases effects and toxicity. Avoid use together.
Theophylline: Causes more adverse reactions than either drug when used alone. Use together cautiously.

Adverse reactions
CNS: insomnia, nervousness, dizziness, headache, euphoria, confusion, delirium, nervousness and excitation with nasal solution.
CV: palpitations, tachycardia, hypertension, precordial pain, tachycardia with nasal solution, arrhythmias.
EENT: dry nose and throat, rebound nasal congestion with long-term or excessive use, mucosal irritation with nasal solution.
GI: nausea, vomiting, anorexia.
GU: urine retention, painful urination from visceral sphincter spasm.
Musculoskeletal: muscle weakness.
Skin: diaphoresis.

Effects on lab test results
None reported.

Overdose and treatment
Signs and symptoms of overdose include exaggeration of common adverse reactions, especially arrhythmias, extreme tremors or seizures, nausea and vomiting, fever, and CNS and respiratory depression.
 Treatment requires supportive and symptomatic measures. If patient is conscious, induce emesis with ipecac followed by activated charcoal. If patient is depressed or hyperactive, perform gastric lavage. Maintain airway and blood pressure. Don’t administer vasopressors. Monitor vital signs closely.
 A beta blocker (such as propranolol) may be used to treat arrhythmias. A cardioselective beta blocker is recommended in asthmatic patients. Phentolamine may be used for hypertension, paraldehyde or diazepam for seizures, and dexamethasone for pyrexia.

Special considerations
• As a pressor agent, ephedrine isn’t a substitute for blood, plasma, fluids, or electrolytes. Correct fluid volume depletion before administration.
• Tolerance may develop after prolonged or excessive use; increased dose may be needed. Also, if drug is discontinued for a few days and readministered, effectiveness may be restored.
Pregnant patients
• It isn’t known whether drug is safe for use during pregnancy. Use drug during pregnancy only when clearly indicated.
Breast-feeding patients
• Avoid use in breast-feeding women.
Pediatric patients
• Use cautiously in children.
Geriatric patients
• Administer cautiously because elderly patients may be more sensitive to effects of drug. Lower doses may be needed.

Patient education
• Instruct patient to clear nose before instilling nasal solutions.
• Tell patient using OTC product to follow directions on label, to take last dose a few hours before bedtime to reduce possibility of insomnia, to take only as directed, and not to increase dose or frequency.
• Advise patient to store drug away from heat and light (not in bathroom medicine cabinet) and to keep out of reach of children.
• Instruct patient who misses a dose to take it as soon as remembered if within 1 hour. If beyond 1 hour, patient should skip dose and return to regular schedule.
• Teach patient to be aware of palpitations and significant pulse rate changes.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use