S12 L1 Epilepsy Flashcards

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1
Q

What is a seizure?

A

Transient occurencer 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

What is the pathophysiology of a seizure?

A
  • Abnormal excessive excitation and synchronisation of a group of neurones in the brain
  • This can be due to a loss of inhibitory signals (GABA) OR and excess of excitatory signals (Glutamate)
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3
Q

What are some causes of seizures?

A
  • Genetic epilepsy syndromes (genetic differences in receptor structure)
  • Exogenous activation of receptors e.g drugs and alcohol
  • Changes in brain chemistry e.g drug withdrawal, metabolic changes like low glucose
  • Damage to any networks e.g stroke or tumour knocking out inhibitory neurones
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4
Q

What are some signs and symptoms of seizures?

A
  • Generalised have loss of consciousness, changes in muscle tone, tongue biting
  • Tonic clonic have initial hypertonic phase then rapid clonus
  • Post-ictal period
  • Often aura before
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5
Q

What is the definition of epilepsy and what is the criteria that has to be met to fulfil this diagnosis?

A

- Tendency towards recurrent seizures unprovoked by a systemic or neurological insult. Due to abnormal hyperactivity in the brain

  • At least 2 unprovoked (or reflex) seizures occuring more than 24 hours apart OR one unprovoked seizurte and a high recurrence risk (60% over 10 years)
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6
Q

What is a reflex seizure?

A
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7
Q

How can we classify seizures?

A

- Generalised: electrical spread across both hemispheres of the brain and result in a loss of consciousness. Absence and tonic-clonic seizures

Focal Onset: no loss of awareness mostly and the most common type of seizure

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8
Q

What are provoked seizures and how do we treat them?

A
  • Seizure as a result of another medical condition
  • Need to treat both the seizure and the underlying condition and unlikely to need ongoing AED treatment if cause treated
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9
Q

What are some differential diagnoses for seizures?

A

Pseudoseizures are a result of psychological causes such as severe mental stress, they won’t response to benzodiazepenes

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10
Q

What is the initial management for a seizure?

A
  • Primary Survey
  • Start a timer
  • Get some help
  • Wait five minutes before giving drugs as most self-terminate
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11
Q

What is status epilepticus?

A
  • Medical emergency as the brain uses up all of its resources and hypoxia occurs. Can lead to sudden death months later due to effects on brain
  • Can also lead to AKI due to rhabdomyolysis from muscle contractions
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12
Q

What is the pharmacological treatment pathway for status epilepticus?

A
  • Wait five mins with A to E
  • Benzodiazepines (Lorazepam IV)
  • Benzodiazepines again
  • Phenytoin Infusion
  • Thiopentone/Anaesthesia but call ICU

Only take next step if not resolving

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13
Q

How do benzodiazepenes work in epilepsy?

A

GABA enhancing drug so cause cells to become hyperpolarised with Cl- ions so less likely to fire

- Lorazempam (IV): Fast acting

- Diazepam (rectally)

- Midazolam (buccal): middle acting

Put in slowly as can always add more

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14
Q

What investigations do clinicians do into seizures to see whether there is a diagnosis of epilepsy/which type of epilepsy a patient has?

A
  • Ask for eyewitness accounts of seizures or videos

- EEG sleep deprived but sometimes shows no abnormalities or normal people have abnormal EEG

- MRI to rule out vascular or structual epilepsy

  • FBC to check ion levels e.g Mg and Ca
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15
Q

Why do we give patients with epilepsy anti-epileptic drugs?

A

- Sudden Unexplained Death in Epilepsy risk higher in people with poor seizure control

- Massive impact on life: cannot drive, swim, have a bath, time out of work and school

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16
Q

How do the main AEDs we use work?

A
  • Many drugs work in several ways e.g valproate

- Na Channel Blockers: Carbamazepine, Lamotrigine, Phenytoin

17
Q

How does carbamazepine work as an AED and what are the side effects and DDIs of this drug?

A

- Block Na channels in central neurones so slows recovery of inactive neurones to closed neurones, reducing neuronal transmission

ADRs: Suicidal thoughts, joint pain, bone marrow failure, dizziness, rashes

DDIs: shortens own half life so dose needs to be altered long term as CYP inducer, lowers effect of warfarin, OC pill, phenytoin

  • Also used to treat bipolar and chronic pain
18
Q

How do voltage gated sodium channel blockers act as AEDs?

A

Bind to channel during depolarisation to prolong the inactive state of the neurone, once the membrane potential goes back to normal the drug detaches

e.g valproate, carbamazepine and phenytoin

19
Q

What are the side effects and DDIs of phenytoin?

A

- Na channel blocker

Side effects: bone marrow suppression, hypotension, arrhythmias when used IV, gum hyperplasia

DDIs: CYP induce so decrease OC effectiveness, highly bound to plasma proteins so when take NSAIDs higher plasma conc as displaces, zero order kinetics so be careful with dose

20
Q

What AEDs are used for each classification of epilepsy?

A

- Lamotrigine: focal or generalised when valproate cannot be used. Can be used for absence due to actions on Ca channels

- Valproate: generalised

- Carbamazepine and Phenytoin: all but absence

21
Q

What are the side effects and DDIs of sodium valproate?

A

- GABA enhancing drug by indirectly increasing GABA synthesis and Na blocker

- Side effects: liver failure, pancreatitis, lethargy, weight gain, ataxic tremor

- ADRs: SSRis and antipsychotics lower valproate levels but aspirin increases it

22
Q

What are the side effects and DDIs of lamotrigine?

A

- VGSC blocker but also Ca channel blocker

  • Safer in pregnancy
  • Lowers OC pill effectiveness
23
Q

What is the MOA of levetiracetam?

A

Synaptic vesicle glycoprotein binder preventing Ca influx in the presynaptic knob so neurotransmitter cannot be released

Used for focal and generalised seizures

Safe in pregnancy

24
Q

What are some side effects of AEDs in general?

A
  • Tiredness/Drowsiness as stopping neuronal transmission
  • Nausea and Vomiting
  • Mood changes and suicial ideation
  • Osteoporosis
  • Steven Johnson syndrome (mostly phenytoin and carbamazepine)
  • Anaemia, thrombocytopenia and bone marrow failure

REGULAR FBCs NEEDED

25
Q

What effect do the AEDs have on CYP450 enzymes?

A
26
Q

How do you start someone on AEDs and how would you transition the from one drug to another?

A
  • Pick a drug and start low dose and work up
  • Check for tolerable side effects and want to be seizure free
  • Can monitor plasma levels but only if neccessary e.g pregnancy or issues with adherance or increase seizure frequency
  • If starting another drug titrate first down and titrate second up
27
Q

What advice needs to be given to young women on AEDs?

A
  • Should be enrolled in pregnancy prevention programme if on valproate as 10% change of congenital malformation
  • Lamotrigine and Levetiracetam are the safest
28
Q

Complete the following table.

A
29
Q

What is unusual about carbamazepines interaction with CYP450 enzymes?

A

Induces its own metabolism so dose has to be altered when given long term

30
Q

When is midazolam useful over lorazepam?

A

When you cannot get IV access in a child, can give buccally or intranasally