Catecholamines

1. Introduction

• Catecholamines are biogenic amines derived from the amino acid tyrosine.

• Named for their catechol nucleus (a benzene ring with two hydroxyl groups) and an amine side chain.

• Function as neurotransmitters in the central and peripheral nervous systems and as hormones in the bloodstream.

• In pharmacology, the term also refers to synthetic and natural drugs that mimic or enhance the actions of endogenous catecholamines.

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2. Endogenous Catecholamines

• Dopamine (DA)

• Norepinephrine (NE, noradrenaline)

• Epinephrine (E, adrenaline)

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3. Biosynthesis Pathway

• Tyrosine (from diet or phenylalanine metabolism) is converted to L-DOPA by tyrosine hydroxylase (rate-limiting step).

• L-DOPA is converted to dopamine by aromatic L-amino acid decarboxylase.

• Dopamine is converted to norepinephrine by dopamine β-hydroxylase.

• Norepinephrine is converted to epinephrine by phenylethanolamine N-methyltransferase (mainly in adrenal medulla).

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4. Storage and Release

• Stored in synaptic vesicles of nerve terminals or chromaffin granules in the adrenal medulla.

• Released into the synaptic cleft or bloodstream in response to nerve stimulation or stress.

• Release is calcium-dependent, triggered by depolarization of the nerve terminal or hormonal signals.

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5. Receptor Types and Actions

• Act on adrenergic receptors (α and β subtypes) and, in dopamine’s case, dopaminergic receptors (D1–D5).

α1 receptors

• Vasoconstriction, increased peripheral resistance, pupil dilation.

α2 receptors

• Inhibition of norepinephrine release, decreased sympathetic outflow, platelet aggregation.

β1 receptors

• Increased heart rate, contractility, and conduction velocity.

β2 receptors

• Bronchodilation, vasodilation in skeletal muscle, glycogenolysis.

β3 receptors

• Lipolysis, thermogenesis in adipose tissue.

Dopaminergic receptors

• Renal vasodilation (D1), modulation of neurotransmitter release (D2).

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6. Physiological Roles

• Fight-or-flight response: increased heart rate, blood pressure, blood glucose, and oxygen delivery.

• Regulation of vascular tone, myocardial contractility, and bronchial smooth muscle tone.

• Central nervous system functions: mood regulation, reward pathways, attention, and motor control.

• Hormonal role: epinephrine and norepinephrine from the adrenal medulla act as systemic hormones.

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7. Pharmacological Catecholamines (Drugs)

Epinephrine

• Non-selective α and β agonist.

• Uses: anaphylaxis, cardiac arrest, severe asthma, local vasoconstrictor with anesthetics.

Norepinephrine

• Potent α1 and β1 agonist, minimal β2 activity.

• Uses: septic shock, hypotension unresponsive to fluids.

Dopamine

• Dose-dependent effects:

  • Low dose: D1 receptor stimulation → renal vasodilation.

  • Moderate dose: β1 stimulation → increased cardiac output.

  • High dose: α1 stimulation → vasoconstriction.

• Uses: shock with compromised cardiac output and renal perfusion.

Isoproterenol

• Non-selective β agonist.

• Uses: heart block, bradycardia, rarely in bronchospasm.

Dobutamine

• Predominantly β1 agonist with some β2 and α1 activity.

• Uses: acute heart failure, cardiogenic shock, cardiac stress testing.

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8. Pharmacokinetics

• Poor oral bioavailability due to rapid metabolism by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).

• Short plasma half-life (minutes); require continuous IV infusion or injection for sustained effect.

• Metabolites excreted in urine mainly as vanillylmandelic acid (VMA), metanephrine, and normetanephrine.

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9. Clinical Indications

• Shock states (septic, cardiogenic, anaphylactic).

• Cardiac arrest and resuscitation.

• Asthma and bronchospasm (acute settings).

• Adjunct to local anesthetics to prolong effect and reduce bleeding.

• Management of severe hypotension unresponsive to other measures.

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10. Contraindications

• Pheochromocytoma (except during pre-surgical preparation with α-blockade).

• Uncontrolled hypertension.

• Certain tachyarrhythmias.

• Use with extreme caution in patients with ischemic heart disease.

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11. Adverse Effects

• Hypertension, tachycardia, arrhythmias.

• Myocardial ischemia and infarction.

• Hyperglycemia, lactic acidosis.

• Peripheral ischemia and necrosis with prolonged vasoconstriction.

• CNS effects: anxiety, tremor, headache.

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12. Drug Interactions

• MAO inhibitors and COMT inhibitors: potentiate catecholamine effects → risk of hypertensive crisis.

• General anesthetics: increased risk of arrhythmias.

• Non-selective β-blockers: unopposed α vasoconstriction may cause severe hypertension.

• Tricyclic antidepressants: enhance norepinephrine effects by inhibiting reuptake.

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13. Monitoring in Clinical Use

• Continuous cardiac monitoring during infusion.

• Frequent blood pressure checks (preferably invasive arterial monitoring in ICU).

• Monitor urine output and renal function in shock states.

• Watch for extravasation; phentolamine infiltration recommended if it occurs.