UWORLD Chapter 70: Seizures/Epilepsy

What is epilepsy and what is it characterized by?

chronic seizure disorder

vary from uncontrolled jerking movements (tonic/clonic seizures) to subtle momentary loss of awareness (absence seizures)

What is used to diagnose a seizure?

EEG

What drugs can cause seizures?

Anti-infectives: quinolones, carbapenems, cephalosporins, penicillins, mefloquine

antidepressants: buproprion

antipsychotics (clozapine)

Lithium

synthetic opioids (tramadol and meperidine)

Where do focal seizures originate?

Within 1 hemisphere in brain

Where do generalized seizures occur?

both sides of the brain

What is a focal aware seizure?

focal seizure with no loss of consciousness

What is a focal seizure with impaired awareness?

A focal seizure that results in loss of consciousness.

What are characteristics of tonic seizures?

rigid, violent muscle contractions with LOC

What are absence seizures?

generalized seizures with non-motor symptoms. present as staring spells

What is status epilepticus?

Seizures that last longer than 5 minutes or 2 or more seizures between which the patient does not regain consciousness, which is a medical emergency.

What are the preferred agents during the initial treatment phase (5-20 minutes) of status epilepticus?

BZD injections

- IV lorazepam, IM midazolam, IV diazepam

Alternatives are rectal diazepam gel, intranasal or buccal midazolam

What does each package of diazepam rectal gel contain?

two rectal syringes prefilled with diazepam rectal gel

What must a pharmacist do before dispensing rectal diazepam gel?

dial and lock the correct prescribed dose

What is a key counseling point for all antiseizure medications?

should not be stopped abruptly as this can lead to increased seizures

What type of cannabis is FDA approved to treat rare forms of epilepsy?

Epidiolex (cannabidiol)

What type of diet can help with refractory seizures? Describe the details of this diet.

Ketogenic diet

4:1 ratio of fats combined protein and carbohydrates

ketosis can lead to a reduction in seizure frequency

What are the names of the broad spectrum ASMs and what types of seizures do they treat?

- lamotrigine, levetiracetam, topiramate, valproic acid

- focal and generalized seizures

What ASMs are used for absence seizures?

ethosuximide

What are side effects/warnings with all ASMs?

CNS depression (confusion, sedation, cognitive impairment, falls)

suicide risk (monitor for changes in mood)

increased fracture risk (supplement with calcium and vitamin D)

What can many ASMs cause?

SJS, TEN, DRESS

What ASMs enhance GABA effects?

BZDs and phenobarbital

What ASMs block sodium channels and increase GABA?

Valproate

What ASM inhibits vesicle fusion by binding SV2A proteins?

Levetiracetam

What ASMs solely block sodium channels to decrease seizures?

Carbamazepine, phenytoin/fosphenytoin, Topiramate

What ASM blocks sodium channels and decreases glutamate to decrease seizures?

Lamotrigine

What ASM blocks T-type Ca channels to decrease seizures?

Ethosuximide

What are the brand names of lamotrigine?

Lamictal (XR, ODT, CD), Lamictal starter kit

What is the initial standard dosing of lamotrigine for weeks 1-2?

25 mg daily (can vary based on drug interactions)

What is lamotrigine used for besides seizures?

bipolar disorder

What are the boxed warnings for lamotrigine?

SJS, TEN, DRESS

What is the main tolerability side effect of lamotrigine and how is it prevented?

alopecia

supplement with biotin, selenium, and zinc

What should be done if a patient discontinues current dose of lamotrigine for 5 or more half lives (> 6 days)?

restart initial dosing titration

What does valproic acid do to lamotrigine concentrations?

increase lamotrigine concentrations more than 2 fold, use lower dose starter kit

What is the interaction between hormonal contraceptives and lamotrigine?

hormonal contraceptives can decrease lamotrigine levels

How do drugs like carbamazepine, phenytoin, phenobarbital, etc. affect lamotrigine levels?

decrease lamotrigine levels by 40%, use higher dose starter kit

What is the blue lamotrigine starter kit and when is it used?

lower starter dose, used if taking valproic acid

What is the orange lamotrigine starter kit and when is it used?

standard starting dose, used if no interacting medications

What is the green lamotrigine starter kit and when is it used?

higher starting dose, used if taking an enzyme inducer and not valproic acid

What is the brand name of levetiracetam?

Keppra, Keppra XR

What is the IV:PO ratio of Keppra?

1:1

What is a safety warning of Keppra?

Psychiatric reactions, including psychotic symptoms, somnolence, fatigue, and aggression

What is a benefit of giving keppra in a patient with many comorbid conditions?

no significant drug interactions

What is the brand names of topiramate?

Topamax

What condition is topiramate used for besides seizures?

migraine prophylaxis

What are safety warnings for topiramate?

metabolic acidosis, oligohydrosis (reduced perspiration), nephrolithiasis (kidney stones), angle-closure glaucoma, hyperammonemia, visual problems, fetal harm

What are tolerability side effects of topiramate?

somnolence, difficulty with memory/concentration/attention, weight loss, anorexia

What are pertinent monitoring parameters of topiramate?

bicarbonate and IOP

What is the interactions between topiramate and hormonal contraceptives?

topiramate can decrease effectiveness of oral contraceptives, non-hormonal contraception is recommended

What is the therapeutic range for valproic acid?

