Adrenaline

Usage

• Adrenaline is prescribed for various medical conditions, including:

  • Cardiac arrest
  • Anaphylaxis
  • Severe asthma attacks
  • Septic shock
  • Bradycardia with adverse signs (e.g., shock, syncope, myocardial ischemia, heart failure)
  • Hypotension (second-line treatment for cardiogenic shock, after dobutamine)
  • During CPR, to increase coronary and cerebral blood flow.
  • Ocular procedures, such as glaucoma surgery, to reduce intraocular pressure.

• Pharmacological Classification: Adrenaline is classified as a vasopressor, inotropic agent, bronchodilator, and sympathomimetic.

• Mechanism of Action: Adrenaline acts on both alpha and beta-adrenergic receptors, mimicking the effects of the sympathetic nervous system. This leads to vasoconstriction (increasing blood pressure), increased heart rate and contractility (improving cardiac output), and bronchodilation (opening airways).

Alternate Names

• Epinephrine (especially in the United States)

• Brand Names:

  • Adrenalin®
  • EpiPen® (auto-injector)
  • Twinject® (auto-injector)
  • Auvi-Q® (auto-injector)
  • Symjepi™ (prefilled syringe)

How It Works

• Pharmacodynamics: Adrenaline exerts its effects by binding to alpha and beta-adrenergic receptors throughout the body. Stimulation of alpha-1 receptors causes vasoconstriction, increasing blood pressure. Activation of beta-1 receptors increases heart rate and contractility, leading to enhanced cardiac output. Stimulation of beta-2 receptors induces bronchodilation, relaxing the smooth muscles of the airways.

• Pharmacokinetics: Adrenaline is rapidly absorbed following intramuscular (IM) or subcutaneous (SC) administration but has limited bioavailability due to rapid metabolism at the injection site and by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver and other tissues. Intravenous (IV) administration provides immediate onset of action, although the effects are short-lived. It is rapidly eliminated mainly through renal excretion.

• Mode of Action: Adrenaline binds to G protein-coupled receptors on the cell surface, activating intracellular signaling cascades and leading to the physiological effects described above.

• Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Adrenaline primarily acts as a receptor agonist, binding to and activating alpha and beta-adrenergic receptors. It does not significantly inhibit enzymes or directly modulate neurotransmitter release.

• Elimination Pathways: Adrenaline is metabolized by COMT and MAO in the liver and other tissues, and its metabolites are excreted primarily by the kidneys.

Dosage

Standard Dosage

Adults:

• Anaphylaxis: 0.3-0.5 mg IM in the anterolateral thigh. May repeat every 5-15 minutes as needed.
• Cardiac arrest: 1 mg IV every 3-5 minutes during CPR.

Children:

• Anaphylaxis: 0.01 mg/kg IM (max single dose of 0.5 mg), repeated every 5-15 minutes as needed. Weight-based dosing is crucial for pediatric patients.
• Cardiac Arrest: 0.01mg/kg (0.1ml/kg of 1:10,000) IV/IO every 3-5 minutes.

Special Cases:

• Elderly Patients: Start with a lower dose and titrate cautiously, monitoring for adverse events.

• Patients with Renal Impairment: Dose adjustment may be necessary depending on the degree of impairment. Consult local guidelines.

• Patients with Hepatic Dysfunction: Dose adjustment is usually not required.

• Patients with Comorbid Conditions: Consider pre-existing cardiovascular disease, hypertension, and diabetes.

Clinical Use Cases:

• Intubation: May be used to manage hypotension or bradycardia during intubation if other measures are ineffective.

• Surgical Procedures: Used in ocular surgery for mydriasis and to reduce bleeding; also used with local anesthetics to prolong their effects.

• Mechanical Ventilation: Not routinely indicated.

• Intensive Care Unit (ICU) Use: Infusion 0.01-1 mcg/kg/min (titrate to effect) via central line for hypotension (second-line treatment for cardiogenic shock).

• Emergency Situations: 1 mg IV push every 3-5 minutes for cardiac arrest; 0.3-0.5 mg IM for anaphylaxis. Higher doses may be considered in refractory cases, under expert guidance and with careful monitoring.

Dosage Adjustments:

• Renal/Hepatic Dysfunction: Dose modification may be needed based on the degree of impairment.

• Metabolic Disorders: Adjust dose based on specific metabolic condition and consult local guidelines.

• Genetic Polymorphisms: No specific dosage adjustments are routinely made for genetic variations. However, consider monitoring response to therapy.

Side Effects

Common Side Effects:

• Anxiety, nervousness, tremors, palpitations, tachycardia, headache, dizziness, sweating, nausea, vomiting.

