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Clinical Pharmacology, Therapeutics & Intro to Prescribing > Lecture 23- Epilepsy > Flashcards

Lecture 23- Epilepsy Flashcards

1
Q

Seizures

A

“Transient occurrence of signs or symptoms due to abnormal electrical activity in the brain, leading to a disturbance of consciousness, behaviour, emotion, motor function or sensation

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2
Q

Pathology of seizures

A
  • The brain is a complicated network of neurones
    • These are either excitatory, inhibitory or interneurons
  • The most important excitatory neurotransmitter is glutamate via the NMDA receptor
  • The most important inhibitory neurotransmitter is GABA, via the GABAa receptor
  • In a normal brain the inhibitory and excitatory sides are in balance

Therefore in a seizure..

  • Abnormal and excessive excitation and synchronisation (all neurones acting at once) 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 part of the brain, and local changes can lead to generalised effects
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3
Q
  • In a normal brain the inhibitory and excitatory sides are in balance
A
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4
Q

Seizures: What causes the imbalance?

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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5
Q

Signs and symptoms of seizure

A
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6
Q

signs of generalised seizure

A

loss of consciousness often with changes in muscle tone and tongue biting

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7
Q

signs of tonic clonic seizure

A

initial hypertonic phase, followed by rapid clonus (shaking/jerking) of the limbs

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8
Q

what is post-ictal period

A

less alert and more vacant after seizure

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9
Q

Defining epilepsy

A
  • Epilepsy is a tendency toward recurrent seizures unprovoked by a systemic or neurological insult
  • Not everyone who has a seizure has epilepsy
  • An epilepsy diagnosis is life changing, and therefore should only be made by a specialist, in an epilepsy or first fit clinic
  • Note not just a disease of the young, over 60s almost as common and incidence increases with age
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10
Q

epilepsy diagnosis

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)
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11
Q

Types of Reflex Seizure

Seizure brought on by a particular stimulus (not provoked e.g. taking drugs )

A
  • Photogenic (strobe lights)
  • Musicogenic
  • Thinking
  • Eating
  • Hot water immersion
  • Reading
  • Orgasm
  • Movement
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12
Q

grand mal

A

generalised seizure

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13
Q

petit mal

A

absence seizure

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14
Q

partial seizure

A

focal seizure

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15
Q

clinical classification of seizure

A

Classification of seizure

  • Focal onset
    • Aware
    • Impaired awareness
    • Motor onset
    • Non motor onset
  • Generalised onset
    • Always lose consciousness
    • E.g. tonic-clonic, myoclonic, atonic, nonmotor
  • Unknown onset
    • Motor
    • unclassified
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16
Q

generalised seizure

A
  • Originate at a specific place in the brain and rapidly engage both hemispheres
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17
Q

Focal seizures

A
  • Originate within networks limited to one hemisphere
  • May be discretely localized or more widely distributed….
  • Usually don’t lose consciousness due to usually affecting one side of the brain
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18
Q

why dont focal seizure make you lose consciousness

A

Usually don’t lose consciousness due to usually affecting one side of the brain

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19
Q

Provoked Seizures

A
  • Seizure as a result of another medical condition
  • Examples include:
    • 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
    • Uncontrolled hypertension
    • Key is to treat both the seizure and the underlying condition. Unlikely to need ongoing AED treatment if cause treated
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20
Q

Differential diagnosis of seizures

A
  • Syncopal episodes e.g vasovagal syncope
  • Cardiac issues including reflex anoxic seizures, arrythmias
  • Movement disorders e.g Parkinsons, Huntingtons
  • TIAs
  • Migraines
  • Non-epileptic attack disorders (formerly pseudo-seizures)
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21
Q

case - outline intiial management of a seizure

A
  • Primary Survey/A to E assessment
  • Airway- Is it patent? Can you do anything about it it?/Adjuncts
  • Breathing- Sats reading, Apply Oxygen
  • Circulation- Expect a high HR, wary of BP
  • Disability- Will have reduced consciousness in generalised seizures, may be awake in partial. Check GLUCOSE
  • Everything else- May want to get them into recovery position if able
  • Do something for the ABC problems if you can
  • Look at a clock/start a timer
  • Get some help
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22
Q

status epilepticus

A

a seizur eof any variety lasdting more than 5 minures or more or multiple seizures without a compelte recovery between them

