Adrenaline + Sodium Metabisulphite

Usage

Adrenaline, combined with sodium metabisulfite (as a preservative), is primarily used for the emergency treatment of severe allergic reactions (anaphylaxis) caused by insect bites or stings, foods, medications, and other allergens. It’s also used in cardiac arrest, severe asthma attacks, and during other emergency situations where low blood pressure or breathing difficulties occur. Adrenaline can be also used during surgeries or some medical procedures to prolong local anaesthetic’s effect.

Pharmacological Classification: Adrenergic agonist, Vasopressor, Bronchodilator, Inotrope.

Mechanism of Action: Adrenaline mimics the effects of the sympathetic nervous system. It acts on alpha- and beta-adrenergic receptors, leading to vasoconstriction (increasing blood pressure), bronchodilation (opening airways), and increased heart rate and contractility.

Alternate Names

• Epinephrine (especially in the US)
• Adrenaline Tartrate
• Epinephrine Bitartrate
• Adrenaline Acid Tartrate
• Epinephrine Hydrogen Tartrate
• Suprarenin

Brand Names:
Many brand names exist depending on the manufacturer and formulation (e.g., EpiPen, Adrenaclick, Twinject).

How It Works

Pharmacodynamics: Adrenaline exerts its effects by stimulating alpha and beta-adrenergic receptors throughout the body. Stimulation of alpha-adrenergic receptors causes vasoconstriction, which raises blood pressure. Stimulation of beta1-adrenergic receptors in the heart increases heart rate and force of contraction. Stimulation of beta2-adrenergic receptors in the lungs causes bronchodilation, relieving bronchospasm.

Pharmacokinetics:

• Absorption: Rapidly absorbed after intramuscular (IM) or subcutaneous (SC) injection. Absorption after intravenous (IV) injection - immediate.
• Metabolism: Rapidly metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver and other tissues.
• Elimination: Metabolites are primarily excreted in the urine.

Mode of Action: Adrenaline binds to adrenergic receptors on the cell surface, triggering a cascade of intracellular events, including the activation of adenylate cyclase and the production of cyclic AMP (cAMP). This leads to smooth muscle relaxation in the bronchi and increased contractility in the heart.

Receptor Binding: Adrenaline acts as an agonist at alpha1, alpha2, beta1, and beta2 adrenergic receptors.

Elimination Pathways: Primarily hepatic metabolism via COMT and MAO, followed by renal excretion of metabolites.

Dosage

Standard Dosage

Adults:

• Anaphylaxis: 0.3-0.5 mg IM (0.3-0.5 mL of a 1:1000 solution) into the anterolateral thigh. This can be repeated every 5-15 minutes as needed. Auto-injectors typically deliver a single 0.3 mg dose.
• Cardiac Arrest: 1 mg IV every 3-5 minutes.

Children:

• Anaphylaxis: 0.01 mg/kg IM (maximum single dose 0.5 mg), repeated every 5-15 minutes as needed.
• Cardiac Arrest: 0.01 mg/kg IV every 3-5 minutes.

Special Cases:

• Elderly Patients: Start with lower doses and titrate cautiously due to increased risk of adverse cardiovascular effects.
• Patients with Renal Impairment: Caution is advised; dosage adjustments may be needed.
• Patients with Hepatic Dysfunction: Caution is advised, especially in severe liver impairment, as adrenaline is metabolized in the liver. Dosage adjustments may be needed.
• Patients with Comorbid Conditions: Use with caution in patients with hypertension, heart disease, diabetes, hyperthyroidism.

Clinical Use Cases

• Intubation: Adrenaline is not typically used for routine intubation but may be given in specific cases (e.g., difficult airway, anaphylaxis during intubation)
• Surgical Procedures: Can be added to local anesthetics to prolong their duration of action and reduce bleeding.
• Mechanical Ventilation: Not routinely used.
• Intensive Care Unit (ICU) Use: As an infusion for managing hypotension/shock refractory to other vasopressors.
• Emergency Situations: (e.g., anaphylaxis, cardiac arrest, severe asthma).

Dosage Adjustments

Dosages may need to be adjusted based on patient response and clinical condition. Close monitoring of blood pressure, heart rate, and other vital signs is crucial, especially during IV administration. Renal and hepatic impairment may necessitate dosage reduction.

Side Effects

Common Side Effects:

Palpitations, tachycardia, anxiety, tremors, headache, dizziness, sweating, nausea, vomiting, pallor.

