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Clinical Pharmacology > 12.1 Epilepsy > Flashcards

12.1 Epilepsy Flashcards

1
Q

What is a seizure?

A

Abnormal electrical activity in the brain leading to transient occurrence of signs of symptoms such as disturbance of consciousness, behaviour, emotion, motor function or sensation

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2
Q

What are the three different types of neurones in the brain?

A

Excitatory
Inhibitory
Interneurones

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3
Q

What is the most important excitatory neurotransmitter and how does it work?

A

Glutamate via the NMDA receptor

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4
Q

What is the most important inhibitory neurotransmitter and how does it act?

A

GABA via the GABAa receptor

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5
Q

Briefly describe the excitatory action of glutamate on neurones?

A

Glutamate binds to the NMDA receptor. The NMDA receptor is a cation channel, letting in Na and Ca and letting K+out. This increases the membrane potential, depolarising the neurone. This makes it more likely to fire an AP with less stimulation as closer to threshold

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6
Q

Describe the inhibitory action of GABA on neurones?

A

GABA binds to a GABAa receptor. The GABAa receptor is an allosteric modulator that results in the opening of a chloride channel. Chloride ions can then move into the neurone, resulting in it hyperpolarising. This moves the resting potential away from the threshold and makes it harder to fire an action potential

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7
Q

What is the pathology of a seizure?

A

A seizure is the clinical manifestation of abnormal and excessive excitation and synchronisation of a group of neurones within the brain
Loss of inhibitory (GABA mediated) signals or too strong an excitatory (NMDA/Glutamate) one.
This imbalance can happen in any point in the brain, and local changes can lead to generalised effects

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8
Q

What causes the imbalance of excitatory and inhibitory signals in the brain?

A
  • Genetic differences in brain chemistry/receptor structure – genetic epilepsy syndromes
  • By exogenous activation of receptors- drugs
  • Acquired changes in brain chemistry- drug withdrawal, metabolic changes
  • Damage to any of these networks- strokes, tumours
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9
Q

What are the common signs and symptoms of a seizure?

A 
Shaking / rapid clonus 
Loss of consciousness
Changes in muscle tone
Tongue biting
Post-octal period
Aura prior to having a seizure
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10
Q

What is the post-ictal period?

A

The period of time immediately following a seizure. Can last minutes to hours. Confusion and vacancy during this time

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11
Q

What age group is most likely to experience epilepsy?

A

disease affects children and teenagers as well as

over 60s almost as common and incidence increases with age

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12
Q

What is epilepsy?

A

Epilepsy is a tendency toward recurrent seizures unprovoked by a systemic or neurological insult

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13
Q

What is the diagnostic criteria of epilepsy?

A

At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk after two unprovoked seizures (at least 60% over the next 10 years)
Or diagnosed with an epilepsy syndrome

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14
Q

What is a reflex seizure?

A

A seizure brought on by a particular stimulus

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15
Q

What are the different types of reflex seizures?

A 
Photogenic 
Musicogenic 
Thinking 
Eating 
Hot water immersion 
Reading 
Orgasm 
Movement
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16
Q

What are the three main categories of basic seizures?

A

Focal onset - only occurs in one particular small part of the brain
Generalised onset - occurs on both sides of the hemispheres
Unknown onset - unknown as to where the seizures occurring.

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17
Q

What are the different types of focal onset seizures that can occur?

A

Aware - maintain consciousness (e.g. only in hand)
Impaired awareness - reduced cognition
Motor onset
Non motor onset
Focal to bilateral tonic-clonic (Development of the seizure)

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18
Q

What are some of the presentations of a generalised onset seizure?

A 
Always lose consciousness
Tonic-cloning = period of hypertonicity followed by rapid jerking movements
Myoclonus = jerking
Atonic = complete loss of muscle tone (sudden drop to the floor)
Non motor (absence) = vacant episodes for minutes to hours
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19
Q

What is the development of a generalised seizure?

A

Originate at some point

within and rapidly engage both hemispeheres

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20
Q

Describe the distribution of the brain affected in a focal seizure

A

• Originate within networks limited to one hemisphere
• May be discretely localized
or more widely distributed.…

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21
Q

What is a Grand mal seizure?

A

Generalised seizure

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22
Q

What is a petit mal seizure?

A

Absence seizure

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23
Q

What is a partial seizure?

A

A focal seizure

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24
Q

What is a provoked seizure?

A

A seizure as a result of another medical condition

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25
Q

Give examples of what can cause a provoked seizure?

