Autonomic & Neuromuscular Pharmacology

Question 1

Describe the mechanism by which drugs can modulate synaptic transmission in the parasympathetic ANS

Answer 1

muscarinic receptor agonist (eg. carbachol, pilocarpine) - muscarinic agonist will mimic the effect of the parasympathetic system: slows heart rate, contract smooth muscles in airways and bladder, increase gut motility, increase bronchial secretion and salvations, constrict pupils

muscarinic antagonist (eg. atropine) - will block effects of the parasympathetic system

Question 2

Describe the mechanisms by which drugs can inhibit synaptic transmission in the sympathetic ANS

Answer 2

neurotransmitter isn’t inactivated by enzyme - block the enzyme that produces noradrenaline (NA)
-block the transporter that fills the vesicle with NA (eg.resepine)
-introduce a ‘false’ transmitter (eg. methyldopa) unable to bind and activate transmitter
1activate inhibitory presynaptic (a2) autoreceptors (eg. methyldopa) inhibit voltage-gated Ca ion channels and then inhibit further transmission
-block a or B postsynaptic receptors (eg. doxazosin or propanol)

Question 3

Describe the mechanisms by which a drug can potentiate synaptic transmission in the sympathetic ANS

Answer 3

stimulate NA release ( eg. amphetamine) - taken up by carrier molecules triggers noradrenaline to be released from terminals

• inhibit uptake into neurons (eg, cocaine & tricyclic antidepressants) or glia (eg. phenoxybenzamine)- blocks transporter so noradrenaline can’t be removed so quickly
• activate postsynaptic receptors (eg.phenylephrine & salbutamol)

Question 4

Describe the mechanisms by which drugs can inhibit synaptic transmission at the neuromuscular junction

Answer 4

• inhibit choline transporters (eg.hemicholin)
• block voltage-gated Ca ion channels (eg. black widow spider venom)
• block vesicle fusion (eg. botulinium toxins)
• use non-depolarising nicotinic receptor blockers (eg. suxamethoneum, succinylcholine)

Question 5

Describe the mechanisms by which drugs can potentiate synaptic transmission at the neuromuscular junction

Answer 5

-block acetylcholinesterase (eg. eserine) - anti-cholinesterase
acetylcholine accumulates which increases activation of receptors and gives bigger response to postsynaptic membrane

Question 6

Describe the clinical applications for drug modulation of the neuromuscular junction

Answer 6

• non-depolarising or depolarising blockers used for paralysis during: surgical procedures, electroconvulsive therapy, controlling spasms in tetanus
• botulinum toxin used for: treating muscle spasms, cosmetic procedures (botox)
• anti-cholinesterase used for: treating myasthenic syndromes, reversing action of non-depolarising blockers(competitive inhibition), countering botulinum poisoning

Question 7

Describe the clinical applications for drug modulations of the ANS

Answer 7

• a1 agonist can be used as decongestant and to dilate the pupils
• a2 agonist can be used in the treatment of hypertension
• B1 antagonists can be used in the treatment of hypertension, angina and cardiac arrhythmias
• B2 agonist can be used in the treatment of asthma