Rare but Serious Side Effects:

Cardiac arrhythmias, myocardial ischemia, hypertension, pulmonary edema, cerebral hemorrhage (especially with IV injection), tissue necrosis (with extravasation).

Long-Term Effects:

Long-term use can lead to cardiovascular complications like cardiomyopathy and heart failure.

Adverse Drug Reactions (ADR):

Anaphylaxis (rarely, due to sodium metabisulfite), severe hypertension, cardiac arrest.

Contraindications

• Hypersensitivity to adrenaline or any component of the formulation (including sodium metabisulfite).
• Close-angle glaucoma
• Shock (other than anaphylactic shock)
• During labor (second stage)

Drug Interactions

• Beta-blockers (can reduce adrenaline’s bronchodilating effects).
• Tricyclic antidepressants (can enhance pressor effects)
• MAO inhibitors (can potentiate adrenaline’s effects)
• Alpha-blockers (can counteract the pressor effects)
• General anesthetics (can increase the risk of cardiac arrhythmias).
• Digoxin, diuretics, levothyroxine.
• OTC drugs and supplements containing sympathomimetics.

Pregnancy and Breastfeeding

Adrenaline is not contraindicated in pregnancy or breastfeeding, but caution is advised. It can reduce placental blood flow, which may affect the fetus. Use only if potential benefit outweighs the risk. It is excreted in breast milk, so breastfeeding should be done cautiously if the mother is receiving adrenaline.

Drug Profile Summary

• Mechanism of Action: Stimulates alpha and beta-adrenergic receptors, leading to vasoconstriction, bronchodilation, increased heart rate and contractility.
• Side Effects: Palpitations, tachycardia, anxiety, tremors, hypertension, arrhythmias (rarely).
• Contraindications: Hypersensitivity, close-angle glaucoma.
• Drug Interactions: Beta-blockers, tricyclic antidepressants, MAO inhibitors.
• Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
• Dosage: 0.3-0.5 mg IM for anaphylaxis (adults), 0.01 mg/kg IM for anaphylaxis (children); 1 mg IV for cardiac arrest (adults), 0.01 mg/kg IV for cardiac arrest (children).
• Monitoring Parameters: Blood pressure, heart rate, ECG, respiratory rate, oxygen saturation, blood glucose.

Popular Combinations

Adrenaline is not typically used in fixed combinations. It may be co-administered with antihistamines and corticosteroids in the management of anaphylaxis. It can also be combined with local anesthetics to prolong their effects.

Precautions

• General Precautions: Use cautiously in patients with cardiovascular disease, hypertension, diabetes, hyperthyroidism. Monitor closely for adverse effects. Avoid IV injection unless trained in its use and patient is monitored closely.
• Specific Populations:
  • Pregnant Women: Use only if essential and benefits outweigh the risks.
  • Breastfeeding Mothers: Use cautiously; monitor infant.
  • Children & Elderly: Age-specific dosage adjustments are necessary.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Adrenaline + Sodium Metabisulphite in anaphylaxis?

A: Adults: 0.3-0.5 mg IM; Children: 0.01 mg/kg IM (max 0.5 mg).

Q2: How is adrenaline administered in cardiac arrest?

A: 1 mg IV every 3-5 minutes.

Q3: What are the common side effects of adrenaline?

A: Palpitations, tachycardia, anxiety, tremors, headache.

Q4: What are the serious side effects of adrenaline?

A: Cardiac arrhythmias, hypertension, pulmonary edema, cerebral hemorrhage (with IV injection).

Q5: Can adrenaline be given during pregnancy?

A: Use with caution only if clearly needed and benefits outweigh the risks to the fetus.

Q6: What are the contraindications to adrenaline administration?

A: Hypersensitivity to adrenaline or components like sodium metabisulfite, closed-angle glaucoma, shock (other than anaphylaxis).

Q7: What are the drug interactions I should be aware of with adrenaline?

A: Beta-blockers, tricyclic antidepressants, MAO inhibitors, some general anesthetics can interact with adrenaline.

Q8: What precautions should I take when administering adrenaline intravenously?

A: IV administration should only be done by healthcare professionals trained in its use. Continuous monitoring of vital signs (BP, HR, ECG) is crucial.

Q9: What is the role of sodium metabisulfite in adrenaline formulations?

A: Sodium metabisulfite acts as a preservative to prevent oxidation and degradation of adrenaline.

Q10: Can adrenaline be given subcutaneously?

A: Yes, adrenaline can be given subcutaneously, but intramuscular injection is preferred for rapid absorption, especially in emergency situations like anaphylaxis.