AEDs Flashcards by Elizabeth Stevens

What happens during a seizure in the brain?

Large groups of neurones are activated repetitively, unrestrictedly and hyper-synchronously, with inhibitory neurones failing

How well did you know this?

Not at all

Perfectly

What are the two main classifications of seizures?

Focal (partial) seizures

Generalised seizures

How well did you know this?

Not at all

Perfectly

What is a focal seizure?

Where the discharges begin in a localised area of the cortex and symptoms reflect the area affected

How well did you know this?

Not at all

Perfectly

What are the types of focal seizures?

Simple focal
Complex focal
Jacksonian (focal motor)
Temporal lobe (feeling of deja vu seizures)

How well did you know this?

Not at all

Perfectly

What are the symptoms of a focal seizure?

Abnormal sensations or thoughts
Change in behaviour
An involuntary motor action

How well did you know this?

Not at all

Perfectly

What happens in generalised seizures?

Generalised centrally and spread through the whole brain, including the reticular system - immediate loss of consciousness

How well did you know this?

Not at all

Perfectly

What are the types of generalised seizures? Symptoms of each?

Absence
-patient stares, eyelids may twitch

Tonic-clonic

vague warning signs
body becomes rigid
tongue is bitten
incontinence can occur
clonic phase: generalised convulsion, frothing at mouth, rhythmic jerking of muscles

Myoclonic
-contraction and relaxation of a group of muscles, patient tends to be conscious

Atonic
-patient falls due to sudden loss of muscle tone

How well did you know this?

Not at all

Perfectly

What is a seizure?

A convulsion or transient abnormal event from episodic discharge of high frequency electrical activity in the brain

How well did you know this?

Not at all

Perfectly

What happens in a complex focal seizure?

The patient loses consciousness

How well did you know this?

Not at all

Perfectly

What is status epilepticus defined as?

A single convulsion lasting more than 30 minutes or convulsions occurring back to back with no recovery between them

How well did you know this?

Not at all

Perfectly

How can status epilepticus cause harm?

Physical injury relating to a fall/crash
Hypoxia
SUDEP (sudden depth in epilepsy)

Brain dysfunction
Cognitive impairment
Serious psychiatric disease

How well did you know this?

Not at all

Perfectly

Difference between primary and secondary epilepsy?

Primary - no identifiable cause (idiopathic)

Secondary - underlying medical condition causes the seizures

How well did you know this?

Not at all

Perfectly

Causes of secondary epilepsy?

Brain injury and hypoxia

Pyrexia (common in children, recurrence rare)

Brain tumours - partial focal or secondary generalised

Alcohol, drugs, drug withdrawal

Encephalitis and inflammatory conditions eg cerebral abscess, neurosyphilis

Metabolic abnormalities eg hypocalcaemia, hypoglycaemia, hyponatraemia

Provoked seizures eg photosensitivity

How well did you know this?

Not at all

Perfectly

In general, what is epilepsy caused by?

Increased excitatory activity
Decreased inhibitory activity
Loss of homeostatic control
Spread of neuronal activity

How well did you know this?

Not at all

Perfectly

How can untreated epilepsy lead to morbidity and mortality?

Status epilepticus 
Physical injury through a seizure
SUDEP
Adverse reaction to medication
Higher risk of psychiatric disease
Cognitive impairment

How well did you know this?

Not at all

Perfectly

What treatment is there for epilepsy if drugs are unsuccessful?

Temporal lobectomy

Corpus callosal section - prevents seizures spreading between hemispheres - useful for generalised seizures. Good for control but rarely become seizure-free

Hemispherectomy - for children who have irreversible damage to the whole hemisphere

How well did you know this?

Not at all

Perfectly

How do voltage-gated sodium channel blockers prevent seizures?

Bind to internal face of sodium channel when in inactivated state
Act preferentially on neurones causing the high frequency discharge that happens in an epileptic fit whilst not interfering with low frequency neurones in their normal state

How well did you know this?

Not at all

Perfectly

How do VGSC blockers act preferentially on high frequency neurones?

Because they depolarise more, so there are more of these neurones in the deactivated state, so the drug can bind to them more

How well did you know this?

Not at all

Perfectly

Name some VGSC blockers

Carbamazepine
Phenytoin
Lamotrigine

How well did you know this?

Not at all

Perfectly

Absorption, protein binding and half-life of carbamazepine?

Well absorbed
75% protein bound
Linear pharmacokinetics

Initially, half life is 30 hours, however is a strong inducer of CYP450 so increases its own metabolism - reduced to 15 hrs with repeated use

How well did you know this?

Not at all

Perfectly

ADRs of carbamazepine?

CNS

dizziness
drowsiness
ataxia
motor disturbance
numbness
tingling

GI - vomiting

CVS

BP variation
contraindicated in AV conduction

Rash

Hyponatraemia

Severe bone marrow depression leading to neutropenia

How well did you know this?

Not at all

Perfectly

Mnemonic to remember CYP450 enzyme inducers?

