Ephedrine

Ephedrine is an alpha and beta-adrenergic agonist belonging to sympathomimetic class

Ephedrine is used in the treatment of Asthma, Hypotension. It is also used to treat Postoperative nausea and vomiting (prevention)

Ephedrine is Readily and completely absorbed from the gastrointestinal tract. Bioavailability: Approx 90% and get distributed throughout the body and accumulates in the liver, lungs, kidneys, spleen, and brain. Crosses the placenta; enters breast milk and Minimally metabolised in the liver, producing small amounts of metabolites, p-hydroxyephedrine, p-hydroxynorephedrine, norephedrine. It is Mainly excreted via urine (approx 77% as unchanged drug and small amount of metabolites). Elimination half-life: Urine pH 5: Approx 3 hours, pH 6.3: Approx 6 hours.

The onset of action of Ephedrine was Within 15-60 minutes.

The Duration of time for Ephedrine was within 2hours.

The Tmax of Ephedrine is approximately 1-2 hous oral administration.

When ephedrine is taken orally at a dose of 25-50 mg, the Cmax ranges from 0.01 to 0.04 mg/L or 10 to 40 µg/mL, and it occurs within 1 to 2 hours after oral administration.

When ephedrine is administered intravenously at a dose of 5-25 mg, the Cmax ranges from 0.05 to 0.5 mg/L or 50 to 500 µg/mL, and it occurs within a few minutes after intravenous administration.

Ephedrine shows common side effects like burning. stinging. increased nasal discharge. dryness inside the nose. sneezing. nervousness. nausea. dizziness.

Ephedrine is available in the form of solution, Injectable solution, Tablet, Prefilled syringe.

Ephedrine is available in India, Germany, Canada, Italy, USA

Ephedrine, a stereoisomer to better-known pseudoephedrine, is a sympathomimetic amine with unique effects due to its indirect mechanism than other sympathomimetic agents like pseudoephedrine and phenylephrine. Ephedrine acts as both a direct and indirect sympathomimetic. It binds directly to both alpha and beta receptors; however, its primary mode of action is indirectly achieved by inhibiting neuronal norepinephrine reuptake and displacing more norepinephrine from storage vesicles.

Ephedrine is available in the form of solution, Injectable solution, Tablet, Prefilled syringe.

Ephedrine is used in the treatment of Asthma, Hypotension (Anesthesia induced).It is also used to treat Postoperative nausea and vomiting (prevention).

Ephedrine is a sympathomimetic that has α- and β- adrenergic activity. It stimulates both adrenergic receptors through direct and indirect mechanisms. It raises the blood pressure by increasing cardiac output, releases the stores of norepinephrine, and causes vasoconstriction of the mucosal blood vessels, thereby resulting in decreased thickness of the nasal mucosa.

Ephedrine is approved for following clinical indications:

Asthma mild intermittent symptoms, Temporary relief of mild symptoms (shortness of breath, chest tightness, wheezing) associated with intermittent asthma, Hypotension (Anesthesia induced)

Although not approved there have been certain off label uses documented for Ephedrine which includes:

Postoperative nausea and vomiting (prevention).

• Asthma, mild intermittent symptoms: Note: Clinical practice guidelines do not recommend nonselective beta agonists or oral beta-2 agonists, including oral ephedrine, for routine management and treatment of asthma due to their potential for excessive cardiac stimulation, especially in high doses
• Hypotension, anesthesia-induced: Note: Ephedrine sulfate 10 mg is equivalent to ephedrine base 7.6 mg; ephedrine hydrochloride 9.4 mg is equivalent to ephedrine base 7.7 mg.
• Ephedrine sulfate IV: Initial: 5 to 10 mg; repeat as needed to maintain BP (maximum total cumulative dose: 50 mg).
• Ephiderine hydrochloride IV: Initial: 4.7 to 9.4 mg; repeat as needed to maintain BP (maximum total cumulative dose: 47 mg).
• Postoperative nausea and vomiting (prevention) (off-label use): IM: 0.5 mg/kg at the end of surgery.

Ephedrine is available in various strengths as23.5 mg/5ml, 50 mg/ml, 5 mg/ml, 5 ml, 12.5 mg, 25 mg.

Ephedrine is available in the form of solution, Injectable solution, Tablet, Prefilled syringe.

Dosage Adjustment for Pediatric Patients:

• Hypotension, anesthesia-induced: Limited data available:

Note: For the parenteral product, two salts are available (sulfate and hydrochloride); ephedrine sulfate 10 mg is equivalent to ephedrine base 7.6 mg; ephedrine hydrochloride 9.4 mg is equivalent to ephedrine base 7.7 mg; clinical relevance of difference between salt forms is unknown. Parenteral products may be available in significantly different concentrations (eg, 50 mg/mL and 5 mg/mL); use caution.

Infants, Children, and Adolescents: Slow IV push: 0.1 to 0.3 mg/kg/dose; use the lowest effective dose; usual adult dose range: 5 to 10 mg/dose; repeat as needed to maintain blood pressure; maximum total dose: 50 mg

• Asthma, intermittent; acute symptom relief : Note: Oral bronchodilator therapy, such as ephedrine, is not recommended for treatment of asthma due to slow onset of action and high rate of adverse effects).
• Children ≥12 years and Adolescents: Oral: 12.5 to 25 mg every 4 hours as needed; maximum daily dose: 150 mg per 24 hours.

