Sympathomimetic (α/β catecholamine)
Adrenaline (epinephrine) is an emergency medicine used mainly to treat anaphylaxis (severe allergic reaction) and in cardiac arrest or shock. In anaphylaxis, the injection must be given immediately — do not wait.
Also known as: Epipen, adrenalina, epinephrine, adrenaline
Epinephrine + theophylline: additive cardiac effects and hypokalaemia.
The epinephrine label explicitly documents the "drugs potentiating the hypokalaemic effects of epinephrine — potassium-depleting diuretics, corticosteroids and theophylline" and recommends "observing for the development of cardiac arrhythmias" with these combinations. Conversely, theophylline "increases release of endogenous catecholamines", with an "increased risk of ventricular arrhythmias" (theophylline label), and lowers the seizure threshold. The combination is mainly relevant in hospital settings (epinephrine infusion + theophylline/aminophylline) and in patients with ischaemic heart disease or pre-existing hypokalaemia. Monitor serum potassium, ECG and signs of toxicity (tremor, palpitations, arrhythmias); correct hypokalaemia and reduce doses whenever possible.
Epinephrine + theophylline: theophylline potentiates epinephrine hypokalaemia and both increase arrhythmia risk. Monitor potassium and cardiac rhythm.
Both are β-adrenergic stimulants; they increase the risk of tachycardia, tremor and hypokalaemia.
Serum potassium and ECG.
Tachyarrhythmias, tremor, symptomatic hypokalaemia.
Monitor potassium and heart rhythm, especially in cardiovascular patients.
DailyMed (FDA) — approved Epinephrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5726eeca-db88-ba8e-e063-6294a90a927d ; approved Theophylline label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e64036a-ee3e-42e7-9e59-881f88a4e298 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Epinephrine + antiarrhythmic: risk of ventricular arrhythmias.
Amiodarone prolongs the QT interval and ventricular repolarisation, and epinephrine, by stimulating beta and alpha receptors, increases automaticity and myocardial oxygen demand. Together they raise the risk of ventricular tachycardias and extrasystoles, especially in emergencies (cardiac arrest, anaphylaxis) or ischaemic heart disease. Hypokalaemia further favours arrhythmias. Monitor the ECG, correct electrolytes (potassium and magnesium) and use the lowest effective epinephrine doses.
Epinephrine + amiodarone: increased risk of ventricular arrhythmias and tachycardia (amiodarone prolongs QT and epinephrine increases automaticity). Use with caution and monitor ECG.
Adrenergic stimulation adds to drugs that prolong repolarisation, increasing arrhythmia risk.
ECG and blood pressure.
Palpitations, tachycardia, ventricular arrhythmias.
Use with caution in cardiac patients; monitor heart rhythm.
DailyMed (FDA) — approved Epinephrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5726eeca-db88-ba8e-e063-6294a90a927d ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Epinephrine + fluoroquinolone: theoretical risk of QTc prolongation.
Both epinephrine and ciprofloxacin can, in particular circumstances, contribute to QT interval prolongation, although the additive risk is essentially theoretical for this combination. In clinical practice the combination arises mainly in emergencies (anaphylaxis in a patient taking ciprofloxacin) or in severe infection with haemodynamic instability. The combination does not need to be avoided, but in patients with risk factors (congenital long QT, hypokalaemia, bradycardia, other QT-prolonging drugs) it is prudent to monitor the ECG and correct electrolytes.
Epinephrine + fluoroquinolone: theoretical risk of QTc prolongation. Monitor the ECG in at-risk patients.
Both may prolong the QTc interval in susceptible patients.
ECG in at-risk patients.
Palpitations, syncope.
Use with caution in patients with QTc risk factors.
DailyMed (FDA) — approved Epinephrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5726eeca-db88-ba8e-e063-6294a90a927d ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c527d138-e32c-418f-9573-a3d8a796279f — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Epinephrine + β2-agonist: additive sympathetic effects and hypokalaemia.
Epinephrine activates alpha and beta receptors (beta1 and beta2) and salbutamol is a selective beta2-agonist; together, the additive beta stimulation increases tachycardia, tremor and intracellular potassium shift — the epinephrine label lists "hypokalaemia" among adverse reactions and the drugs that "potentiate the hypokalaemic effects of epinephrine", recommending watching for arrhythmias; salbutamol "may produce significant hypokalaemia in some patients... with the potential to produce adverse cardiovascular effects". The combination occurs mainly in emergency settings (anaphylaxis/acute asthma in a patient using beta2-agonists at home) and intensive care. Monitor cardiac rhythm and potassium, especially with repeated doses or in patients with coronary disease.
