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IC Part 2 > Drugs for Seizure Disorders > Flashcards

Drugs for Seizure Disorders Flashcards

1
Q

Anticonvulsants

A

tx seizure disorders

  • excessive, random discharge of neurons in brain
  • imbalance between excitatory and inhibitory systems
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2
Q

Partial seizures

A 
No loss of consciousness
localized to specific area
-elementary symptamology- cortical focal
-complex symptomatology- psychomotor
-increasing electrical activity at a focu followed by synch of the surrounding neurons, abnormal firing can then spread to adjacent neurons
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3
Q

Generalized siezures

A

always involves loss of consciousness

  • tonic clonic
  • absence
  • status epilepticus
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4
Q

Tonic clonic (grand mal) siezures

A

focal seizure activity in one hemisphere spreads throughout the brain
-generalized seizure

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5
Q

Absence (petit mal) seizure

A

generalized seizure

  • brief interruptions of consciousness manifested as motionless staring
  • school aged children
  • abnormal synch of thalamocortical and cortical cells, activation of T-type calcium channels that are normally active during sleep
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6
Q

Status epilepticus (absence or tonic clonic)

A

generalized seizures
5 min w/o regaining consciousness
med emergency

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7
Q

MOA

A

1) Prolong inactivation of Na channels- reduce ability of neurons to fire at high frequency (phenytoin, carbamazzepine, valproic acid, lacosamide, lamotrigine, topiramate, zonisamide)
2) Enhance GABA-ergic activity- inc receptor response to neurotransmitter (barbs, benzos) or inc synaptic activity of GABA (tiagabine, levetiracetam)
3) Inhibit T-type Ca+ channels (active during sleep, efficacious for absence seizures) (ethosuximide, valproic acid, trimethadione)
4) Other- dec excitatory neurotransmission by binding to subunits of voltage gated Ca channels within CNS; enhance K+ channel opening (gabapentin, pregabalin, ezogabine)

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8
Q

Benzos- Diazepam

A

Bind to BZ site on GABA receptor and inc affinity of GABAa receptors for GABA- inc likelihood of Cl channel opening
Drug of choice for tx of status epilepticus (iv)
Effective for tonic clonic and absence seizures but only for 2-3 weeks due to tolerance to anticonvulsant effects

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9
Q

Barbiturates

A

Bind to barbiturate binding site on GABAa receptor- inc Cl ion channel flux by inc channel opening time
-Dec glutametergic neurotransmission

Phenobarbital- tonic clonic seizures, very sedating, abrupt withdrawal can precipitate status epilepticus, induces microsomal enzymes, possible teratogen
can lead to stevens-johnson syndrome

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10
Q

Primidone

A
  • Converted to phenobarbital and then phenylethylmalonamid (All three are active)
  • frequently effective in pts not responding to phenytoin or phenobarbital (combo with phenytoin but NOT with phenobarbital)
  • drowsiness, ataxia, nausea, vomiting, rash, diplopia, blood dyscrasias, impotence
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11
Q

Hydantoins

A
  • Phenytoin (ethotoin, fosphenytoin, mephenytoin)
  • Prolongs inactivation of Na channels, decreases glutamate release
  • Tonic clonic and partial seizures drug of choice
  • generally less sedating than barbs
  • numerous drug interactions- highly bound to plasma proteins, induces P450s and other enzymes increasing metabolism and can lead to vit D deficiency
  • metabolism- first order, hepatic metabolic capacity saturates in therapeutic concentration range (changes to zero order), small dose increases- large changes in drug concentration and toxicity
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12
Q

Side effects of hydantoins

A
  • diplopia, ataxis, drowsiness, nausea vomiting, rashes
  • hirsutism, hyperplasia of gums, megaloblastic anemia, teratogenic (fetal hydantoin syndrome), coarsening of facial features, osteomalacia
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13
Q

Valproid acid

A
  • broad spectrum
  • inc Na channel inactivation, inhibit T type Ca channels, enhances GABA transmission, modifies AA metabolism
  • tonic clonic seizures
  • idiosyncratic hepatotoxicity (esp in children <2 yo or taking multiple drugs- fatal)
  • sedation uncommon
  • SE: pancreatitis, nausea, vomiting, diplopia,
  • IV for status epilepticus
  • P450 inhibitor- inhibits metabolism of other drugs!!!
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14
Q

Which anticonvulsant is a p450 inhibtor

A

valproic acid

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15
Q

Carbamazepine

A
  • partial seizures
  • relatively safe and nontoxic
  • diplopia, ataxia, drowsiness, not typically sedating, induces microsomal enzymes
  • blood dyscrasias
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16
Q

Oxcarbazepine

A

much lower half life than carbamazepine
-no blood dyscrasias
fewer drug interactions
-partial seizures

17
Q

Lamotrigine

A

Inc inactivation of Na channels

  • inhibit T type Ca channels and decrease glut release
  • nausea, diplopia, rashes, sedation, headache, dizziness
  • valproic acid increases 1/2 life, so reduce dose if given in combo
  • partial or possibly absence seizures
  • add on or monotherapy
18
Q

Topiramate

A
  • add on, now used as monotherapy
  • inc inactivation of Na channels, enhances GABA and dec glut activity
  • partial, generalized tonic clonic, maybe absence seizures
  • sedation, mental dulling, parasthesia, dec serum bicarb (met acidosis)
  • teratogenic
  • decrease efficacy of oral contraceptives
19
Q

Levitiracetam

A

Modifies synaptic release of GABA (and glutamate) by binding to synaptic vesicular protein SV2A
-not metabolized by P450
SE: agitation, nausea, drowsiness, asthenia, muscle weakness
-Partial seizures monotherapy or add on

20
Q

Lacosamide

A

enhances slow inactivation of Na channels
-partial seizures
monotherapy or add on

21
Q

Gabaptenin/Pregabalin

A
  • add ons
  • pregabalin more potent
  • dec glutamate release by binding to voltage gated Ca channels containing alpha-beta subunit (also augment GABA release)
  • refractory partial seizures when used in combo with other drugs (carbamazepine or phenytoin)
22
Q

Tiagabine

A

Inhibits GABA reuptake

Add on for partial and tonic clonic seizures

23
Q

Zonisamide

A

Add on for partial seizure
Inc inactivation of Na channels (maybe also Ca channels)
Not metabolized by P450
Drowsiness, anorexia

24
Q

Ezogabine

A

Add on for partial seizure

-K channel facilitator

25
Q

Perampenel

A

AMPA glutamate receptor antagonist

add on for partial seizure

26
Q

Eslicarbazepine

A

-pro drug
add on for partial seizures
voltage gated Na channel blocker

27
Q

Ethusuximide

A

Drug for absence seizures
Inhibit T type Ca channels
-drug of choice

SE: GI upset, lethargy, headache
pts may develop tonic clonic seizures, often administered with primidone or phenytoin

28
Q

Other drug for absence seizures

A 
Valproic acid
-inhibits T type Ca channels 
Drug of choice 
Also effective in tonic-clonic seizures
Idiopathic hepatotoxicity

Also- methsuximide, lamotrigine, trimethadione, clonazepam

29
Q

Black box warning on anticonvulsants

A

inc risk of suicidal behavior or ideation when used in tx of epilepsy, psych disorders, other conditions

30
Q

Other uses for these drugs- bipolar disorder

A

carbamazepine
valproic acid
lamotrigine

31
Q

Migraine prophylxis

A

valproic acid

topiramte

IC Part 2 (27 decks)

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