Sympathomimetic Drugs: Agonists and Receptor Activity

• Sympathomimetic drugs mimic the effects of sympathetic nervous system activation.
• Norepinephrine differs from amphetamine due to the presence of -OH groups.
• The presence of -OH groups in Norepinephrine makes it a catecholamine.
• Absence of one or both -OH groups leads to decreased potency at adrenergic receptors.
• Absence of one or both -OH groups increases susceptibility to COMT.
• Addition of a group on the α-carbon makes the compound resistant to MAO.
• Addition of a group on the amino end alters receptor affinity.
• Larger groups on the amino end decrease α-receptor activity and increase β-receptor activity.

Direct Acting Agonists

• Direct-acting agonists directly bind to and activate adrenergic receptors.

Mixed Acting Agonists

• Mixed-acting agonists have both direct and indirect actions on adrenergic receptors.
• Norepinephrine has receptor affinities of α1=α2, β1>>β2, requiring very high concentrations to activate β2.
• Epinephrine has receptor affinities of α1=α2, β1=β2, and binds to all receptors due to its methyl group.

Alpha Adrenergic Agonists

• Phenylephrine has receptor selectivity of α1>>α2.
• Clonidine has receptor selectivity of α1>α2.
• Yohimbine has receptor selectivity of α1>α2

Beta Adrenergic Agonists

• Propranolol has receptor affinities of β1=β2.
• Butoxamine has receptor selectivity of β2>>>β1.
• In most organs, the sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) are physiological antagonists.
• Adrenergic antagonists often have the same effect as PSNS activation.

Effects of Adrenergic Antagonists on the Eye

• Blocking α1 receptors causes pupil constriction.
• Blocking β2 and β1 receptors decreases the production of aqueous humor.

Effects of Adrenergic Antagonists on the Heart

• Blocking β1 receptors decreases heart rate and force of contraction.

Effects of Adrenergic Antagonists on Blood Vessels

• Blocking α1 receptors causes vasodilation.
• Blocking β2 receptors causes vasoconstriction.

Baroreceptor Reflex Response

• The baroreceptor reflex is a homeostatic mechanism that helps maintain blood pressure.

Beta-Blockers and Baroreceptor Reflex

• Inhibition of β1 receptors decreases heart rate and force of contraction.
• Baroreceptors detect decreased blood pressure.
• Decreased blood pressure leads to decreased PSNS and increased SNS activation.
• Increased SNS activation causes vasoconstriction via α1 receptors.

Alpha-Blockers and Baroreceptor Reflex

• Inhibition of α1 receptors in blood vessels leads to vasodilation.
• Baroreceptors detect decreased blood pressure, leading to decreased PSNS and increased SNS activation.
• Increased SNS activation increases heart rate via β1 receptors.

Effects of Adrenergic Antagonists on the Bronchi

• Blocking β2 receptors causes bronchoconstriction.

Effects of Adrenergic Antagonists on the GI Tract

• Blocking β2 receptors increases motility.
• Blocking α2 receptors increases ACh release and motility.
• Blocking α1 receptors relaxes the sphincter.

Effects of Adrenergic Antagonists on the Urinary Bladder

• Blocking β2 receptors contracts the bladder wall.
• Blocking α1 receptors relaxes the sphincter.

Overview of sympathomimetic drugs, focusing on how they mimic the sympathetic nervous system. Explains the impact of -OH groups, resistance to MAO, and receptor affinity. Discusses direct and mixed-acting agonists, including norepinephrine and epinephrine.