Autonomic and N.M.J pharmacology Flashcards
what is botulinium toxin and how does it modulate transmission at NMJ
neurotoxic protein produced by the bacterium Clostridium botulinum
ACh is not released as vesicle fusion is blocked. Leads to paralysis
how do black widow and joro spider toxins modulate transmission at NMJ
they block calcium channels and so ACh cannot be released
hemicholineum
blocks choline transport so ACh cannot be taken back up and resynthesised
How do competitive ACh antagonists work?
they bind to nicotinic receptors but don’t open ion channels so ACh cannot bind and no end-plate potential is produced
causes rapid weakening and paralysis of muscles, including those of the respiratory tract, which can lead to respiratory arrest and death.
how can you modulate sympathetic transmission at NMJ with drug examples?
introduce a false transmitter like methyldopa
block enzyme that produces adrenaline
block alpha or beta post synaptic receptors (by doxazosin drug or propanol)
how can you drugs effect para- sympathetic transmission at NMJ with examples?
muscarinic receptor antagonists- atropine
muscarinic receptor agonists- carbachol, pilocarpine that bind and activate ACh receptors
clinical applications of drugs at NMJ
non-depolarising or depolarising blockers used for paralysis during surgical procedures, controlling spasms in tetanus etc
botulinum toxin is used for treating muscle spasm or cosmetic procedures
anti-cholinesterases are used for treating myasthenic syndromes (neuromuscular disease) or countering botulinum posining
what are some potential sites of action for drugs at the NMJ?
inhibit choline transporter
block voltage gated Ca2+ channels
block vesicle fusion
use non-depolarising nicotinic receptor blockers
or depolarising nicotinic receptor blockers
prolong the action potential
block acetylcholinesterase
example of a depolarising nicotinic receptor blocker
succinylcholine
example of a non-depolarising nicotinic receptor blockers
d-tubocurarine
how can you stop transmission at the connection between pre and post ganglionic autonomic fibres
so its ACh and nicotinic in both sympathetic and para sympathetic
Inhibit choline transporter (eg hemicholinium)
Block voltage gated Ca2+ channels (eg black widow spider venom)
Block vesicle fusion (eg botulinium toxins)
Block ACh activated channel (eg hexamethoneum)
Non-depolarising nicotinic receptor blockers (eg mecylamine)
Depolarising nicotinic receptor blockers (eg suxamethoneum)
why are there no clinical applications with ganglionic transmission?
too many widespread side effects so next to no clinical applications
how do drugs affect postganglionic transmission in parasympathetic nerves and their targets
ACh acts on muscarinic receptors here
so either muscarinic receptor agonist ( carbachol, pilocarpine) or antagonist (atropine)
what will a muscarinic agonist do?
mimic the effect of the parasympathetic system ie slow heart rate, contract smooth muscle in airways and bladder, increase gut motility, constrict pupil)
what will a muscarinic antagonist do?
block effects of parasympathetic system so increase heart rate, relax smooth muscle in airways (useful in asthma+anaesthesia) and bladder, reduce gut motility (useful in IBS), pupils dilating- useful in eye examination
Glaucoma
muscarinic agonists are used in the treatment of glaucoma
they contract the ciliary muscle supporting the lens and contracts the sphincter muscle of the pupil which should drain fluid out of the eye reducing the intra occular pressure
inhibiting post ganglionic sympathetic transmission
potential sites of action
NA and alpha or beta receptors
block enzymes that produce NA (carbidopa)
block transporter that fills up vesicles with NA (reserpine)
introduce a false transmitter (methyldopa)
block alpha or beta postsynaptic receptors
which enzyme that produces NA is blocked?
dopa decarboxylase
improving postganglionic sympathetic transmission (sympathomimetics)
stimulating NA release by amphetamine
inhibit uptake into neurones (cocaine) or glia (phenoxybenzamine)
activate post-synaptic receptors (salbutamol or phenylephrine)
what are sympathomimetics
sympathomimetics- make synapses work better
can be indirect or direct
clinical applications of postganglionic sympathetic transmission
alpha 1 agonists-
alpha 1 agonists function
decongestants and to dilate the pupil (mydriatics)
alpha 2 agonists function
treatment of hypertension (high bp)
by vasodilation not heart
beta 2 agonists
mimic the sympathetic response so vasodilation
treatment of asthma
doesn’t affect the heart
beta 1 antagonists
treatment of hypertension, angina, cardiac arrhythmias and glaucoma
because it is an antagonist- sympathetic effects are not carried out so there is no increase in heart rate etc
which receptor is usually activated in the lungs
beta 2- sym
muscarinic- para sym
which receptor is usually activated in the heart in sympathetic system
B1 on pacemaker cells
which receptor is usually activated in the eye in sympathetic
Beta 2- ciliary muscle
Alpha 1 - radial muscle
which receptor is usually activated in the eye in para sympathetic
muscarinic- on ciliary muscle to focus eye up close
sphincter muscle contracts to make pupil smaller
neostigmine
inhibits acetylcholinesterase
