(L)-Ephedrine

CAS RN: 299-42-3

Toxicity Summary

IDENTIFICATION: Ephedrine is a colorless or white solid powder or crystals. It has a bitter taste and is odorless or slight aromatic odor. It is soluble in water, alcohol, chloroform, ether, glycerol, olive oil and in liquid paraffin. Ephedrine and its optical isomer pseudoephedrine are structurally very similar to methamphetamine. In illicit drug laboratories simple dehydrogenation is used to make methamphetamine from ephedrine. Indications: The most important uses are: as a bronchodilator; nasal decongestant; and treatment for syndrome of Stokes-Adams; as a mydriatic and hypertensor in the spinal anesthesia. It is also used as an herbal diet supplement under the name Ma-huang as an anorectic and CNS stimulant. HUMAN EXPOSURE: Contraindications: Cardiovascular disease; hypertension; hyperthyroidism; pheochromocytoma and closed angle glaucoma. Ephedrine should not be given in patients being treated with MAOI (or have stopped treatment in the last 14 days). It should be used with caution in patients with prostatic enlargement or with renal impairment. Routes of exposure: Oral: Abuse of ephedrine-containing diet pills is a common occurrence. Inhalation: Ephedrine salts are used as nasal drops or sprays in the relief of nasal congestion associated with cold or rhinitis. Ephedrine can be abused by the nasal route by subjects who have developed dependence to its vasoconstrictive effect. Dermal: As an ointment is well absorbed. Eye: Eye-drops at 0.1% are effective in congestion of conjunctival allergy. Parenteral: Subcutaneous or intramuscular injections. Kinetics: Absorption by route of exposure: Ephedrine is readily and completely absorbed from the gastrointestinal tract; plasma peak concentrations are reached an hour after ingestion. Biological half-life by route of exposure: It has a plasma half-life ranging from 3 to 6 hours depending on urinary pH. No change in half-life from that seen with therapeutic dosing was observed in an otherwise healthy patient with massive overdose. Metabolism: Only a small amount of ephedrine is metabolized in the liver. Elimination by route of exposure: It is largely excreted unchanged in the urine, with some deaminated metabolites and N-demethylated metabolites. Elimination is enhanced in acid urine. Mode of action: Toxicodynamics: Ephedrine can produce stimulation at the adrenergic receptors and neuronal norepinephrine release. Pharmacodynamics: Ephedrine has both alpha- and beta-adrenergic activities, and both direct and indirect effects on receptors. It raises blood pressure both by increasing cardiac output and inducing peripheral vasoconstriction. It can produce bronchodilation. In local application it causes pupils dilation. The main metabolic effects in overdose are hyperglycemia and hypokalemia. Ephedrine is a centrally acting respiratory stimulant and can increase motor activity. Interactions: A serotonin syndrome has been reported in a patient taking paroxetine and an over the counter cold medicine containing ephedrine. Combination of ephedrine and a monoamine oxidase inhibitor can produce life-threatening reactions. It should also be avoided in patients undergoing anesthesia with cyclopropane, halothane or other volatile anesthesia. An increased risk of arrhythmias may occur if given to patients receiving cardiac glycosides, quinidine or tricyclic antidepressants, ergot alkaloids and oxytocin. Main adverse effects: Central effects of sympathomimetic agents include: tremor, fear, anxiety, confusion, irritability, insomnia, and psychotic states. Paranoid psychosis, delusions and hallucinations may also follow ephedrine overdose. Effects on the cardiovascular system are complex: vasoconstriction, hypertension, or hypotension and bradycardia, tachycardia, palpitations, cardiac arrest. It can cause local ischemia in chronic topical use. Clinical effects Acute poisoning: Ingestion: Early clinical manifestations of ingestion of high doses of ephedrine consist of nausea and vomiting, followed by insomnia, cardiac arrhythmia, myocardial ischemia, agitation, psychosis and seizures. Parenteral exposure: The parenteral use of ephedrine may cause intracerebral hemorrhage as a result of a rise in arterial pressure. Ventricular arrhythmias have been described. Ingestion: Neurological symptoms that have been described include headache, anxiety, tremor, insomnia, dizziness, seizures. Several cases of psychosis have been reported. Cardiovascular disorders associated with the chronic use of ephedrine may include chest pain, hypertension, arrhythmia, myocardial infarction, cerebral vasculitis and stroke. Skin exposure: Local applications of ephedrine may cause contact dermatitis. Parenteral exposure: The intravenous use of ephedrine causes similar effects as oral ingestion. Other: The vasoconstrictive effects of ephedrine applied topically as nasal spray or drops may cause local ischemia. Course, prognosis, cause of death: Early clinical manifestations of ephedrine overdose consist of nausea and vomiting, followed by headache, agitation, anxiety, tremor, seizures, tachycardia and hypertensive crisis. Severe rise in blood pressure may produce cerebral hemorrhage and myocardial infarction. Ventricular arrhythmia may progress to cardiac arrest and death. Although fatalities have been reported the prognosis is usually good. Systematic description of clinical effects: Cardiovascular: The most common symptoms are arterial hypertension and tachycardia; ventricular arrhythmia, chest pain, myocardial infarction, ischemic or hemorrhagic stroke, cardiac arrest may rarely occur. Respiratory: Respiratory stimulation, bronchodilation, pulmonary edema and apnea. Neurological: CNS: CNS stimulation: anxiety, agitation, tremor, mental confusion, hallucinations, mania, paranoid psychosis may occur; convulsions have been reported. Autonomic nervous system: Ephedrine causes stimulation of the sympathetic nervous system acting on both alpha and beta receptors. Symptoms include tachycardia, arterial hypertension, tremor, sweating, mydriasis. Skeletal and smooth muscle: Ephedrine produces relaxation of smooth muscle. In overdose it may also cause rhabdomyolysis. Gastrointestinal: Nausea and vomiting are common. Urinary: Ephedrine relaxes the vesical detrusor muscle, and increases contraction of the vesical sphincter (alpha agonist action), and can produce acute retention of urine. Dermatological: Eye, ear, nose, throat: local effects: Chronic administration of nasal drops or spray can result in rebound nasal congestion and rhinorrhea. Hematological: Leukopenia. Metabolic: Acid base disturbances and metabolic acidosis or has been observed. Fluid and electrolyte disturbances: Hypokalemia resulting from intracellular shift. Allergic reactions: Contact dermatitis after local application. Sensitization and systemic allergic reactions (severe eczema) have been reported after oral administration. Other clinical effects: Special risks: Ephedrine is present in breast-milk in sufficient concentrations to be harmful to the baby, and is contraindicated in women who are breast-feeding. Patients with ischemic heart disease, hypertension, acute angle glaucoma, hyperthyroidism, prostatic enlargement, or taking monoamine oxidase inhibitor antidepressants should also avoid ephedrine. Other: Chronic use can lead to tolerance with dependence. Ephedrine abuse is a common occurrence and has been associated with several deaths.
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