Ephedrine is contraindicated in a patient with acute hypertension or tachycardia. Ephedrine increases both chronotropy and inotropy and therefore increases myocardial oxygen demand, and its use requires caution in patients with ischemic heart disease or heart failure. Additionally, it should be avoided in situations where tachycardia would be undesirable, such as aortic stenosis. Alpha-adrenergic stimulation caused by ephedrine results in contraction of the smooth muscle at the base of the bladder, resulting in resistance to urine outflow, and caution is necessary for patients with urinary retention and prostatic hyperplasia.

Concerns related to adverse effects:

• Cardiovascular effects: May cause hypertension if used prophylactically for hypotension (only indicated for treatment of hypotension).

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; increased elimination half-life may occur. Carefully monitor patients with renal impairment for adverse reactions.

Special populations:

• Older adult: Use with caution in the elderly.

Other warnings/precautions:

• Self-medication (OTC use): Prior to self-medication, patients should contact health care provider if they have diabetes, heart disease, hypertension, narrow angle glaucoma, psychiatric or emotional conditions, seizures, thyroid disease, trouble urinating due to an enlarged prostate, ever been hospitalized for asthma, are taking any medications for asthma, depression, obesity, psychiatric or emotional conditions, or are taking any medications that contain caffeine, ephedrine, phenylephrine, or pseudoephedrine (eg, allergy, cough/cold, or pain medications). Avoid foods or beverages that contain caffeine and dietary supplements that have a stimulant effect. Discontinue use and contact health care provider if asthma is not better in 60 minutes or gets worse, >2 asthma attacks in a week, need >6 caplets in 24 hours or >4 caplets in 24 hours for ≥3 days, or if insomnia, nervousness, a rapid heartbeat, seizures, or tremors occur.

• Tolerance: Tachyphylaxis and tolerance may develop with repeated, prolonged, or excessive administration; temporary cessation of therapy restores its effectiveness.

Pregnancy Category C: Teratogenicity studies have been performed in animals.

• Common Adverse effects:

Rebound nasal congestion, mucosal ulceration, epistaxis, discomfort including dryness, stinging, burning (nasal), Hypertension (IV).

• Less Common Adverse effects:

Palpitations, cardiac arrhythmias, tachycardia

• Rare Common Adverse effects:

Headache, dizziness, insomnia, irritability, tremors, tolerance.

May increase risk of arrhythmias with halogenated anaesthetics (e.g. halothane, cyclopropane), cardiac glycosides, quinidine, and TCAs. May block the antihypertensive effect of adrenergic neurone blockers (e.g. guanethidine). Increased risk of vasoconstrictor or pressor effects with ergot alkaloids and oxytocin. May increase the incidence of nausea, insomnia and nervousness with theophylline. May increase clearance of dexamethasone. May potentiate stimulant effect of caffeine.

Potentially Fatal: May enhance the adverse or toxic effect of other indirect sympathomimetics (e.g. phenylephrine, phenylpropanolamine, pseudoephedrine, methylphenidate) and α-sympathomimetic agents. Enhanced hypertensive effect with MAOIs.

The common side effects of Ephedrine include the following Rebound nasal congestion, mucosal ulceration, epistaxis, discomfort including dryness, stinging, burning (nasal), Hypertension (IV).

Symptoms: Nausea, vomiting, headache, fever, hypertension, restlessness, ventricular and supraventricular arrhythmias, respiratory depression, convulsion, paranoid psychosis, delusions and hallucinations.

Management: Supportive and symptomatic treatment. May administer benzodiazepine or neuroleptic agent for CNS stimulant effects. For severe hypertension, may give parenteral antihypertensives such as nitrates, Ca channel blockers, Na nitroprusside, labetalol or phentolamine. Perform emesis or gastric lavage for severe oral ephedrine overdosage.

Pharmacodynamic

Ephedrine acts as both a direct and indirect sympathomimetic. It binds directly to both alpha and beta receptors; however, its primary mode of action is indirectly achieved by inhibiting neuronal norepinephrine reuptake and displacing more norepinephrine from storage vesicles.This action allows norepinephrine to be present in the synapse longer to bind postsynaptic alpha and beta receptors.

Pharmacokinetics

• Absorption: Readily and completely absorbed from the gastrointestinal tract. Bioavailability: Approx 90%.
• Distribution: Distributed throughout the body and accumulates in the liver, lungs, kidneys, spleen, and brain. Crosses the placenta; enters breast milk.
• Metabolism: Minimally metabolised in the liver, producing small amounts of metabolites, p-hydroxyephedrine, p-hydroxynorephedrine, norephedrine.
• Excretion: Mainly via urine (approx 77% as unchanged drug and small amount of metabolites). Elimination half-life: Urine pH 5: Approx 3 hours, pH 6.3: Approx 6 hours.

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Ephedrine?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/