Anti-Seizure Flashcards
What are seizures
Transient (Short time) alteration of behaviour caused by excessive and synchronous neuronal activity
What is epilepsy
Disorder of brain function characterized by periodic and unpredictable seizures
Occurs spontaneously and unprovoked
What’s the difference between epilepsy and seizures
You can have seizures without epilepsy
But epilepsy is characterized by seizures
What is symptomatic epilepsy
Epilepsy that occurs due to a known event (blunt trauma)
What is asymptomatic epilepsy
Epilepsy that occurs due to poorly defined genetic factors
How do neurons normally fire
Asynchronously
What is surround inhibition
The primary afferent stimulated will produce more action potentials than those on the periphery
The peripheral neurons are strongly inhibited
What are the three steps of a seizure
Initiation
Propagation
Termination
What are the two events of seizure initiation
High frequency bursts of action potentials
High synchronization of neuronal population
What can overcome the barriers preventing bursting neuronal activity
Increasing extracellular potassium (Efflux of potassium is unfavoured and hyperpolarization does not occur)
Increasing calcium in presynaptic terminals will lead to enhanced neurotransmitter release
Activating NMDA receptors will cause more calcium influx and a greater neuronal activation
How does potassium flow in hyperpolarization
High potassium inside cell flows out of cell
Loss of positive ions inside the cell causes the cell to be more negative and thus, harder to depolarize
What are the likely reasons why seizures resolve
Loss of ionic gradients
Depletion of ATP
Depletion of neurotransmitters (Glutamate)
Activation of inhibitory circuits (GABA)
What is status epilepticus
Seizures that last more than 5 minutes or more than 1 seizures within a 5 minute period
Can be life threatening
What is postictal period
The period 5-30 minutes after a seizure, characterized by drowsiness, depression, and psychosis
Occurs because of increased inhibition the neurons perform in response to the increased excitatory activity they just experienced
What are the 3 types of seizures
Focal Seizures
Generalized Seizures
Non-convulsive (absence) seizures
What are focal seizures
Occur in one particular spot, can spread wider across cortex and result in a generalized seizure
What are Automatisms
Unusually activities that are not consciously created, like smacking the lips
What are simple seizures
Retain consciousness during focal seizure
What are complex seizures
Loss of consciousness during focal seizure
What is Jacksonian March
Jerking activity that starts in specific muscles and spreads to surrounding muscle groups
What are generalized seizures, and what are the different types
Seizures that effect a wide area, always involve loss of consciousness and happen without warning
Tonic-clonic and Myoclonic
What are tonic-clonic seizures (Grand mal seizures)
Generalized seizure
Sustained contractions (tonic) of muscles alternating with periods of relaxation (clinic)
Occurs throughout the body
What are myoclonic seizures
Generalized seizure
Brief 1 second shock-like contractions of muscles
Can be localized or generalized
What are non-conclusive seizures
Absence and atonic seizure
What are absence seizures (Petit mal seizures)
Loss of connection with environment
Abrupt impairment of consciousness, slight head turn or staring
Person does not fall over and can return to normal after a few seconds
There may be a period of postictal disorientation
What are atonic seizures
Disconnect from body
Sudden loss of muscle strength. Person usually maintains consciousness but may fall down
What is the mechanism of anti-seizure drugs
Blocking ionic conductance (sodium, calcium, and potassium)
Blocking neurotransmitter release
Inhibiting excitatory postsynaptic neurons or activating inhibitory postsynaptic neurons
Benzodiazepines
Positive allosteric modulators at GABA type A receptors
Enhance the activity of GABA
GABA needs to be present for benzodiazepines to work
Mechanism behind benzodiazepines
Increases the frequency GABA type A receptors open
(Increases potency of GABA)
Not as much GABA is needed for stronger effect as benzodiazepines are aiding in opening GABA receptors
Barbiturates
Positive allosteric modulators at GABA type A receptors
Enhance the activity of GABA
GABA does not need to be present, barbituates can act as GABA agonists instead at higher concentrations
Mechanism behind Barbiturates
Increases the duration of the GABA type A receptors opening
(Increases efficacy of GABA)
Channel is open for longer, more flow of Cl- leading to a stronger GABA effect and increasing the maximum possible effect,
Barbiturates can function as GABA and open the receptor
Benzodiazepines and Barbituates have a risk of overdose, which one is riskier
Barbiturates because they can directly gate the GABA receptor, works without GABA easier to overdose
What are the symptoms of Benzodiazepines and Barbiturate overdose
Slughisness, incoodination, faulty judgement, and death
Benzodiazepines and Barbiturate should not be taken with what kind of drug
CNS depressants like alcohol and opioids
Increases overdose chances of opioids/alcohol
Additive risk
Vigabatrin
Inhibits GABA aminotransaminase (GABA-T)
GABA-T degrades GABA, which would lead to less inhibition
Tiagabine
Inhibits GABA transporter (GAT-1 located in neurons and Gila)
Prolongs action of neurotransmitters by lowering clearing of GABA
Carbamazepine
Block voltage-gated sodium channels
Mechanism behind Carbamazepine
Causes a conformational change of red I (the inactivation gate) which then blocks the sodium channel
Block prioritizes neurons with a higher level of neuronal discharge
Propagates the inactivated state of thee sodium channel and the refractory period of the neuron
Gabapentin
Looks like GABA with cyclohexane attach and can cross BBB
However, does not bind to GABA receptors and instead inhibits voltage-gated calcium channels
Mechanism behind GABApentin
Binds to a2σ subunit of calcium channel
Does not directly block, but disrupts the regulatory function of the a2σ subunit
Reduces the effect of glutamatergic neurons
Perampanel
Non-compeitive antagonist at AMPA receptor
Blocks excitation driven by glutamate binding to AMPA and NMDA
Causes serious psychiatric and behavioural changes
Why is homeostasis of glutamate important? What happens if this is not maintained
Important in how our brain functions
Too much glutamate: Psychiatric, hallucinations
Too little glutamate: Depression, death
How often are anti-seizure drugs usually used
Used for long periods of time to prevent recurrence of seizures, thus, interactions with other drugs must be considered
Anti-seizure drugs have what pharmacokinetic properties
Well absorbed, good bioavailability, and cross BBB
What is the extraction ratio of anti-seizure drugs
Liver extracts a very low amount, can be long-acting in body
Lots of possible drug-drug interactions
