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PT4024 > L1: Epilepsy > Flashcards

L1: Epilepsy Flashcards

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1
Q

there is excessive __ in epilepsy

A

there is excessive firing in epilepsy

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2
Q

define epileptic seizures

A

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

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3
Q

what is the incidence of epilepsy?

A

0.5% of the population

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4
Q

what is primary epilepsy?

A

idiopathic (unknown cause): genetic & environment

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5
Q

what is secondary epilepsy?

A

epilepsy resulting from brain damage

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6
Q

what does a benzodiazepine pen do and where is it administered?

A

it reduces the duration of the seizure, it is administered in the buccal cavity

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7
Q

what are partial seizures?

A

local/focal, discharge localised to one brain region and one brain hemisphere.

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8
Q

what is a simple partial seizure?

A

consciousness unaffected

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9
Q

what is a complex partial seizures?

A

where consciousness is affected, can involve temporal lobe (hippocampus)

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10
Q

what do 30% of patients with partial seizures experience?

A

they sometimes can have generalized seizures, these are then known as secondary generalized seizures

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11
Q

what are generalized seizures?

A

discharge involving both hemispheres and reticular system, affecting consciousness

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12
Q

what are absense/petit mal seizures?

A

3 “spike and wave” discharges/second, oscillating feedback between cortex and thalamus. most common in children, presents as “staring spells”

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13
Q

what are tonic-clonic/grand-mal seizures?

A

tonic phase: muscle spasm, respiration stops, bowel/bladder discharge
clonic phase: release
physical signs include violent jerking, unable to stand.

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14
Q

what type of neurotransmission is increased and what type of neurotransmission is decreased in epilepsy?

A

excitatory neurotransmission via glutamate is increased and inhibitory neurotransmission via GABA is decreased

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15
Q

what does the altered neurotransmission often cause in epileptic patients?

A

excitotoxicity

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16
Q

what can BDNF do to neurons?

A

BDNF can increase membrane excitability

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17
Q

what is the chemical animal model of epilepsy?

A

IV Kainate injections (glutamate agonist)

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18
Q

what is the physical animal model of epilepsy?

A

Kindling, repeated low intensity brain stimulation via electrodes

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19
Q

what is the main aim of antiepileptic drugs?

A

to decrease excitatory (Glutamate) neurotransmission and increase inhibitory (GABA) neurotransmission

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20
Q

give examples of use-dependent Na+ channel block

A

phenytoin, carbemazepine, lamotrigine, valproate

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21
Q

give examples of Ca2+ channel inhibitors

A

ethosuximide, gabapentin, phenytoin, valproate

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22
Q

what antiepileptic drugs enhance GABAa activation

A

phenobarbital, benzodiazepines

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23
Q

what drugs inhibit GABA deaminase (inhibt GABA degradation)

