Pharm - lecture 12 - drugs acting on the SNS

• What is the primary neurotransmitter in the SNS

  Noradrenaline
• Describe the synthesis of noradrenaline

  Tyrosine → DOPA (via tyrosine hydroxylase) → Dopamine (via DOPA decarboxylase) → Noradrenaline (via dopamine β-hydroxylase
• How is noradrenaline stored and released?

  tored in vesicles and released via exocytosis when a nerve impulse triggers its release.
• How is noradrenaline action terminated?

  Through reuptake into the presynaptic neuron and metabolism by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT).
• What are the two main classes of noradrenergic receptors?

  Alpha (α) and Beta (β) adrenergic receptors.
• What are the functions of α1-adrenergic receptors?

  Vasoconstriction, pupil dilation, increased blood pressure, and contraction of smooth muscle.
• Where are α2-adrenergic receptors located, and what do they do?

  Found presynaptically, they inhibit neurotransmitter release, forming a negative feedback loop.
• What are the functions of β1-adrenergic receptors?

  Increase heart rate and contractility, affecting the SA node of the heart.
• What are the functions of β2-adrenergic receptors?

  Bronchodilation, vasodilation of limb muscles, and relaxation of smooth muscle.
• What is the main function of β3-adrenergic receptors?

  Lipolysis (breakdown of fat for energy).
• What drug acts as an agonist for all adrenergic receptors (α1, α2, β1, β2)?

  Adrenaline
• What is clonidine, and what is it used for?

  α2-agonist → inhibits noradrenaline release, used to treat hypertension and opioid withdrawal.
• How does dobutamine affect the heart?

  β1-agonist → increases heart rate and contractility, used for heart failure.
• What β2-adrenergic agonist is used for asthma?

  Salbutamol (causes bronchodilation).
• What is clenbuterol, and why is it controversial?

  β2/β3 agonist → used for asthma, but also increases metabolic rate and muscle growth, leading to misuse in sports.
• What is an α1-antagonist, and what is it used for?

  Prazosin/Tamsulosin → causes vasodilation, used to treat hypertension and urinary retention (BPH).
• What are the effects of β-blockers (β-antagonists)?

  Decrease heart rate, blood pressure, and oxygen demand. Used to treat hypertension and angina.
• Why is propranolol contraindicated in asthma patients?

  It is a non-selective β-blocker, blocking β2-receptors, leading to bronchoconstriction.
• How does methyldopa lower blood pressure?

  It acts as a false substrate for DOPA decarboxylase, reducing noradrenaline synthesis.
• What is the mechanism of action of reserpine?

  It disrupts noradrenaline storage in synaptic vesicles, reducing sympathetic activity.
• What drugs block noradrenaline reuptake?

  Cocaine, amphetamines, tricyclic antidepressants (desipramine), and reboxetine.
• How do monoamine oxidase inhibitors (MAOIs) affect noradrenaline levels?

  They block noradrenaline metabolism, increasing its availability.
• What is the "cheese reaction"?

  MAOIs block the metabolism of dietary amines (e.g., tyramine in cheese), causing hypertensive crises.