From the Guidelines
Ephedrine acts as a sympathomimetic drug that stimulates both alpha and beta adrenergic receptors in the body, causing the release of norepinephrine from sympathetic neurons and directly stimulating adrenergic receptors, resulting in vasoconstriction, bronchodilation, increased heart rate, and elevated blood pressure. The mechanism of action of ephedrine is complex and involves multiple pathways. It works primarily by causing the release of norepinephrine from sympathetic neurons and by directly stimulating adrenergic receptors 1. This dual mechanism results in several physiological effects, including:
- Vasoconstriction
- Bronchodilation
- Increased heart rate
- Elevated blood pressure Ephedrine also crosses the blood-brain barrier, producing central nervous system stimulation. Unlike direct-acting sympathomimetics such as epinephrine, ephedrine has a longer duration of action because it is not rapidly metabolized by monoamine oxidase. Clinically, ephedrine is used at doses of 25-50 mg orally (or 5-25 mg intravenously) to treat hypotension, particularly during anesthesia, and has historically been used for bronchodilation in asthma (though now largely replaced by more selective agents) 1. Its mechanism explains both its therapeutic effects and side effects, which can include anxiety, insomnia, tremor, and cardiac arrhythmias. The drug's ability to promote weight loss through increased metabolism and appetite suppression led to its inclusion in many weight loss supplements, though regulatory restrictions have since limited this use due to safety concerns.
From the FDA Drug Label
Ephedrine sulfate is a sympathomimetic amine that directly acts as an agonist at α- and β-adrenergic receptors and indirectly causes the release of norepinephrine from sympathetic neurons. Pressor effects by direct alpha- and beta-adrenergic receptor activation are mediated by increases in arterial pressures, cardiac output, and peripheral resistance. Indirect adrenergic stimulation is caused by norepinephrine release from sympathetic nerves.
The mechanism of action of ephedrine is through its action as a:
- sympathomimetic amine
- α-adrenergic receptor agonist
- β-adrenergic receptor agonist
- norepinephrine-releasing agent This results in:
- Increased arterial pressures
- Increased cardiac output
- Increased peripheral resistance
- Bronchodilation due to activation of β-adrenergic receptors in the lungs
- Positive inotrope and chronotrope action due to stimulation of β-1 adrenoceptors 2 2
From the Research
Mechanism of Action of Ephedrine
The mechanism of action of ephedrine involves its stimulant activity on α- and β-adrenergic receptors, which leads to an increase in heart rate, cardiac output, peripheral resistance, and blood pressure 3. This is due to its direct adrenergic actions as well as its indirect role in releasing epinephrine and norepinephrine, thus increasing the activity of these neurotransmitters at the postsynaptic α and β receptors 4.
Key Effects of Ephedrine
- Increases heart rate and cardiac output
- Increases peripheral resistance and blood pressure
- Releases epinephrine and norepinephrine, increasing their activity at postsynaptic receptors
- Has a mixed adrenergic agonist effect, stimulating both alpha- and beta-adrenergic receptors 5
Comparison with Other Vasopressors
Ephedrine has been compared to other vasopressors, such as phenylephrine, in terms of its effectiveness in treating spinal anesthesia-induced hypotension in parturients undergoing high-risk caesarean section 6. While phenylephrine is often preferred due to its less detrimental effect on umbilical artery pH, ephedrine may be better at increasing maternal arterial blood pressure while preserving uteroplacental blood flow 7.
Sympathomimetic Actions
The sympathomimetic actions of ephedrine are thought to be due to its ability to release norepinephrine from sympathetic nerves, rather than direct receptor activation 7. This indirect mechanism may partly explain why ephedrine is preferred over alpha-adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia-induced hypotension in obstetrics.