MEDICAL EMERGENCY

20% mortality

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23
Q

treatment of most seizures doesnt include

A

drugs

  • The majority of seizures will self terminate without the use of drugs
  • Wait for 5 minutes and if still going then give seizure terminating drugs à this is called Status Epilepticus (also series of seizures that take place for more than 5 minutes)
  • Be aware of how long it takes to get and prepare drugs
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24
Q

Pharmacological treatment for status

A

1) Full dose of benzodiazepine (5 mins)
2) Full 2nd dose of “ (0-15 mins)
3) Consider IV thiamine if alcohol use
4) 2nd line anti-epileptic if still in seizure (15-45) e.g. phenytoin, levetiracetam
5) 45+ = thiopentone/anaesthesia (will need ventilating)

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25
Q

benzodiazepines drug class

A

GABAa agonists

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26
Q

benzodiazepines end in

A

–apam, come in various flavours

  • Intravenous lorazepam
  • Diazepam rectally
  • Buccal or intranasal midazolam (don’t lose a finger)
27
Q

Uses of GABAa agonist se..g benzos

A
  • Status epilepticus
  • Also used as anxiolytics, sleep aids, alcohol withdrawal
28
Q

Mode of action of benzos

A
  • GABAa agonists
    • Increased Cl- conductance, = more negative resting potential, less likely to fire.
  • Work best when membrane positive i.e in seizures
  • No firing neurones=no more seizure
29
Q

Adverse drug response of benzos

A
  • Be wary of addiction
  • cardiovascular collapse
  • airway issues

*remember you can always put more in but you cant take it out so go slowly*

30
Q

Diagnosis of Epilepsy

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
31
Q

inevstigations

A

EEG and Imagging e.g. MRI

32
Q

electrocephalogram (EEG)

A
  • Electroencephalography:
    • 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
33
Q

Imaging

A
  • MRI is the imaging of choice
  • 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
34
Q

But why treat epilepsy?

A
  • Sudden Unexplained Death in Epilepsy (SUDEP)
  • Occurs in 0.1% adults with epilepsy per year
  • More frequent in people with poor seizure control
  • Massive burden- can impact ability to drive, swim, have a bath, time out of school or university
35
Q

Anti-Epileptic Drugs (AEDs)

A
  • There are numerous AEDs, with varying mechanisms of action
  • We will concentrate on 6:
    • Carbamazepine
    • Phenytoin
    • Valproate
    • Lamotrigine
    • Levetiracetam
    • Benzodiazepines for seizure termination (already done)
  • I will refer to trade names too where applicable, generally patients should stay on the same formulation
  • NB it is not required of you to know these trade names
36
Q

How do anti-epileptic drugs work?

A
  • sodium channel blockade
  • calcium channel blockade
  • GABA agonist
  • SV2 vesicle inhibition
37
Q

Sodium Channel Blockade

A
  • Blocking of Na channels in central neurones
  • This slows recovery of neurones from inactive to closed state
  • Reduces neuronal transmission
38
Q

name 5 sodium channel bloackades

A

sodium valproate

carbamazepines

Lamotrigine

Phenytoin

39
Q

sodium valproate uses

A

generalsied epilepsies

40
Q

sodium valproate MOA

A

Mode of action

  • Probably a mix of GABAa effects and sodium channel blockade
    • Blocking of Na channels in central neurones
    • This slows recovery of neurones from inactive to closed state
    • Reduces neuronal transmission
41
Q

Adverse drug response of sodium valproate

A
  • Liver failure
  • Pancreatitis
  • Lethargy
42
Q

carbamazepine uses

A
  • Anti-epileptic
  • Bipolar
  • Chronic pain e.g. trigeminal neuralgia
43
Q

Mode of action of carbamazepine

A
  • Blocking of Na channels in central neurones
  • This slows recovery of neurones from inactive to closed state
  • Reduces neuronal transmission
44
Q

