Epilepsy Tutorial Flashcards
Classic drug targets for anti epileptic drugs
TIRE
Transport proteins- eg. synaptic vesicle protein
Ion channels- VGNaC
Receptors - NMDA/AMPA
Enzymes - GABA transaminase
What is the drug target for diazepam and how can it be used to treat seizures
The drug target for diazepam is the GABA receptor - this would be effective because it enhances the activity of GABA binding to the GABA receptor, and increasing the influx of GABA, thus the influx of chloride ions, increasing hyperpolarisation, thus decreasing the action potentials. Temporal lobe is the location .
How does lamotrigine work ?
Clue ; voltage gated sodium channel
Lamotrigine would prevent the influx of Na+ ions from the excitatory presynaptic neurone which would decrease the amount of EPSPs/less depolarisation and thus the number of action potentials . Stop exocytosis of glutamate
How does pregabalin work ?
Clue; voltage gated calcium channel
Pregabalin prevents the influx of calcium thus preventing the movement of the glutamate vesicles/exocytosis/efflux of glutamate into the synaptic cleft thus the activation of the postsynaptic receptors thus decreasing ESPSs/less depolari
Where does Levetiracetam act ? Clue ; not is usual drug target
Synaptic Vesicle Protein. Prevents the priming and fusion of glutamate vesicles to the presynaptic membrane and thus exocytosis of glutamate into the synaptic cleft, less depolarisation. In the presynaptic terminal of the glutamate synapse
Tiagabine is used as an add on therapy . Target is GABA reuptake transporter . How does it work?
Tiagabine would prevent the reuptake of GABA and thus increase the concentration of GABA in the synaptic cleft, increasing the influx of GABA into the post synaptic neurone, thus increasing the hyperpolarisation of the PSN, decreasing the AP
How does a Vigabatrin work ? Target is GABA transaminase.
Vigabatrin would prevent the breakdown of GABA into succinic semialdehyde which would increase the concentration of GABA in the preS inhibitory neurone and thus the efflux of GABA (because there would be more in the vesicles) into the synaptic cleft and thus the influx of GABA into the postSN, and thus the hyperpolarisation and thus decrease the excitatory effect.
Ultimately the effect is that GABA accumulated in synaptic cleft and has inhibitory effect
The neurologist chose not to prescribe sodium valproate to Miss F since it is an anti-epileptic drug that should not be used in female patients with childbearing potential. Sodium valproate has low selectivity. What does this mean and what are the potential consequences of this?
Low selectivity means that the effect will be more generalised across
- the same target in different tissues
- different targets (similar) in the same and different tissues
This could mean that the drug could have adverse side effects as it acts on many other enzymes, receptors, channels and proteins.
Off-target effects.
