Autonomic pharma of NMJ Flashcards
(33 cards)
Which set of receptors are ionotropic?
Nicotinic receptors
How many nicotinic subtypes are there?
2
How many muscarininc substypes?
3
How many adreneric subtypes?
5
How is synaptic tranmission curtailed?
TRansmitter binds to presynaptic autoreceptors which inhibit release of more transmitter
How is neurotransmitter in the synaptic cleft dealt with?
usually uptake to neurons or glia (except Ach is broken down)
NAme 5 ways to inhibit the NMJ
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))
2 ways to improve NMJ function
Prolong action potential (make Ca2+ potential longer by inhibitin entry of K+ in order to release more Ach)
Block acetylcholinesterse
Clinical applications of non-depolarising (comp antagonists) and depolarising (sticky agonists) nictotinic receptor blockers?
Nicotinic receptor blockers used for paralysis:
- surgical procedures
- electroconvulsive therapy
- controlling tetanus spasms.
Clinical applications for blocking vesicle fusion
Botulinum toxin used:
- treating muscle spasm
- cosmetic
clinical application of anti-cholinesterases
- treating myasthenic syndromes (e.g. myasthenia gravis)
- Reversing action of non-depolarising blockers
- Countering botulinim poisoning
Whats ganglionic transmission?
Transmission between preganglionic and postganglionic autonomic fibres
How can ganglionic transmission be blocked that NMJ transmission cant?
By blocking the Ach activated ion channel in the post-synaptic membrane
How to increase ganglionic tranmission?
artificially activate nicotinic receptors (e.g. using nicotine which works better at ganglions than NMJ)
Why is there little to no clincal applications of altering ganglionic transmission?
Drugs would modulate sympathetic, parasympathetic and some NMJ transmission so the massive side-effects make it not worth while.
How can post-ganglionic parasympathetic transmission be modulated that the NMJ cant?
Muscarinic antagonists and muscarinic agonists.
Clinical applications of muscarinic antagonists
Blocks action of parasympathetic system so:
- relaxes smooth muscle in airways/bladder
- Reduces gut motility
- dilates pupil etc
Clinical applications of muscarinic agonists
Mimic effect of parasympathetic system so:
- slows heart rate
- constricts pupil
- contracts smooth muscle in airway/bladder
Muscarinic agonists in glaucoma (high intraoccular pressure) treatment
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.
4 ways to block postganglionic sympathetic transmission
- 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
What are the 3 steps in producing NA from tyrosine?
Tyrosine -> DOPA
DOPA -> Dopamine
Dopamine -> Noradrenaline
What enzymes are used converting tyrosine to NA?
Tyrosine hydroxylase
DOPA decarboxylase
Dopamine hydroxylase
What blocks tyrosine hydroxylase?
Alpha-methyl-tyrosine
What blocks dopa decarboxylase?
carbidopa
