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Pharmacology > Anti-Seizure Drugs > Flashcards

Anti-Seizure Drugs Flashcards

1
Q

what are the different drugs effective for generalized onset of seizures?

A

Valproate (first line/DOC)
Topiramate
Zonisamide

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2
Q

what is the first line broad-spectrum anti-seizure drug for px with generalized epilepsies?

A

valproate

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3
Q

in what population can u not give valproate?

A

women of childbearing age & pregnant women

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4
Q

what are the clinical uses of valproate?

A
  • generalized onset tonic-clonic seizures
  • generalized absence seizure
  • myoclonic seizures
  • atonic seizures
  • focal seizures
  • status epilepticus
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5
Q

what is the MOA of valproate?

A

it inhibits enzymes involved in GABA degradation -> DEC GABA degradation -> INC GABA increasing

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6
Q

what are other uses for valproate?

A

headache
mania in bipolar disorder

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7
Q

can valproate be taken with food?

A

food delays absorption so give it after meals

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8
Q

what are D/I of valproate?

A
  • inhibit metabolism of other anti-seizure drugs
  • INC free fraction of phenytoin -> toxicity
  • INC conc of phenobardibtal -> stupor/coma
  • DEC clearance of lamotrigine & rufinamide
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9
Q

what are the AEs of valproate?

A

dose-related: GIT (nausea, vomiting, abdominal pain, heartburn)

reversible: INC weight, INC appetite, hair loss

Higher levels: fine tremors

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10
Q

what is a rare toxic effect of valproate?

A

Idiosyncratic hepatotoxicity
idiosyncratic thrombocytopenia

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11
Q

what are C/Is of valproate?

A
  • PLUMS: Pregnancy, Liver dis, Urea dis, Mitochondrial dis, Suspected disorders <2 yrs
  • Pregnancy: @1st trim risk of NTD
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12
Q

what are D/I of Topiramate?

A
  • INC clearance of contraceptives
  • INC clearance of topiramate when given w/ CYP3A4 enzyme inducers
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13
Q

what is the MOA of Topiramate?

A

blocks voltage-gated Na channels –> INC GABA receptor activity -> reduce membrane depolarization by AMPA or kainate receptors

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14
Q

what are the clinical uses of Topamirate?

A
  • primary generalized tonic-clonic seizures
  • focal seizures
  • atonic seizures
  • prohylaxis in migraine
  • infantile spasms in WEST SYNDROME
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15
Q

What are AE of Topiramate?

A
  • cognitive impairments -> discontinued bcos of this
  • DOSE-RELATED during initiation = Paresthesias
  • Long term therapy = significant weight loss, Urolithiasis
  • Prompt withdrawal = acute myopia, angle-closure glaucoma
  • Metabolic acidosis (DEC HCO3) = rare
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16
Q

what is the teratogenic effect of Topiramate?

A

1st trimester = oral cleft formation in newborns

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17
Q

what is the MOA of Zonisamide?

A

blocks voltage-gated Na channels & T-type Ca channels

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18
Q

what are the clinical uses of Zonisamide?

A
  • focal & generalized tonic-clonic seizures
  • atypical absence seizures
  • some myoclonic epilepsies
  • infantile spasms
  • adjunct therapy in tx of focal seizures w/ or w/o secondary generalization in adults
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19
Q

what aer AEs of Zonisamide?

A
  • potentially serious skin rashes
  • low birth weight
  • weight loss
  • metabolic acidosis, kidney stones, oligohydrosis (rare)
  • drowsiness
  • cognitive impairment
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20
Q

what are drugs effective for generalized onset of seizures?

A

Generalized motor
* valproate
* Topiramate
* Zonisamide

Generalized absence
* Valproate
* Ethosuximide
* Lamotrigine
* Trimethadione

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21
Q

what is the MOA of Ethosuximide?

A

inhibits low-voltage-activated T type Ca channel

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22
Q

what is the main indicationfor Ethosuximide?

A
  • childhoos generalized absence seizures
  • atypical absence seizures
  • epileptic negative myoclonus (rare)
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23
Q

what is the main goal of Ethosuximide?

