Updated: 1/3/2019

Epileptic Drugs

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  • A 17-year-old man presents with myoclonic seizures followed by generalized a tonic-clonic seizure after awakening. He denies any recent head trauma or substance abuse. He reports to being sleep deprived for the past week due to final examinations. Routine EEG testing is significant for 5-Hz bilateral polyspike and slow wave discharges. Valproic acid is prescribed. (Juvenile myoclonic epilepsy)
Introduction
  • Antiepileptic drugs (AED) can be separated by mechanism of action (MOA) affecting the following
    • voltage-gated Na+ channels
    • Ca2+ channels
    • GABA activity
  • Choice of AED is dependent on seizure type, patient, cost, and side-effect profile
Affecting Voltage-Gated Na+ Channels
  • Phenytoin
    • uses
      • parital (simple and complex)
      • generalized (tonic-clonic)
      • prophylaxis for status epilepticus
    • mechanism
      • blocks voltage-gated Na+ channels
        • stops seizure propogation
    • kinetics
      • induction of P450
      • zero-order kinetics with saturation of degradative liver enzymes
    • toxicity
      • nystagmus/ataxia/diplopia
      • sedation/CNS depression
      • SLE-like syndrome
      • gingival hyperplasia  
      • peripheral neuropathy
      • osteopenia
      • megaloblastic anemia (↓ folate absorption)
      • tetratogenic
        • fetal hydantoin syndrome
          • cleft lip and palate
    • notes
      • fosphenytoin for parenteral use
  • Carbamazepine
    • uses
      • partial (simple and complex)
      • generalized (tonic-clonic)
    • mechanism
      • ↑ refractory period of voltage-gated Na+ channels
        • likely binds to the inactivated state, inhibiting action potential generation
    • kinetics
      • induction of P450
        • reduces its own levels
    • toxicity
      • diplopia/ataxia
      • agranulocytosis
      • aplastic anemia
      • hepatotoxicity
      • SIADH
      • Stevens-Johnson syndrome
      • teratogenic
        • cleft lip and palate
        • spina bifida
    • notes
      • first-line for trigeminal neuralgia
      • also used for bipolar disorders
  • Lamotrigine
    • uses
      • partial (simple and complex)
      • generalized (tonic-clonic)
      • absence
    • mechanism
      • blocks voltage-gated Na+ channels and glutamate receptors
    • toxicity
      • Stevens-Johnson syndrome
Affecting Calcium Channels
  • Ethosuximide 
    • uses
      • absence seizures
    • mechanism
      • blocks thalamic T-type Ca2+ channels 
    • toxicity
      • GI distress
      • fatigue
      • headache
      • Stevens-Johnson syndrome
Affecting GABA Activity
  • Phenobarbital
    • uses
      • partial (simple and complex) in pregnant women and children
      • generalized (tonic-clonic) in pregnant women and children
    • mechanism
      • ↑ GABAA action
    • kinetics
      • induction of P450
      • tolerance/dependence
    • toxicity
      • sedation
  • Benzodiazepines
    • uses
      • acute treatment for status epilepticus
      • alcohol withdrawal syndrome
    • mechanism ↑ GABAA action
    • notes
      • also used for seizures of eclampsia
        • 1st-line is MgSO4
  • Tiagabine
    • uses
      • partial (simple and complex)
    • mechanism
      • inhibition of GABA reuptake
  • Vigabatrin
    • uses
      • partial (simple and complex)
    • mechanism
      • irreversible inhibition of GABA transaminase
Multiple Mechanisms of Action
  • Valproic acid
    • uses
      • partial (simple and complex)
      • generalized (tonic-clonic and absence)
    • mechanism
      • ↑ refractory period of voltage-gated Na+ channels
      • ↑ GABA concentration via inhibition of GABA transaminase
      • inhibition of thalamic T-type Ca2+ channels
    • toxicity
      • pancreatitis
      • hepatoxicity
        • accumulation of toxic metabolite
      • tetratogenic
        • neural tube defects
      • tremor
      • hyperammonemia
      • thrombocytopenia
      • anemia
      • myelodysplasia
    • notes
      • first-line for myoclonic seizures
      • can be used as prophylactic treatment for migraines
  • Topiramate
    • uses
      • partial (simple and complex)
      • generalized (tonic-clonic)
      • migraine prophylaxis
    • mechanism
      • blocks voltage-gated Na+ channels
      • ↑ GABA action
    • toxicity
      • sedation/mental dulling
      • renal stones
      • weight loss
Other
  • Levetiracetam
    • uses
      • partial (simple and complex)
      • complex (tonic-clonic)
    • mechanism
      • unknown
  • Gabepentin
    • uses
      • partial (simple and complex)
    • mechanims
      • inhibit voltage-gated Ca2+ channel via α2δ subunit
      • structurally similar to GABA
    • toxicity
      • sedation
      • ataxia
    • notes
      • also used for peripheral neuropathy/neuropathic pain
 

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Questions (7)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.NE.4671) A 16-year-old boy with history of seizure disorder is rushed to the Emergency Department with multiple generalized tonic-clonic seizures that have spanned more than 30 minutes in duration. He has not regained consciousness between these episodes. In addition to taking measures to ensure that he maintains adequate respiration, which of the following is appropriate for initial pharmacological therapy? Review Topic

QID: 107138
1

Phenytoin

25%

(21/84)

2

Carbamazepine

10%

(8/84)

3

Gabapentin

2%

(2/84)

4

Valproic acid

13%

(11/84)

5

Lorazepam

46%

(39/84)

M1

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PREFERRED RESPONSE 5
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(M1.NE.37) An 8-year-old boy is being seen in your neurology clinic for seizures of the type observed in video V. While speaking with the child, you notice that he frequently asks you to repeat yourself, and looks at you occasionally with a blank stare. Which of the following medications would be most appropriate for this patient? Review Topic

QID: 101701
FIGURES:
1

Gabapentin

1%

(1/106)

2

Valproic acid

42%

(44/106)

3

Phenytoin

12%

(13/106)

4

Ethosuximide

37%

(39/106)

5

Lorazepam

7%

(7/106)

M1

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PREFERRED RESPONSE 2
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