Anti-convulsion drugs Flashcards
Why do convulsions occur?
Imbalance between inhibitory and excitatory signals in the CNS.
Too much excitatory signalling.
Two options for drugs- increase inhibition or decrease excitation.
Main symptoms of epilepsy
Unprovoked seizures.
Hyperexcitibility of a group of neurons
How are the different classes of epilepsy named?
By the type of seizure experienced- not by the underlying cause of the seizure
Where does the seizure begin?
Focus- neurons fire too many APs
Partial seizure
Only one hemisphere
Generalised seizure
Spreads to both hemispheres
Simple seizure
No loss of conciousness
Complex seizure
Always a loss of consciousness
Causes?
Head injury Stroke Infection Tumours Genetic factors such as mutations in ion channels
Where are the mutations
Nav channels
NAChR
K+ channels
What will you see if the seizure spreads to the hypothalamus?
Loss of control of autonomic processes such as-
Sweating
Salivating
Bladder/bowel control
What will you see if the seizure spreads to the reticular formation?
Loss of consciousness- complex
Triggers?
Flashing lights C Certain sounds Alterations in blood pH or glucose Stress Fatigue
How do you diagnose epilepsy
EEG- electroencephalogram
Electrodes in each side of the brain
Look at focus and if there is spread- if spread then the electrodes on both sides of the brain will be activated (generalised)
What happens if there is a rapid onset of activity
Whole body convulsions
Loss of consciousness
Muscle contraction
Patient goes rigid and falls to the floor
What is another side effect of epilepsy
Neurotoxicity- if the neurons are being overexcited- they will become damaged which will lead them to dying and thus there is neurodegeneraion
Absence Seizures
Person is absent for a few seconds No loss of consciousness No convulsions Oscillatory pattern in the EEG- very intermittent and short Mediated by Cav channels
Treatment- increasing inhibition
Target GABAa receptors- use benzodiazepines to enhance GABA effects and thus inhibition
Also prevent the metabolism of GABA in the cleft- if is around more so it will initiate more APs.
What do paramedics administer in an uncontrolled seizure?
Intravenous benzodiazepines to switch off the electrical activity of that part of the brain
What drugs can be used to treat epilepsy?
Benzodiazepines- used for status epilepticus (uncontrolled). Can lead to sedation, tolerance, withdrawal symptoms.
Uptake inhibitors- tiagabine
Metabolic inhibitors- valprolate inhibits breakdown of GABA by inhibiting GABA transaminase. However it also binds glutamate and NDMA receptors. It also targets chromatin remodelling proteins- can promote the transcription of GABA as well as inhibiting its breakdown
How is GABA produced
Side product of the Krebs cycle.
Produced from glutamate by glutamic acid decarboylase. Only neurons which produce GABA have this enzyme which makes it easy to stain for GABAergic neurons.
Why is valprolate called a suicide inhibitor?
It is used as an anti-convulsant- when the drug binds to GABA transaminase. it completely inhibits the breakdown of GABA.
How is excitatory signalling inhibited?
Nav blockers- Use dependent Na+ channels inhibitors. This inhibits the release of glutamate which is an excitatory NT. This class of drug only binds to activated Na+ channels- they can only interact with open state channels because of their configuration/structure. By doing this- prolong the inactivated state and thus less channels can open. The neuron has to be firing a lot of APs to have a lot of activated channels- drugs therefore preferentially target highly active neurons.
Why Na+ blockers in instead of benzodiazepines?
Side effects of benzodiazepines mean that there is increased incidence of sedative effects and patients can become tolerant/dependent. Epilepsy is a lifelong disease which means that these types of drugs are unsuitable.