A

valproate, vigabatrin

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24
Q

what drugs inhibit GABA reuptake

A

Tigabin

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25
what drugs inhibit glutaminergic transmission
NMDA, AMPA, mGluR antagonists have shown efficacy in animal models.
26
name some other antiepileptic drug options
Carbonic anhydrase inhibitors, hormones, cannabidiol, ketogenic diet
27
what is cannabidiol (CBD) approved for?
Dravett''s syndrome
28
what is the mutation in Dravett's syndrome?
mutation in voltage-gated sodium channel (Na(V)1.1)
29
what are the three states that Na+ channels can exist in?
open, closed, inactivated
30
which state do use-dependent Na+ channel blockers act on Na+ channels?
in the inactivated state
31
describe the mechanism of use-dependent Na+ channel blockers?
enter when ion channel inactive, brings membrane potential to 0, stabilising the receptor
32
what does Na+ channel blockers preferentially inhibt?
Na+ channel blockers preferentially inhibit neurons that fire repetitively with high frequency, mainly affect neurons that have high-frequency discharge.
33
what is the most widely used antiepileptic?
Carbemazepine
34
describe CBZ metabolism (hint: phase 1)
epoxidation to CBZ-10, 11-epoxide, hydrolysis to CBZ-10,11-trans-dihydrodiol
35
CBZ is a strong _ of P450 enzymes
CBZ is a strong inducer of P450 enzymes
36
CBZ can _ _ its own _, decreasing its half life from 30 hours to 15 hours
CBZ can autoinduce its own metabolism, decreasing its half life from 30hrs to 15hrs
37
side effects of CBZ?
ataxia, drowsiness, dizziness, cognitive and motor disturbances, hypersensitivity reactions
38
difference between carbemazepine and oxcarbamazepine
ox is the prodrug analogue of CBZ
39
when dos oxCBZ block Na+ channels?
when metabolized by the liver
40
ox-CBZ has less drug interactions, but still interacts with?
oral contraceptive pill
41
what receptor does both CBZ and oxcarbemazepine act on?
they are both GABA agonists and have been used for schizophrenia and neuropathic pain
42
what dos phenytoin inhibit?
Calcium and sodium channels
43
what % of phenytoin binds to albumin
80-90% of phenytoin binds to plasma albumin
44
what other AED can displace phenytoin from albumin?
valproate
45
phenytoin is metabolised by and increases the enzyme expression and activity of?
phenytoin is metabolized by and increases the enzyme expression and activity of CYP450.
46
what effect might phenytoin have of CBZ, barbiturates, and valproate?
it can increase the metabolism of CBZ, Valproate and barbiturates
47
phenytoin adverse effects?
gum hyperplasia, vitamin D deficiency, teratogenesis
48
what is the therapeutic range of phenytoin?
40-100 microM
49
What is associated with a plasma conc. of more than 100 microM of phenytoin?
vertigo, ataxia, headache
50
what is associated with a plasma conc. of more than 150 microM of phenytoin?
confusion, intellectual deterioration.
51
what is the name of the safer, prodrug of phenytoin
fosphenytoin
52
what type of AED is Lamotrigine?
a Na+ channel blocker
53
what other effect does the Na+ channel blocker Lamotrigine have?
inhibits presynaptic depolarisation of glutaminergic neurons to decrease glutamate release
54
what is lamotrigine usually combined with?
valproate
55
what Na+ channel AED is suitable for pregnancy and why?
Lamotrigine, non-teraogenic
56
what does Zoisamide inhibit?
Na+ and Ca2+ channels
57
describe Zonisamide metabolism
CYP450 and then glucuronidation
58
what is Zonisamide half-life and why is this beneficial?
60 hour half-life, useful for drug compliance as only needs to be taken once a day or once every two days
59
why do AEDs target Calcium channels?
because calcium channels release the calcium that activates proteases needed for vesicle fusion
60
ethosuximide mechanism
ehtosuximide is a calcium channel inhibing AED that blocks T-type calcium channels (pre and post-synaptic)
61
other effects of ethosuximide
inhibits Na+/K+ATPase and inhibit GABA deaminase
62
side effects of ethosuximide
nausea, anorexia, lethargy, dizziness, sometimes hypersensitivity
63
what is GABApentin?
a presynaptic L-type calcium channel inhibitor
64
what does GABApentin bind
GABApentin binds the alpha-2-delta subunit of calcium channels in cerebral neocortex, hippocampus, and spinal cord
65
effect of GABApentin
decreased release of glutamate, increases GABA due to mild stimulation of glutamic acid decarboxylase
66
what is the more potent version of GABApentin
pregabalin
67
valproate mechanism
increases GABA
68
how does valproate increase GABA in the brain
it stimulate glutamate decarboxylase, inhibits gaba deaminase
69
side effects of valproate
teratogenesis and hepatotoxicity
70
vigabatrin mechanism
increases GABA, irreversibly inhibits GABA deaminase
71
side effects of vigabatrin
depression, psychotic disturbances
72
what is Tigabine
a lipophillic GABA analogue, penetrates BBB, irreversibly inhibits GABA transporter 1 (GAT-1), preventing GABA reuptake and prolongs GABA effect at inhibitory synapses
73
phenobarbital is a strong P450 __
Phenobarbital is a strong P450 inducer,
74
what is the main effect of phenobarbital
to increase GABAa receptor response
75
what is there a high risk of with phenobarbital
overdose due to sedative effect
76
what are some examples of benzodiazepines
diazepam, lorazepam, clonazepam
77
what develops over time with benzos
tolerance
78
what is felbamate
an NMDA glutamate receptor antagonist
79
what is topiramate
an AMPA glutamate receptor antagonist, D-Fructose analogue
80
carbonic anhydrase inhibitor example and effect
acetazolamide, inhibits carbonic anhydrase, increasing carbonic acid and decreasing cellular pH.
81
what effect does a decrease in pH have on the cell
causes a K+ efflux, hyperpolarisation.
82
effect of pregesterone on seizures
anticonvulsant, increases GABAa conductance, reduces glutaminergic excitation, alters GAD and GABAa expression
83
effect of oestrogen on seizures
proconvulsant, reduces GABAa conductance, NMDA agonist in hipppocampus

PT4024 (6 decks)

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