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Anti-Seizure Drugs Flashcards

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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
what is drug for generalized onset seizures that is not used anymore?
Trimethadione --> AE: **Hemeralopia (day blindness)**
26
what are the drugs effective for seizures assoc with **Lennox-Gastaut syndrome**?
* **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
27
what is a **caution** to note for **Lennox-Gastaut syndrome**?
**phenobarbital & Vigabatrin** = worsens atonic seizures **Dravet syndrome/Mycolonic epilepsy** = diverse generalized & focal seizure types
28
what is the **clinical use of** **Clobazam**?
Lennox-Gastaut syndrome
29
What are **AEs of Clobazam**?
* somnolence, dysarthria, drooling, behavioral changes * tolerance with chronic admin * withdrawal symptoms after abrupt discontinuation
30
what is the **MOA of Rufinamide**?
blovks voltage-gated Na channels
31
what is the **clinical use of Rufinamide**?
atonic seiures
32
what are important **D/I of Rufinamide**?
* Valproate = decrease clearance of Rufinamide * Concomitant use requires **dec in valproate dose**
33
what are drugs effective for **Dravet syndrome**?
Stripentol Fenfluramine Cannabidiol
34
what is the **cause of Dravet syndrome**?
mutations of **SCN1A gene**
35
what are **AEs of Stripentol**?
sedation/drowsiness, slowing of mental function, ataxia, diplopia, nausea, DEC appetite, abdominal pain
36
what are **AEs of Cannabidiol**?
somnolence decreased appetite diarrhea fatigue liver function abnormality
37
what **program restricts** ppl form aquiring **Fenfluramine**?
Risk Evaluation and Mitigation Strategy program
38
what is the **main metabolite formed in Fenfluramine** that causes **BBW**?
Norfenfluramine -> causes valvular <3 disease & pulmonary HTN
39
what are drugs effective for **infantile spasms in West syndrome**?
Vigabatrin Everolimus
40
what are the **goals of treatment in cessation of seizures in infantile spasms in west syndorme**?
1. ACTH IM injection 2. oral corticosteroids (predinosine, hydrocortisone) 3. Vigabatrin
41
what is the **MOA of Vigabatrin**?
irreversible inhibits GABA transaminase -> sustained INC extracellular GABA in the brain
42
What aer **AEs of Vigabatrin**?
* most important: **irreversible retinal dysfunction** * less common: psychosis, agitation, confusion, | **VIG**abatrin = **VI**sion loss & weight **GA**in
43
what drug for **West syndrome** treats **focal seizures in Tuberous Sclerosis Complex**?
Everolimus
44
what are the most common **AEs of Everolimus**?
Stomatitis Diarrhea Pyrexia
45
What are the specific drugs for seizure syndromes?
* **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
What are other drugs that can be ued in managing **seizures & epilepsy**?
Carbonic anhyrdase inhibitors Benzodiazepines
47
what is the **MOA of Carbonic anhydrase inhibitors**?
inhibition of CA II & CA VII --> DEC intracellular HCO3 & DEC depolarizing action
48
what are the 2 prototypes of Carbonic anhydrase inhibtors?
* **Sulthiamine** = benign focal epilepsy w/ centrotemporal spikes * **Acetazolamide** = Intermittent tx of menstrual seizure exacerbations
49
what are the different **Benzodiazepines & their clinical indications**?
* **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
what condition is defined as **abnormally prolonged or repetitive seizures**?
Status epilepticus forms: **Convulsive SE, Non-convulsive SE, Focal SE**
51
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**?
Convulsive status epilepticus
52
what is the treatment for convulsive status epilepticus?
* 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
what form of status epilepticus occurs at least 30 mins after treatment with first and 2nd therapy agents?
refractory status epilepticus
54
what is the tx for refractory status epilepticus?
anesthetic doses of **Phenobarbital, Propofol, Midazolam or Thiopental, Ketamine**
55
What is known as status epilepticus that continues or recurs 24 hrs after anesthesia wears off
super refractory status epilepticus
56
what form of status epilepticus **has persistent change in behavior or mental processes with continuous eileptiform EEG w/o major motor signs**?
Non-convulsive Status epilepticus
57
what are the tx for **Non-convulsive status epilepticus**?
Benzodiazepine (1st) IV Valproate/oral NGT Ethosuximide (2nd)
58
what is the form of status epilepticus that has prolonged, generalized absence seizure that lasts hours/days?
Absence status epilepticus
59
what type of status epilepticus **has or does not have altered awareness**?
focal status epilepticus
60
what are group of seizures **that occur more frequently that the px habitual freq**?
acute reptitive seizures (seizure clusters) | complete recovery betw seizures
61
what is the tx for **acute repetitive seizures**?
**IV Benzodiazepines **(emergency) **Rectal diazepam** (out of hospital) Alternatives: * Buccal midazolam * Intranasal modazolam, diazepam, lorazepam
62
For how long should u** taper drug withdrawal**?
slowly over 1-3 months period or longer -> rebound status epilepticus if abrupt discontinuatoin
63
what are risk factors for seizure recurrence?
* abnormal neuro exam/EEG * + neurologic deficits * longer duration of epilepsy * seizure control * certain epilepsy syndromes * abrup cessation of AEDs
64
What anti-seizure drugs are C/I in prengnacy/teratogenic?
* Phenobarbital: cardiac effects * Topiramate = oral cleft * Valproate = congenital malformations
65
What anti-seizure drugs can penetrate through breastfeeding in relatively high conce?
Primidone Levetiracetam Gabapentin Lamotrigine Topiramate Barbiturates & BZD = sedation of bby
66
What anti-seizure drugs can penetrate through breastfeeding in relatively high conce?
Primidone Levetiracetam Gabapentin Lamotrigine Topiramate Barbiturates & BZD = sedation of bby

Pharmacology (19 decks)

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