Rare but Serious Side Effects:

• Cardiac arrhythmias (e.g., ventricular fibrillation, ventricular tachycardia), myocardial ischemia, pulmonary edema, hypertensive crisis, cerebral hemorrhage.

Long-Term Effects: Generally, not applicable, as adrenaline is used for short-term treatment. Chronic use may lead to cardiovascular complications (e.g., cardiomyopathy, hypertension).

Adverse Drug Reactions (ADR):

• Angina, dyspnea, pallor, cyanosis, altered mental status, seizures.

Contraindications:

• Hypersensitivity to adrenaline or any of its components.
• Angle-closure glaucoma (for ophthalmic use).
• Use with nonselective beta-blockers.
• During the second stage of labor (epidural block).
• With local anesthetics in areas with end-arterial circulation (fingers, toes, penis, nose, ears).

Drug Interactions

• Beta-blockers: May antagonize the effects of adrenaline.

• Tricyclic antidepressants (TCAs): May potentiate the cardiovascular effects of adrenaline.

• MAO inhibitors: May potentiate the pressor effects of adrenaline.

• COMT inhibitors: May increase and prolong the effects of adrenaline.

• General anesthetics (halogenated): May increase the risk of cardiac arrhythmias.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Category C (FDA). Adrenaline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Fetal Risks: Potential for reduced uterine blood flow and fetal hypoxia.

• Breastfeeding: Adrenaline is likely present in breast milk; use with caution.

Drug Profile Summary

• Mechanism of Action: Agonist of alpha and beta-adrenergic receptors.

• Side Effects: Anxiety, tremors, tachycardia, palpitations, headache, hypertension, arrhythmias.

• Contraindications: Hypersensitivity, angle-closure glaucoma.

• Drug Interactions: Beta-blockers, TCAs.

• Pregnancy & Breastfeeding: Category C; use with caution.

• Dosage: Varies by indication and patient factors; consult dosage guidelines.

• Monitoring Parameters: Heart rate, blood pressure, oxygen saturation, cardiac rhythm.

Popular Combinations

• Adrenaline is frequently used in combination with local anesthetics (e.g., lidocaine) to prolong their duration of action and reduce bleeding.

Precautions

• Monitor patients closely for adverse reactions.

• Use cautiously in elderly patients, those with pre-existing cardiovascular disease, and those receiving interacting medications.

• Administer through central venous access whenever possible for infusions. Avoid peripheral venous administration unless absolutely necessary due to the risk of extravasation and tissue necrosis. If given peripherally, closely monitor IV site.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Adrenaline?

A: The dosage varies based on the indication and patient factors. Consult the detailed dosage guidelines provided above.

Q2: What is the preferred route of administration for adrenaline in anaphylaxis?

A: Intramuscular (IM) injection into the anterolateral thigh is the preferred route for anaphylaxis.

Q3: How often can adrenaline be administered in anaphylaxis?

A: It can be repeated every 5-15 minutes as needed, based on the patient’s response and the severity of the reaction.

Q4: What is the dose of adrenaline for cardiac arrest?

A: 1 mg IV push every 3-5 minutes during CPR for adults.

Q5: What are the common side effects of adrenaline?

A: Common side effects include anxiety, tremors, palpitations, tachycardia, headache, and dizziness.

Q6: Can adrenaline be administered during pregnancy?

A: Adrenaline is a Pregnancy Category C drug, meaning it should be used only if the potential benefit justifies the potential risk to the fetus.

Q7: What are the critical drug interactions to be aware of with adrenaline?

A: Beta-blockers can antagonize the effects of adrenaline. Tricyclic antidepressants (TCAs) can enhance the cardiovascular effects. MAO and COMT inhibitors can both potentiate the pressor effects of adrenaline.

Q8: What precautions should be taken when administering adrenaline through a peripheral IV line?

A: Due to the vasoconstrictive properties, adrenaline should be administered through a central venous access. It can cause extravasation and tissue necrosis if given peripherally. If a peripheral line is used, ensure it is patent, administer slowly, and closely monitor the IV site for signs of extravasation.

Q9: What is the role of adrenaline during mechanical ventilation?

A: Adrenaline is generally not indicated for routine use during mechanical ventilation. However, it may be used to treat specific conditions like severe hypotension or bradycardia refractory to other treatments, under careful monitoring and as directed by a specialist.

Q10: Can adrenaline be mixed with other drugs in the same IV line?

A: Ideally, adrenaline should be administered through a dedicated IV line to avoid potential incompatibilities and to ensure accurate delivery. If using the same line, consult compatibility charts and local guidelines before administering other medications, as some drugs are incompatible with adrenaline.