Usage
Ephedrine is prescribed for the treatment of clinically significant hypotension during anesthesia, including hypotension resulting from spinal or epidural anesthesia. It’s also used to treat breathing problems (as a bronchodilator), nasal congestion (as a decongestant), and myasthenia gravis. Other uses include treatment for narcolepsy, menstrual problems (dysmenorrhea), or urine-control problems.
It is classified pharmacologically as a sympathomimetic amine.
Ephedrine’s mechanism of action involves both direct and indirect stimulation of adrenergic receptors. Directly, it activates alpha and beta-adrenergic receptors. Indirectly, it enhances the release of norepinephrine and inhibits its reuptake. These actions lead to increased heart rate, cardiac output, and peripheral vascular resistance, thus raising blood pressure. Bronchodilation occurs due to beta-adrenergic receptor activation in the lungs.
Alternate Names
The International Nonproprietary Name (INN) is Ephedrine. Common salt forms include ephedrine hydrochloride and ephedrine sulfate. There are numerous brand names for ephedrine-containing products, varying by country and formulation, examples include Akovaz and Emerphed. Ephedrine is also a component of many combination products often found over-the-counter.
How It Works
Pharmacodynamics: Ephedrine increases blood pressure, heart rate, and cardiac output. It also variably increases peripheral vascular resistance, causing bronchodilation and increased resistance to urine outflow.
Pharmacokinetics:
- Absorption: Ephedrine is readily absorbed orally and parenterally.
- Metabolism: Primarily metabolized in the liver to norephedrine.
- Elimination: Both ephedrine and norephedrine are excreted in the urine. Elimination is affected by urine pH; excretion is increased in acidic urine and reduced in alkaline urine. The plasma elimination half-life after oral administration is approximately 6 hours, which may be prolonged in patients with renal impairment.
Mode of Action: Ephedrine is a direct and indirect-acting sympathomimetic amine. It directly activates alpha and beta-adrenergic receptors, leading to vasoconstriction, bronchodilation, and increased heart rate. Indirectly, it displaces norepinephrine from storage vesicles in presynaptic neurons, increasing norepinephrine levels in the synaptic cleft and further potentiating adrenergic effects.
Receptor Binding, Enzyme Inhibition, Neurotransmitter Modulation: Ephedrine primarily binds to alpha and beta-adrenergic receptors. It modulates the release and reuptake of the neurotransmitter norepinephrine. There is no significant enzyme inhibition associated with its therapeutic effects.
Elimination Pathways: Renal excretion is the primary route of elimination for both ephedrine and its metabolite, norephedrine. Metabolism occurs primarily in the liver.
Dosage
Standard Dosage
Adults:
- Hypotension associated with anesthesia: 5 to 10 mg IV bolus, repeated as needed, maximum total dose 50 mg. Alternative regimens include 3 to 7.5 mg (maximum 10 mg) slow intravenous injection every 3-4 minutes, maximum 30 mg. Dosage should be titrated to the desired blood pressure.
- Asthma/Bronchospasm (Oral): 25 mg every four hours, not to exceed 150 mg/day.
- Other indications: Dosing varies depending on indication and formulation. Parenteral: 25 to 50 mg IM or SC.
Children:
- Limited data exist to support dosing in children. Safety and efficacy haven’t been fully established.
- Unofficial guidelines suggest 0.5 mg/kg IM or SC. For other routes and indications, further consultation with pediatric specialists is necessary, with careful monitoring.
Special Cases:
- Elderly Patients: Start with the lowest dose due to increased risk of adverse effects and potential for decreased organ function. Close monitoring is essential.
- Patients with Renal Impairment: Reduce dosage and monitor closely due to the potential for decreased clearance and prolonged half-life.
- Patients with Hepatic Dysfunction: Caution advised, dose adjustment may be needed.
- Patients with Comorbid Conditions (e.g., diabetes, cardiovascular disease): Careful monitoring required; dose adjustments may be necessary.
Clinical Use Cases
- Intubation: May be used to support blood pressure during intubation.
- Surgical Procedures: Commonly employed to address hypotension during surgery.
- Mechanical Ventilation: May be beneficial in managing hypotension in ventilated patients.
- Intensive Care Unit (ICU) Use: Utilized for blood pressure support.
- Emergency Situations: Can be used in specific emergency situations, such as during cardiac arrest or severe hypotension.
Dosage Adjustments
Dose modifications are necessary based on patient-specific factors including renal or hepatic dysfunction, age, and the presence of comorbid conditions. Close monitoring of physiological parameters like heart rate and blood pressure is important. Genetic polymorphisms affecting drug metabolism have not been studied extensively and are not currently part of routine dosing considerations.
Side Effects
Common Side Effects
Nervousness, anxiety, dizziness, headache, nausea, loss of appetite, insomnia, tachycardia, palpitations, sweating, vomiting.
