Ch. 71 Seizures/Epilepsy

Stabinsky

background

some drugs can lower the seizure threshold and should be avoided in someone with a seizure history

epilepsy is a chronic seizure disorder

seizure symptoms vary from uncontrolled jerking movements (tonic-clonic seizure) to a subtle momentary loss of awareness (absence seizures)

an ECG is the most common test used to diagnose epilepsy

key drugs that can cause seizures

analgesics --> opioids (especially tramadol, meperidine)

anti-infectives --> quinolones, carbapenems, cephalosporins, penicillins, mefloquine

psych meds --> bupropion, antipsychotics (esp. clozapine), lithium, TCAs

classification of seizure types

focal seizures start on one side of the brain but can spread to the other side

generalized seizures start on both sides

focal aware seizure --> no loss of consciousness

focal seizure with impaired awareness --> loss of consciousness

rigid and tense muscles --> tonic

generalized seizures with non-motor symptoms are called absence seizures

acute seizure managements

status epilepticus is a seizure that lasts 5 minutes or more --> medical emergency

initial treatment is a benzo injection

if not able to get IV access, midazolam can be given IM

if patient is not receiving urgent medical care, diazepam rectal gel is an option

status epilepticus treatment

stabilization phase 0-5 minutes -->

- stabilize circulation, airway, and breathing

- time the seizure, start ECG

- check ASM levels and electrolytes

- if blood glucose is low, treat with dextrose

initial treatment phase 5-20 minutes -->

- if seizures continue, give IV lorazepam, IM midazolam, or IV diazepam

- alternatives: rectal diazepam, intranasal or buccal midazolam

second treatment phase 20-40 minutes -->

- if seizures continue, give nonbenzo ASM: IV fosphenytoin, valproic acid, or levetiracetam

- alternative: IV phenobarbital

third treatment phase (refractory) -->

- no clear evidence to guide therapy

- repeat second-line treatment or midazolam, phenobarbital, or propofol

**** diastat acudial is prescribed for patients who are at risk of long-lasting seizures

diastat acudial

each package contains two rectal syringes prefilled with diazepam rectal gel

each syringe MUST be dialed to the right dose and locked BEFORE DISPENSING

syringes come in 2.5, 10, and 20mg

pharmacist instructions for locking in the dose are included on a card in the package

- hold the barrel of the syringe in one hand with the cap facing down and the dose window visible. do not remove the cap

- use the other hand to grab the cap firmly and turn to adjust the dose

- confirm the correct dose shows in the window. hold the locking ring at the bottom of the syringe barrel and push upward on both sides of the ring. Once locked, the green band should say "READY" and the syringe cannot be unlocked

- repeat these steps with the second syringe in the case. when counseling, check both syringes with the patient before they leave the pharmacy to ensure they are dialed and locked.

chronic seizure management

ASMs should NOT be stopped abruptly as this can lead to increased seizures

medical marijuana

epidiolex, or cannabidiol (CBD), was the first cannabis-derived medication approved by the FDA to treat rare forms of epilepsy

ketogenic diet

can be used in patients with refractory seizures

usually contains a 4:1 ratio of fate to combined protein and carbs

this elevated ketone state is called ketosis, and can lead to a reduction in seizure frequency

antiseizure meds

broad-spectrum ASMs treat both focal and generalized seizures

a few ASMs are used for isolated conditions, such as ethosuximide for absence seizures

common concerns with ASMs

CNS and psych effects

bone loss

rash

CNS and psych effects

all ASMs increase the risk of CNS depression (confusion, sedation) and increase the risk for cognitive impairment and falls

all ASMs also have a warning for suicide risk and require monitoring for changes in mood

bone loss

ASMs increase fracture risk

all patients on ASMs should be supplemented with calcium and vitamin D

rash

increased risk of SJS and TEN

DRESS is a multiorgan HSR

take your vitamins with ASMs, supplement with:

all ASMs --> calcium and vitamin D

women of child bearing age --> folate

valproic acid --> possibly carnitine

lamotrigine and valproic acid --> if alopecia develops, supplement with biotin, selenium, and zinc

ASM description

seizures can occur due to a deficiency of the inhibitory NT, GABA, or an excess of the excitatory NT, glutamate

ASMs work by either increasing GABA, or decreasing glutamate

what drugs enhance GABA effect

benzos

phenobarbital

what drugs block sodium channels and increase GABA

valproate

what drugs inhibit vesicle fusion by binding SV2A proteins

levetiracetam

what drugs block sodium channels

carbamazepine

phenytoin/fosphenytoin

topiramate

what drugs block sodium channels and decrease glutamate

lamotrigine

what drugs block T-type calcium channels

ethosuximide

lamotrigine

lamictal

also used for bipolar disorder

initial standard dosing: weeks 1 and 2 --> 25mg daily

BBW --> serious skin reactions (SJS/TEN)

warnings --> multiorgan HSR (DRESS)

