Seizures Flashcards

1
Q

Lamotrigine [Lamictal®]

A
  • 25 mg daily (slow titration to 375 mg/day); differs in presence of CYP enzyme inhibitors/inducers – PO only
  • Consider for severe impairment (renal)
  • Broad-Spectrum
  • 40-50% Protein binding
  • Focal Seizure; tonic-clonic; absence, atonic
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2
Q

Keppra

Levetiracetam

A
  • Renal Adjustment
  • Broad-Spectrum
  • < 10 %
  • No significant DDI’s
  • Focal, Tonic-Clonic, Myoclonic
  • SE : psychosis (elderly population)
  • Use cautiously in pt’s with pre-existing psychosis
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3
Q

Topiramate

(Topamax)

A
  • Renal Adjustment
  • Broad Spectrum / Myoclonic Seizures
  • 15% protein binding
  • 3A4 inducer at doses ≥ 200 mg/day)
  • SE: weight loss ; Reduced Cognition; acute angle glaucoma; oligohydrosis; Nephrolithiasis
  • Teratogenic - cleft lip and/or palate
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4
Q

Valproate/Divalproex/ Valproic Acid Derivatives [Depakote, Depakote ER, Depakote Sprinkles, Depakene]

A
  • Broad Spectrum- Focal, Tonic-Clonic, Absence, Myoclonic, Atonic
  • Hepatic Adjustment
  • 90-95% protein binding **significant**
  • 10-15 mg/kg/day (max 60 mg/kg/day) – PO and IV
  • ER formulation – increase dose by 10-20%
  • the extended release formulation has a lower bioavailability compared to the IR, IV, and DR formulations, meaning that if the same dose of valproic acid is ingested, only 80-90% of the ER formulation is absorbed and reaches the systemic circulation to have an effect in the body.
  • DDI’s with Capapennems (inducers)
  • Inhibits Lamotrigine Metabolism

SE: Hepatotoxicity (Monitor LFTs at baseline and periodically (q 6 months), Weiht Gain; Blood Dyscrasias (anemia, leukopenia) ; Osteoporosis

  • ​​o Fatal pancreatitis
  • o Hyperammonemia (treat with levocarnitine or lactulose in symptomatic patients)
  • o Polycystic ovary-like syndrome (increased incidence in females <20 years or overweight)
  • o Menstrual cycle irregularities, hirsutism, alopecia, acne
  • Tertogenic - Reduced IQ and neural tube defects
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5
Q

Zonisamide (Zonegran®)

A
  • Consider slower titration/ frequent monitoring for renally and hepatic adjustment
  • 40-60% protein binding
  • SE : Weight Loss; Skin rash ( with sulfa drugs); Reduced Cognition; Oligohydrosis, Nephrolithiasis;
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6
Q

Carbamazepine [Tegretol®, Tegretol XR®, Carbatrol®, Epitol®]

A
  • Narrow-Spectrum; Focal; Tonic-Clonic
  • Hepatically adjustment
  • 40-90% (could be significnt) protein binding
  • Auto-inducer
  • SE: Skin Rash (consider testing for HLA-A* 3101 in for carbamazepine) ; Osteoporosis ; Diplopia ; Hyponatremia
  • Teratogenic
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7
Q

Fosphenytoin [Cerebyx®]

-prodrug of phenytoin

A
  • Consider adjustments for severe impairment (hepa, renal)
  • 95-99%
  • -only used short-term when oral phenytoin is not possible
  • Inducers
  • SE: Hepatotoxicity; Blood Dyscrasias (anemia, leukopenia) ;Skin rash (**Test for HLA-B* 1502 gene in Asian patients ); Reduced Cognition; Blurry Vision;

o Cerebellar syndrome (occurs with high serum levels; monitor for gait and muscle coordination changes)

o Connective tissue changes

o Skin thickening (more common in children), gingival hyperplasia

o Folate deficiency

o Hirsutism, acne, coarsening of facial features

  • ​Teratogenic
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8
Q

Gabapentin [Neurontin®, Gralise®, Fanatrex®]

A
  • Renal Adjustment
  • 0 protein binding
  • no significant DDI
  • SE: weight gain
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9
Q