A

seizure conrtol with monotherapy

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24
Q

what are the AEs of Ethosuximide?

A
  • Common: Gastric distress (pain, nausea, vomiting)
  • Others: euphoria
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25
Q

what is drug for generalized onset seizures that is not used anymore?

A

Trimethadione –> AE: Hemeralopia (day blindness)

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26
Q

what are the drugs effective for seizures assoc with Lennox-Gastaut syndrome?

A
  • Valproate: Myocolonic seizures
  • Valproate + Iamotrigine + BZD: Atonic seizures
  • Topiramate, Felbamate, Iamotrigine, Clobazam, Rufinamide, Valproate: Lennox-Gastaut Syndrome
  • Stripentol, Cannabidiol, Fenfluramine: Dravet syndrome
  • IM ACTH, oral corticosteroid or Vigabatrin: Infantile spasms in West syndrome
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27
Q

what is a caution to note for Lennox-Gastaut syndrome?

A

phenobarbital & Vigabatrin = worsens atonic seizures

Dravet syndrome/Mycolonic epilepsy = diverse generalized & focal seizure types

28
Q

what is the clinical use of Clobazam?

A

Lennox-Gastaut syndrome

29
Q

What are AEs of Clobazam?

A
  • somnolence, dysarthria, drooling, behavioral changes
  • tolerance with chronic admin
  • withdrawal symptoms after abrupt discontinuation
30
Q

what is the MOA of Rufinamide?

A

blovks voltage-gated Na channels

31
Q

what is the clinical use of Rufinamide?

A

atonic seiures

32
Q

what are important D/I of Rufinamide?

A
  • Valproate = decrease clearance of Rufinamide
  • Concomitant use requires dec in valproate dose
33
Q

what are drugs effective for Dravet syndrome?

A

Stripentol
Fenfluramine
Cannabidiol

34
Q

what is the cause of Dravet syndrome?

A

mutations of SCN1A gene

35
Q

what are AEs of Stripentol?

A

sedation/drowsiness, slowing of mental function, ataxia, diplopia, nausea, DEC appetite, abdominal pain

36
Q

what are AEs of Cannabidiol?

A

somnolence
decreased appetite
diarrhea
fatigue
liver function abnormality

37
Q

what program restricts ppl form aquiring Fenfluramine?

A

Risk Evaluation and Mitigation Strategy program

38
Q

what is the main metabolite formed in Fenfluramine that causes BBW?

A

Norfenfluramine -> causes valvular <3 disease & pulmonary HTN

39
Q

what are drugs effective for infantile spasms in West syndrome?

A

Vigabatrin
Everolimus

40
Q

what are the goals of treatment in cessation of seizures in infantile spasms in west syndorme?

A
  1. ACTH IM injection
  2. oral corticosteroids (predinosine, hydrocortisone)
  3. Vigabatrin
41
Q

what is the MOA of Vigabatrin?

A

irreversible inhibits GABA transaminase -> sustained INC extracellular GABA in the brain

42
Q

What aer AEs of Vigabatrin?

A
  • most important: irreversible retinal dysfunction
  • less common: psychosis, agitation, confusion,

VIGabatrin = VIsion loss & weight GAin

43
Q

what drug for West syndrome treats focal seizures in Tuberous Sclerosis Complex?

A

Everolimus

44
Q

what are the most common AEs of Everolimus?

A

Stomatitis
Diarrhea
Pyrexia

45
Q

What are the specific drugs for seizure syndromes?

A
  • Valproate: Juvenile Myoclonic Epilepsy
  • Clobazam, Rufinamide: Lennox-Gastaut syndrome
  • Stiripentol, Cannabidiol, Fenfluramine: Dravet syndrome
  • Vigabatrin: Infantile spasms in west syndrome
  • Vigabatrin & Everolimus: Tuberous Sclerosis Complex
46
Q

What are other drugs that can be ued in managing seizures & epilepsy?

A

Carbonic anhyrdase inhibitors
Benzodiazepines

47
Q

what is the MOA of Carbonic anhydrase inhibitors?