A

Drug use or withdrawal
Alcohol withdrawal
Head trauma and intracranial bleeding
Metabolic disturbances e.g hyponatraemia, hypoglycaemia
CNS Infections: meningitis and encephalitis
Febrile seizures in infants (any illness that causes fever)
Uncontrolled hypertension

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26
Q

What are differential diagnosis of seizures?

A

Syncopal episodes e.g vasovagal syncope
Cardiac issues including reflex anoxic seizures, arrythmias (hypoxic brain can cause jerking)
Movement disorders e.g Parkinsons, Huntingtons
TIAs
Migraines
Non-epileptic attack disorders (formerly pseudo-seizures)

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27
Q

What is the initial management of a seizure?

A
  • primary survey (Airway, Breathing, Circulation, Disability,exposure/everything else)
  • apply oxygen as in high metabolic state
  • lock at clock/start a timer
  • get some help
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28
Q

What is status epilepticus?

A

A seizure of any variety lasting more than 5 minutes or more, or multiple seizures without a complete recovery between them. Medical emergency

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29
Q

When are drugs used to treat seizures?

A

In status epilepticus - if the seizure/ episode lasts longer than 5 minutes

30
Q

What is the pharmalogical treatment for status epilepticus?

A
  • full does of benzodiazepines
  • if no improvement in 5 minutes give another 2nd full dose of benzodiazapine
  • if after 15 minutes no improvement give 2nd line anti-epileptic drugs (phenytoin, levetiracetam). Need to monitoring patient
  • consider IV thiamine if alcohol use
  • if still no improvement get anaesthetist and consider general anaesthesia (thiopentone) with support
31
Q

What are benzodiazepines mechanism of action?

A

GABAa agonists

Increased Cl- conductance, = more negative resting potential, less likely to fire.

32
Q

Why are benzodiazapines not used as a preventative drug for having seizures?

A

As Work best when membrane positive i.e in seizures. Also have significant side effects. Be wary of addiction, cardiovascular collapse, airway issues.

33
Q

What are benzodiazepines used for?

A

Stopping seizures (status epilepticus )
Anxiolytics
Sleep aids
Alcohol withdrawal

34
Q

What are the different benzodiazepine options for treating status epilepticus?

A 
Intravenous Lorazepam (need IV access- can be hard) 
Diazepam rectally 
Buccal or intranasal Midazolam – Don’t lose a finger
IO/IM can also work, and various IM preparations are on different local guidelines
35
Q

How is epilepsy diagnosed?

A

Epilepsy diagnosis should be made by a specialist, in a dedicated first fit or epilepsy clinic
Largely based on history from patient and eyewitnesses to attacks
Video can be very helpful in determining this

36
Q

What investigations are done to diagnose epilepsy?

A

Electroencephalography

MRI

37
Q

What is electroencephalography?

A

Record of electrical pattern of activity in the brain. Can be very useful, especially if an attack is caught while being recorded-Can make this more likely with sleep deprived EEG. But relies on either capturing an episode or an abnormal pattern. Many people without epilepsy have an abnormal EEG. A single EEG may show abnormalities in as few as 30% of adults with epilepsy

38
Q

Why are MRIs used in epilepsy diagnosis?

A

May detect vascular or structural abnormalities that can account for epilepsy
Generally not required when there is a degree of confidence that there is a generalised epilepsy syndrome e.g generalised seizures in a young
person, associated with sleep deprivation

39
Q

What are the 6 different anti-epileptic drugs?

A 
Carbamazepine
Phenytoin
Valproate
Lamotrigine
Levetiracetam
Benzodiazepines
40
Q

Why do patients generally stay on the same type of anti-epileptic?

A

Different brands will have slightly different pharmacodynamics and pharmacokinetics
Should stay on same formulation so in a steady state

41
Q

Why is it vital to have good seizure control?

A

As sudden unexplained death in epilepsy (SUDEP) is more frequent in patients with poorer seizure control
Massive burden- can impact ability to drive, swim, have a bath, time out of school or university

42
Q

Why are sodium channel blockers useful for treatment of epilepsy?

A

Blocking of Na channels in central neurones slows recovery of neurones from inactive to closed state. Reduces neuronal transmission

43
Q

What is the mechanism of action of carbamazepines?

A

Sodium channel blocker. Slows recovery of recently fired neurones, reducing the neuronal transmission.

44
Q

What are carbamazepines used for?

A

Epilepsy
Bipolar disorder
Chronic pain / neuropathic pain (trigeminal neuralgia)

45
Q

What are the ADRs of carbamazepines?

A

Suicidal thoughts
Joint pain
Bone marrow failure

46
Q

Give an example of a carbamazepine

A

Tegretol

47
Q

What is the mechanism of action of phenytoin?

A

Sodium channel blocker.

48
Q

What is the common indications for phenytoin?

