Catecholamines

Drug interaction

Common interactions

DrugPharmacodynamic interactionsPharmacokinetic interactionsCautions
α-adrenoceptor antagonists:
- Doxazosin
- Phenoxybenzamine
- Phentolamine
- Prazosin
- Terazosin
Antagonize the vasopressor response of catecholaminesMonitor BP
Inhibitors of neuronal uptake of catecholamines
- Cocaine
- Tricyclic antidepressants
They can potentiate the pressor and proarrhythmic effects of catecholaminesAvoid the combination. Consider monitoring BP and the ECG
Drugs that sensitize the heart to cardiac arrhythmias:
- Digitalis
- Halogenated hydrocarbon general anesthetics
- Thyroid hormones
Increased risk of cardiac arrhythmiasMonitor the ECG
Ergot alkaloids:
- Ergotamine
- Ergonovine
- Methysergide
- Oxytocin
May enhance the vasopressor and pressor effects of adrenaline and noradrenaline Monitor BP. Close attention to peripheral perfusion

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Adrenaline

Stimulates both α- and β-adrenergic receptors, being more selective for β-receptors (β2 > β1 > α1 = α2)

DrugPharmacodynamic interactionsPharmacokinetic interactionsCautions
β-adrenoceptor antagonists Severe hypertension and reflex bradycardia may occur with non-selective β-adrenoceptor antagonists (propranolol) due to α-mediated vasoconstriction
They, especially non-cardioselective agents, can also antagonise the cardiac and bronchodilator effects of adrenaline
Patients with severe anaphylaxis taking non-cardioselective drugs may not respond to adrenaline treatment.
Atenolol and metoprolol intearct minimally
COMT inhibitors:
- Entacapone
- Tolcapone
Enhance the arrhythmogenic effects of adrenalineCaution with the combination
Drugs that increase the risk of hypertension and cardiac arrhythmias:
- Digoxin
- Histamine H1-receptor antagonists: diphenhydramine, tripelannamine, dexchlorpheniramine
- Levothyroxine
- MAO inhibitors: Isocarboxazid,
They increase the risk of development of hypertension and/or cardiac arrhythmiasMonitor BP and the ECG
Drugs that induce hypokalemia:
- Aminophylline
- Corticosteroids
- Potassium-depleting diuretics
- Theophylline
They can potentiate the hypokalemic effect of adrenaline
Insulin or oral hypoglycaemic agentsThe hyperglycemic effect of adrenaline may lead to a loss of the glycemic control in patients treated with insulin or oral hypoglycaemic agentsMonitor glucose plasma levels
LevodopaAdrenaline increases the risk of cardiac adverse effects of levodopa
PhenothiazinesThey block α-adrenergic receptors, which may cause vasodilation due to unoppossed β-adrenergic activationAdrenaline should not be used to counteract circulatory collapse or hypotension caused by phenothiazines

Adrenaline can cause sinus tachycardia and may induce myocardial ischaemia and arrhythmias, thus ECG monitoring is required.

The β2-receptor stimulation required for catecholamine-induced hypokalemia can be potentiated by corticosteroids, potassium-depleting diuretics, aminophylline and theophylline.

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Dobutamine

Synthetic analogue of dopamine that stimulates β1-adrenergic receptors; it also has mild β2- and α1-adrenergic receptor agonist effects (β1 >β2 >α)

DrugPharmacodynamic interactionsPharmacokinetic interactionsCautions
AntidepressantsHypertension and risk of arrhythmias in patients receiving tricyclic antidepressants. Avoid dobutamine in patients treated with MAOI inhibitors or within 14 days of its termination.Monitor the ECG and BP
β-blockersInhibit the cardiac effects of dobutamine. Dobutamine counteracts the effect of β-blockers.
Non-selective beta-blockers (e.g. propranolol) can increase BP, due to alpha-mediated vasoconstriction, and reflex bradycardia
Avoid the combination
CarvedilolMay cause hypotension due to vasodilation caused via stimulation of β2-receptors.Monitor the BP
CimetidineInhibits the hepatic metabolism of dobutamine and increase in the degree and duration of its action.Monitor the ECG
ClonidineIt can increase the BP response to dobutamineMonitor the BP
DigoxinIncreases the risk of arrhythmiasMonitor the BP
DipirydamoleCan produce severe hypotensionMonitor BP. Avoid in patients with coronary artery disease
DoxapramIncreases the risk of hypertensionMonitor BP
COMT inhibitors:
- Entacapone
- Tolcapone
Potentiate the effects of dobutamineCaution with the combination
OxytocinMay enhance the pressor effects of sympathomimeticsMonitor the BP
RasagilineAvoid the combination
VancomycinDobutamine increases renal clearance and reduces the plasma levels of vancomycinMonitor the dose and response to vancomycin

