Drug action in CNS

Question 1

Describe the structure of a neurone

Answer 1

Composed of cell body, dendrites, axon and axon terminal
Dendrites receive information from other neurones
Cell body contains nucleus, stores DNA and rough ER which builds protein and mitochondria
Axon carries information in form of electrical signal i.e. action potential
Axon terminal converts chemical signal into electrical signal and releases neurotransmitters

Question 2

In which region do neurones communicate with one another?

Answer 2

Synapse

Question 3

Synaptic transmission can only be chemical. True or false?

Answer 3

False can be electrical or chemical

Electrical synapses are very rare in the adult brain

Question 4

What is the gap at the chemical synapse between the pre and post synaptic neurones called?

Answer 4

Synaptic cleft

Question 5

What happens when an AP reaches the pre-synaptic terminal?

Answer 5

Ca2+ channels open and neurotransmitter release is initiated

Question 6

Where in the synapse are neurotransmitters stored?

Answer 6

Pre-synaptic terminal

Question 7

How is ACh synthesised?

Answer 7

Acetyl CoA + choline –> ACh + coenzyme A
Choline acetyltransferase is an enzyme which transfers an acetate ion from acetyl coA to choline. It is specific to cholinergic neurones and present in neuronal terminal in excess i.e. not saturated

Question 8

What is the effect of increasing the amount of choline in terms of ACh synthesis?

Answer 8

You can increase the synthesis of ACh

Question 9

Where is ACh stored?

Answer 9

Synaptic vesicles in the axonal terminal

Question 10

When is ACh released?

Answer 10

Released into the synaptic cleft upon arrival of an AP and influx of Ca2+

Question 11

When ACh is released, where does it bind?

Answer 11

Binds to post-synaptic receptors - muscarinic (M1 and M5) and nicotinic

Question 12

What are the 5 subunits that nicotinic receptors are composed of?

Answer 12

Alpha, beta, gamma, epsilon and delta

Question 13

Nicotinic receptors are divided into two main types. What are they?

Answer 13

Muscle and neuronal

Question 14

Where are muscle nicotinic receptors located?

Answer 14

Neuromuscular junction

Question 15

Where are neuronal nicotinic receptors located?

Answer 15

Autonomic ganglia and CNS

Question 16

What is ACh broken down by?

Answer 16

Acetyl cholinesterase breaks it down into acetate ion and choline molecule. Choline is transported back to pre-synaptic terminal

Question 17

What is the role of autoreceptors and where are they located?

Answer 17

Located on pre-synaptic terminal. They are activated by neurotransmitter and can control the synthesis or release of a neurotransmitter - almost like a feedback loop

Question 18

What is the neuromuscular junction?

Answer 18

A chemical synapse between a motor neurone and skeletal muscle fibre

Question 19

How does the action of ACh at the NMJ cause muscle to contract?

Answer 19

AP -> motor neurone -> Ca2+ release and ACh release.
ACh binds to nicotinic receptors on post-synaptic neurone and they open -> Na+ release -> depolarisation. AP then generated in skeletal muscle -> Ca2+ release -> contraction

Question 20

Name a disorder that affects the NMJ

Answer 20

Myasthenia Gravis

Question 21

What is myasthenia gravis?

Answer 21

An autoimmune condition that prevents muscles from contracting as a result of damage to the muscle acetylcholine receptors

Question 22

Which drug is used in myasthenia gravis to improve symptoms and how does it work?

Answer 22

Pyridostigmine - cholinesterase inhibitor so prevents the breakdown of ACh and improves muscle contraction

Question 23

How is dopamine synthesised?

Answer 23

L-tyrosine -> L-dopa -> Dopamine

Question 24

Which post-synaptic receptors does dopamine bind to upon being released?

Answer 24

D1 family - excitatory

D2 family - inhibitory

Question 25

What are the two ways in which dopamine can be inactivated?

Answer 25

Metabolic enzymes - COMT and MOA

Reuptake processes - catecholamines and DAT

Question 26

What are ionotropic receptors?

Answer 26

Receptor is part of ligand-gated ion channel protein and activation results in ion conductance changes. Receptor is opened by transmitter to allow passage of either Na+ (excitatory) or K+/Cl- (inhibitory). They are involved in fast transmission

Question 27

Describe metabotropic receptors

Answer 27

The receptor protein in the membrane is coupled to effector mechanism via G-proteins. In this signalling mechanism, agonist molecule combines with receptor proteins in the membrane. The resulting conformational change causes activation of membrane-associated enzymes via G-protein