50-100 mcg/mL

What are the brand names of divalproex?

Depakote, Depakote ER, Depakote Sprinkle

What are the uses for valproic acid and depakote besides seizures?

bipolar disorder and migraine prophylaxis

What are the boxed warnings for valproic acid?

Fetal harm, hepatic failure, pancreatitis

What are safety warnings for valproate?

hyperammonemia (treat with carnitine if symptomatic)

thrombocytopenia

What are tolerability side effects of topiramate?

alopecia (supplement with biotin, selenium, and zinc)

nausea, vomiting

weight gain

somnolence, tremors

What should be monitored while taking valproate?

LFTs (baseline and frequently in the first 6 months)

platelets

What drugs can valproate increase concentrations for?

lamotrigine (serious rash can occur), phenobarbital, phenytoin, warfarin, and zidovudine

What is the brand name of lacosamide?

Vimpat

What is the IV:PO conversion of lacosamide?

1:1

What are safety warnings for lacosamide?

Prolongs PR interval and increases risk of arrhythmias, multiorgan hypersensitivity reactions (DRESS(

What control class is lacosamide?

C-V

What is the brand name of carbamazepine?

Tegretol, Tegretol XR

What is the therapeutic range of carbamazepine?

4-12 mcg/mL

What are the boxed warnings of carbamazepine?

serious skin reactions: HLA-B 1502 allele testing

aplastic anemia and agranulocytosis

What are contraindications to carbamazepine?

myelosuppression

What are safety warnings of carbamazepine?

hyponatremia, SIADH, hypothyroidism, fetal harm

What is an important note of the metabolism of carbamazepine?

inducer and auto inducer (decreases the levels of other drugs and itself)

What CYP enzymes is carbamazepine an inducer of and therefore decreases which drugs?

CYP3A4 and PGP, decreases warfarin, levothyroxine, and hormonal contraceptives

What is the brand name of oxcarbazepine?

Trileptal

What are safety warnings for oxcarbazepine?

SJS/TEN, test for HLA-B 1502 gene, Hyponatremia

What are the drug interactions for oxcarbazepine?

decrease hormonal contraceptive effectiveness, not an auto inducer

What are the brand names of phenytoin?

Dilantin, Infatabs

What are the therapeutic total and free ranges of phenytoin?

- Total: 10-20 mcg/mL

- Free: 1-2 mcg/mL

What is the IV:PO conversion of phenytoin?

1:1

What is the boxed warning of phenytoin and fosphenytoin?

Phenytoin IV administration rate should not exceed 50 mg/min and fosphenytoin IV should not exceed 150 mg PE/minute. If given faster, hypotension and cardiac arrhythmias can occur

What are safety warnings for phenytoin and fosphenytoin?

Extravasation leading to purple glove syndrome

Avoid phenytoin with positive HLA-B 1502 test

Fetal harm

What are dose related side effects of phenytoin/fosphenytoin?

Nystagmus, ataxia, diplopia/blurred vision

What are chronic side effects of phenytoin/fosphenytoin?

gingival hyperplasia, hair growth, hepatotoxicity

What is the brand name of fosphenytoin?

Cerebyx

What is the prodrug of phenytoin?

fosphenytoin

What should be monitored with phenytoin/fosphenytoin?

Serum phenytoin concentration, LFTs

IV: continuous cardiac and respiratory function

What are pertinent interaction facts for phenytoin?

strong inducer of CYP2C19, 2C8, 2C9, 3A4

Use nonhormonal contraceptives

High protein binding

What is the phenytoin correction formula?

total phenytoin measured / (0.2 x albumin) + 0.1

What can happen when metabolism of phenytoin is saturated?

small increase in dose can lead to large increases in drug concentration

What are safety warnings of phenobarbital?

potential for drug dependency, fetal harm, respiratory depression

What are side effects of phenobarbital?

physiological dependence, tolerance, hangover effect (residual sedation)

What is the prodrug of phenobarbital?

primidone

What are drug interactions with phenobarbital?

strong inducers of CYP3A4 and Pgp

Use non-hormonal contraceptives

What do carbamazepine, oxcarbazepine, and eslicarbazepine cause?

hyponatremia, rash, enzyme induction

What side effects do gabapentin and pregabalin cause?

weight gain, peripheral edema, and mild euphoria

Used primarily in neuropathic pain

What side effects do phenobarbital and primidone cause?

sedation, dependence/tolerance, enzyme induction

What side effects do topiramate and zonisamide cause?

weight loss, metabolic acidosis, and nephrolithiasis

oligohydrosis and hyperthermia in children

What is the boxed warning of BZDs?

use with opioids can result in profound sedation, respiratory depression, and death

What BZD drugs can't stop an active seizure?

Clobazam

What control status are all BZDs?

C-IV

What is the brand name of cannabidiol?

Epidiolex

What drug is the active metabolite of oxcarbazepine?

eslicarbazepine

What is the brand name of ethosuximide?

Zarontin

What is ethosuximide used for?

absence seizures

What are safety warnings for ethosuximide?

SJS/TEN, blood dyscrasias

What are the boxed warnings of felbamate?

hepatic failure and aplastic anemia