PC BRAS
Phenytoin
Carbamazepine
Barbiturates 
Rifampicin 
Alcohol (chronic)
Sulphonylureas

How well did you know this?

Not at all

Perfectly

DDIs of carbamazepine?

Reduces phenytoin, warfarin, corticosteroid and OCP levels

Antidepressants can interfere with its actions

Phenytoin can decrease its binding, increasing carbamazepine’s plasma concentration

Epilepsy types treated with carbamazepine?

Generalised tonic-clonic

All types of partial

Protein binding and half-life of phenytoin?

90% bound Non-linear pharmacokinetics at therapeutic levels so has a variable half life: 6-24 hours

ADRs of phenytoin?

``` Dizziness Ataxia Headache Nystagmus Nervousness ``` Gingival hyperplasia Hypersensitivity rashes including Stevens-Johnson syndrome

DDIs of phenytoin?

Enzyme inducer Competitive binding with valproate, NSAIDs, salicyclate to increase its plasma levels, exacerbating non-linear pharmacokinetics Decreases levels of OCP Cimetidine increases phenytoin levels

How is phenytoin level monitored?

Use salivary levels as indicator of free plasma levels

When is phenytoin used?

Generalised tonic-clonic All types of partial IV in status epilepticus

How does lamotrigine work?

Prolongs VGSC inactivation state (like carbamazepine and phenytoin) Also is a possible calcium channel blocker, and decrease glutamate release

Half-life of lamotrigine?

24 hours, phase II metabolism

ADRs of lamotrigine

Less marked CNS symptoms but - dizziness - ataxia - somnolence - nausea Mild and severe skin rashes

DDIs of lamotrigine?

Can be used as an adjunct therapy with other AEDs OCP reduces plasma LTG levels Valproate increases plasma LTG levels due to competitive binding

When is lamotrigine used?

Partial seizures Generalised - tonic clonic - absence First line AED in epilepsy Safer in pregnancy Not in paeds due to increased risk of ADRs

How do drugs causing GABA-mediated inhibition help epilepsy?

Enhance activation of GABA receptors by facilitating GABA-mediated opening of chloride ion channels Causes an inhibitory effect on neurones by increasing threshold for action potential due to Cl Makes membrane potential more negative, reducing likelihood of epileptic neuronal hyper-activity

Name some drugs which enhance GABA-mediated inhibition

Valproate sodium | Benzodiazepines

Mechanism of action of valproate sodium?

Increases GABA content of brain by stimulating GABA-synthesising enzymes Inhibit GABA inactivating enzymes

Is valproate sodium protein bound? | Half-life?

Yes Half-life of 15 hours with linear PK

ADRs of valproate sodium?

``` Less severe than other AEDs CNS -ataxia -tremor -weight gain ``` Hepatic - increases transaminase effects - hepatic failure (rarely)

DDIs of valproate sodium?

Antidepressants inhibit its action Antipsychotics antagonise it by lowering convulsive threshold Aspirin competitively binds in plasma, increasing free valproate

What monitoring is required with valproate sodium?

Free plasma concentration using salivary levels Monitor for blood, metabolic and hepatic disorder

When is valproate sodium used?

Partial seizures Generalised -tonic-clonic -absence

Mechanism of action of benzodiazepines?

Act at a distinct receptor site on GABA chloride binding channel Binding if GABA or BZD enhances eachother's binding, act as positive allosteric effectors Increases the chloride current into the neurone, increasing threshold for action potential generation

How much are benzodiazepines absorbed and how much are they protein bound in plasma? Half-life?

Well absorbed - 90-100% 85-100% plasma protein bound Linear PK - half-life varies from 15-45 hours

ADRs of benzodiazepines?

``` Sedation Tolerance with chronic use Confusion and impaired coordination Aggression Dependence and withdrawal with chronic use Abrupt withdrawal seizure trigger Respiratory and CNS depression ```

How to treat an overdose of benzodiazepines?

IV flumazenil however this may precipitate an arrhythmia or seizure

When and which benzodiazepines are used?

Lorazepam/diazepam - status epilepticus Clonazepam - absence seizure, short-term use Side effects limit first line use

What is the first line treatment for generalised seizures?

Valproate sodium

What is the first line treatment for partial seizures?

Carbamazepine

What is the first line treatment for generalised and partial seizures in women of child-bearing age?

Lamotrigine - less effect on OCP - fewer teratogenic effects

First line of treatment for status epilepticus?

Basic ABCS Benzodiazepines (lorazepam) IV Phenytoin - zero order kinetics means therapeutic levels can be reached more quickly Also paralysis, sedation, intubation

How can AEDs be teratogenic?

Valproate can cause neural tube defects Congenital malformations Facial and digital hypoplasia Learning difficulties

What can be given with AEDs to reduce the risk of neural tube defects?

Folate supplements

Why is vitamin k given in pregnancy with AEDs?

They can cause vitamin K deficiency so reduces risk of cerebral haemorrhage and coagulopathy

What tests should be done in emergency management of status epilepticus?

``` Blood glucose U&Es Plasma calcium Blood gases Imaging ```