Adrenergic Pharmacology: B- Sympathomimetics

Vascular Effects of Sympathomimetics:

• Systolic Blood Pressure (SBP) depends on Cardiac Output (COP) and Peripheral Resistance (PR).
• Diastolic Blood Pressure (DBP) depends on Total Peripheral Resistance (TPR).
• PR: Increased with activation of α1 receptor and decreased with activation of β2 receptor.
• SBP: Increased by α1 and β1.
• DBP: Increased with ↑PR and decreased with ↓PR.
• Activation of α2 receptors decreases Blood Pressure through:
  • Reduction of Central Sympathetic Outflow
  • Reduction of NE Release From Sympathetic Neurons
  • Reduction of Renin Release

Epinephrine Doses

• Clinical Dose: Affects α1, β1, and β2 receptors.
• Experimental Dose:
  • Low dose: High affinity to B2 receptor: ↑SBP and ↓DBP
  • Epinephrine Reversal in Animals: After α-blockade, β2-mediated hypotensive effect is unmasked.

Therapeutic Uses of Sympathomimetics

• Norepinephrine (Levarterenol):
  • Uses: Septic shock, 2nd line in cardiogenic shock (I.V. infusion).
  • Adverse Effects: Gangrene of tissues with extravasation; use local α blocker.
• Epinephrine:
  • Uses: Anaphylactic shock (I.M.), with local anesthetic (α1), acute asthma attack (inhalation) (β2 & α1), cardiac arrest (I.V. or intracardiac) (β1), arrest bleeding (α1).
• Isoproterenol:
  • Uses: Refractory Bradycardia and AV Block.
• Selective β1 Agonist:
  • Dobutamine: Short term in acute Heart Failure & Cardiogenic shock (I.V. infusion).
• Selective β2 Agonists:
  • Short acting (Albuterol & terbutaline): Acute asthma attack.
  • Long acting (Salmeterol & Formeterol): Prophylaxis of asthma.
• Alpha Agonists:
  • Oxymetazoline: Local nasal and eye decongestant: Short term use to avoid rebound congestion.
  • Clonidine: Hypotension state.
  • Phenylephrine: Local nasal decongestant.

Adverse Effects of Sympathomimetics

• B2 Agonist: Anxiety, Arrhythmia, Tachycardia, Tolerance, Tremors, Hypotension, Hypokalemia.
• Alpha 1 Agonist: Hypertension, Reflex bradycardia, Rebound nasal congestion.
• Epinephrine: Tachycardia, Tremors, Hypertension, Anxiety, Arrhythmia.

Drugs Acting on Dopamine Receptors

• Dopamine:
  • D1-agonist (at low dose): VD of renal blood vessels →↑renal blood flow.
  • β1-agonist (at moderate dose): Cardiac stimulation.
  • α1-agonist (at high dose): VC ↑Blood Pressure
• Dobutamine:
  • β1-agonist: Acute HF & cardiogenic shock. Chronic refractory HF (short term).
• Fenoldopam: D1 receptor agonist → peripheral VD. Use: IV for severe hypertension in hospitalized patients.

Indirect Acting Sympathomimetics

• Amphetamine:
  • Uses: ADHD, Narcolepsy.
  • Adverse Effects: CNS & CVS stimulation & Marked Anorexia.

Mixed- or Dual-acting Sympathomimetic

• Ephedrine and pseudoephedrine
  *Uses: Oral nasal decongestants (pseudoephedrine), Spinal shock (ephedrine), Nocturnal enuresis, Urine incontinence.
  *Adverse Effects: Minimal CNS & CVS stimulation and Urinary retention.