Seizures Flashcards
Lamotrigine [Lamictal®]
- 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
Keppra
Levetiracetam
- 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
Topiramate
(Topamax)
- 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
Valproate/Divalproex/ Valproic Acid Derivatives [Depakote, Depakote ER, Depakote Sprinkles, Depakene]
- 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
Zonisamide (Zonegran®)
- 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;
Carbamazepine [Tegretol®, Tegretol XR®, Carbatrol®, Epitol®]
- 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
Fosphenytoin [Cerebyx®]
-prodrug of phenytoin
- 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
Gabapentin [Neurontin®, Gralise®, Fanatrex®]
- Renal Adjustment
- 0 protein binding
- no significant DDI
- SE: weight gain
Lacosamide [Vimpat®]
- -more evidence for focal seizures
- Renal/heptatotoxic Adjustment
- <15% protein binding
- Focal Seizures( Narrow)
- No significant DDIs
- SE : ECG changes ( PR interval increase)
Oxcarbazepine (Trileptal®, Oxtellar XR®)
- 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
Eslicarbazepine Acetate [Aptiom®]
- -prodrug of oxcarbazepine
- Use not recommended for severe hepatic impairment
- Renal Adjustment
- < 40% PB
- Skin rash; Osteoporosis; Diplopia; Hyponatremia
Phenobarbital C-IV
- 50% PB
- Renal/ Hepato Adjustment
- Hepatotoxicity ;Blood Dyscrasias (anemia, leukopenia) ; Skin Rash ; Reduced Cognition ; Osteoporosis
- Teratogenic
Phenytoin and Phenytoin ER (Dilantin®, Phenytek®)
- 90% PB - significant
- Renal/ Hepatic Adjustment
- Inducer
- Similar SE as Fosphenytoin
- Hepatotoxicity
- Blood Dyscrasias (anemia, leukopenia)
- Skin Rash
- Reduced Cognition
- Osteoporosis
- Vision Changes
- Teratogenic
Pregabalin (Lyrica®) C-V
- 0% PB
- Renal Adjustment
- SE: Weight Changes; Blood Dyscrasias (anemia, leukopenia) ; Vision Changes ; ECG Changes (PR interval increase)
- No Significant DDI’s
Ethosuximide (Zarontin®)
- Absence Seizure;
- Avoid with severe impairment (renal/hepatic)
- 0% PB
- Inhibited by Valproate
- SE: weight loss; Blood Dyscrasias (anemia, leukopenia) ;Skin Rash
Tiagabine (Gabitril®)
- -more evidence for focal seizures
- 95% PB
- SE: vision changes (blurry);
Anticonvulsants WITHOUT significant drug interactions include
▪ Lacosamide
▪ Levetiracetam
▪ Gabapentin
▪ Pregabalin
▪ Vigabatrin
Do not require renal adjustments
- VPA
- Carbamazepine
- Clobazam (onfi)
- Clonazepam ( klonopin)
- Tiagabine
- Rufinamide
- Brivaracetam
Do not require Hepatic Adjustment
- Keppra
- Topamax
- Gabapentin
- Lyrica
- Tiagabine
- Vigabatrin
When to check levels:
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
Phenytoin Toxicity – Signs/Symptoms
- 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
Impending GCSE (0-30 minutes) – use ONE of the following:
- Lorazepam (longest duration of action)
- Diazepam
- Midazolam (extremely short duration of action – maintenance infusion doses may be required)
Established GCSE (30- 60 minutes) – use first line first unless contraindicated/allergic:
- First Line:
- Phenytoin 10-15 mg/kg IV
- Fosphenytoin 15-20 mg PE/kg IV
- Second Line:
- Phenobarbital
- Valproic Acid
- Third Line:
- Lacosamide
- Levetiracetam
Refractory GCSE (> 120 minutes):
Medications:
Midazolam (benzodiazepine) infusion
Pentobarbital infusion
Propofol infusion
Super-refractory GCSE (>24 hours):
Medications/Interventions:
Ketamine
Hypothermia
Lidocaine
Topiramate
Inhaled Anesthetics
Immunomodulating Therapies
Ketogenic Diet
Vagus Nerve Stimulator
Polyethylene glycol
- 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.
OC and Lamotrigine
OC reduces Lamotrigine serum concentration
LAMOTRIGINE DOSING SCHEDULE
- 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.
underlying general pathophysiologic process at the heart of all epilepsies is _____
neuronal hyperexcitability and hypersynchronization.
epilepsy etiologies that could be generally classified into six categories reviewed here
(1) genetic
(2) structural
(3) infectious
(4) metabolic
(5) immune
6) unknown.
six types of generalized onset seizures
- (1) absence seizures,
- (2) myoclonic seizures,
- (3) tonic-clonic seizures,
- (4) clonic seizures,
- (5) tonic seizures,
- (6) atonic seizures.
a person is considered to have epilepsy if they meet any of the following conditions:
(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.
GCSE treatment steps
- benzo
- Phenytoin/ Fosphenytoin
- Phenobarbital or VPA
- Lacosamine or Keppra
Midazolam
- Vital Signs (BP/HR)
- Resp. depression
Fosphenytoin
- Vital Signs
- ECG
- Purple Gloves Syndrome