Lacosamide [Vimpat®]

A
  • -more evidence for focal seizures
  • Renal/heptatotoxic Adjustment
  • <15% protein binding
  • Focal Seizures( Narrow)
  • No significant DDIs
  • SE : ECG changes ( PR interval increase)
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10
Q

Oxcarbazepine (Trileptal®, Oxtellar XR®)

A
  • prodrug of carbamazepine
  • Focal; Tonic- Clonic (Narrow)
  • Do not use ER with severe hepatic impairment
  • Renal Adjustment
  • 40% PB
  • SE: Skin Rash (**Test for HLA-B* 1502 gene in Asian patients ); Osteoporosis ; Diplopia ;Hyponatremia
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11
Q

Eslicarbazepine Acetate [Aptiom®]

A
  • -prodrug of oxcarbazepine
  • Use not recommended for severe hepatic impairment
  • Renal Adjustment
  • < 40% PB
  • Skin rash; Osteoporosis; Diplopia; Hyponatremia
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12
Q

Phenobarbital C-IV

A
  • 50% PB
  • Renal/ Hepato Adjustment
  • Hepatotoxicity ;Blood Dyscrasias (anemia, leukopenia) ; Skin Rash ; Reduced Cognition ; Osteoporosis
  • Teratogenic
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13
Q

Phenytoin and Phenytoin ER (Dilantin®, Phenytek®)

A
  • 90% PB - significant
  • Renal/ Hepatic Adjustment
  • Inducer
  • Similar SE as Fosphenytoin
    • Hepatotoxicity
    • Blood Dyscrasias (anemia, leukopenia)
    • Skin Rash
    • Reduced Cognition
    • Osteoporosis
    • Vision Changes
    • Teratogenic
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14
Q

Pregabalin (Lyrica®) C-V

A
  • 0% PB
  • Renal Adjustment
  • SE: Weight Changes; Blood Dyscrasias (anemia, leukopenia) ; Vision Changes ; ECG Changes (PR interval increase)
  • No Significant DDI’s
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15
Q

Ethosuximide (Zarontin®)

A
  • Absence Seizure;
  • Avoid with severe impairment (renal/hepatic)
  • 0% PB
  • Inhibited by Valproate
  • SE: weight loss; Blood Dyscrasias (anemia, leukopenia) ;Skin Rash
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16
Q

Tiagabine (Gabitril®)

A
  • -more evidence for focal seizures
  • 95% PB
  • SE: vision changes (blurry);
17
Q

Anticonvulsants WITHOUT significant drug interactions include

A

▪ Lacosamide

▪ Levetiracetam

▪ Gabapentin

▪ Pregabalin

▪ Vigabatrin

18
Q

Do not require renal adjustments

A
  • VPA
  • Carbamazepine
  • Clobazam (onfi)
  • Clonazepam ( klonopin)
  • Tiagabine
  • Rufinamide
  • Brivaracetam
19
Q

Do not require Hepatic Adjustment

A
  • Keppra
  • Topamax
  • Gabapentin
  • Lyrica
  • Tiagabine
  • Vigabatrin
20
Q

When to check levels:

A

 New phenytoin start

o Obtain blood draw one hour after IV loading dose OR 24 hours after oral loading dose

o 3-4 days after maintenance dose – level must be drawn (blood must be collected) at least 8 hours after the last dose

 After dose adjustment (6-7 days after a dose adjustment) – level must be drawn (blood must be collected) at least 8 hours after the last dose

 Concern for non-adherence - can draw levels at any point in time

 Concern for toxicity - can draw levels at any point in time

21
Q

Phenytoin Toxicity – Signs/Symptoms

A
  • Central nervous system effects: lethargy/fatigue, dizziness, confusion, nystagmus, ataxia
  •  Gastrointestinal side effects: nausea, vomiting, anorexia
  •  Toxicity Levels:
    •  > 20 mcg/mL: nystagmus
    •  > 30 mcg/mL: 45° ataxia, slurred speech, N/V, dizziness
    •  > 40 mcg/mL: decreased mentation (confusion), lethargy/fatigue
    •  > 50 mcg/mL: coma, seizures
    •  > 100 mcg/mL: death
22
Q

