Lecture on Sympathomimetics

Introduction

• Sympathomimetics: Drugs that mimic the stimulation of the sympathetic system.
• Adrenergic Receptors: Includes alpha 1, alpha 2, beta 1, beta 2, and beta 3.
• Classification:
  • By Mechanism of Action: Direct or indirect acting.
  • By Chemical Nature: Catecholamines and non-catecholamines.

Classification by Mechanism of Action

• Direct Acting Sympathomimetics: Directly stimulate adrenergic receptors.
• Indirect Acting Sympathomimetics:
  • Cause the release of norepinephrine.
  • Inhibit MAO enzyme, preventing norepinephrine breakdown.

Classification by Chemical Nature

• Catecholamines:
  • Contain a catechol ring (tyrosine-derived).
  • Not absorbed orally, don't cross the blood-brain barrier, and are quickly broken down by MAO and COMT.
• Non-Catecholamines:
  • Lack the catechol ring, allowing for absorption and BBB crossing.

Prototype Drug: Adrenaline (Epinephrine)

• History: Discovered in 1904 and chemically synthesized.
• Scientific Term: Epinephrine; trade name is adrenaline.
• Headlines for Drug Discussion:
  1. Chemistry
  2. Pharmacokinetics
  3. Mechanism of Action
  4. Uses
  5. Administration
  6. Adverse Effects
  7. Contraindications
  8. Precautions

Chemistry of Adrenaline

• Natural Occurrence: In sympathetic nervous system and suprarenal medulla.
• Chemical Structure: Contains catechol ring and OH groups.

Pharmacokinetics

• Absorption: Not orally absorbed; limited skin and eye absorption.
• Distribution: Cannot cross the blood-brain barrier.
• Metabolism: Metabolized by MAO and COMT.
• Excretion: Excreted as metaniphrine or valenyl mandelic acid.

Mechanism of Action

• Receptors Activated: All adrenergic receptors (alpha and beta) except significant alpha 2 effect.
• Molecular Mechanism:
  • Alpha 1 increases IP3 and calcium.
  • Betas increase cyclic AMP leading to various effects.

Effects on the Body

• Heart: Increases heart rate (positive chronotropic) and force of contraction (positive inotropic).
• Blood Pressure:
  • Therapeutic dose increases systole and decreases diastole.
  • High doses increase both systole and diastole.
• Other Systems:
  • Bronchodilation in bronchi.
  • Vasoconstriction in blood vessels.
  • Eye effects reduce intraocular pressure.
  • Temporary effects on blood sugar and potassium levels.

Uses of Adrenaline

• Emergencies:
  • Acute anaphylactic shock.
  • Acute bronchospasm.
  • Cardiac arrest (IV route).
• Local Anesthesia: Prolongs duration and reduces bleeding.

Adverse Effects

• High Blood Pressure: Risk of cerebral hemorrhage.
• Tremors and Arrhythmias: Risk of ventricular fibrillation.
• Pulmonary Edema: Due to increased heart contractility and systemic vasoconstriction.

Contraindications

• Hypertension and Cardiovascular Issues:
• High Dose with Local Anesthesia: Risk of tissue necrosis.
• Cardiac Outflow Obstruction: Such as hypertrophic obstructive cardiomyopathy.
• Hyperthyroidism: Increased sensitivity and effects due to beta receptor upregulation.

Conclusion

• Adrenaline Uses: Mainly in emergencies due to its rapid action but with significant risks.
• Contraindications: Important to avoid in specific medical conditions.
• Future Lessons: Will cover other sympathomimetics in less detail.