Anti-convulsion drugs Flashcards Preview

Physiology and Pharmacology of Cells > Anti-convulsion drugs > Flashcards

Flashcards in Anti-convulsion drugs Deck (29)
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1
Q

Why do convulsions occur?

A

Imbalance between inhibitory and excitatory signals in the CNS.
Too much excitatory signalling.
Two options for drugs- increase inhibition or decrease excitation.

2
Q

Main symptoms of epilepsy

A

Unprovoked seizures.

Hyperexcitibility of a group of neurons

3
Q

How are the different classes of epilepsy named?

A

By the type of seizure experienced- not by the underlying cause of the seizure

4
Q

Where does the seizure begin?

A

Focus- neurons fire too many APs

5
Q

Partial seizure

A

Only one hemisphere

6
Q

Generalised seizure

A

Spreads to both hemispheres

7
Q

Simple seizure

A

No loss of conciousness

8
Q

Complex seizure

A

Always a loss of consciousness

9
Q

Causes?

A
Head injury 
Stroke 
Infection 
Tumours 
Genetic factors such as mutations in ion channels
10
Q

Where are the mutations

A

Nav channels
NAChR
K+ channels

11
Q

What will you see if the seizure spreads to the hypothalamus?

A

Loss of control of autonomic processes such as-
Sweating
Salivating
Bladder/bowel control

12
Q

What will you see if the seizure spreads to the reticular formation?

A

Loss of consciousness- complex

13
Q

Triggers?

A
Flashing lights C
Certain sounds 
Alterations in blood pH or glucose 
Stress 
Fatigue
14
Q

How do you diagnose epilepsy

A

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)

15
Q

What happens if there is a rapid onset of activity

A

Whole body convulsions
Loss of consciousness
Muscle contraction
Patient goes rigid and falls to the floor

16
Q

What is another side effect of epilepsy

A

Neurotoxicity- if the neurons are being overexcited- they will become damaged which will lead them to dying and thus there is neurodegeneraion

17
Q

Absence Seizures

A
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
18
Q

Treatment- increasing inhibition

A

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.

19
Q

What do paramedics administer in an uncontrolled seizure?

A

Intravenous benzodiazepines to switch off the electrical activity of that part of the brain

20
Q

What drugs can be used to treat epilepsy?

A

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

21
Q

How is GABA produced

A

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.

22
Q

Why is valprolate called a suicide inhibitor?

A

It is used as an anti-convulsant- when the drug binds to GABA transaminase. it completely inhibits the breakdown of GABA.

23
Q

How is excitatory signalling inhibited?

A
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.
24
Q

Why Na+ blockers in instead of benzodiazepines?

A

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.

25
Q

What is use dependence?

A

This is a property of Na+ channel blockers- they select for active channels and therefore neurons which are firing APs frequently.
The inactivated state of the channel ony occurs after the firing of APs.
Drugs will only bind to this conformation- only bind to channels which have previously been activated.

26
Q

What are the 3 types of Na+ channel blockers.

A

Phenytoin- non-sedative and anti-convulsant. Very complex pharmacokinetics- can cause vertigo, ataxia, headaches, rashes. Can be useful for grand mal and partial epilepsy- not useful for absent seizures.
Carbamazepine- most widely used. Problems include microsomal enzyme induction- it also cannot be used together with other drugs.
Lamotrigine- problems include nausea, dizziness, ataxia and rashes

27
Q

Do Na+ blockers cure or control epilepsy? What dies this mean?

A

Control- they only alleviate the symptoms. This means that any factor which will affect the concentration in the body increase chance the seizure- have to be wary of taking other drugs- could affect metabolism.

28
Q

Drugs for absent seizures

A

Ca2+ channel blockers-
T-type Ca channels are used for absent seizures.
Not involved in other processes such as muscle contraction and NT release- means that drugs will not affect these processes.
Ethosuximide and GABApentin (prevents trafficking of the channel to the membrane).

29
Q

New drug targets for epilepsy?

A

Levetiracetam- doesn’t target the receptor- thought to act via glutamate signalling- either affects the amount of glutamate in vesicles and thus excitatory signalling or interferes with docking and fusion of the vesicle with the membrane.