Pharmacology of the Sympathetic Nervous System

Question 1

What neurotransmitter regulates the sympathetic NS?

Answer 1

Adrenaline and Noradrenaline

Question 2

Give some typical examples of the symapathetic nervous system on..

• the cardiovascular system
• the digestive system

Answer 2

Cardiovascular =
Increased force of contraction, increase heart rate, increased stroke volume, vasoconstriction of arteries to get more blood into the heart

Digestive = reduced blood supply to GI tract, increased blood glucose (increased gluconeogenesis, reduced secretion of insulin

Question 3

What is the site of drug intervention in the Systemic nervous system?

Answer 3

Sympathetic nerves in the CNS (all drugs will need to penetrate the blood brain barrier and are likely to have a widespread effect)
Sympathetic Ganglion (Ach mediated transmission meaning effects will likely be widespread and non-specific 
Neuroeffector Junction (allows for specific targeting)

Question 4

Describe the mechanism of noradrenergic neurotransmission and how it is regulated

(big answer)

Answer 4

1. Synthesis of noradrenaline from tyrosine. Tyrosine forms DOPA which then goes on to form dopamine, noradrenlaine and then to adrenaline
2. Noradrenaline Storage - (noradrenaline is taken into vesicles via the VMAT which is the vesicular monoamine transporter) Reserpine blocks the VMAT which prevents noradrenline uptake into vesicles whereas monooxide breaks down the content of the vesicles so there is no new synthesisof noradrenaline
3. Release - Negative feedback mechanism where the alpha adrenergic receptor is activated. Clonidine is an alpha adrenergic receptor specific agonist which inhibits neurotransmitter release.
   Promoting NA release is amphetamine which displaces NA from its storage sites leading to leakage to the synaptic cleft.
4. Interaction with receptors:
   Adrenergic receptors are G-proteins.
5. Transmitter Activation and NA signalling inactivation
   Noradrenaline not taken up diffuses away and is taken up and metabolised by tissues.
   Endogenous and exogenous catecholamines are metabolised by 2 enzymes. Noradrenaline forms DOMA when it is broken down by MAO.

Question 5

What are some affects of alpha 1 adrenergic receptors?

What type of receptor is it?

Answer 5

• smooth muscle contraction
• relaxation of muscle in GI track
• increased glycogen metabolism
• pupil dilation
• increased salivary gland secretion

Gq, negative feedback auto-receptor,

Question 6

What is the one main affect of the alpha 2 adrenergic receptor?
What type of receptor is it/

Answer 6

Inhibition of transmitter release

It is an inhibitory receptor as it inhibits adenlyl cyclase and increases cAMP stimulation which activates kinase A.

Question 7

What type of receptor is the beta adrenergic receptor and what is it main affects?

Answer 7

It is a Gs, G coupled receptor. It increases heart rate and force of contraction by stimulating adenylyl cyclase and increasing cAMP production (leading to the beta and gamma subuntis being released.

Question 8

What are adverse effects of beta blockers?

Answer 8

• Fatigue
• Reduced Peripheral Blood flow
• Bronchoconstriction
• Increased risk of cardiac failure
• Risk of hypoglyceamia