Ephedrine

Ephedrine is a stimulant that affects the central nervous system and mimics the action of the sympathetic nervous system. Its primary medical use is to prevent low blood pressure during anesthesia. While it has been tried for asthma, narcolepsy, and obesity, it is no longer the first choice for these issues. Its effectiveness for nasal congestion is uncertain.

The drug can be taken orally or injected into a muscle, vein, or under the skin. When injected into a vein, effects appear quickly; injection into a muscle takes about 20 minutes, and oral doses take roughly an hour to work. Effects last about an hour when injected and up to four hours when taken by mouth.

Common side effects include insomnia, anxiety, headache, hallucinations, elevated blood pressure, rapid heart rate, loss of appetite, and difficulty urinating. More serious risks include stroke and heart attack. Use during pregnancy is probably safe, but it has not been well studied; breastfeeding while taking it is not advised. Ephedrine works by triggering the release of norepinephrine, which indirectly activates alpha and beta adrenergic receptors.

Chemically, it is a substituted amphetamine, specifically the (1R,2S)-enantiomer of beta-hydroxy-N-methylamphetamine. First isolated in 1885, ephedrine entered commercial use in 1926. It is on the World Health Organization's List of Essential Medicines and is available as a generic drug. It occurs naturally in plants of the Ephedra genus.

Medical uses

Over-the-counter dietary supplements containing ephedrine are banned in the United States, except when used in traditional Chinese medicine, where it is listed as má huáng. As a non-catecholamine sympathomimetic, ephedrine has cardiovascular effects similar to adrenaline (epinephrine), including raising blood pressure, heart rate, and the force of heart contractions. Like pseudoephedrine, it acts as a bronchodilator, though pseudoephedrine is much weaker in this regard. Ephedrine can reduce motion sickness, but it is mainly used to counteract the sedation caused by other motion sickness medications.

It has also shown quick and lasting benefits in congenital myasthenic syndrome, both in early childhood and in adults with a specific COLQ gene mutation. The drug is given as intravenous boluses. Repeated doses often need to be increased because the body develops tachyphylaxis, likely due to depletion of catecholamine stores.

Weight loss

Ephedrine promotes modest short-term weight loss, particularly fat loss, but its long-term effects are unknown. In mice, it stimulates thermogenesis in brown adipose tissue, but since adult humans have little brown fat, thermogenesis in people is thought to occur mainly in skeletal muscle. Ephedrine also slows gastric emptying. Methylxanthines like caffeine and theophylline enhance its weight-loss effects, leading to combination products.

Available forms

One such product, the ECA stack, combines ephedrine with caffeine and aspirin and is popular among bodybuilders aiming to reduce body fat before a competition. A 2021 systematic review found that taking 60 to 150 mg of ephedrine daily, with or without caffeine, for 4 to 24 weeks resulted in about 2 kilograms (4.4 pounds) more weight loss than a placebo, along with increased heart rate, lower LDL cholesterol, and higher HDL cholesterol, with no significant change in blood pressure. In the United States, ephedrine is available by prescription as an intravenous solution under brand names such as Akovaz, Corphedra, Emerphed, and Rezipres, as well as in generic forms. It is also sold over-the-counter as 12.5 mg and 25 mg oral tablets for use as a bronchodilator and as a 0.5% nasal spray for decongestion.

Contraindications

Combination products with guaifenesin are available as oral tablets and liquids. Ephedrine is supplied as the hydrochloride or sulfate salt in pharmaceutical formulations. Ephedrine should not be taken with certain antidepressants, specifically norepinephrine-dopamine reuptake inhibitors (NDRIs), because this raises the risk of side effects from excessive norepinephrine levels. Bupropion, an NDRI with an amphetamine-like structure similar to ephedrine, is one such antidepressant; its main action involves norepinephrine and, to a lesser degree, dopamine, and it also releases some serotonin.

Using it with ephedrine may increase side effects. Caution is needed in patients with inadequate fluid replacement, impaired adrenal function, hypoxia, hypercapnia, acidosis, high blood pressure, overactive thyroid, enlarged prostate, diabetes, cardiovascular disease, during delivery if maternal blood pressure is above 130/80 mmHg, and during breastfeeding. Ephedrine is contraindicated in closed-angle glaucoma, pheochromocytoma, asymmetric septal hypertrophy (idiopathic hypertrophic subaortic stenosis), concurrent or recent (within 14 days) use of monoamine oxidase inhibitors (MAOIs), general anesthesia with halogenated hydrocarbons (especially halothane), tachyarrhythmias or ventricular fibrillation, and in those with hypersensitivity to ephedrine or other stimulants.

It should not be used during pregnancy unless specifically prescribed by a qualified physician and only when no other options exist. Ephedrine is a potentially dangerous natural compound. As of 2004, the US Food and Drug Administration had received over 18,000 reports of adverse effects in people using it. Adverse drug reactions are more common when the drug is given systemically (by injection or orally).