Pharmacology Lecture 6: Adrenergic Agonists

Characteristics of Adrenergic Agonists

• Adrenergic drugs primarily derive from β-phenylethylamine, varying based on side chain and benzene ring modifications.
• Key features affecting receptor interaction: number/position of OH substitutions on the benzene ring and nature of amino nitrogen substituents.

Catecholamines

• Include epinephrine, norepinephrine, isoproterenol, and dopamine.
• High potency due to presence of -OH groups at positions 3 and 4 on the benzene ring.
• Metabolized quickly by Catechol-O-methyltransferase (COMT) and Monoamine oxidase (MAO), resulting in brief action when given parenterally and ineffectiveness when administered orally.
• Polar nature results in poor central nervous system (CNS) penetration but can cause CNS-related side effects (e.g., anxiety, tremors).

Non-Catecholamines

• Lack catechol hydroxyl groups, leading to longer half-lives due to less susceptibility to COMT inactivation.
• Examples include phenylephrine, ephedrine, and amphetamine.
• Increased lipid solubility enhances CNS access and prolongs duration of action.

Mechanism of Action

• Direct-acting agonists: Stimulate α or β receptors directly; examples include epinephrine and norepinephrine.
• Indirect-acting agonists: Block norepinephrine reuptake or promote its release; examples include cocaine (reuptake inhibitor) and amphetamines (release promoters).
• Mixed-action agonists: Stimulate receptors and release norepinephrine; examples are ephedrine and pseudoephedrine.

Norepinephrine

• Causes significant vasoconstriction without compensatory vasodilation, making it less suitable for asthma treatment.
• Increases blood pressure and stimulates baroreceptors, leading to bradycardia through vagal activity, which can be counteracted by atropine.
• Therapeutically used for shock treatment by increasing vascular resistance and blood pressure.

Isoproterenol

• A synthetic catecholamine stimulating both β1 and β2 receptors, rarely used due to non-selectivity.
• Increases heart rate, contractility, and cardiac output comparably to epinephrine.
• Side effects include tremor and may lead to tachycardia or arrhythmia, particularly in patients with existing heart conditions.

Salmeterol and Formoterol

• Long-acting β agonists (LABAs) selective for β2 receptors.
• Provide prolonged bronchodilation (up to 12 hours) compared to albuterol.
• Recommended in combination with corticosteroids, not monotherapy.

Mirabegron

• A β3 agonist that relaxes detrusor smooth muscle, increasing bladder capacity, and used for overactive bladder treatment.
• May raise blood pressure, contraindicated in patients with uncontrolled hypertension.

Cocaine

• Unique as a local anesthetic that blocks norepinephrine transporter, enhancing sympathetic activity.
• Accumulated norepinephrine leads to magnified effects of catecholamines and prolonged action duration.

Mixed-Action Adrenergic Agonists

• Ephedrine and pseudoephedrine stimulate α and β receptors while releasing stored norepinephrine.
• Both exhibit long durations of action and good oral absorption, but are less potent than epinephrine.
• Used to treat hypotension through vasoconstriction and cardiac stimulation, while inducing slower-acting bronchodilation compared to other catecholamines.

In this quiz, you will explore the characteristics and structural features of adrenergic agonists as discussed in Pharmacology Lecture 6 by Dr. Salem Abukres. Understand the role of these compounds in affecting alpha and beta receptors. Test your knowledge on the derivatives of β-phenylethylamine and their impact on the central nervous system.