Anti-Seizure

Question 1

What are seizures

Answer 1

Transient (Short time) alteration of behaviour caused by excessive and synchronous neuronal activity

Question 2

What is epilepsy

Answer 2

Disorder of brain function characterized by periodic and unpredictable seizures

Occurs spontaneously and unprovoked

Question 3

What’s the difference between epilepsy and seizures

Answer 3

You can have seizures without epilepsy

But epilepsy is characterized by seizures

Question 4

What is symptomatic epilepsy

Answer 4

Epilepsy that occurs due to a known event (blunt trauma)

Question 5

What is asymptomatic epilepsy

Answer 5

Epilepsy that occurs due to poorly defined genetic factors

Question 6

How do neurons normally fire

Answer 6

Asynchronously

Question 7

What is surround inhibition

Answer 7

The primary afferent stimulated will produce more action potentials than those on the periphery

The peripheral neurons are strongly inhibited

Question 8

What are the three steps of a seizure

Answer 8

Initiation
Propagation
Termination

Question 9

What are the two events of seizure initiation

Answer 9

High frequency bursts of action potentials
High synchronization of neuronal population

Question 10

What can overcome the barriers preventing bursting neuronal activity

Answer 10

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

Question 11

How does potassium flow in hyperpolarization

Answer 11

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

Question 12

What are the likely reasons why seizures resolve

Answer 12

Loss of ionic gradients
Depletion of ATP
Depletion of neurotransmitters (Glutamate)

Activation of inhibitory circuits (GABA)

Question 13

What is status epilepticus

Answer 13

Seizures that last more than 5 minutes or more than 1 seizures within a 5 minute period

Can be life threatening

Question 14

What is postictal period

Answer 14

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

Question 15

What are the 3 types of seizures

Answer 15

Focal Seizures
Generalized Seizures
Non-convulsive (absence) seizures

Question 16

What are focal seizures

Answer 16

Occur in one particular spot, can spread wider across cortex and result in a generalized seizure

Question 17

What are Automatisms

Answer 17

Unusually activities that are not consciously created, like smacking the lips

Question 18

What are simple seizures

Answer 18

Retain consciousness during focal seizure

Question 19

What are complex seizures

Answer 19

Loss of consciousness during focal seizure

Question 20

What is Jacksonian March

Answer 20

Jerking activity that starts in specific muscles and spreads to surrounding muscle groups

Question 21

What are generalized seizures, and what are the different types

Answer 21

Seizures that effect a wide area, always involve loss of consciousness and happen without warning

Tonic-clonic and Myoclonic

Question 22

What are tonic-clonic seizures (Grand mal seizures)

Answer 22

Generalized seizure

Sustained contractions (tonic) of muscles alternating with periods of relaxation (clinic)
Occurs throughout the body

Question 23

What are myoclonic seizures

Answer 23

Generalized seizure

Brief 1 second shock-like contractions of muscles
Can be localized or generalized

Question 24

What are non-conclusive seizures

Answer 24

Absence and atonic seizure

Question 25

What are absence seizures (Petit mal seizures)

Answer 25

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

Question 26

What are atonic seizures

Answer 26

Disconnect from body Sudden loss of muscle strength. Person usually maintains consciousness but may fall down

Question 27

What is the mechanism of anti-seizure drugs

Answer 27

Blocking ionic conductance (sodium, calcium, and potassium) Blocking neurotransmitter release Inhibiting excitatory postsynaptic neurons or activating inhibitory postsynaptic neurons

Question 28

Benzodiazepines

Answer 28

Positive allosteric modulators at GABA type A receptors Enhance the activity of GABA GABA needs to be present for benzodiazepines to work

Question 29

Mechanism behind benzodiazepines

Answer 29

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

Question 30

Barbiturates

Answer 30

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

Question 31

Mechanism behind Barbiturates

Answer 31

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

Question 32

Benzodiazepines and Barbituates have a risk of overdose, which one is riskier

Answer 32

Barbiturates because they can directly gate the GABA receptor, works without GABA easier to overdose

Question 33

What are the symptoms of Benzodiazepines and Barbiturate overdose

Answer 33

Slughisness, incoodination, faulty judgement, and death

Question 34

Benzodiazepines and Barbiturate should not be taken with what kind of drug

Answer 34

CNS depressants like alcohol and opioids Increases overdose chances of opioids/alcohol Additive risk

Question 35

Vigabatrin

Answer 35

Inhibits GABA aminotransaminase (GABA-T) GABA-T degrades GABA, which would lead to less inhibition

Question 36

Tiagabine

Answer 36

Inhibits GABA transporter (GAT-1 located in neurons and Gila) Prolongs action of neurotransmitters by lowering clearing of GABA

Question 37

Carbamazepine

Answer 37

Block voltage-gated sodium channels

Question 38

Mechanism behind Carbamazepine

Answer 38

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

Question 39

Gabapentin

Answer 39

Looks like GABA with cyclohexane attach and can cross BBB However, does not bind to GABA receptors and instead inhibits voltage-gated calcium channels

Question 40

Mechanism behind GABApentin

Answer 40

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

Question 41

Perampanel

Answer 41

Non-compeitive antagonist at AMPA receptor Blocks excitation driven by glutamate binding to AMPA and NMDA Causes serious psychiatric and behavioural changes

Question 42

Why is homeostasis of glutamate important? What happens if this is not maintained

Answer 42

Important in how our brain functions Too much glutamate: Psychiatric, hallucinations Too little glutamate: Depression, death

Question 43

How often are anti-seizure drugs usually used

Answer 43

Used for long periods of time to prevent recurrence of seizures, thus, interactions with other drugs must be considered

Question 44

Anti-seizure drugs have what pharmacokinetic properties

Answer 44

Well absorbed, good bioavailability, and cross BBB

Question 45

What is the extraction ratio of anti-seizure drugs

Answer 45

Liver extracts a very low amount, can be long-acting in body Lots of possible drug-drug interactions