Direct and Indirectly Acting Sympathomemitics

 Sympathomimetics are drugs that mimic the effects of the sympathetic nervous system by activating adrenergic receptors. These drugs are classified into directly acting and indirectly acting sympathomimetics based on their mechanism of action.

1. Directly Acting Sympathomimetics

• Mechanism: These drugs bind directly to adrenergic receptors (α and β receptors) and activate them, simulating the effect of endogenous catecholamines like norepinephrine and epinephrine.
• Examples:
  • Epinephrine: Stimulates both α and β receptors, used in anaphylaxis, cardiac arrest.
  • Norepinephrine: Primarily stimulates α1 receptors and some β1 receptors, used in septic shock to increase blood pressure.
  • Phenylephrine: Selectively stimulates α1 receptors, used as a decongestant and to increase blood pressure.
  • Dobutamine: Selectively stimulates β1 receptors, used in heart failure to increase cardiac output.

2. Indirectly Acting Sympathomimetics

• Mechanism: These drugs do not directly stimulate adrenergic receptors. Instead, they increase the levels of endogenous catecholamines (like norepinephrine) in the synaptic cleft by:
  • Promoting release from nerve terminals.
  • Inhibiting reuptake of norepinephrine.
  • Inhibiting breakdown of catecholamines by enzymes (e.g., MAO, COMT).
• Examples:
  • Amphetamine: Increases the release of norepinephrine and dopamine, used in ADHD and narcolepsy.
  • Tyramine: Found in certain foods; it can increase norepinephrine release but is broken down by MAO. Dangerous in combination with MAO inhibitors (leading to hypertensive crisis).
  • Cocaine: Blocks the reuptake of norepinephrine and dopamine, leading to heightened adrenergic activity.
  • Ephedrine: Both directly stimulates adrenergic receptors and indirectly increases the release of norepinephrine.

Key Difference

• Directly Acting: Drugs bind and activate adrenergic receptors directly.
• Indirectly Acting: Drugs increase the availability of endogenous neurotransmitters to act on receptors.