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Brain and Behavior Exam 3 > Lec 44 Antiepileptic Drugs > Flashcards

Lec 44 Antiepileptic Drugs Flashcards

1
Q

What are the main types of seizures?

A
  • partial = begin locally
  • –> simple
  • –> complex
  • –> sexondarily generalized
  • generalized with or without convulsions
  • –> absence
  • –> myoclonic
  • –> tonic
  • –> clonic
  • –> tonic-clonic
  • –> atonic
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2
Q

What is use of narrow-spectrum anti-epileptic drugs?

A
  • effective in partial seizures [including secondarily generalized]
  • less effective in primary generalized tonic-clonic seizures
  • not useful for myoclonic or absence
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3
Q

What is use of broad spectrum anti-epileptic drugs?

A
  • effective in partial

- effective in generalized [primary or secondary]

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4
Q

use narrow-spectrum or broad spectrum drugs for myoclonic or absence seizures?

A

broad spectrum!!! narrow spectrum not useful and may even worsen

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5
Q

Why are some particular brain regions more likely to become epileptic foci?

A
  • because of intrinsic burst firing or automaticity characteristics of the cell types
  • because of close packing of neurons in sheets
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6
Q

What are some anti-epileptic drugs that inhibit Na channels?

A
  • carbamazepine
  • lamotrigine
  • phenytoin
  • topiramate
  • valproate
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7
Q

What is first line drug of choice for simple focal seizure?

A

carbamazepine

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8
Q

What is first line drug of choice for complex focal seizure?

A

carbamazepine

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9
Q

What are the 3 first line options for generalized tonic-clonic seizure?

A
  • phenytoin
  • carbamazepine
  • valproic acid
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10
Q

phrase for remembering the 4 broad spectrum anti-epileptics we need to learn?

A

Lamb values a top clone

  • lamotrigine
  • valproate
  • topiramate
  • clonazepam
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11
Q

What is the first line for absence seizures?

A

ethosuximide

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12
Q

What is the first line of acute vs prophylaxis status epilepticus?

A 
prophylaxis = phenytoin
acute = benzodiazepines
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13
Q

Which Na channels are likely to be inhibited first by AEDs?

A

preferentially inhibit channels that are open with high freq/burst firing

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14
Q

What is mech of action of benzodiazepines?

A
  • increase activity of GABA-A receptors
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15
Q

What is mech of phenobarbital [barbiturate]?

A
  • increase activity of GABA-A receptors
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16
Q

What is mech of topiramate?

A

blocks NA channels AND increases GABA-A receptor action

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17
Q

What is mech of action tiagabine?

A

increases synaptic levels of GABA by blocking GABA reuptake

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18
Q

What is mech of action gabapentin?

A
  • may increase release of GABA

- may also inhibit high voltage activated Ca channels or Na channels

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19
Q

What is function of T-type Ca channels? what type of epilepsy are they associated wtih?

A
  • exist in thalamocortical neurons and involved in generating sleep spindles

excess firing through T-type Ca leads to absence seizure

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20
Q

Which 4 types of drugs can be used to treat absence epilepsy?

A
  • ethosuximide = first line
  • valproate
  • lamotrigine
  • clonazepam = less used
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21
Q

What drug inhibits N/P type Ca channels?

A

lamotrigine

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22
Q

When do you start treatment for status epilepticus? What is initial treatment?

A

treat ASAP to protect against neuronal damage

initial = benzodiazepine [lorazepam, etc] PLUS fosphenytoin or phenytoin to prevent recurrence

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23
Q

What are refractory treatments for status epilepticus if cannot be controlled with standard benzo + phenytoin?

A
  • give phenobarbital or valporate IV

- if not controlled in 1 hr, give general anesthesia

24
Q

What is induction of elimination?

A

if drug A increases expression of enzyme –> drug B is eliminated at higher rate

25
Q

What is competition of elimination?

A

drug A and B are substrates for same enzyme

if drug A has higher affinity for enzyme –> drug B elimination is slowed

26
Q

What is inhibition of elimination?

A

drug A is an inhibitor, not a substrate, for the enzyme so slows elimination of drug B

27
Q

What type of enzymes usually involved in drug interactions due to altered elimination?

A

usually Phase 1 cyp450 enzymes

28
Q

Which 3 anti-epileptic drugs are notable CYP450 inducers? which specific isoform primarily?

