Learning Objective

By the end of this note, the learner should be able to describe the mechanisms, physiological effects, clinical uses, and important reflex responses associated with α₁-adrenergic agonists.

α₁ Agonists – Summary Note

Mechanism of Action

• α₁ receptors are Gq-coupled → ↑ IP₃, DAG, Ca²⁺ → smooth muscle contraction.
• Main effect: vasoconstriction of arterioles and veins.

Physiological Effects

Cardiovascular Effects

• ↑ Mean blood pressure (MAP) is due to increased total peripheral resistance (TPR).
• Reflex bradycardia due to baroreceptor-mediated vagal response.
• Cardiac output may:
  • Decrease (from increased afterload).
  • It is partially offset by ↑ venous return (venoconstriction).

Eye

• Mydriasis (pupil dilation) without cycloplegia (ciliary muscle not affected).

Nasal Mucosa

• Vasoconstriction → reduced congestion.

Clinical Uses

Midodrine

• Treats autonomic insufficiency
• Used in orthostatic hypotension

Phenylephrine

• Nasal decongestant
• Ophthalmology: induces mydriasis (no cycloplegia)
• Hypotension, including:
  • Anesthesia-related hypotension
  • Shock (adjunct, not first-line)

Important Concept:  Bradycardia with α₁ Agonists

• Systemic vasoconstriction → ↑ BP
• Baroreceptors → ↑ vagal tone → ↓ HR

Activity