Epinephrine + salbutamol: beta-adrenergic overlap — additive tachycardia, tremor and potassium loss. Monitor cardiac rhythm and potassium.
Overlapping β-adrenergic effects increase tachycardia, tremor and potassium loss.
Potassium and heart rhythm.
Palpitations, tremor, hypokalaemia.
Monitor potassium and cardiovascular symptoms in at-risk patients.
DailyMed (FDA) — approved Epinephrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5726eeca-db88-ba8e-e063-6294a90a927d ; approved Salbutamol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3236f82c-14e9-dfd4-e063-6294a90ac43d — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Epinephrine + digoxin: risk of arrhythmias (myocardial sensitisation).
Digoxin sensitises the myocardium to sympathetic stimulation: epinephrine, by stimulating beta and alpha receptors, increases automaticity and can precipitate ventricular arrhythmias, including ventricular tachycardia, in digitalised patients. The risk is higher with hypokalaemia (which digoxin itself favours) and with high epinephrine doses. This combination arises mainly in emergencies (cardiac arrest, anaphylaxis) or in patients with advanced heart failure. Monitor the ECG during administration, correct electrolytes (especially potassium and magnesium) and use the lowest effective epinephrine doses.
Epinephrine + digoxin: increased risk of ventricular arrhythmias (digoxin sensitises the myocardium to beta-adrenergic stimulation). Use with caution and monitor the ECG.
Both increase myocardial automaticity; potentiated hypokalaemia increases arrhythmia risk.
ECG and serum potassium.
Arrhythmias, palpitations, hypokalaemia.
Monitor heart rhythm and potassium in cardiac patients.
DailyMed (FDA) — approved Epinephrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5726eeca-db88-ba8e-e063-6294a90a927d ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Caffeine may potentiate the adrenergic effects of epinephrine (tremor, tachycardia).
Limit caffeine intake during treatment.
EMC-UK (MHRA) — approved Epinephrine SmPC: https://www.medicines.org.uk/emc/product/3673/smpc
Epinephrine may markedly raise blood pressure.
Use with caution and monitor blood pressure.
EMC-UK (MHRA) — approved Epinephrine SmPC: https://www.medicines.org.uk/emc/product/3673/smpc
Hyperthyroidism potentiates the effects of epinephrine (tachycardia, arrhythmias).
Use with caution and monitor cardiovascular symptoms.
EMC-UK (MHRA) — approved Epinephrine SmPC: https://www.medicines.org.uk/emc/product/3673/smpc
Epinephrine increases myocardial work and may precipitate ischaemia/arrhythmias.
Use with caution in ischaemic heart disease; monitor.
EMC-UK (MHRA) — approved Epinephrine SmPC: https://www.medicines.org.uk/emc/product/3673/smpc
Epinephrine is used in emergencies (anaphylaxis) in pregnancy when benefit outweighs risk; the risk of untreated maternal/fetal hypoperfusion exceeds exposure risk.
Use only in emergencies under medical guidance.
Does not contraindicate breastfeeding after acute use.
No specific additional contraception.
EMC-UK (MHRA) — approved Epinephrine SmPC: https://www.medicines.org.uk/emc/product/3673/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Catecholamine (agonist of α- and β-adrenergic receptors). Rapid onset and short duration of action: the blood pressure rise after an intravenous dose begins in less than 5 minutes and the effect ends about 20 minutes later. At low doses β2 vasodilation predominates (with a fall in diastolic pressure); at higher doses, peripheral α1 vasoconstriction. It increases glycogenolysis, reduces glucose uptake and inhibits insulin release, with hyperglycaemia.
It acts on α- and β-adrenergic receptors: direct myocardial stimulation (positive inotropic action), increased heart rate (positive chronotropic action) and peripheral vasoconstriction. In anaphylaxis it reduces vasodilation and vascular permeability (α) and relaxes bronchial smooth muscle (β), relieving bronchospasm, wheezing and dyspnoea.
After parenteral administration, onset is rapid and duration short; after intravenous injection, epinephrine is rapidly cleared from plasma with an effective half-life of less than 5 minutes; steady state during continuous infusion is reached within 10 to 15 minutes.
Extensively metabolised, with a small amount excreted unchanged; rapidly degraded to vanillylmandelic acid (inactive metabolite) by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Organs with the highest contribution to removal: liver (32%), kidneys (25%), skeletal muscle (20%) and mesenteric organs (12%).
Effective half-life of less than 5 minutes after intravenous injection; dose-proportional pharmacokinetics during continuous infusion (0.03 to 1.7 mcg/kg/min). Body weight influences the pharmacokinetics — higher weights associate with higher clearance and a lower concentration plateau.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