SEs --> alopecia (supplement with biotin, selenium, and zinc)

notes -->

- use starter kit when initiating treatment

- if DC, restart initial dosing titration

lamotrigine drug interactions

valproic acid can increase lamotrigine; use lower dose starter kit (blue box)

when using drugs that decrease lamotrigine, use the higher dose starter kit (green box)

lamictal starter kits by color

lamotrigine dose needs to be just right --> too much leads to a higher risk of severe rash and too little leads to seizures

blue --> lower starting dose; use if taking valproic acid

orange --> standard starting dose; use if no interacting meds

green --> higher starting dose; use if taking an enzyme inducer (carbamazepine, phenytoin, phenobarbital, primidone) and not taking valproic acid

levetiracetam

keppra

IV:PO --> 1:1

warnings --> psych reactions, including psychotic symptoms, somnolence, fatigue

notes --> no significant drug interactions

topiramate

topamax

also used for migraine prophylaxis

warnings --> metabolic acidosis, oligohidrosis (reduced perspiration), nephrolithiasis, angle-closure glaucoma, hyperammonemia, visual problems, fetal harm

SEs --> somnolence, difficulty with memory/concentration/attention, weight loss, anorexia

monitoring --> bicarbonate, IOP

topiramate drug interactions

non-hormonal contraception is recommended

valproic acid and divalproex

valproate and divalproex (depakote)

therapeutic range --> 50-100

also used for bipolar disorder and migraine prophylaxis

valproate and divalproex BBW

hepatic failure

fetal harm (neural tube defects and decreased IQ scores)

pancreatitis

valproate and divalproex warnings

hyperammonemia (treat with carnitine in symptomatic adults only)

thrombocytopenia

valproate and divalproex SEs

alopecia

N/V

weight changes (gain > loss)

somnolence

tremor

valproate and divalproex monitoring

LFTs (baseline and frequently in the first 6 months)

platelets

valproate drug interactions

can increase levels of lamotrigine and warfarin

use caution with lamotrigine due to risk of rash

lacosamide

vimpat

C-V

warnings --> prolongs PR interval and increases risk of arrhythmias; DRESS

carbamazepine

tegretol

therapeutic range --> 4-12

carbamazepine BBW

serious skin reactions --> HLA-B*1502 allele testing

aplastic anemia and agranulocytosis

carbamazepine CIs

myelosuppression

carbamazepine warnings

hyponatremia (SIADH)

fetal harm

carbamazepine monitoring

CBC with differential

Na

carbamazepine notes

inducer, auto-inducer --> decrease level of other drugs and itself

carbamazepine drug interactions

autoinducer --> will decrease its own levels

strong inducer of CYP3A4 and P-gp --> can decrease levels of warfarin and contraceptives (non-hormonal is recommended)

oxcarbazepine

trileptal

warnings --> HLA-B*1502, hyponatremia

monitoring --> Na

oxcarbazepine drug interactions

not an autoinducer

non-hormonal contraception is recommended

phenytoin/fosphenytoin

phenytoin (dilantin) --> therapeutic range 10-20 (total) or 1-2 (free); IV:PO = 1:1

fosphenytoin (cerebyx) --> prodrug of phenytoin

phenytoin and fosphenytoin BBW

phenytoin IV rate should not exceed 50mg/min and fosphenytoin IV should not exceed 150mg PE/min --> if given faster, cardiac arrythmias can occur

phenytoin and fosphenytoin warnings

extravasation (leading to purple glove syndrome)

avoid if positive for HLA-B*1502

fetal harm

phenytoin and fosphenytoin SEs

dose-related toxicity --> nystagmus, ataxia, diplopia

chronic --> gingival hyperplasia, hepatotoxicity

phenytoin and fosphenytoin monitoring

serum phenytoin concentration

LFTs

IV --> cardiac and respiratory function

phenytoin and fosphenytoin drug interactions

strong inducers of several enzymes

non-hormonal contraception recommended

both have high protein binding

phenytoin/fosphenytoin administration

IV phenytoin -->

- do not exceed 50mg/min

- monitor BP, resp. function, and ECG

- requires a filter

- dilute in NS, stable for 4 hours, do not refrigerate

NG tube phenytoin -->

- enteral feedings decrease phenytoin absorption

- hold feedings 1-2 hours before and after admin

IV fosphenytoin -->

- do not exceed 150mg PE/min

- monitoring same as above

- lower risk of purple glove syndrome than phenytoin

phenytoin monitoring/adjusting doses

the metabolism of phenytoin can become saturated --> a small increase in the dose can lead to a large increase in the drug concentration

phenytoin follows michaelis-menten kinetics, also called saturable kinetics

if albumin is low (<3.5) and CrCl is 10 or higher, adjust the total level with the formula:

phenytoin correction = total phenytoin measured/(0.2 x albumin) + 0.1

free levels do not require correction

phenobarbital

sezaby

therapeutic range --> 20-40 (adults)

warnings --> potential for drug dependency, respiratory depression, fetal harm

SEs --> dependence, tolerance, residual sedation

phenobarbital drug interactiosn

strong inducer

non-hormonal contraception

ASM cousins

carbamazepine, oxcarbazepine, eslicarbazepine --> hyponatremia, rash, enzyme induction