A
  • phenytoin
  • carbamzepine
  • phenobarbitol

primarily = 3A4 –> ~1/2 of all drugs metabolized by CYP450 isoforms are metabolized by 3A4

29
Q

What happens if you give carbamazepine and phenytoin?

A
  • decreased carbamazepine [increased metabolism]

- variable change in phenytoin level

30
Q

What happens if you give valproate and phenobarbital?

A

increased phenobarbitol [inhibited metabolism]

31
Q

What happens if you give valproate and lamotrigine?

A

increased lamotrigine [due to competition for phase 2 enzyme]

32
Q

What happens if you give valproate and clonazepam?

A

may precipitate absence status epilepticus

33
Q

Which drug is an inhibitor of CYP450 enzymes?

A

valproate

34
Q

What is stevens-johnson syndrome?

A
  • malaise + fever followed by rapid onset erythematous/purpuric macules [oral/ocular/genital], skin lesions progress to epidermal necrosis and sloughing
35
Q

What 5 drugs associated with hypersensitivity/ stevens-johnson syndrome?

A
  • phenytoin
  • carbamazepine
  • lamotrigine
  • ethosuximide
  • phenobarbital
36
Q

What 4 drugs associated with teratogenicity?

A
  • phenytoin
  • carbamazepine
  • phenobarbital
  • valproate
37
Q

What 5 drugs associated with cognitive slowing?

A
  • topiramate
  • phenobarbital
  • carbamazepine
  • phenytoin
  • valproate
38
Q

What 2 drugs most likely to cause increase in seizure activity?

A

phenytoin

tiagabine

39
Q

Which AED associated with gingival hyperplasia?

A

phenytoin

40
Q

What is fosphenytoin? use?

A
  • ester prodrug of phenytoin
  • higher aqueous solubility
  • use IV for emergency treatment for seizure and during surgery
41
Q

What is therapeutic window for phenytoin? pharmacokinetics?

A
  • non-linear pharmacokinetics in therapeutic window

- narrow therapeutic window [10-20 ug/mL] 30 = toxic

42
Q

Is steady state conc [Css] for phenytoin proportional to dose?

A

NO!

43
Q

Are pharmacokinetics constant or variable between pts treated with phenytoin?

A

VARIABLE!

44
Q

What is equation for rate of elimination [V] of a drug?

A

V = Vmax *C / [Km + C]

45
Q

What is equation for rate of elimination [V] of a drug under first order kinetics?

A

C «< Km so
V = Vmax C / [Km + C]
== C Vmax/ Km

so Clearance is constance Vm/Km with changes in C

46
Q

What is equation for rate of elimination [V] of a drug under zero order kinetics?

A

C&raquo_space; Km so
V = Vmax *C / [Km + C]
== Vmax * C/C == Vmax

*clearance rate decreases as C increases since Vmax is a function of C

47
Q

What 3 antiepileptics can also be used to treat bipolar disorder?

A
  • valproate
  • carbamazepine
  • lamotrigine
48
Q

What antiepileptic is first line for trigeminal neuralgia?

A
  • carbamazepine
49
Q

What antiepileptic is also used to treat peripheral neuropthy + post-herpetic neuralgia

A
  • gabapentin
50
Q

What 2 anti-epileptics also used for migraine prevention?

A
  • topiramate

- valproate

51
Q

What types of seizures are benzodiazepines used to treat?

A
  • status epilepticus [1st line acute]
  • –> esp lorazepam
  • also clonazepam used absence and myoclonic/atonic
52
Q

What types of seizures is ethosuximide used to treat?

A

first line for absence seizures only

53
Q

What type of seizures is phenytoin used to treat?

A
  • partial
  • first line for tonic-clonic
  • first line for prophylaxis of status epilepticus
54
Q

What type of seizures is tiagabine used to treat?

A

focal only [simple and complex]

55
Q

What type of seizures is lamotrigine used to treat?

A
  • focal [simple + complex]
  • tonic-clonic
  • absence
56
Q

What type of seizures is valproic acid used to treat?

A
  • focal simple + complex
  • tonic-clonic
  • absence
57
Q

Which anti-epilepsy drugs are primarily eliminated by renal?

A
  • gabapentin and topiramate

- all the rest are primarily hepatic

Brain and Behavior Exam 3 (32 decks)

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