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PT4024 > L1 Epilepsy > Flashcards

L1 Epilepsy Flashcards

1
Q

Definition of epileptic seizures

A

Episodic high frequency discharges by a localised group of neurons in the brain

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2
Q

Symptoms of motor cortex seizure

A

Convulsions

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3
Q

Symptoms of seizure affecting hypothalamus

A

Peripheral autonomic effects

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4
Q

Symptoms of seizure in reticular formation

A

Loss of consciousness

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5
Q

Drug treatment is effective in what percentage of epileptic patients?

A

~70%

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6
Q

Epilepsy incidence

A

~0.5% of the general pop (1:200)

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7
Q

Cause of primary epilepsy

A

Idiopathic

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8
Q

Cause of secondary epilepsy

A

Result of brain damage, or a tumour acting on a particular brain region

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9
Q

Forms of epilepsy

A
  1. Partial seizures (focal): simple or complex
  2. Generalised seizures: absence or tonic-clonic
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10
Q

Difference between partial and generalised seizures

A

Partial seizures - discharge localised to one brain region and hemisphere
Generalised seizures - discharge involves both hemispheres and reticular system (consciousness affected)

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11
Q

What percentage of patients with partial seizures can sometimes experience a secondary generalised seizure?

A

~30%

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12
Q

Absence (petit mal) seizures are most common in __ and are characterised by __

A

children
staring spells

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13
Q

How is neurotransmission altered in epilepsy?

A
  • increased excitatory neurotransmission
  • decreased inhibitory neurotransmission
  • repeated discharge (excitotoxicity)
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14
Q

Animal models of epilepsy

A
  • Chemical: ICV Kainate injections (glutamate agonist)
  • Physical: Kindling - repeated low intensity brain stimulation (electrodes)
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15
Q

Main aims of AEDs

A
  • Reduce electrical excitability of excitatory neurons (glutamate)
  • Increased inhibitory (GABA) neurotransmission
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16
Q

Main mechanisms of AEDs

A
  1. Use-dependent Na⁺ channel block
  2. Ca²⁺ channel inhibition
  3. Increase GABA-mediated neural inhibition
  4. Inhibit glutamatergic transmission
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17
Q

List Na⁺ channel blockers used to treat epilepsy

A
  • Carbamazepine
  • Oxcarbazepine
  • Phenytoin
  • Lamotrigine
  • Zonisamide
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18
Q

Na⁺ channel blocker stabilises the receptor in its __ state

A

inactivated

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19
Q

Na⁺ channel blockers mainly affect neurons with __ frequency discharge

A

high

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20
Q

What is the most widely-used AED?

A

Carbamazepine

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21
Q

CBZ metabolism

A
  • Epoxidation to CBZ-10,11-epoxide, hydrolysis to CBZ-10,11-trans-dihydrodiol
  • Strong inducer of CYP450 enzymes
  • Autoinducer of its own metabolism
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22
Q

CBZ increases metabolism of…

A

phenytoin, warfarin, oral contraceptives

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23
Q

CBZ half-life

A

30h for single dose, decreased to 15h on repeated dosing

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24
Q

CBZ side effects

A
  • Neurological: drowsiness, dizziness, ataxia, cognitive & motor disturbances
  • Hypersensitivity reactions (skin, liver)
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25
Q

Pro-drug analogue of CBZ

A

Oxcarbazepine

26
Q

Advantage of oxcarbazepine over CBZ

A
  • Less P450 induction, therefore less drug interactions
  • Does not interact with warfarin, cimetidine, erythromycin
27
Q

Why have CBZ and oxcarbazepine been used for neuropathic pain and schizophrenia?

A

because they also act as GABA receptor agonists

28
Q

First-line treatment for partial and secondary generalised seizures

A

Phenytoin

29
Q

Phenytoin MOA

A

Na⁺ and Ca²⁺ channel inhibitor

30
Q

Combination of phenytoin and __ is not recommended due to toxicity risk

A

valproate

31
Q

Phenytoin is highly bound to __

A

plasma albumin (80-90%)

32
Q

Why are drug interactions common with phenytoin?

