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Drugs And The Brain > anticonvulsants > Flashcards

anticonvulsants Flashcards

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1
Q

focal seizures treatment

A

first line: carbamazepine, lamotrigine

second line: oxcarbazepine, valproate, levetiracetam

adjunct: combinations + gabapentin, topiramate

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2
Q

tonic clonic seizures treatment

A

first line: valproate (not WCBA), lamotrigine

second line: carbamazepine, oxcarbazepine

adjunct: combinations + levetiracetam, topiramate, clobazam

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3
Q

absence seizure treatment

A

first line: valproate (not WBCA), ethosuximide

second line: lamotrigine

adjunct: combinations + specialist advice

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4
Q

WCBA

A

women who are of child bearing age

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5
Q

mechanisms of anticonvulsants

A

calcium channel inhibition
GABAergic potentiation
-receptor potentiation
-uptake inhibition
-metabolism inhibition
sodium channel inhibition

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6
Q

phenytoin

A

stabilises voltage-gated sodium channels in inactivated state

effective against tonic clonic and partial seizures

can worsen absence and myoclonic seizures

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7
Q

phenytoin side effects

A

teratogenic
increased lupus risk
cerebellar atrophy
acne, hirsuitism
gingival overgrowth

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8
Q

gingival overgrowth

A

gums start to grow

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9
Q

carbamazepine mechanism

A

blocks voltage-gated sodium channels

may have secondary actions on GABA A receptors

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10
Q

uses of carbamazepine

A

focal seizures
useful for tonic-clonic seizures
mood stabiliser
to treat neuropathic pain

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11
Q

drugs related to carbamazepine

A

oxcarbazepine and eslicarbazepine

similar mechanisms, better side effect profile, fewer interactions

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12
Q

carbamazepine pharmacokinetics

A

auto-induces CYP3A4

-CYP3A4 metabolises carbamazepine so as people take more of the drug they produce more of this enzyme
-can take a while for the drug to reach a plateau

-means other drugs will be metabolised much more quickly, so must be careful with drug interactions

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13
Q

what inhibits enzyme CYP3A4

A

a component of grapefruit juice

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14
Q

side effects of carbamazepine

A

teratogenic
risk of lupus
worsens JME, absence seizures
cognitive problems
mood changes
psychosis in some people

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15
Q

mechanism of lamotrigine

A

sodium channel blocker

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16
Q

uses of lamotrigine

A

first line tonic clonic
second line absence
(can make myoclonic seizures worse at higher doses)
mood stabiliser- bipolar
can be asses to antipsychotic drugs for the treatment of schizophrenia

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17
Q

side effects of lamotrigine

A

not as bad as carbamazepine and phenytoin

sedation
sleep disturbances
rash
binds to eye pigment
steven-Johnsons syndrome (rare)

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18
Q

mechanism of benzodiazepines

A

potentiate actions of GABA A receptors by binding to allosteric sites on the receptor

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19
Q

clobazam

A

adjunct meditation
also used to treat anxiety
benzodiazepine

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20
Q

clonazepam

A

treat refractory epilepsy
benzodiazepine
also acts on calcium channels
only prescribed by specialists/ only on types of epilepsy not treatable by other drugs

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21
Q

diazepam

A

only really used for status epilepticus

acute serious situations, long term use = dependence

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22
Q

benzodiazepine side effects

A

sedation
tolerance and dependence build up very quickly
some cases: seizures on withdrawal

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23
Q

barbiturates as anticonvulsants

A

allosteric potentiators of GABA A receptors

side effects far worse, can directly activate the receptor making them dangerous in overdose

only prescribed by a specialist in difficulty situations

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24
Q

tiagabine mechanism

A

GAT1 inhibitor - increases the synaptic concentration of GABA as it cannot be taken up into the presynaptic nerve terminal

increasing inhibitory signals

25
Q

what is tiagabine used for?

A

adjunct medication for focal seizures
panic attacks?
neuropathic pain?

26
Q

tiagabine side effects

A

sedation
dizziness
paraesthesia
provokes seizures in non epileptic patients

27
Q

tiagabine overdose

A

very sedating
causes seizures, amnesia and confusion

28
Q

Vigabatrin mechanism

A

irreversible GABA transaminase inhibitor (short half life doesn’t matter as it will covalently modify enzyme)

increases presynaptic GABA concentration by stopping metabolism of GABA to SSA

29
Q

uses of vigabatrin

A

adjunct medication
addictions?
panic attacks?