gabapentin and pregabalin --> weight gain, peripheral edema, mild euphoria, used primarily for neuropathic pain

phenobarbital and primidone --> sedation, dependence/tolerance/overdose risk, enzyme induction

topiramate and zonisamide --> weight loss, metabolic acidosis, nephrolithiasis and oligohidrosis/hyperthermia (in children)

benzos

C-IV

BBW --> use with opioids can lead to respiratory depression, death

eslicarbazepine

oxcarbazepine is the active metabolite

can cause decreased Na (monitor)

ethosuximide

used for absence seizures

warnings --> SJS/TEN, blood dyscrasias

felbamate

BBW --> aplastic anemia

fenfluramine

BBW --> valvular heart disease, PAH

warnings --> decreased appetite/weight loss

gabapentin

neurontin

SEs --> somnolence, peripheral edema, weight gain, mild euphoria

notes --> used for neuropathic pain

pregabalin

lyrica

C-V

used for neuropathic pain

primidone

prodrug of phenobarbital

vigabatrin

BBW --> permanent vision loss

zonisamide

CI --> sulfa allergy

SEs --> oligohidrosis/hyperthermia, nephrolithiasis

monitoring

phenytoin, valproic acid, carbamazepine, and phenobarbital have therapeutic drug level ranges

drug interactions

can be caused by protein binding or enzyme-mediated effects

some are highly protein bound (phenytoin, valproate)

many ASMs are enzyme inducers

valproic acid is an enzyme inhibitor

higher lamotrigine levels increases risk for severe rash

ASM enzyme inducers

carbamazepine

oxcarbazepine

phenytoin

fosphenytoin

phenobarbital

primidone

ASM enzyme inhibitors

valproic acid (increases lamotrigine)

use in pregnancy

several ASMs have teratogenicity risk

valproic acid has the highest risk --> NTDs and decreased IQ

levetiracetam has the lowest risk --> preferred in pregnancy

take folate to prevent NTDs

women on ASMs should avoid unplanned pregnancy

many ASMs reduce the efficacy of oral hormonal contraceptives

ASMs contribute to bone loss --> adequate calcium and vitamin D supplementation

ASM levels decline during pregnancy, which can be harmful to the baby

use in children

topiramate and zonisamide can cause reduced sweating --> sun exposure should be limited

lamotrigine-induced rash occurs more commonly in children

use formulations that are easy to swallow --> lamotrigine ODT or chewable tablets, levetiracetam ODT or oral solutions

all ASM counseling

can cause suicidal thoughts or behaviors and drowsiness

seizures can become worse when the drug is suddenly stopped. The dose must be gradually decreased

many drug interactions, including drugs that worsen drowsiness and drugs that lower the seizure threshold

supplement with calcium and vitamin D while taking this med

carbamazepine counseling

can cause severe rash and rare but serious blood disorders. you will need to have your blood checked while on this med

avoid in pregnancy

lamotrigine counseling

can cause severe rash (most likely in the first 2-8 weeks of treatment)

chewable tablets can be swallowed whole, chewed, or mixed in water or diluted juice. if mixed, drink the whole amount right away

oxcarbazepine counseling

can cause low sodium levels. contact your HCP if you experience fatigue, HA, nausea, or confusion

can cause severe rash

take ER (oxtellar XR) on an empty stomach at least one hour before or two hours after food

shake oral suspension for 10 seconds before using. It can be mixed in a small glass of water

phenytoin counseling

can cause severe rash, gingival hyperplasia, changes in vision, abnormal eye movements

avoid in pregnancy

phenobarbital counseling

abuse and dependence can occur

avoid in pregnancy

topiramate counseling

can cause problems with concentration, attention, memory, or speech, eye damage, decreased sweating and increased body temp, and weight loss

sprinkle capsules can be swallowed whole or opened and sprinkled on a teaspoon of soft food. swallow whole; do not chew. follow with a glass of water

drink plenty of fluids to prevent kidney stones

avoid in pregnancy

valproic acid counseling

can cause liver damage and weight gain

avoid in pregnancy

take with food to help avoid stomach upset

diazepam rectal gel counseling

the green ready band should be visible before leaving the pharmacy

admin instructions -->

put the person on their side in a safe place

get med syringe and lubricating jelly

remove syringe cap by pushing up with thumb

apply lubricating jelly to syringe tip

turn the person on their side facing you and bend upper leg forward to expose the rectum

separate buttocks and gently insert syringe tip into the rectum until the rim is snug against the rectal opening

slowly count to 3 while gently pushing the plunger until it stops

count to 3 before removing the syringe from rectum

remove the syringe and count to 3 again while holding the butt together to prevent leakage

make note of the time given and observe

call 911 if seizure continues 15 minutes after giving the medication

to dispose of any medication remaining in the syringe, first remove the plunger from the syringe, then replace it. aim the application tip over the sink or toilet. push the plunger down to remove any remaining medication in the syrinege