week 4 pharmacology on NMJ and ANS

Question 1

what are 5 ways to inhibit transmission of the neuromuscular junction

Answer 1

1. inhibit choline transporter
2. block voltage gated calcium channels
3. block vesicle fusion
4. use non-depolarising nicotinic receptor blockers
5. use depolarising nicotinic receptor blockers

Question 2

what is one way to potentiate transmission in the NMJ

Answer 2

• block acetylcholinesterase

Question 3

what does inhibiting choline transport do in the NMJ

Answer 3

• stops choline being taken up into the pre-synaptic vesicles so it can’t be made into acetylcholine and eventually the terminal will run out of acetylcholine so will block transmission across synapse

Question 4

what does blocking voltage gated calcium channels do in the NMJ

Answer 4

• will stop calcium coming into the cell and will therefore not allow calcium dependent exocytosis so you won’t get any acetylcholine released and that will block transmission at the junction

Question 5

what does blocking vesicle fusion do in the NMJ

Answer 5

• vesicles can fuse and so prevents transmitter release and so stops NMJ working

Question 6

what do non-depolarising nicotinic receptor blockers do in the NMJ

Answer 6

• mimic the action of acetylcholine
• they bind to acetylcholine nicotinic receptors but don’t open the channels
• therefore acetylcholine can bind and it can’t produce its effect and the NMJ will be blocked

Question 7

what do depolarising nicotinic receptors blockers do in the NMJ

Answer 7

• bind to nicotinic acetylcholine receptors and opens the channel so sodium comes in
• this will fire a few action potentials and depolarise the cell
• but then the cell won’t be able to hyperpolarsie because the voltage gated sodium channels have become inactivated
• so cells stays in the refractory period and you won’t be able to stimulate it again and won’t be able to contract the muscle again

Question 8

what does blocking acetylcholinesterase do in the NMJ

Answer 8

• acetylcholine will be allowed to accumulate once it is released and allowed to accumulate longer so will activate more receptors and get a big response in the post synaptic membrane (potentiates transmission)

Question 9

what are non-depolarising or depolarising blockers in the NMJ used for clinically

Answer 9

used for paralysis during:

• surgical procedures
• electroconvulsive therapy
• controlling spasms in tetanus

Question 10

what is botulinum toxin used for clinically in the NMJ

Answer 10

• treating muscle spasm

- cosmetic procedures (botox)

Question 11

what is anti-cholinesterase in the NMJ used for clinically

Answer 11

• treating myasthenic syndromes (syndromes where you get muscle weakness)
• reversing action of non-depolarising blockers
• countering botulinum poisoning

Question 12

what is post-ganglionic parasympathetic transmission

Answer 12

• when acetylcholine binds to muscarinic receptors

Question 13

what do muscarinic receptor agonists do in the post-ganglionic parasympathetic transmission

Answer 13

• muscarinic receptor agonists will mimic the effect of the parasympathetic system (i.e. slow heart rate)

Question 14

what do muscarinic receptor antagonists do in the post-ganglionic parasympathetic transmission

Answer 14

• block the effects of the parasympathetic nervous system (e.g. the antagonists will increase heart rate, relax bladder, etc.)

Question 15

what post ganglionic parasympathetic transmission drug is used in the treatment of glaucoma

Answer 15

• muscarinic agonists are used in the treatment of glaucoma i.e. high intra-ocular pressure
• muscarinic agonists contract the ciliary muscle supporting the lens and contract the sphincter muscle of the pupil
• this increases the drainage of the aqueous humour

Question 16

what is post-ganglionic sympathetic transmission

Answer 16

• when noradrenaline binds to alpha or beta receptors

Question 17

what are 4 ways to inhibit post-ganglionic sympathetic transmission

Answer 17

1. block the enzymes that produce noradrenaline
2. block the transporter that fills the vesicles with noradrenaline
3. introduce a ‘false’ transmitter (this is packaged into vesicles instead of noradrenaline)
4. activate inhibitory pre-synaptic (alpha 2) auto receptors (typically inhibits calcium channels so no transmitter release)
5. block alpha or beta post-synaptic receptors

Question 18

what are ways to potentiate post-ganglionic sympathetic transmission

Answer 18

1. stimulate noradrenaline, adrenaline release
2. inhibit uptake into neurones or glia
3. activate post-synaptic receptors
   (the first two really only happen in abuse of drugs not therapeutically)

Question 19

what are the clinical applications of alpha 1 agonists

Answer 19

• can be used as decongestants and to dilate the pupil

Question 20

what are the clinical applications of alpha 2 agonists

Answer 20

• treatment of hypertension

Question 21

what are the clinical applications of beta 2 agonists

Answer 21

• treatment of asthma

Question 22

what are the clinical applications of beta 1 antagonists

Answer 22

• treatment of hypertension, angina and cardiac arrhythmias