L7 - Principles of drug action on NT

Question 1

Local anaesthetics:

Answer 1

Inhibit nerve conduction by blocking sodium channels.

Question 2

Nerves:
Autonomic:
Somatic:

Answer 2

Sympathetic and parasympathetic nerves go to tissue using ganglia - autonomic NS (involuntary).

Motor nerve goes to NMJ and skeletal muscles - somatic NS (voluntary).

NA released from sympathetic neurons.
ACh released from parasympathetic neurons, ganglia and NMJ.

Question 3

Different types of NT and location:

Answer 3

NA to sympathetic terminals.
ACh to parasympathetic terminals, ganglia and NMJ. 
Dopamine to parts of CNS.
Serotonin (5-HT) to parts of CNS. 
Nitric Oxide (NO) to odd places.

Question 4

Anatomy of SNS:

Answer 4

Emanates from thoracolumbar segments of SC (midsection).

Ganglia typically close to spinal cord in the paravertebral chain.
Ensures one way neurotransmission. Lump of tissue between where nerve originates and ends.

Question 5

Anatomy of PNS:

Answer 5

NT is acetylcholine and is released from cranial/sacral area.
Cranial has glossopharyngeal, vagal, oculomotor and facial nerves.
Sacral has nervi erigentes.

Ganglia close to or inside target tissues.

Question 6

Neuroeffector junction:

Answer 6

Action potential causes depolarisation. Voltage gated Ca channels opens. Ion channels change orientation and open pore. Allow Ca to enter nerve terminal. NT diffuses out into synaptic cleft in vesicle via exocytosis. Act on target protein (receptor) and stimulate it - postsynaptic agonism.
NT can also act on receptor on preSN and this is called presynaptic autoinhibitory agonism. Prevents NT diffusing out.

Question 7

How is NT synthesised:

How neurotransmission is a target for development of therapeutic drugs:

Answer 7

How NT is synthesised:

1. Precursor enter neuron
2. Enzyme cascade converts it to NT
3. NT is then stored in vesicle

Can test out different drugs on neurotransmission and can see how it effects certain processes.
E.g. botulinum prevents vesicle fusion at preSN so inhibits ACh.
Blocking the presynaptic receptor that causes autoinhibition enhances transmission.

Hemicholinium prevents choline uptake so no ACh synthesis.
AMPT prevents enzyme cascade to form NA.
Reserpine inhibits NA being stored in vesicle.
L-DOPA increases precursors to make dopamine.

Question 8

Agonist and antagonist action on receptors:

Answer 8

Agonists have affinity and efficacy and they stimulate receptors and mimic transmitter.
Antagonists have affinity but not efficacy. Block binding site and inhibit transmitter.

More antagonist have therapeutic uses than agonists.

Question 9

Sites of drug action:

Answer 9

1. Synthesis (Precursor to NT)
2. Storage (before stored in vesicles)
3. Release (before exocytosis)
4. Receptors
5. Cessation (enzymatic degradation, termination, re-uptake in preSN, autoinhibition).

Question 10

SUMMARY:

Answer 10

Synapse is an important target for drug action because:
It is the site of neurotransmission.
It is where NT is synthesised, stored and released.
It is a major location for receptors and target for agonist and antagonists. It is where most drugs act and where communication is.
Receptors allow you to produce drugs which are highly selective and so can have reduced side-effects.