Autonomic pharma of NMJ

Question 1

Which set of receptors are ionotropic?

Answer 1

Nicotinic receptors

Question 2

How many nicotinic subtypes are there?

Answer 2

2

Question 3

How many muscarininc substypes?

Answer 3

3

Question 4

How many adreneric subtypes?

Answer 4

5

Question 5

How is synaptic tranmission curtailed?

Answer 5

TRansmitter binds to presynaptic autoreceptors which inhibit release of more transmitter

Question 6

How is neurotransmitter in the synaptic cleft dealt with?

Answer 6

usually uptake to neurons or glia (except Ach is broken down)

Question 7

NAme 5 ways to inhibit the NMJ

Answer 7

Inhibit choline transporter
Block voltage gated Ca2+ channels
Block vesicle fusion (botulinim toxins)
Non-depolarising (competetive antagonist) nicotinic receptor blockers
Depolarising nicotinic receptor blockers (agonist that keeps ion channel open (brief twitch then paralysis))

Question 8

2 ways to improve NMJ function

Answer 8

Prolong action potential (make Ca2+ potential longer by inhibitin entry of K+ in order to release more Ach)
Block acetylcholinesterse

Question 9

Clinical applications of non-depolarising (comp antagonists) and depolarising (sticky agonists) nictotinic receptor blockers?

Answer 9

Nicotinic receptor blockers used for paralysis:

• surgical procedures
• electroconvulsive therapy
• controlling tetanus spasms.

Question 10

Clinical applications for blocking vesicle fusion

Answer 10

Botulinum toxin used:

• treating muscle spasm
• cosmetic

Question 11

clinical application of anti-cholinesterases

Answer 11

• treating myasthenic syndromes (e.g. myasthenia gravis)
• Reversing action of non-depolarising blockers
• Countering botulinim poisoning

Question 12

Whats ganglionic transmission?

Answer 12

Transmission between preganglionic and postganglionic autonomic fibres

Question 13

How can ganglionic transmission be blocked that NMJ transmission cant?

Answer 13

By blocking the Ach activated ion channel in the post-synaptic membrane

Question 14

How to increase ganglionic tranmission?

Answer 14

artificially activate nicotinic receptors (e.g. using nicotine which works better at ganglions than NMJ)

Question 15

Why is there little to no clincal applications of altering ganglionic transmission?

Answer 15

Drugs would modulate sympathetic, parasympathetic and some NMJ transmission so the massive side-effects make it not worth while.

Question 16

How can post-ganglionic parasympathetic transmission be modulated that the NMJ cant?

Answer 16

Muscarinic antagonists and muscarinic agonists.

Question 17

Clinical applications of muscarinic antagonists

Answer 17

Blocks action of parasympathetic system so:

• relaxes smooth muscle in airways/bladder
• Reduces gut motility
• dilates pupil etc

Question 18

Clinical applications of muscarinic agonists

Answer 18

Mimic effect of parasympathetic system so:

• slows heart rate
• constricts pupil
• contracts smooth muscle in airway/bladder

Question 19

Muscarinic agonists in glaucoma (high intraoccular pressure) treatment

Answer 19

aqueous humour normally drains through trabecular network into schlemm canal
Muscarinic agonist contract ciliary muscle and contract sphincter muscle
These open trabecular network and increase drainage of aqueous humour.

Question 20

4 ways to block postganglionic sympathetic transmission

Answer 20

• block enzymes producing the NA
• Block transporter that fill NA vesicles
• Use false transmitter to activate inhibitory presynaptic autoreceptors (alpha2)
• block alpha/beta postsynaptic receptors

Question 21

What are the 3 steps in producing NA from tyrosine?

Answer 21

Tyrosine -> DOPA
DOPA -> Dopamine
Dopamine -> Noradrenaline

Question 22

What enzymes are used converting tyrosine to NA?

Answer 22

Tyrosine hydroxylase
DOPA decarboxylase
Dopamine hydroxylase

Question 23

What blocks tyrosine hydroxylase?

Answer 23

Alpha-methyl-tyrosine

Question 24

What blocks dopa decarboxylase?

Answer 24

carbidopa

Question 25

What blocks dopamine hydroxylase?

Answer 25

6-hydroxydopamine

Question 26

What is tyrosine converted to, by what and what blocks it?

Answer 26

Tyrosine -> DOPA using tyrosine hydroxylase which is blocked by alpha-methyl-tyrosine

Question 27

What is DOPA converted to, how and hows it blocked?

Answer 27

DOPA -> dopamine by dopa carboxylase which is blocked by carbidopa

Question 28

What is dopamine converted to, by what and what blocks it?

Answer 28

Dopamine -> noradrenaline by dopamine hydroxylase which is blocked by 6-hydroxydopamine

Question 29

How to improve postganglionic sympathetic transmission? (sympathomimetics)

Answer 29

• Stimulate NA release
• Inhibit uptake into neurones
• Activate postsynaptic receptors

Question 30

Clinical aplications of alpha1 agonists

Answer 30

decongestants and to dilate pupil (mydriatics)

Question 31

Clinical applications of alpha2 agonists?

Answer 31

treat hypertension (stops vesicle packaging of NA)

Question 32

Clincal applications of Beta2 agonists?

Answer 32

Treats asthma (relaxes smooth muscle in airways causin dilation.)

Question 33

Clinical applications of Beta1 antagonists?

Answer 33

treating hypertension, angina, cardiac, arrhythmias and glaucoma.