Rare but Serious Side Effects
Hypertension, cardiac arrhythmias, stroke, seizures, acute urinary retention (particularly in males with prostatic hypertrophy).
Long-Term Effects
Tachyphylaxis can develop with prolonged or repeated use. Chronic complications from long-term use are not well-documented, but potential cardiovascular risks should be considered.
Adverse Drug Reactions (ADR)
Severe hypertension, cardiac ischemia, dysrhythmias, pulmonary edema, stroke.
Contraindications
Hypersensitivity to ephedrine, closed-angle glaucoma, pheochromocytoma, concomitant use of non-selective MAOIs (or within 14 days of their discontinuation). Relative contraindications include: cardiovascular disease, hyperthyroidism, diabetes, prostatic hypertrophy, and concomitant use of halogenated anesthetics, cardiac glycosides, or tricyclic antidepressants. Concurrent or recent use with other sympathomimetic drugs is generally avoided.
Drug Interactions
Ephedrine can interact with MAOIs, tricyclic antidepressants, some anesthetics, and other sympathomimetic agents, potentially causing severe hypertension or cardiac arrhythmias. Beta-blockers may diminish or negate ephedrine’s effects. It can also interact with some antihypertensive medications. Coadministration with oxytocin may increase the risk of hypertension.
Pregnancy and Breastfeeding
Ephedrine should be used during pregnancy only if the potential benefits outweigh the risks. It’s unknown if it passes into breast milk, and due to potential risks to the infant, breastfeeding while using ephedrine is generally not recommended.
Drug Profile Summary
- Mechanism of Action: Directly and indirectly activates adrenergic receptors, increasing blood pressure and causing bronchodilation.
- Side Effects: Nervousness, anxiety, dizziness, headache, insomnia, tachycardia, palpitations. Severe effects: hypertension, cardiac arrhythmias.
- Contraindications: Hypersensitivity, closed-angle glaucoma, pheochromocytoma, concomitant use of MAOIs.
- Drug Interactions: MAOIs, tricyclic antidepressants, certain anesthetics, other sympathomimetics, oxytocin.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks during pregnancy; not recommended while breastfeeding.
- Dosage: Varies by indication and patient factors; commonly 5-10 mg IV bolus for hypotension, 25 mg oral for asthma.
- Monitoring Parameters: Heart rate, blood pressure, electrocardiogram (ECG), respiratory status.
Popular Combinations
Ephedrine is sometimes used in combination with guaifenesin in some oral formulations for asthma and bronchospasm. Some older, unapproved formulations combined ephedrine with caffeine and aspirin for weight loss, but these are no longer recommended due to safety concerns.
Precautions
- General Precautions: Monitor vital signs, assess for pre-existing conditions, screen for drug interactions.
- Specific Populations: Avoid or use with extreme caution in pregnancy and breastfeeding. Adjust dosage in elderly and patients with renal impairment.
- Lifestyle Considerations: May impair ability to operate machinery or drive. Caution patients about potential interactions with alcohol and caffeine.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ephedrine for hypotension during anesthesia?
A: 5-10 mg IV bolus, repeated as needed to a maximum of 50 mg. Other regimens may be used depending on clinical context.
Q2: How does Ephedrine work to raise blood pressure?
A: It directly and indirectly activates adrenergic receptors, leading to increased heart rate, cardiac output, and peripheral resistance.
Q3: What are the common side effects of Ephedrine?
A: Nervousness, anxiety, insomnia, tachycardia, palpitations, headache, dizziness.
Q4: What are the contraindications for Ephedrine use?
A: Hypersensitivity, closed-angle glaucoma, pheochromocytoma, concurrent use of MAOIs.
Q5: Can Ephedrine be used in patients with renal impairment?
A: Yes, but with caution. Reduced dosage and careful monitoring are required.
Q6: Is Ephedrine safe to use during pregnancy?
A: Use only if the potential benefits outweigh the risks. It’s best to avoid use if possible.
Q7: Can Ephedrine interact with other medications?
A: Yes. Significant interactions can occur with MAOIs, tricyclic antidepressants, certain anesthetics, and other sympathomimetics.
Q8: What should I monitor in patients receiving Ephedrine?
A: Closely monitor heart rate, blood pressure, ECG, and respiratory status.
Q9: What is the maximum recommended daily dose of Ephedrine for adults?
A: For oral formulations, the maximum dose is generally 150mg/day. For parenteral administration, the maximum total dose depends on the indication, but should generally not exceed 50mg for IV bolus administration, and 150mg total over a 24 hour period.
Q10: How should Ephedrine be administered intravenously?
A: It should be given as a slow intravenous injection or bolus, diluted according to package instructions when necessary. Take care to avoid extravasation.
