Centrally-acting sympatholytic drugs

Question 1

What are centrally-acting sympatholytic drugs?

Answer 1

Agents which interfere with the synthesis and/or release of noradrenaline in the SNS.

Question 2

The biosynthetic pathway for noradrenaline occurs in three steps:

Answer 2

1. Tyrosine is hydroxylated to form DOPA
2. DOPA is decarboxylated to form dopamine
3. Dopamine is B-hydroxylated to form noradrenaline

Question 3

Methyldopa in the biosynthetic pathway for noradrenaline

Answer 3

Methyldopa competes with DOPA at step 2 in this pathway and thereby acts as a competitive inhibitor of DOPA decarboxylase. The drug thereby reduces noradrenaline production in favour of a-methylnoradrenaline.

Question 4

What is a-methlydopa metabolised to? What is its method of action?

Answer 4

Metabolised to a-methylnoradrenaline

Potent agonist for pre-synaptic A2 receptors, by negative feedback cause presynaptic inhibition of NAd release

Question 5

What is clonidine and what is its MOA?

Answer 5

A2 selective agonist, by negative feedback cause presynaptic inhibition of NAd release

Question 6

What are the side effects of a-methyldopa?

Answer 6

Produces many side effects, some clearly associated with disruption of dopaminergic pathways e.g. tremor, gynaecomastia and depression
Known to be safe in pregnancy so mainly reserved for treatment of gestational hypertension

Question 7

What is clonidine used to treat?

Answer 7

Effective in treatment of hypertension but sudden withdrawal can precipitate hypertensive crisis

Question 8

What are the side effects of A2 stimulation?

Answer 8

A2 stimulation has other CNS effects including sedation

Question 9

Give examples of other A2 agonists and their uses

Answer 9

Detomidine, dexmedetomidine, medetomidine and xylazine are A2 agonists used as sedatives and in anaesthesia especially veterinary

Question 10

What does sympatholytic mean?

Answer 10

The term sympatholytic implies inhibition of sympathetic neurotransmission.