Anticonvulsants, Anxiolytics and Hypnotics Flashcards
What is Epilepsy?
‘the condition of recurrent, spontaneous seizures arising from abnormal, synchronous and sustained electrical activity in the brain.’
- It is essentially too much excitation in the brain, or not enough inhibition which leads to excitation. Have excessive activity that isn’t controlled with no sort of feedback – resulting in seizure like qualities.
What is a Seizure?
an episode of neurological dysfunction of abnormal firing of neurones manifesting as changes in motor control / sensory perception / behaviour / autonomic function.
What is the Pharmacological Treatment for Epilepsy?
What does it depend on?
AED’s - act to restore inhibitory function in the brain and therefore suppress seizure activity.
Depends in part on the type of seizure experienced by the patient, which will then in turn determine an appropriate Anti-Epileptic.
What are the different types of Seizures and what is the first line treatment?
GENERALISED - Carbazepine, Lamotrigine, Na Valproate, Oxcarbazepine
TONIC/ATONIC - Na Valproate
ABSENCE - Ethosuximide, Lamotrigine, Na Valproate
MYOCLONIC - Levetiracetam, Na Valproate, Topiramate
FOCAL - Lamotrigine, Leventiracetam, Oxcarbazepine, Na Valproate
What are GABA and Glutamate?
Major Neurotransmitters in the CNS - most abundant. Involved in many metabolic activities so you have a separate pool of GABA and Glutamate.
- They regulate and control many functions in the brain
- Potential for role in very wide range of neuroscience disease states
- Challenge is achieving benefit without side-effects
What is GABA?
The main inhibitory neurotransmitter - activates receptors that result in an inhibitory signal being passed on.
What is Glutamate?
The main excitatory neurotransmitter - If we have too much excitation, then we need to try and restore that inhibitory tone and they would be then useful for anticonvulsants. Therefore, inhibiting some of these Glutamate receptors may be best.
What is Neuronal Firing?
Seizure control for epilepsy by balancing factors that influence Excitatory Post-Synaptic Potential (EPSP) and those that influence Inhibitory Post-Synaptic Potential (IPSP)
What are the 2 physiological protection against repetitive firing?
Occurs via inhibition at 2 levels:
- The cellular level (e.g. Na+ channel inactivation)
- The network level (e.g. GABA-mediated inhibition)
What happens if you have too much IPSP?
Instead of Sodium rushing in, the Chloride rushes in, bringing the potential down away from this threshold of generating an Action Potential.
What are the four main categories for anti-convulsants?
1) Drugs that inhibit Na+ channels
2) Drugs that inhibit calcium channels
3) Drugs that enhance GABA-mediated inhibition
4) Drugs that inhibit glutamate receptors
Tell me about how Drugs that inhibit Na+ channels work?
When you reach the threshold, the Na+ channels open very fast and anti-epileptics might cause some sodium channels to sit more in this inactive state, to keep thing stable with not much excitation.
Tell me about how Drugs that inhibit Ca2+ channels work?
Need influx of calcium when the AP arrives at the pre-synaptic terminal, that’s why you might block or subdue.
If you block these - you will shut down transmission, so just want to subdue it a little bit to reduce this excitation.
How do Drugs that enhance GABA-mediated inhibition work?
Synthesis mediated by Glutamic Acid Decarboxylase (GAD).
Storage: GABA is packaging into presynaptic vesicles by a transporter (VGAT).
Action Potential causes elevation of intracellular Ca2+, GABA released into synaptic cleft; fusion of GABA-containing vesicles with pre-synaptic membrane. Released it activates receptors.
Influx of Cl- dis-inhibitory signals and glutamate can’t fire excessively. GABA re-uptake inhibitors increase synaptic availability of GABA and therefore increases inhibition and decreases excitation.
How do drugs that inhibit Glutamate Receptors work?
NMDA allows Ca2+ in - channel blocked by magnesium in resting state. AMPA and Kainite allows vast amount of sodium to enter. NMDA gives Glutamate extra boost, normal resting potential blocked by Mg2+; Activation of AMPA to increase potential, then removes depolarisation and NMDA can allow Ca2+ in. Calcium is very important when it comes to functions like learning and memory.