A

because it’s metabolised by and induces CYP450 enzyme activity, which increases metabolism of CBZ, phenobarbital and valproate

33
Q

Phenytoin side effects

A
  • Plasma conc. >100µM: vertigo, ataxia, headache
  • Plasma conc. >150µM: confusion, intellectual deterioration
  • Hypersensitivity reactions (skin, liver)
  • Gum hyperplasia
  • Vit D def
  • Teratogenesis
34
Q

Safer pro-drug of phenytoin

A

Fosphenytoin

35
Q

Sodium-blocking AED that also inhibits presynaptic depolarisation of glutamatergic neurons

A

Lamotrigine

36
Q

Lamotrigine is usually combined with __

A

valproate

37
Q

Why is Lamotrigine preferred in the elderly?

A

Low CNS toxicity

38
Q

Can Lamotrigine be used in pregnancy?

A

Yes

39
Q

Zonisamide MOA

A
  • Inhibits both Na⁺ and Ca²⁺ channels
  • Neuroprotective by free radical scavenging
  • Metabolised by CYP450, then glucuronidation
40
Q

Half-life of Zonisamide

A

60h, less when combined with phenytoin, CBZ or valproate
(well-tolerated, not prone to serious DDIs)

41
Q

Low threshold __ Ca²⁺ channels implicated in periodic discharges of partial seizures

A

T-type

42
Q

T-type Ca²⁺ channel blocker used to control absence seizures

A

Ethosuximide

43
Q

What is gabapentin?

A

Pre-synaptic L-type Ca²⁺ channel inhibitor that binds α₂𝛿 subunit of Ca²⁺ channels in cerebral neocortex, hippocampus & SC to decrease release of glutamate and increase GABA levels (by stimulating GAD)

44
Q

More potent pro-drug of gabapentin

A

Pregabalin

45
Q

Valproate MOA

A

Increases GABA by stimulating glutamate decarboxylase and inhibiting GABA deaminase. Also weak block of Na⁺ and Ca²⁺ channels

46
Q

Side effects of valproate

A

Hepatotoxicity, teratogenesis

47
Q

How does vigabatrin increase GABA in the brain?

A

by irreversibly inhibiting GABA deaminase

48
Q

What is tiagabine?

A

Lipophilic GABA analogue that irreversibly inhibits GAT-1 in neurons & glia to prevent GABA re-uptake, prolonging GABA effect at inhibitory synapses

49
Q

Pharmacological agents that increase GABAa receptor response to reduce seizure duration

A
  • Phenobarbital
  • Benzodiazepines e.g. diazepam, lorazepam, clonazepam
50
Q

What happens if you overdose on phenobarbital?

A

Severe respiratory and circulatory depression, coma

51
Q

When are benzodiazepines used?

A

in emergency (status epilepticus) - IV admin, fast-acting

52
Q

Felbamate MOA

A

NMDA glutamate receptor antagonist. Also weakly blocks Na⁺ and Ca²⁺ channels

53
Q

Topiramate MOA

A

AMPA glutamate receptor antagonist. Also blocks Na⁺ channels, raises GABA levels, and weakly blocks carbonic anhydrase

54
Q

__ channel blockers better in partial seizures

A

Na⁺

55
Q

__ channel blockers better in generalised seizures

A

Ca²⁺

56
Q

Carbonic anhydrase inhibitor that increases carbonic acid levels to increase seizure threshold

A

Acetazolamide

57
Q

Progesterone is __-convulsant

A

anti (increases GABAa conductance, reduces glutamatergic excitation)

58
Q

Oestrogen is __-convulsant

A

pro (reduces GABAa conductance)

59
Q

What is Dravet syndrome?

A

Severe myoclonic epilepsy of infancy (SMEI)

60
Q

What is cannabidiol?

A
  • CBD: non-psychoactive component of cannabis plant
  • Oil extracted from a plant high in CBD & low in THC
  • Can help in MS, Dravet syndrome, chemo-induced nausea or loss-of-appetite

PT4024 (12 decks)

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