30
Q

vigabatrin side effects

A

visual disturbances
depression
psychosis
sedation
teratogenic actions?

31
Q

three forms of sodium valproate

A

sodium valproate, valproic acid and valproate semisodium (mixture of the two)

32
Q

mechanism of sodium valproate

A

unclear
most likely GABA transaminase inhibitor (increasing GABA synthesis)
enhance post synaptic GABA function?
inhibit sodium channels?
inhibit calcium channels?

33
Q

uses of sodium valporate

A

treat epilepsy
treat bipolar disorder
treat migraines
sometimes add on treatment for schizophrenia

34
Q

side effects of valproate

A

Liver toxicity (can be sudden onset)

Teratogenic

Cognitive changes/brain structure changes with long term use (debatable/?reversible when drug is withdrawn ).

35
Q

what teratogenic side effects are associated with valproate?

A

Increased risk of: anencephaly, spina bifida (20 fold increased risk), autistic spectrum disorders, cleft palate, limb defects + many others…

36
Q

presentation of foetal valproate syndrome

A

high forehead
flat nasal bridge
broad base of nose
shallow philtrum
long upper lip

37
Q

gabapentinoids

A

gabapentin and pregablin

38
Q

believed action of gabapentin and pregabalin

A

act on alpha 2 - delta subunit of calcium channel

when this site is bound by natural ligands (leucine and isoleucine?) calcium channel complex transported to the cell surface

if a gabapentinoids bind this site, the calcium channel is retained within the cell and broken down

decreases the number of calcium channels at the cell surface

39
Q

pregabalin secondary effect

A

increases glutamate decarboxylase (GAD) levels
therefore
increases synthesis of GABA

40
Q

uses of gabapentinoids

A

Gabapentin and pregabalin: adjunct medication for focal seizures, neuropathic pain

pregabalin: monotherapy and licenced for anxiety treatment

41
Q

gabapentinoid side effects

A

Sedation/dizziness

Suicidal thoughts
Abuse potential
(when you put these two together very worrying)

Seizures upon withdrawal
-precipitate return of epilepsy or even seizures you didn’t have before
-particular problem for this drug

42
Q

ethosuximide mechanism

A

blocks T type calcium channels

43
Q

use of Ethosuximide

A

first choice drug for absence seizures, rarely used for other types of epilepsy (can exacerbate them)

44
Q

what may ethosuximide be preferred to valproate?

A

lacks the liver toxicity
there is an increased risk of birth defects, however this is less than with valproate

45
Q

how does valproate produce teratogenic side effects?

A

at least partly by acting as a folic acid antagonist

46
Q

side effects of ethosuximide

A

increased risk of birth defects
sedation
nausea
mood changes

47
Q

use of levetiracetam

A

can be used to treat focal, myoclonic and tonic-clonic seizures

48
Q

mechanism of levetiracetam

A

inhibits presynaptic calcium channels?
binds to SV2A?

reduces neurotransmitter release

49
Q

side effects of levetiracetam

A

Psychiatric
common: depression, agitation, aggression
rarer: suicide ideation, psychosis

Steven Johnson syndrome- rarer

50
Q

Steven Johnsons syndrome

A

some sort of immune reaction against the medication or a virus the patient has

More serious form: toxic epidermal necrolysis

51
Q

potential mechanism of topiramate

A

potentiation of GABAA receptors
block of AMPA and kainate receptors
block of sodium channels
block of calcium channels
inhibition of carbonic anhydrase

52
Q

when is topiramate used?

A

an adjunct treatment for focal seizures and tonic-clonic seizures
sometimes used in the treatment of migraines, bipolar disorder and alcoholism.

53
Q

topiramate side effects

A

sedating
can cause cognitive problems and have psychiatric side effects
known to be teratogenic

54
Q

what percentage of people are antiepileptic drugs successful for?

A

70%

55
Q

what is suggested when antiepileptic drugs do not work

A

ketogenic diet
-classic diet: 90% calories from fat therefore need professional dietician

about 50% of children on it see a decrease in the number of seizures, some become seizure free

56
Q

epilepsy surgery

A

localise the area of tissue generating the seizure and remove it or destroy it
benefits often outweigh issues that may arise from surgery

57
Q

corpus callosotomy

A

used for intractable epilepsy
sever white matter tract, preventing seizures spreading from one hemisphere to the other

58
Q

side effects corpus callosotomy

A

cognitive impairments
difficulty with language
alien hand syndrome

59
Q
A

Drugs And The Brain (9 decks)

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