Drugs on synaptic transmission Flashcards
what are the various steps in neurotransmission
1) synthesis
2) storage
3) arrival of action potential at pre-synaptic bouton
4) depolarisation of terminal to activate vgccs
5) release (calcium dependant)
6) neurotransmitter binds to receptors
7) uptake/breakdown of neurotransmitter
what do local anaesthetics and anti epileptics do
they block voltage gated sodium channels so no action potentials can propagate down the axons.
what do analgesics do
block voltage gated calcium channels so that neurotransmitters can’t be released
where is Ach synthesised
NMJ
ganglia
parasympathetic post-ganglionic fibres
CNS
what is the enzyme that synthesises acetylcholine
choline acetyltransferase (ChAT)
what is acetyl coA produced by
cellular respiration
what are the consequences of ChAT inhibitors
(fa64a)
they are ChAT inhibitors - very dangerous biological weapons - all ganglia would not work and NMJ would not work
what does the botulism toxin do (chloristrodium botulism)
degrades Ach containing vesicles so ANS and motor fibres are inhibited
what does beta bungarotoxin do
type of snake venom
prevents Act release
what is acetylcholine broken down (inactivated) by
acetylcholinesterase (AchE) loaded on post-synaptic membrane
what are anti-choline esterases
drugs that enhance on prolong chmlinergic transmission
cause increase in parasympathetic actions e.g. bradycardia, bronchoconstrictoin etc.
short actin drugs
e.g. edrophonium
used for diagnostic purposes
improves myasthenia gravis
medium acting drugs
e.g. neostigmine
used to reverse neuromuscular block after surgery
long acting drugs
irrervsible
new AchE needs to be synthesised and so is very dangerous
where is A and NA synthesised
CNS
sympathetic post ganglionic fibres and
adrenal medulla
what is the equation to get DOPA decarboxylase
tyrosine + DOPA > DOPA decarboxylase (rate limiting step)
uses tyrosine hydroxylase in cytoplasm
how do you get dopamine
DOPA decarboxylase > Dopamine
uses dopamine decarboxylase
how do you get NA
Dopamine > NA
uses dopamine hydrolase
how do you get A
NA > A
uses PNMT in adrenal medulla
how and where is NA stored
in vesicles in a complex with ATP
because ATP is also a nuerotransmiter at noradrenergic synapses
what is Resperpine
a drug that disrupts the complex between ATP and NA so that NA leaks out of the cytoplasm
this reduces the ability for vesicles to take up NA
causes a reduction in adrenergic transmission
used as early treatment for hypertension
what is guanethidine
an adrenergic neuron blocker
inhibits release of NA
how is NA removed
by reuptake unchanged back into pre-synaptic terminal
high affinity carrier =
uptake 1 (neuronal sites, ANS, CNS)
low affinity carrier =
uptake 2 (non-nueronal sites)
how is NA metabolised in neurones
by Monoamine oxidase (MAO)
how is NA metabolised in non-neuronal sites (e.g. adrenal medulla)
cathecol-O-methyltransferase (COMT)
what drugs may target this uptake mechanisms
Cocaine
tricyclic anti depressant
(inhibit uptake 1 = increase adrenergic transmission)
what is MAO inhibitor used as
an antidepressent