A

inhibition of CA II & CA VII –> DEC intracellular HCO3 & DEC depolarizing action

48
Q

what are the 2 prototypes of Carbonic anhydrase inhibtors?

A
  • Sulthiamine = benign focal epilepsy w/ centrotemporal spikes
  • Acetazolamide = Intermittent tx of menstrual seizure exacerbations
49
Q

what are the different Benzodiazepines & their clinical indications?

A
  • Diazepam: first line for status epilepticus
  • Lorazepam: status epilepticus
  • Midazolam: out of hospital for status epilepticus
  • Clonazepam: PO: absence, atonic, myoclonic seizures, infantile spasms
  • Nitrazepam: PO: infantile spasms, myoclonic seizures
  • Clorazepate dipotassium: PO: focal seizures
  • Clobazam: PO: seizures assoc with LGS, focal seizures
50
Q

what condition is defined as abnormally prolonged or repetitive seizures?

A

Status epilepticus

forms: Convulsive SE, Non-convulsive SE, Focal SE

51
Q

what form of status epilepticus is a life-threatening emergency with repeated generalized tonic-clonic seizures with persistent postical depression of neuro function betw seizures?

A

Convulsive status epilepticus

52
Q

what is the treatment for convulsive status epilepticus?

A
  • begin when seizure duration reaches: 5 mins for gen tonic-clonic seizures, 10mins for focal seizures without impairment of cosnciousness
  • IV Lorazepam or Diazepam: first line
  • if it continues: IV Fosphenytoin or phenytoin, IV Valproate or Levetiracetam, IV Phenobarbital
53
Q

what form of status epilepticus occurs at least 30 mins after treatment with first and 2nd therapy agents?

A

refractory status epilepticus

54
Q

what is the tx for refractory status epilepticus?

A

anesthetic doses of Phenobarbital, Propofol, Midazolam or Thiopental, Ketamine

55
Q

What is known as status epilepticus that continues or recurs 24 hrs after anesthesia wears off

A

super refractory status epilepticus

56
Q

what form of status epilepticus has persistent change in behavior or mental processes with continuous eileptiform EEG w/o major motor signs?

A

Non-convulsive Status epilepticus

57
Q

what are the tx for Non-convulsive status epilepticus?

A

Benzodiazepine (1st)
IV Valproate/oral NGT Ethosuximide (2nd)

58
Q

what is the form of status epilepticus that has prolonged, generalized absence seizure that lasts hours/days?

A

Absence status epilepticus

59
Q

what type of status epilepticus has or does not have altered awareness?

A

focal status epilepticus

60
Q

what are group of seizures that occur more frequently that the px habitual freq?

A

acute reptitive seizures (seizure clusters)

complete recovery betw seizures

61
Q

what is the tx for acute repetitive seizures?

A

**IV Benzodiazepines **(emergency)
Rectal diazepam (out of hospital)
Alternatives:
* Buccal midazolam
* Intranasal modazolam, diazepam, lorazepam

62
Q

For how long should u** taper drug withdrawal**?

A

slowly over 1-3 months period or longer -> rebound status epilepticus if abrupt discontinuatoin

63
Q

what are risk factors for seizure recurrence?

A
  • abnormal neuro exam/EEG
    • neurologic deficits
  • longer duration of epilepsy
  • seizure control
  • certain epilepsy syndromes
  • abrup cessation of AEDs
64
Q

What anti-seizure drugs are C/I in prengnacy/teratogenic?

A
  • Phenobarbital: cardiac effects
  • Topiramate = oral cleft
  • Valproate = congenital malformations
65
Q

What anti-seizure drugs can penetrate through breastfeeding in relatively high conce?

A

Primidone
Levetiracetam
Gabapentin
Lamotrigine
Topiramate
Barbiturates & BZD = sedation of bby

66
Q

What anti-seizure drugs can penetrate through breastfeeding in relatively high conce?

A

Primidone
Levetiracetam
Gabapentin
Lamotrigine
Topiramate
Barbiturates & BZD = sedation of bby

Pharmacology (19 decks)

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