A

Status epilepticus

Adjunct in generalised seizures

49
Q

Why must physicians take care when adjusting doses of phenytoin?

A

Exhibits zero order kinetics

50
Q

What are the ADRs of phenytoin?

A

Bone marrow suppression
Hypotension
Arrhythmia (IV use)

51
Q

What is the mechanism of action of sodium valproate?

A

Probably a mix of GABAa effects and sodium channel blockade

52
Q

What is the 1st line treatment of generalised epilepsies in adults?

A

Sodium valproate

53
Q

Give examples of sodium valproate drugs

A

Epilim

Depakote

54
Q

What are the ADRs of sodium valproate?

A

Liver failure
Pancreatitis
Lethargy

55
Q

What is lamotrigine?

A

Primarily a sodium channel blocker, may also affect calcium channels (stopping in flux of +ve ions, hyperpolarising membrane, further away from seizure threshold)

56
Q

What is lamotrigine used for?

A

Good for focal epilepsy

Used often where valproate contraindicated in generalised epilepsy

57
Q

What is the mechanism of action of levetiracetam?

A

Synaptic vesicle glycoprotein binder. Stops the release of neurotransmitters into
synapse and reduces neuronal activity

58
Q

What are levetiracetam used for?

A

Focal seizures
Generalised seizures
May start being used for status epilepticus
Safe in pregnancy

59
Q

Why is levetiracetam a preferential treatment option for epilepsy?

A

Well tolerated
Easy dosing
Safe in pregnancy

60
Q

What are the common side effects of AEDs?

A

Largely common across all drugs:
Tiredness/drowsiness
Nausea and vomiting
Mood changes and suicidal ideation
Cause or increase risk of Osteoporosis
Rashes, including Steven Johnson syndrome can be caused by all. Most likely in carbamazepine or phenytoin (1 in 1000)
Many can cause anaemia, thrombocytopenia or bone marrow failure

61
Q

What are the key drug drug interactions of anti epileptics?

A

Patients on anti-epileptics and warfarin will need close monitoring
Ideally patients on AEDs should not consume alcohol Carbamazepine and phenytoin may decrease the effectiveness of oral contraceptive pills
Carbamazepine and phenytoin may decrease the effectiveness of some antibiotics
Valproate can increase the plasma concentration of other AEDs

62
Q

Why is Levetiracetam preferred over other older anti epileptic drugs?

A

Newer AEDs have less side effects, or are metabolised in other ways, not including the CYP450 enzymes (levetiracetam)

63
Q

What commonly prescribed drugs are CYP450 inducers?

A 
Phenytoin
Carbamazepine
Barbituates
Rifampicin
Alcohol (chronic)
Sulphonylureas
64
Q

What drugs are CYP450 inhibitors?

A 
Omeprazole
Disulfiram
Erythromycin
Valproate
Isoniazid 
Ciprofloxacin
Ethanol
Sulphonamides
65
Q

How do you start someone on anti epileptic drugs?

A
  1. Based on guidelines, pick a drug
  2. Start on a low dose and build up
  3. Trial drug - ADR and efficacy
  4. Aim is seizure free with minimal or acceptable side effects
  5. Plasma levels can be monitored e.g. pregnant,loses seizure control, issues with adherence
  6. transition to new drug carefully
  7. Should be overseen by a specialist
66
Q

Why should valproate not be prescribed in women?

A

As in women of childbearing age, there is a high risk of major malformation in pregnancy.
Only prescribed if they meet the conditions of a
pregnancy prevention programme (contraception and signing of form)

67
Q

What antiepileptic drugs are prescribed to women of childbearing age

A

Lamotrigine and particularly Levetiracetam are the safest

68
Q

How does Epilepsy affect driving?

A

Need to ask all patients with seizures about
driving and will temporarily lose license and need to be seizure free for one year before reapplying
For bus lorry or coach drivers you need to be seizure free for 5 years off medication for a single seizure, or 10 years if had multiple Patients responsibility to inform DVLA

69
Q

A 26 year old arrives in resus fitting. The ambulance crew state this began 10 minutes ago, she has received a single dose of IV lorazepam.
What is the first step in your management?

A

Primary assessment
Apply oxygen
2nd dose of benzodiazepines
Get help

70
Q

You have treated her with further a further dose of lorazepam, and given a loading dose of phenytoin. It is 30 minutes later and she continues to fit. What do you do next?

A

Give thiopentone and call intensive care

71
Q

She has now stopped seizing, and you see her in 2 weeks later in the epilepsy clinic. She is not on any contraception. Which of the following drugs should be avoided?

A

Valproate

Clinical Pharmacology (26 decks)

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