Adverse drug response of carbamazepine

A
  • Suicidal thoughts
  • Joint pain
  • Bone marrow failure
45
Q

lamotrigine uses

A
  • Focal epilepsies
    • Used often where valproate contraindicated in generalised epilepsy
46
Q

Mode of action of iamotrigine

A
  • Primarily a sodium channel blocker, may also affect calcium channels
    • Blocking of Na channels in central neurones
    • This slows recovery of neurones from inactive to closed state
    • Reduces neuronal transmission
47
Q

phenytoin uses

A
  • Used mainly in status epilepticus or as an adjunct in generalised seizures
48
Q

MOA of phenytoin

A
  • Blocking of Na channels in central neurones
  • This slows recovery of neurones from inactive to closed state
  • Reduces neuronal transmission
49
Q

Adverse drug response of Phenytoin

A

Exhibit zero order kinetics- care when adjusting doses

  • Bone marrow suppression
  • Hypotension
  • Arrythmias (IV use)
50
Q

levetiracetam is a

A

anticonvulsant

51
Q

levetiracetam uss

A
  • Option for focal seizures and generalised seizures
    • Anecdotally being used more frequently, easy dosing and well tolerated
    • Safe in pregnancy
52
Q

Mode of action of Levetiracetam

A
  • Novel mechanism of action
  • Synaptic vesicle glycoprotein binder.
  • Stops the release of neurotransmitters into synapse and reduces neuronal activity
53
Q

Side Effects of AEDs

A
  • Largely common across all drugs:
  • Tiredness/drowsiness
  • Nausea and vomiting
  • Mood changes and suicidal ideation
  • 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
54
Q

drug drug interactions of anti-epileptis

A
  • AEDs can be both inducers and inhibitors of CYP enzymes
  • They therefore interact with a wide variety of drugs, including each other
55
Q

Practically what does AED drug drug interactions mean?

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
  • Newer AEDs have less side effects, or are metabolised in other ways (levetiracetam)
56
Q

How to start someone on AEDs?

A
  • Pick a drug- There are guidelines for this for various types of epilepsy (they will have changed by the time you have to know)
  • Start at a low dose and build up
  • Trial of drug and see how patient responds- look for efficacy and tolerable side effects
  • Aim for all anti-epileptic treatment is to be seizure free with minimal or acceptable side effects
  • Plasma levels can be monitored, but should not necessarily be done regularly without reason (e.g patient becomes pregnant, loses seizure control, issues with adherence)
  • Transition to a new agent should be done carefully
  • Should be overseen by epilepsy specialist
57
Q

family planning and AEDs

A
  • There is some risk of congenital malformations with all AEDs
    • The risk is greatest with Valproate (as high as 10% risk of a major malformation)
    • Valproate should not be prescribed to any woman of childbearing age unless they meet the conditions of a pregnancy prevention programme
  • Lamotrigine and particularly Levetiracetam are the safest
58
Q

which drug should not be prescribed to a women of childbirthing age

A

sodium valproate

  • The risk is greatest with Valproate (as high as 10% risk of a major malformation)
  • Valproate should not be prescribed to any woman of childbearing age unless they meet the conditions of a pregnancy prevention programme
59
Q

whcih AEDs are safest for women of childbearing age

A
  • Lamotrigine and particularly Levetiracetam are the safest
60
Q

Epilepsy and driving

A
  • Need to ask all patients with seizures about driving
  • 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
61
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

Further dose of lorazepam (benzodiazepam)

62
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
    • B. Wait a further 5 minutes
    • C. Give levetiracetam
    • D. Call intensive care
    • E. Hide in a cupboard and pretend its not happening
A
  • A. Give thiopentone
  • B. Wait a further 5 minutes
  • C. Give levetiracetam
  • D. Call intensive care
  • E. Hide in a cupboard and pretend its not happening
63
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. Levetiracetam
    • B. Valproate
    • C. Lamotrigine
    • D. Carbamazepine
    • E. I’m still hiding in the cupboard from question
A

valproate

Clinical Pharmacology, Therapeutics & Intro to Prescribing (39 decks)

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