Impending GCSE (0-30 minutes) – use ONE of the following:

A
  •  Lorazepam (longest duration of action)
  •  Diazepam
  •  Midazolam (extremely short duration of action – maintenance infusion doses may be required)
23
Q

Established GCSE (30- 60 minutes) – use first line first unless contraindicated/allergic:

A
  • First Line:
  •  Phenytoin 10-15 mg/kg IV
  •  Fosphenytoin 15-20 mg PE/kg IV
  • Second Line:
    •  Phenobarbital
    •  Valproic Acid
  • Third Line:
    •  Lacosamide
    •  Levetiracetam
24
Q

Refractory GCSE (> 120 minutes):

A

Medications:

 Midazolam (benzodiazepine) infusion

 Pentobarbital infusion

 Propofol infusion

25
Q

Super-refractory GCSE (>24 hours):

A

Medications/Interventions:

 Ketamine

 Hypothermia

 Lidocaine

 Topiramate

 Inhaled Anesthetics

 Immunomodulating Therapies

 Ketogenic Diet

 Vagus Nerve Stimulator

26
Q

Polyethylene glycol

A
  • diluent found in parenteral medications commonly used in clinical practice
  • adverse effects including hypotension, bradyarrhythmias, vein irritation, and metabolic acidosis
  • The presence of polyethylene glycol requires a slower titration to prevent polyethylene glycol related adverse effects, and this is why the maximum infusion rate for phenytoin is only 50 mg/min while for fosphenytoin is 150 mg PE/min.
27
Q

OC and Lamotrigine

A

OC reduces Lamotrigine serum concentration

28
Q

LAMOTRIGINE DOSING SCHEDULE

A
  • Inducers : (carbamazepine, oxcarbazepine, phenobarbital/primidone, phenytoin/fosphenytoin):
    • Weeks 1-2: 50mg once daily
    • Weeks 3-4: 50mg BID
    • Week 5 and onward: ↑100mg every 1-2 weeks
    • Target Max: 300 – 500mg daily (in divided doses)
  • Normal Dosing
    • Weeks 1-2: 25mg once daily
    • Weeks 3-4: 50mg once daily
    • Week 5 and onward: ↑ 50mg every 1-2 weeks
    • Target Max: 225 – 375mg daily (in divided doses)
  • Inhibitor ( valproate)
    • Weeks 1-2: 25mg every other day
    • Weeks 3-4: 25mg once daily
    • Week 5 and onward: ↑25-50mg every 1-2 weeks
    • Target Max with only VPA: 100 – 200mg daily (in divided doses)
    • Target Max with VPA + Lamotrigine Inducer: 100 – 400mg daily (in divided doses)
  • Clinical cases point to the idea that the risk of SJS/TEN may be increased by
    • (1) coadministration of lamotrigine with valproate,
    • (2) exceeding the recommended initial dose of lamotrigine,
    • 3) exceeding the recommended dose escalation for lamotrigine.
29
Q

underlying general pathophysiologic process at the heart of all epilepsies is _____

A

neuronal hyperexcitability and hypersynchronization.

30
Q

epilepsy etiologies that could be generally classified into six categories reviewed here

A

(1) genetic
(2) structural
(3) infectious
(4) metabolic
(5) immune
6) unknown.

31
Q

six types of generalized onset seizures

A
  • (1) absence seizures,
  • (2) myoclonic seizures,
  • (3) tonic-clonic seizures,
  • (4) clonic seizures,
  • (5) tonic seizures,
  • (6) atonic seizures.
32
Q

a person is considered to have epilepsy if they meet any of the following conditions:

A

(1) At least two unprovoked (or reflex) seizures occurring greater than 24 hours apart
(2) One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years
(3) Diagnosis of an epilepsy syndrome.

33
Q

GCSE treatment steps

A
  1. benzo
  2. Phenytoin/ Fosphenytoin
  3. Phenobarbital or VPA
  4. Lacosamine or Keppra
34
Q

Midazolam

A
  • Vital Signs (BP/HR)
  • Resp. depression
35
Q

Fosphenytoin

A
  • Vital Signs
  • ECG
  • Purple Gloves Syndrome