Sympathetic Nervous System Medications

Nervous System Overview

• The nervous system is divided into:
  • Central Nervous System (CNS): Brain and spinal cord.
  • Peripheral Nervous System (PNS): All nervous tissue outside the CNS.
    • Autonomic Nervous System: Controls involuntary functions ("automatic").
      • Sympathetic Nervous System: "Fight or flight".
      • Parasympathetic Nervous System: "Feed or breed".
    • Somatic Nervous System: Controls voluntary "motor" functions.

Sympathetic Nervous System Medications

• Drugs Affecting the Sympathetic System:
  • Adrenergic Receptors
  • Adrenergic Agonists
  • Adrenergic Antagonists

Adrenergic Drugs (Sympathomimetics)

• Produce effects similar to those produced by the sympathetic nervous system.
• Classified according to their action:
  • Direct-acting: Drugs directly stimulate the receptor site (e.g., epinephrine, norepinephrine, isoproterenol).
  • Indirect-acting: Drugs release endogenous norepinephrine, which then stimulates the receptor (e.g., amphetamine).
  • Dual-acting (mixed action): Drugs either directly stimulate the receptor or release endogenous norepinephrine (e.g., ephedrine and Pseudoephedrine).

Catecholamines - Actions of Adrenergic Drugs

• Central Nervous System (CNS):
  • Produce CNS excitation or alertness.
  • Higher doses produce anxiety, restlessness, and tremors.
• Cardiovascular System:
  • Increase the force and rate of contraction of the heart.
  • Increase blood pressure.
  • Increase total peripheral resistance.
• Eye:
  • Lower intraocular pressure.
  • Can cause mydriasis (pupil dilation).
• Respiratory System:
  • Cause relaxation of bronchiole smooth muscles.

Catecholamines

• Can be natural or synthetic; examples include:
  • Dobutamine
  • Dopamine
  • Epinephrine
  • Norepinephrine
  • Isoproterenol

Catecholamines - Pharmacokinetics

• Widely distributed throughout the body.
• Predominantly metabolized by the liver.
• Excreted primarily in the urine.

Catecholamines - Uses

• Catecholamines that stimulate alpha receptors are used to treat hypotension.
• Catecholamines that stimulate beta1-receptors are used to treat:
  • Bradycardia
  • Heart Block
  • Low Cardiac Output
• Catecholamines that stimulate beta2-receptors are used to treat:
  • Acute and Chronic Bronchial Asthma
  • Emphysema
  • Bronchitis

Drug Interactions/Adverse Reactions of Adrenergic Drugs

• Can be serious, including:
  • Hypertension
  • Arrhythmias
  • Anxiety
  • Tremors
  • Tachycardia
  • Seizures
  • Hyperglycemia

Adrenergic Blocking Drugs (Sympatholytic Drugs)

• Used to disrupt SNS function by blocking impulse transmission at adrenergic receptor sites.
• Classified according to their site of action:
  • Alpha-adrenergic Blockers
  • Beta-adrenergic Blockers

Alpha-Adrenergic Blockers

• Pharmacodynamics - MOA:
  • Block the synthesis, storage, release, and uptake of norepinephrine by neurons.
  • Antagonize epinephrine and norepinephrine at alpha receptor sites, resulting in:
    • Relaxation of the smooth muscle in the blood vessels.
    • Increased dilation of blood vessels.
    • Decreased blood pressure.

Alpha₁ Antagonism Examples

• prazosin (Minipress®)
• doxazosin (Cardura®)
• phentolamine (Regitine®)

Alpha-Adrenergic Blockers - Pharmacotherapeutics

• Used to treat:
  • Hypertension
  • Peripheral vascular disorders
  • Benign Prostatic Hypertrophy

Alpha-Adrenergic Blockers - Drug Interactions/Adverse Reactions

• Severe hypotension

Types of Beta-Adrenergic Blockers

• Selective beta1-blockers: Reduce stimulation of the heart (cardioselective beta-adrenergic blockers) e.g., Metoprolol, Atenolol, Bisoprolol & Esmolol.
• Nonselective beta1 and beta2-blockers: Reduce stimulation of the heart but can also cause the bronchioles of the lungs to constrict e.g., Propranolol, nadolol and carteolol.
• Mixed alpha and beta blockers: e.g., Labetalol & Carvedilol

Beta Antagonists (β Blockers)

• Frequently used; lower Blood Pressure
  • Beta1 Selective Blockade
    • Atenolol (Tenormin®)
    • Esmolol (Brevibloc®)
    • Metoprolol (Lopressor®)
  • Nonselective
    • Propranolol (Inderal®)
    • Sotalol (Betapace®)
  • Mixed
    • Labetalol (Normodyne®, Trandate®)

Beta-Adrenergic Blockers - Pharmacotherapeutics

• Used to treat:
  • Heart attacks
  • Angina
  • Hypertension
  • Supraventricular arrhythmias
  • Anxiety
  • Migraine Headaches
  • Open-angle Glaucoma

Beta-Adrenergic Blockers - Drug Interactions/Adverse Reactions

• Cardiac and Respiratory Depression
• Arrhythmia
• Severe Bronchospasm
• Severe Hypotension