Noradrenergic transmission

Question 1

Which drugs affect noradrenaline synthesis?

Answer 1

1. α-methyltyrosine
2. Carbidopa
3. Disulfiram
4. α-Methyldopa

Question 2

What is the mechanism of action of α-methyltyrosine and its clinical use?

Answer 2

Mechanism: Inhibits tyrosine hydroxylase

Clinical: Phaeochromocytoma

Question 3

What is the mechanism of action of carbidopa and its clinical use?

Answer 3

Mechanism: Inhibits DOPA decarboxylase (DDC)

Clinical: Parkinson’s (counters peripheral effect of L-DOPA)

Question 4

What is the mechanism of action of disulfiram and its clinical use?

Answer 4

Mechanism: Inhibits dopamine β-hydroxylase

Clinical: Chronic alcoholism

Question 5

What is the mechanism of action of α-methyldopa and its clinical use?

Answer 5

Mechanism (False transmitter):

1. Inhibits DDC and DBH
2. Displaces NA from vesicles and causing MAO breakdown
3. Binds to pre-synpatic α2 receptors and inhibits NA release via feedback inhibition

Clinical: Hypertension

Question 6

Which drugs block noradrenaline storage and release?

Answer 6

1. Reserpine: Inhibits VMAT and thus NA uptake into vesicles (loss of stored NA over time due to leakage)
2. Guanethidine: Possibly inhibits exocytosis of NA and displaces NA from vesicles to cause gradual depletion over time

Question 7

What are the indirect sympathomimetics?

Answer 7

• Tyramine (found in foods)
• Ephedrine (nasal congestion)
• Dextroamphetamine (narcolepsy & ADHD)

Question 8

Which drugs selectively act on α₁ adrenreceptors?

Answer 8

Agonists: Phenylephrine

Antagonists:

1. Prazosin
2. Tamsulosin

Question 9

Which drugs selectively act on α₂ adrenoreceptors?

Answer 9

Agonists:

1. Clonidine
2. α-methylnoradrenaline

Antagonists:

1. Yohimbine

Question 10

Which drugs non-selectively act on α adrenoreceptors?

Answer 10

Agonists:

1. Topical decongestants (e.g. xylometazoline)

Antagonists:

1. Phenozybenzamine
2. Phentolamine

Question 11

Which drugs selectively act on β₁ adrenoreceptors?

Answer 11

Agonists:

1. Dobutamine

Antagonists:

1. Metoprolol
2. Nebivolol

Question 12

Which drugs selectively act on β₂ adrenoreceptors?

Answer 12

Agonists:

1. Salbutamol
2. Salmeterol
3. Terbutaline
4. Clenbuterol

Antagonists:

1. Butoxamine

Question 13

Which drugs act selectively on β₃ adrenoreceptors?

Answer 13

Agonists:

1. Mirabegron

Question 14

Which drugs act non-selectively on β adrenoreceptors?

Answer 14

Agonists: Isoprenaline

Antagonists: Propanolol

Question 15

Which drugs act non-selectively on adrenoreceptors in general?

Answer 15

Agonists:

1. Adrenaline
2. Noradrenaline

Antagonists:

1. Labetalol
2. Carvedilol

Question 16

What is an example of a MAO-A inhibitor and what are their clinical uses?

Answer 16

• Clorygline
• Treatment of depression

Question 17

What is an example of a MAO-B inhibitor and what are their clinical uses?

Answer 17

• Selegyline
• Treatment of Parkinson’s

Question 18

What is an example of a non-specific MAO inhibitor?

Answer 18

Tranylcypromine

Question 19

What is an example of a COMT inhibitor and what are their clinical uses?

Answer 19

• Entacapone
• Parkinson’s (administered with L-DOPA and carbidopa and reduces peripheral metabolism of L-DOPA)

Question 20

Which drugs inhibit NET and ‘Uptake 1’?

Answer 20

• Tricyclic antidepressants (e.g. imipramine)
• Cocaine

Question 21

Which drugs inhibit EMT and ‘Uptake 2’?

Answer 21

• Corticosteroids (e.g. hydrocortisone): Inhibits EMT (uptake 2)
• Normetnephrine: Inhibits EMT (uptake 2)

Question 22

Which drugs inhibit both NET and EMT?

Answer 22

Phenoxybenzamine

Question 23

What are the additional effects of nebivolol metabolite?

Answer 23

• Metabolite is β₃-adrenoreceptor agonist and increases NO production, causing vasodilation.