Epilepsy

Question 1

is epilepsy acute or chronic

Answer 1

it can be both

note epilepsy was known as the sacred disease by the ancient greeks

Question 2

the most common ages affected in epilepsy

note it can affect all ages

Answer 2

under 20 and over 65

Question 3

possible causes of epilepsy

Answer 3

cause mostly unknown in most cases

Brain infection, e.g. meningitis
* Birth complications leading to lack of oxygen
* Stroke
* Brain tumour
* Head injury
* Drug/alcohol abuse
* Genetic element

Meningitis is a serious infection of the membranes that surround the brain and spinal cord

Question 4

the main characteristic of epilepsy

Answer 4

Abnormal and excessive discharge of a set of neurons in the brain, resulting to seizures.

note that the seizures in epilepsy are unprovoked and recurrent, so 2 or more

discharge= depolarization basically

Question 5

what is resting membrane potential

Answer 5

-70mv

Question 6

where in a neuron is an action potential generated

Answer 6

the axon hilock

Question 7

difference between seizures and convulsions

Answer 7

A broader term encompassing any abnormal brain electrical activity, which can cause various symptoms including convulsions, altered consciousness, or even subtle changes in behavior
while

convulsions refer to the physical manifestation of rapid, uncontrolled muscle contractions and jerking movements that can happen during some types of seizures.

not all seizures are charatcerised by convulsions

Question 8

some symptoms of seizures

note that there are differnt types of seizures, and symptoms are dependent on the type

Answer 8

Convulsions

Abnormal sensory experience

Effects on mood and behaviour

Loss of consciousness

Increased salivation

Stereotyped movements (e.g. rubbing

Question 9

the types of seizures and their descriptions

Answer 9

simple: there is no loss of consciousness

complex : there is impaired consciousness

partial: does not involve the entire brain

generalised: affects the whole brain, or a larger portion of it

status epilepticus: Uninterrupted seizure activity (life threatening condition)

Status epilepticus (SE) is a medical emergency that occurs when a seizure lasts longer than five minutes or when a person has multiple seizures without regaining consciousness

Question 10

types of partial seizures

Answer 10

simple
complex
secondary generalised(eventually develops into generalised)

Question 11

types of generalised seizures

Answer 11

tonic-clonic(Period of increased muscle tone and jerking)

absence(Loss of motor activity)

myoclonic
atonic(drop attacks)
clonic (repetitive jerks )
tonic(Immediate increase of muscle tone)

A drop attack is a sudden fall to the ground without losing consciousness.

Question 12

how can we diagnose epilepsy

Answer 12

The description of symptoms(patient history)

Blood tests

EEG (Electroencephalogram)

MRI (Magnetic Resonance Imaging)

An electroencephalogram (EEG) is a painless test that measures the electrical activity of your brain. It’s also known as a brain wave test.

Question 13

epileptogenesis

Answer 13

Epileptogenesis is the process of developing epilepsy

Question 14

the main mechanisms of action of antiepileptic drugs

Answer 14

Enhancement of GABA action( GABA selectivity)

Inhibition of sodium channels

Inhibition of calcium channels

these are all aimed at producing an inhibitory effect, to prevent excitation of the neurons

glutamate and calcium channel inhibition can also help in epilepsy

Question 15

how can the action of GABA be enhanced for the treatment of epilepsy

GABA is a neurotransmitter btw

Answer 15

Activation of GABA receptors by allosteric modulation

Inhibition of GABA transaminase

Inhibition of GABA reuptake( preventing the reabsorption of GABA from the synapse)

Allosteric modulation of GABA receptors is a process that involves binding of a compound to a receptor at a different site than the neurotransmitter GABA. This changes the receptor’s conformation, which in turn affects the receptor’s affinity for GABA

Question 16

GABA transaminase function

Answer 16

An enzyme that helps break down a brain chemical (neurotransmitter) called GABA when it is not needed

Question 17

inactivated sodium channels description and their functions

Answer 17

After a sodium channel opens and allows sodium ions to flow into the neuron, the channel quickly enters the inactivated state. In this state, the channel cannot reopen immediately, even though it is still technically “open” in the sense that it’s not in its resting state.

Essential for the refractory periods after depolarisation

prevents repetitive firing..etc

the inactivated channels are also referred to as the second gates, and while one sodium channel opens to allow influx, these close to prevent further sodium influx, preventing repetitive firing.

Question 18

what does it mean when we say sodium channel inhibitors in epilepsy are use-dependent

Answer 18

Use-dependence means that the more often the sodium channels are activated (i.e., the more frequently a neuron fires), the more the sodium channel inhibitor binds to the channels and prevents further activation. In essence, the drug is more effective when the neuron is firing more rapidly.

Question 19

the primary target for calcium channel blockers/inhibitors in epilepsy

Answer 19

t-type calcium channels

T-type calcium channels are important for
the discharge associated with absence
seizures

Question 20

antiepileptic drugs can be known as anticonvulsant drugs, true or false

Answer 20

true

Question 21

some common examples of use dependent sodium channel blockers

Answer 21

phenytoin
carbamazepine

lidocaine
mexiletine
flecainide

Question 22

phenytoin MoA

Answer 22

acts on the sodium channels in both neuronal and cardiac tissue. Blocks the channels

note , it is effective for most forms of seizures apart from absent seizures

Question 23

plasma half life of phenytoin

Answer 23

20 hours

Question 24

what are some of the side effects of phenytoin(usually at concentrations over 100micromole/L)

Answer 24

Ataxia
Gum hyperplasia
- Confusion
- Headache
- Skin rashes
- Teratogenesis risk
- Anaemia (can be corrected with folic acid)

Question 25

is carbamazepine effective against absent seizures

note that it is similar to phenytoin

Answer 25

no

Question 26

how does carbamazepine work

Answer 26

it blocks sodium channels, just like phenytoin. it is use-dependent

most effective in treating partial seizures, like psychomotor epilepsy

Question 27

Unlike most antiepileptic drugs, which one is effective against both tonic-clonic and absense seizures

Answer 27

valporate

it is also effective against most other forms of seizures

Question 28

MoA of valporate

Answer 28

enhances GABA action by inhibiting GABA transaminase, and Inhibiting succinic semialdehyde dehydrogenase

note that it also causes weak inhibition of sodium channels

Succinic semialdehyde dehydrogenase (SSADH) is an enzyme that helps break down gamma-aminobutyric acid (GABA), a neurotransmitter in the brain

Question 29

which drug is known as the designer drug for epilepsy , and how does it work

Answer 29

vigabatrin

it is a very specific inhibitor of GABA transaminase. It binds irreversibly to the enzyme, and so has a long lasting effect

has a short plasma half life

Question 30

main drawback of vigabatrin

Answer 30

depression or psychotic disturbances
in some patients

Question 31

what do you know about Tiagabine and it’s use in epilepsy treatment

Answer 31

GABA uptake inhibitor

• Short plasma half-life
• Main side-effects:
• Drowsiness
• Confusion

Question 32

ethosuximide MoA

Answer 32

Inhibition of T-type calcium channels

it is effectively mainly against **absence seizures **

Main side-effects:
- Nausea
- Anorexia

Plasma half life = 50hrs