Ephedrine
9 August 2026
Quick answer
Ephedrine is a simple and accessible sympathomimetic for managing hypotension and bradycardias intra operatively
Contents
Introduction
Ephedrine is a sympathomimetic that works both directly, on alpha and beta adrenergic receptors, and indirectly, by releasing noradrenaline from nerve endings. It is the drug most of us reach for when the blood pressure sags a bit after induction or a spinal, and this episode covers where it came from, what it does to each system, its kinetics, and why it is a contested choice in obstetrics.
Initially classified as ‘medium bitter’ herb in 2760 BC by Emperor Shen Nung (China) noting it as working with the lung and bladder meridians, in 1596 AD noted in China to be a circulatory stimulant and an ‘antipyretic and cough suppressant’ [like pseudoephedrine].
Ephedra plant
Ephedrine Molecule
Pharmacology
Physico-chemical properties
| Property | Detail |
|---|---|
| Name | Ephedrine |
| Class | Sympathomimetic |
| Chemical make-up | Phenethylamine Alkaloid |
| History | Derived originally from the Ephedra species of plants (many types). Nagayoshi Nagai (1844–1929) initially isolated it in 1885. It was handed over to a physiologist type, who experimented with it - and was promptly branded a dangerous agent - and not safe to do anything more than drop it in your eyes to counter atropine! 30 years later someone else dabbled (probably in more careful doses) identifying it to have similar effects to adrenaline and tyramine. In 1923, in China, some western physiologist types were exploring some of the pharmacopoeia of China - and checked out Ma Huang (Ephedra) identifying its sympathomimetic properties, and its effects on various systems (BP/HR/Pupils/Bronchial Smooth muscle) Was originally used as an Asthma treatment up til the 1950s (isoprenaline came in) |
| Isomer status | There are four isomers of ephedrine, the only active one is L-ephedrine |
| Presentation | Intravenous, tablet, nasal drops |
| Molecular weight | 165 g/mol |
Pharmacodynamics and side effects
| Property | Detail |
|---|---|
| Mechanism of action | Directly stimulates alpha and beta adrenergic receptors, Indirectly - releases noradrenaline from nerve endings, Inhibits monoamine oxidase (impairs noradrenaline breakdown) |
| Treatment for | Hypotension, Nocturnal enuresis, Narcolepsy, Diabetic ANS neuropathy, Hiccups, Nasal decongestion, in a pinch briefly helps myasthenia |
| Dose | 3-9 mg IV - 15-60 mg Orally/IM TDS |
| Cardiovascular | Increased HR, Increased BP, in overdose tachyarrhythmias, in anaesthesia doses will potentiate adrenaline - in massive doses, inhibits the effect of adrenaline and potentiates vasodilation + increased myocardial O₂ demand |
| Respiratory | Bronchodilator + stimulant to breathe |
| CNS | Crosses the blood brain barrier causing stimulatory effects, wakes rabbits from some anaesthetic agents (not barbiturates tho), Insomnia, tremor, headaches, nausea / vomiting |
| Eyes | Mydriasis |
| GI/GU | Relaxes GI Smooth muscle and slows peristalsis, alpha agonism constricts urinary sphincters |
| Hepatic | Increased glycogenolysis |
| Cautions | historic overuse can lead to dependence, withdrawal and psychosis! (it does behave a bit like methamphetamines, and indeed is a precursor to crystal meth). Can also cause hyperthermia (hypothalamic effects). |
| Obstetric Cautions | May result in a worse cord gas, although the study that says phenylephrine is the best choice comparatively, ‘isn’t built on the best foundation’. |
| Other Notes | Exhibits tachyphylaxis as noradrenaline stores deplete |
| Toxic | Mixed with MAOIs / Beta blockers / Ergot alkaloids = Hypertensive crisis |
Pharmacokinetics
| Parameter | Detail |
|---|---|
| Absorption | Well absorbed orally / IM / SC - Oral Bioavailability 88% |
| Distribution | Volume of distribution: 122-320 L (3 L/kg); Crosses the BBB and the Placenta, pKa ~10 |
| Metabolism | Resistant to MAO / COMT - small amount metabolised by N-demethylation into phenylpropanolamine (norephedrine). Also deaminated into benzoic acid, hippuric acid and 1-phenylpropane-1,2-diol |
| Elimination | 65% excreted unchanged in urine - Elimination half-life 6.3 hours (shorter HL in acidic urine) |
In anaesthesia
In which patient cohort is ephedrine relatively contraindicated?
- Classically not reached for during LSCS as it has been found to alter fetal pH for the worse.
- However some obstetric anaesthetists don’t tie their hands behind their back in this regard (I would recommend sticking with the phenylephrine and giving them a terrifically awful dry mouth with glycopyrrolate, to avoid the obvious ‘that’s not practice’ conversation.)
Which groups of patients respond poorly to ephedrine?
- The elderly populus, either secondary to fewer adrenergic receptors and a ‘tired’ sympathetic nervous system or the fact that they are beta blocked!
Which groups of patients may respond dramatically to ephedrine?
