ANS and NMJ Pharmacology

Question 1

Give the steps of synaptic transmission

8 steps

Answer 1

1.Synthesis and packaging of neurotransmitter (usually) in presynaptic terminals
2.Na+ action potential reaches terminal
3.Activates voltage gated Ca2+ channels
4.Triggers Ca2+-dependent exocytosis of pre-packaged vesicles of transmitter
5.Transmitter diffuses across cleft and binds to ionotropic and/or metabotropic receptors to evoke postsynaptic response
6.Presynaptic autoreceptors inhibit further transmitter release
7.Transmitter is (usually) inactivated by uptake into glia or neurons
8.Transmitter is metabolised within cells

Question 2

What is the neuromuscular junction

Answer 2

synapse between a motor neuron (somatic NS) and a (skeletal) muscle fiber

Question 3

How can we (pharmacologically) inhibit transission at the NMJ

Answer 3

• Inhibit choline transporter (e.g. hemicholinium)
• Block voltage gated Ca2+ channels (e.g. black widow spider venom)
• Block vesicle fusion (e.g. botulinium toxins)
• Use non-depolarising nicotinic receptor blockers (e.g. d-tubocurarine) - high affinity and low efficacy (don’t activate receptor)
• Use depolarising nicotinic receptor blockers (e.g. suxamethoneum = succinylcholine) - high affinity and efficacy

Question 4

Way to (pharmacologically) potentiate transmission

(increase transmission)

Answer 4

Block acetylcholinesterase (e.g. eserine) - stops ACh from being reabsorbed so it remains in the synaptic cleft (to bind again)

Question 5

Clinical applications of pharmacological modification: non-depolarising/depolarising blockers?

function/use

Answer 5

Used for paralysis during:
* Surgical procedures
* Electroconvulsive therapy
* Controlling spasms in tetanus

Question 6

Clinical applications of pharmacological modification: botulinum toxin?

Answer 6

• treating muscle spasms
• cosmetic procedures (paralysis of facial muscles)

Question 7

Clinical applications of pharmacological modification: Anti-cholinesterases?

Answer 7

• Treating myasthenia gravis
• Reversing action of non-depolarising blockers
• Countering botulinum poisoning

Question 8

Neurotransmitter released at neruomuscolar junction

Answer 8

Acetylcholine (ACh)

Question 9

Explain what is possible with ganglionic transmission in terms of pharmacology

Answer 9

• You could target transmission at the autonomic ganglia with any of the drugs that affect the NMJ
• However, it will affect both sympathetic and parasympathetic ganglia leading to complex effects with many side effects
• There are no clinical applications

Question 10

What is evidence that not all nicotinic recepotors are the same

Answer 10

hexamethonium blocks nicotinic receptors at the autonomic ganglia but not the NMJ

Question 11

How can we affect parasympathetic postganglionic transmission

Answer 11

• Muscarinic receptor agonists (e.g. carbachol, pilocarpine)= mimic the effect of the parasympathetic system (i.e. slow heart rate, contract smooth muscle in airways and bladder, increase gut motility, increase bronchial secretions and salivation, constrict pupil)
• Muscarinic receptor antagonists (e.g. atropine)= block effects of the parasympathetic system (therefore increase heart rate, relax smooth muscle in airways and bladder, reduce gut motility, bronchial secretions and salivation, dilate pupil)

Question 12

treatment of glaucoma - parasympathetic postganglionic transmission

not sure if need to know???

Answer 12

• Muscarinic agonists (e.g. pilocarpine) are also used in the treatment of glaucoma - i.e. high intraoccular pressure
• Aqueous humour normally drains through the trabecular network into the canal of Schlemm
• Muscarinic agonists contract the ciliary muscle supporting the lens and contracts the sphincter muscle of the pupil
• One or both of these opens up the trabecular network and increase drainage of the aqueous humour

Question 13

ANS transmitters and receptors

Answer 13

Acetylcholine (Acts on cholinergic receptors):
* nicotinic=> transmitters- N1 ganglia, N2 NMJ
* muscarinic=> transmitters- M1 neuronal (receptor= PLC), M2 cardiac and presynaptic (receptor= AC), M3 smooth muscle and glands (receptor= NOS)

Noradrenaline & adrenaline (Acts on adrenergic receptors):
* transmitter= a1, receptor= PLC
* transmitter= a2, receptor= AC
* transmitter= B1, receptor= AC
* transmitter= B2, receptor= AC

Question 14

Process of inhibiting transmission in sympathetic postganglionic transmission

Answer 14

• Block the enzymes that produce noradrenaline (e.g. carbidopa)
• Introduce a “false” transmitter (e.g. methyldopa) - structurally similar to noradrenaline
• Activate inhibitory presynaptic (α2) autoreceptors (e.g. methyldopa)
• Block α or β postsynaptic receptors (e.g. doxazosin or propranolol - a/B blockers)

Question 15

Process of potentiating transmission sympathetic postganglionic transmission

Answer 15

• Stimulate noradrenaline release (e.g. amphetamine)
• Inhibit uptake into neurons (e.g. cocaine and tricyclic antidepressants) or glia (e.g. phenoxybenzamine)
• Activate postsynaptic receptors (e.g. phenylephrine and salbutamol)

Question 16

clinical applications of sympathetic postganglionic transmission

Remember this one!!! :)

Answer 16

• α1 agonists as decongestants and to dilate the pupil (mydriatics)
• α2 agonists for the treatment of hypertension
• β2 agonists for the treatment of asthma
• β1 antagonists for the treatment of hypertension, angina and cardiac arrhythmias