Adrenergic Receptors, Agonists & Antagonists

Dr. Salisbury, PhD

Learning Objectives

• Understand the drugs/agents influencing the cardiovascular system via adrenergic receptors.

  • Specific drugs used

  • Pharmacokinetic properties of these drugs

  • Sites of action of adrenergic agents

  • Mechanisms of effects induced by these drugs

  • Therapeutic applications for these drugs

  • Possible adverse effects from drug use

Adrenergic and Cholinergic Nerves Overview

• Nerve Types:

  • Parasympathetic

  • Somatic

  • Central Nervous System (CNS)

• Neurotransmitters:

  • Nn (Nicotinic receptors)

  • NE (Norepinephrine)

  • α (alpha) and β (beta) receptors

  • ACh (Acetylcholine)

  • Muscarinic receptors

• Key Points:

  • CNS effects include cardiac inhibition, regulation of smooth muscle, and glandular secretion.

  • Effector targets impacted by adrenergic receptors include:

  • Cardiac tissues

  • Blood vessels

  • Liver

  • Skeletal muscle

  • Gastrointestinal tract

  • Bladder

Overview of Adrenergic Neurons and Norepinephrine (NE)

• Important Points:

  • Synthesis: How NE is formed in the body.

  • Storage: NE is stored in vesicles until release.

  • Release Trigger: Calcium ions (Ca²⁺) induce the release of NE.

  • Receptors:

  • α & β receptors respond to NE and its actions.

  • Uptake: Mechanism by which NE is recycled post-action.

  • Metabolism: Breakdown and removal of NE from the synapse.

Sympathomimetic Drugs

• Classification:

  • Sympathomimetic drugs can be classified into:

  • Catecholamines

  • Non-catecholamines

• Effects and Metrics:

  • Include impacts on blood pressure (BP) and pulse rate, supplemented with graphs.

  • Consideration of receptor selectivity and therapeutic indications.

  • Adverse and side effects of sympathomimetic drugs must be understood.

Classification of Adrenergic Agonists

• Direct-Acting Agonists: Directly stimulate adrenergic receptors.

• Indirect-Acting Agonists: Enhance the effects of norepinephrine by different mechanisms of action.

  • Effects of these drugs might not be reduced by prior treatment with reserpine.

Adrenergic Agent Interactions

• Interactions between blockers (antagonists), releasers, stabilizers, and agonists are significant.

• Indirect Acting: Release agents like Tyramine, Amphetamine, and Ephedrine that also influence norepinephrine activity.

• NET1 Antagonists: Cocaine, Methylphenidate, TCAs (e.g., Imipramine), and MAO inhibitors (e.g., Tranylcypromine) which potentiate NE effects.

Catecholamines Overview

• Chemical Structure i.e., chemical formula representation of:

  • Epinephrine (Epi)

  • Isoproterenol

  • Norepinephrine (NE)

  • Dopamine

  • Dobutamine

• Pharmacokinetics: Rapid metabolism by COMT; ineffective orally.

Activity and Clinical Uses of Catecholamines

• Epinephrine:

  • Agonist at α1, α2, β1, β2 receptors

  • When used, significant effects include increasing heart rate, cardiac output, and blood pressure while influencing vascular tone.

• Norepinephrine:

  • Primarily employed as a vasopressor.

  • Effects: Significant in reversing hypotension and hypotensive states.

• Dopamine: Dose-dependent responses, particularly used in cardiogenic shock and acute renal failure.

• Dobutamine: Acts as an inotrope and is vital in CHF and cardiac decompensation.

• Isoproterenol: Used for bronchodilation and in emergency cardiac situations.

Non-Catecholamine Adrenergic Agonists

• Selective α1-receptor agonists:

  • Phenylephrine (effects include vasoconstriction, increased total peripheral resistance).

• Selective α2-receptor agonists:

  • Clonidine (effects include decreased sympathetic outflow and NE release).

• Selective β2 agonists:

  • Indications include asthma and COPD treatment.

Adrenergic Antagonists Overview

• α Receptor Antagonists:

  • Competitive antagonism illustrated by significant medications such as Phenoxybenzamine and Prazosin.

• β Receptor Antagonists:

  • Variations in selectivity towards β1 vs. β2 such as Propranolol (non-selective) and Atenolol (β1-selective).

• Mechanisms of Action: Inhibition of NE and Epi action, impacting various therapeutic pathways.

Non-Selective & Selective β Blockers

• First Generation Non-Selective: e.g., Propranolol, Nadolol with various side effects including bronchoconstriction, hypotension.

• Second Generation β1 Selective: e.g., Bisoprolol with reduced adverse effects on bronchial constriction and safer for diabetics.

• Third Generation drugs such as Carvedilol demonstrating additional vascular effects.

Conclusion

• Understanding the various classifications, mechanisms, effects, therapeutic usages, and adverse effects of both adrenergic agonists and antagonists is crucial for the effective clinical application in treating cardiovascular and other conditions.