Lecture on Adrenergic Agonists

Introduction

• Overview of adrenergic agonists (drugs affecting adrenergic receptors)
• Importance of understanding adrenergic neurons, norepinephrine synthesis and release
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Adrenergic Neurons and Norepinephrine

• Synthesis:
  • Begins with tyrosine from diet
  • Tyrosine taken up by adrenergic neurons via co-transport with sodium
  • Converted to L-DOPA, then dopamine, and finally norepinephrine within vesicles
• Release Mechanism:
  • Action potentials stimulate voltage-gated calcium channels
  • Calcium influx triggers exocytosis of norepinephrine into synapse
• Receptor Binding:
  • Norepinephrine binds to adrenergic receptors (alpha and beta types)
  • Effects vary based on receptor type and target organ

Adrenergic Receptors

• Alpha Receptors:
  • Alpha-1: Increases calcium, causing smooth muscle contraction
  • Alpha-2: Reduces cyclic AMP, inhibits norepinephrine release
• Beta Receptors:
  • Beta-1: Increases cyclic AMP, affects heart and kidneys, increases contraction
  • Beta-2: Increases cyclic AMP, causes smooth muscle relaxation (e.g., bronchioles)
  • Beta-3: Causes relaxation of smooth muscle, notably in bladder

Norepinephrine Metabolism and Reuptake

• Metabolism:
  • Catechol-O-methyltransferase (COMT) and monoamine oxidases break down norepinephrine
• Reuptake:
  • Norepinephrine can be recycled back into vesicles or broken down

Role of Epinephrine

• Released from adrenal medulla along with norepinephrine
• Similar structure and effects
• Circulates in the bloodstream affecting various target organs

Adrenergic Agonists Classification

• Direct Agonists:
  • Bind directly to adrenergic receptors
  • Some are selective for specific receptor types
• Indirect Agonists:
  • Increase norepinephrine levels in synapse without direct receptor binding
  • Examples: Cocaine, amphetamines
• Mixed Agonists:
  • Both stimulate receptors and increase norepinephrine levels
  • Examples: Pseudoephedrine

Physiological Effects of Receptors

• Alpha-1 Receptors:
  • Vasoconstriction increases blood pressure
  • Sphincter contraction inhibits urination and defecation
  • Pupil dilation
• Alpha-2 Receptors:
  • Inhibits norepinephrine release
  • Decreases insulin release
• Beta-1 Receptors:
  • Increases heart rate and contractility
  • Stimulates renin release from kidneys
• Beta-2 Receptors:
  • Relaxes bronchial and uterine smooth muscle
  • Increases blood glucose
• Beta-3 Receptors:
  • Relaxes bladder muscle, inhibiting urination

Drugs and Their Effects

• Alpha-1 Agonists:
  • Used in hypotension (e.g., phenylephrine)
  • Can cause reflex bradycardia
• Alpha-2 Agonists:
  • Lower blood pressure and can treat ADHD (e.g., clonidine)
• Beta-1 Agonists:
  • Increase heart rate and contractility (e.g., dobutamine)
• Beta-2 Agonists:
  • Used in asthma and COPD for bronchodilation (e.g., albuterol)
  • Used as tocolytics to delay labor (e.g., terbutaline)
• Beta-3 Agonists:
  • Treat overactive bladder (e.g., mirabegron)

Mixed Receptor Agonists

• Epinephrine/Dopamine:
  • Primarily beta agonists, used in shock, bradycardia
  • High doses act on alpha receptors, raising blood pressure
• Isoproteranol:
  • Non-selective beta agonist, increases heart rate
  • Used primarily for bradycardia

Hemodynamic Effects Comparison

• Norepinephrine: Primarily alpha agonist, increases both systolic and diastolic BP
• Epinephrine: Increases heart rate and systolic BP, decreases diastolic BP slightly
• Isoproteranol: Increases heart rate, decreases diastolic BP, resulting in a drop in MAP

Conclusion

• Recap of adrenergic agonists and their mechanisms
• Importance of understanding their effects for proper medical application

This lecture provides a comprehensive overview of adrenergic agonists, their mechanisms, receptor types, and the physiological and clinical implications of their use. By understanding these, healthcare professionals can better manage conditions related to adrenergic system dysregulation.