Noradrenergic transmission Flashcards
Which drugs affect noradrenaline synthesis?
- α-methyltyrosine
- Carbidopa
- Disulfiram
- α-Methyldopa
What is the mechanism of action of α-methyltyrosine and its clinical use?
Mechanism: Inhibits tyrosine hydroxylase
Clinical: Phaeochromocytoma
What is the mechanism of action of carbidopa and its clinical use?
Mechanism: Inhibits DOPA decarboxylase (DDC)
Clinical: Parkinson’s (counters peripheral effect of L-DOPA)
What is the mechanism of action of disulfiram and its clinical use?
Mechanism: Inhibits dopamine β-hydroxylase
Clinical: Chronic alcoholism
What is the mechanism of action of α-methyldopa and its clinical use?
Mechanism (False transmitter):
- Inhibits DDC and DBH
- Displaces NA from vesicles and causing MAO breakdown
- Binds to pre-synpatic α2 receptors and inhibits NA release via feedback inhibition
Clinical: Hypertension
Which drugs block noradrenaline storage and release?
- Reserpine: Inhibits VMAT and thus NA uptake into vesicles (loss of stored NA over time due to leakage)
- Guanethidine: Possibly inhibits exocytosis of NA and displaces NA from vesicles to cause gradual depletion over time
What are the indirect sympathomimetics?
- Tyramine (found in foods)
- Ephedrine (nasal congestion)
- Dextroamphetamine (narcolepsy & ADHD)
Which drugs selectively act on α1 adrenreceptors?
Agonists: Phenylephrine
Antagonists:
- Prazosin
- Tamsulosin
Which drugs selectively act on α2 adrenoreceptors?
Agonists:
- Clonidine
- α-methylnoradrenaline
Antagonists:
- Yohimbine
Which drugs non-selectively act on α adrenoreceptors?
Agonists:
- Topical decongestants (e.g. xylometazoline)
Antagonists:
- Phenozybenzamine
- Phentolamine
Which drugs selectively act on β1 adrenoreceptors?
Agonists:
- Dobutamine
Antagonists:
- Metoprolol
- Nebivolol
Which drugs selectively act on β2 adrenoreceptors?
Agonists:
- Salbutamol
- Salmeterol
- Terbutaline
- Clenbuterol
Antagonists:
- Butoxamine
Which drugs act selectively on β3 adrenoreceptors?
Agonists:
- Mirabegron
Which drugs act non-selectively on β adrenoreceptors?
Agonists: Isoprenaline
Antagonists: Propanolol
Which drugs act non-selectively on adrenoreceptors in general?
Agonists:
- Adrenaline
- Noradrenaline
Antagonists:
- Labetalol
- Carvedilol
What is an example of a MAO-A inhibitor and what are their clinical uses?
- Clorygline
- Treatment of depression
What is an example of a MAO-B inhibitor and what are their clinical uses?
- Selegyline
- Treatment of Parkinson’s
What is an example of a non-specific MAO inhibitor?
Tranylcypromine
What is an example of a COMT inhibitor and what are their clinical uses?
- Entacapone
- Parkinson’s (administered with L-DOPA and carbidopa and reduces peripheral metabolism of L-DOPA)
Which drugs inhibit NET and ‘Uptake 1’?
- Tricyclic antidepressants (e.g. imipramine)
- Cocaine
Which drugs inhibit EMT and ‘Uptake 2’?
- Corticosteroids (e.g. hydrocortisone): Inhibits EMT (uptake 2)
- Normetnephrine: Inhibits EMT (uptake 2)
Which drugs inhibit both NET and EMT?
Phenoxybenzamine
What are the additional effects of nebivolol metabolite?
- Metabolite is β3-adrenoreceptor agonist and increases NO production, causing vasodilation.
