BS1060 T2

Basic steps of neurotransmission

1. uptake of precursors

2. synthesis of transmitter

3. vesicular storage of transmitter

4. degradation of transmitter

5. depolarization by propagated action

potential

6. depolarization-dependent influx of Ca2+

7. exocytotic release of transmitter

8. diffusion to post-synaptic membrane

9. interaction with post-synaptic receptors

10. inactivation of transmitter

11. re-uptake of transmitter (neuronal)

12. re-uptake of transmitter (non-neuronal)

13. interaction with pre-synaptic receptors

autonomic nervous system

Self governing nervous system

How can we pharmacologically intervene to alter ANS activity?

At the points of chemical communication

What does the ANS do?

Controls all involuntary functions

Is separate from the voluntary motor system

Is entirely efferent (conducted outwards by internal environment)

Mechanisms of termination of neutransmitter

Inactivation of transmitter

Re-uptake of transmitter (neuronal)

Where are the sites of drug action in neurotransmission?

Degradation of transmitter

Interaction with post-synaptic receptors

inactivation of transmitter

re-uptake of transmitter (neuronal)

Interaction with pre-synaptic neurons

Acetylcholine synthesis

AcetylCoA + Choline (CAT) --> ACh + coenzyme A

CAT = choline acetyltransferase

ACh degradation

Acetylcholine (AChE) —> acetate and choline

AChE = acetylcholineesterase

Potential therapeutic interventions in cholinergic transmission

Nicotine acetylcholine receptors at the autonomic ganglia and the somatic neuromuscular junction are structured differently - some drugs are ganglion blocking so are selective to the automatic ganglia and not the rest of the body

Actions of ACh can be enhanced by cholinesterase inhibitors

Problems with the lack of sensitivity of cholinergic drugs

Means unwanted side effect limit their usage

E.g a non-selective muscarinic ACh receptor agonist can cause autonomic side effects

Examples of autonomic side effects

Heart - decreased heart rate & cardiac output

Exocrine glands - sweating and salivation

Smooth muscle - peristalsis in GI tract and bronchocontrictnon

Muscarinic ACh receptors agonists

Pilocarpine and Bethanechol to treat glaucoma

Muscarinic ACh receptors antagonists

Ipratropium an tiotropium for asthma

Which type of drugs cause severe side effects

Drugs with affinity for muscarinic ACh receptors and act as antagonists

—> as they impair CNS and autonomic actions so increased risk in elderly

What is the key amino acid precursor used in noradrenaline synthesis

Tyrosine

Noradrenergic transmission termination

NET transports noradrenaline by rep-uptake into the pre-synaptic terminal (uptake 1)

Any NA not re-captured by uptake 1 is taken up by a lower affinity non-neuronal mechanism

In the pre-synaptic terminal any NA not taken up into vesicle is metabolised by monoamine oxidase (MAO) and COMPT

FEV-1

Index of how well the airways are working

Forced expiratory volume in 1 second