Patients already on agents that inhibit MAO (MAOIs) will have an outlandish response, as well as those already ‘running away from a tiger’ courtesy of large doses of cocaine / methamphetamine or serotonergic/dopaminergic agents.
For the truly and deeply curious individuals
From the chapter on Ephedra in the book The Healing Hand: Man and Wound in the Ancient World by Guido Majno (Harvard University Press, 1975), a book I very much enjoyed reading about the care of the wound throughout history, there is an interesting historical finding that is little documented (and may be entirely made up). Carl F. Schmidt and Ko Kuei Chen between 1923-1924 working at Peking Union Medical College were testing Chinese medicinal herbs, isolating ephedrine and identifying its clinical benefit. However as we know it was isolated some 38 years earlier, but back at that earlier time the researchers had inadvertently been injecting highly potent, large doses into animals killing them off - writing off this asthma treatment as lethal for a further time! The irony here is that in some very old texts courtesy of Pliny the Elder and Dioscorides, they had isolated an impure decoction of the stuff and this would have done the trick for said asthmatic ills.
As an aside, a great book to read, describing a method of locating where to cut for an empyema in ancient Egypt by slathering someone with clay and stabbing at the bit that dried the fastest (the warmest, most inflamed patch).
Summary
Ephedrine is likely one of the most ancient of drugs lurking in your cupboard! (Atropine - 4th century BC - Theophrastus using a mandrake wine for sleeplessness and pain)
- Class: Sympathomimetic, a phenethylamine alkaloid
- Mechanism: Directly stimulates alpha and beta adrenergic receptors, indirectly releases noradrenaline from nerve endings
- Dose: 3-9 mg IV; 15-60 mg orally/IM TDS
- Kinetics: Oral bioavailability 88%; Vd 122-320 L (3 L/kg); resistant to MAO/COMT with a small amount N-demethylated to norephedrine; 65% excreted unchanged in urine; elimination half-life 6.3 hours
- Side effects: Tachyarrhythmias in overdose, insomnia, tremor, headaches, nausea and vomiting, mydriasis, tachyphylaxis as noradrenaline stores deplete
- Interactions: MAOIs, beta blockers and ergot alkaloids - hypertensive crisis
References
- PubChem, Compound Summary: Ephedrine. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/compound/Ephedrine
- White, L.M., Gardner, S.F., Gurley, B.J., Marx, M.A., Wang, P.-L. and Estes, M. (1997), Pharmacokinetics and Cardiovascular Effects of Ma-Huang (Ephedra sinica) in Normotensive Adults. The Journal of Clinical Pharmacology, 37: 116-122. https://doi.org/10.1002/j.1552-4604.1997.tb04769.x
- Deranged Physiology, Ephedrine. https://derangedphysiology.com/main/pharmacopeia/ephedrine
- Pharmacological Effects of Ephedrine. ResearchGate. https://www.researchgate.net/publication/278707660_Pharmacological_Effects_of_Ephedrine
- González-Juárez DE, Escobedo-Moratilla A, Flores J, Hidalgo-Figueroa S, Martínez-Tagüeña N, Morales-Jiménez J, Muñiz-Ramírez A, Pastor-Palacios G, Pérez-Miranda S, Ramírez-Hernández A, et al. A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties. Molecules. 2020; 25(14):3283. https://doi.org/10.3390/molecules25143283
- Gaddum JH. Ephedrine. Br Med J. 1938 Apr 2;1(4030):713-7. doi: 10.1136/bmj.1.4030.713. PMID: 20781356; PMCID: PMC2086103.
- Elhadef, Khaoula, Smaoui, Slim, Fourati, Mariam, Ben Hlima, Hajer, Chakchouk Mtibaa, Ahlem, Sellem, Imen, Ennouri, Karim, Mellouli, Lotfi, A Review on Worldwide Ephedra History and Story: From Fossils to Natural Products Mass Spectroscopy Characterization and Biopharmacotherapy Potential, Evidence-Based Complementary and Alternative Medicine, 2020, 1540638, 22 pages, 2020. https://doi.org/10.1155/2020/1540638
Further reading
Common questions
In which patient cohort is ephedrine relatively contraindicated?
Classically not reached for during LSCS as it has been found to alter fetal pH for the worse, however ,some obstetric anaesthetists don't tie their hands behind their back in this regard (I would recommend sticking with the phenylephrine and giving them a terrifically awful dry mouth with glycopyrrolate, to avoid the obvious 'that's not practice' conversation.)
Which groups of patients respond poorly to ephedrine?
The elderly populus, either secondary to fewer adrenergic receptors and a 'tired' sympathetic nervous system or the fact that they are beta blocked!
Which groups of patients may respond dramatically to ephedrine?
Patients already on agents that inhibit MAO (MAOIs) will have an outlandish response, as well as those already 'running away from a tiger' courtesy of large doses of cocaine / methamphetamine or serotonergic/dopaminergic agents. Equally you may see an outsized response when given to a patient with a heart transplant, much like the exaggerated adrenaline response.
Thanks for listening. Take it day by day, don't overcook yourself — keep studying.
Transcript
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