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Dopamine (DA)

Endogenous catecholamine and the precursor of noradrenaline and adrenaline. At low doses (<3 μg/kg/min) DA stimulates mainly peripheral DA1 and DA2 dopaminergic receptors, producing renal and mesenteric vasodilation; at higher doses (<3-5 μg/kg/min) stimulates both β1-adrenergic and dopaminergic receptors, producing cardiac stimulation and renal vasodilation; at large dose (<5 μg/kg/min) stimulates α-adrenergic receptors
DrugPharmacodynamic interactionsPharmacokinetic interactionsCautions
α-adrenoceptor blocking drugsAntagonise the peripheral vasoconstriction caused by high doses of dopamineMonitor the BP
β-adrenoceptor blocking drugsAntagonize the cardiac effects of DAMonitor the patients
ClonidineDecreases the BP response to dopamineMonitor the BP
COMT inhibitors:
- Entacapone
- Tolcapone
Potentiate the effects of dobutamineCaution with the combination
DiureticsCoadministration of low-dose DA and diuretic agents may produce an additive effect on urine flowMonitor diuresis
DoxapramMay cause hypertension in patients receiving dopamineMonitor BP
MAO inhibitors
- Isocarboxazid
- Phenelzine
- Rasagiline
- Safinamide
- Selegiline
- Tranylcypromine
Increase and prolong the effects of DAThe initial dose of DA should be reduced to at least one-tenth of the usual dose.
OxytocinMay enhance and prolong the pressor effects of sympathomimeticsMonitor BP
PhenytoinCan produce hypotension and bradycardiaAvoid, if possible, this combination.
VancomycinDobutamine increases renal clearance and reduces the plasma levels of vancomycinMonitor the dose and response to vancomycin

The renal and mesenteric vasodilation induced by dopamine is mediated by DA1 receptor stimulation and is not antagonised by either α or β- adrenergic blocking agents.

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Isoprenaline

Pure nonselective β-adrenergic receptor agonist (β1=β1 >> α1/α2)

DrugPharmacodynamic interactionsPharmacokinetic interactionsCautions
AdrenalineThis combination may lead to serious arrhythmiasBoth catecholamines can be administered alternately provided a proper interval has elapsed between doses
Inhalational anestheticsSensitize the myocardium to effects of sympathomimetic aminesAvoid the combination with halothane

Titrate infusion rate according to clinical response and/or side effects. The dose can be increased every 2-3 minutes until appropriate response obtained.

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Noradrenaline (NA)

Produces the simultaneous stimulation of α- and β-adrenergic receptors in the heart and vessels (α1 = α2 = β1 >> β2)

DrugPharmacodynamic interactionsPharmacokinetic interactionsCautions
LithiumDecreases the pressor response to NA Monitor BP
Cardiac sensitising agents:
- Linezolid
- MAO inhibitors
- Tricyclic antidepressants
- Volatile halogenated anaesthetic agents
Severe, prolonged hypertension and possible arrhythmias may result.Avoid the combination. Only under close medical supervision

Noradrenaline should be administered used with extreme caution in patients receiving MAO inhibitors or antidepressants of the triptyline or imipramine types, because severe, prolonged hypertension may result.

  • Special caution in patients with coronary, mesenteric or peripheral vascular thrombosis because noradrenaline may increase the ischemia and extend the area of infarction
  • Similar caution in patients with hypotension following MI, Prinzmetal’s variant angina, diabetes, hypertension or hyperthyroidism.
  • Extravasation of the solution may cause local tissue necrosis

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Cautions

The risk of cardiac arrhythmias increases in patients with profound hypoxia or hypercarbia.


Abbreviations

AADs: antiarrhythmic drugs
BP: blood pressure
COMT: catechol-O-methyl transferase
DA: dopamine
ECG: electrocardiogram
MAO: monoamino oxidase
MI: myocardial infarction
T/VF: ventricular trachycardia/ventricular fibrillation.