Epilepsy Dr. Thomason Pt. 2 Flashcards
Which agent would be appropriate in a patient with a seizure disorder and additional has migraine or
a bipolar disorder?
-Valproic acid, divalproex (Depakote)
-> NOT for young women in childbearing age
-> most teratogenic antiseizure drug
(can also be used for absent seizures)
also:
-Carbamazepine (FDA approved)
-Lamotrigine
Appropriate drug for absence seizures
Ethosuximate
Valproic acid
What is the BBW for Valproic acid, Depakote?
-Hepatoxcicty in patients under the age of 2
ADE: GI, nausea, drowsiness
-> that’s why they made Depakote (delayed release)
Antiseizure drugs associated with hepatotoxicity
Valproic acid
Ethosuximide
Felbamate
Antiseizure drugs metabolized hepatically
Carbamazepine
Oxcarbazepine
Phenobarbital
Phenytoin
Primidone
Clonazepam
Ethosuxumide
Felbamate
Valproic acid
Zonisamide
Lamotrigine
Levetiracetam (to 30%)
…
Idiosyncratic side effects of Valproic acid?
-Thrombocytopenia -> check RBC
-Osteoporisis
-weight gain (common)
-polycystic ovarian syndrome (abdominal fat distribution, irregular menstrual cycle, hair growth on the face, fertility decreases)
-hyperammonemia -> encephalopathy (looks like dementia)
-pancreatis
-tremor
-alopecia
Which parameters should be checked with the use of Carbamazepine and Valproic acid?
Carbamazepine: WBC
Valproic acid: RBC
What are the consequences of an elevated serum concentration of valporic acid?
tremor, usually in the hands
-normal serum concentration (therapeutic range): 50 - 100 mg/L
How should Carbamazapeine be titrated?
Titrated up slowly over 3-4 weeks (4-12 weeks)
-usually start with 100-200 mg BID -> go up every week
-due to autoinduction (it is also a CYP inducer to other drugs)
Idiosyncratic side effects of Carbamazepine
-aplastic anemia
-leucopenia (lack of leukocytes WBC)
-hyponatremia (Oxcarbazepine higher risk)
-heart block
-RASH -> can go to SJS
-> Asians should be tested for the HLA-B 1502 allele!!!
Indication/Contrainidcation Carbamezpine
-good for partial and secondarily generalized tonic-clonic seizure; also for bipolar disorder
-may make absence or myoclonic seizure worse
-dont keep in a humid place (makes it concert, or hard)
Indication for pregabalin and gabapentin
-not actually for seizures
-more often used for neuropathy and other pain syndromes
-adjunct for partial seizures
-generalized anxiety
Most common side effects of Pregabalin and Gabapentin
-Lower peripheral edema
-weight gain
-myoclonus (tighten muscle, rare)
-dose-related ADE (does too high): ataxia (look drunk), somnolence, blurred vision, dizziness
Which drugs should be tapered off?
Pregabalin - over 1 week or even more
Gabapentin -> addictive, especially hard to taper off for patients with substance use disorder
for Gabapentin: caution with concurrent use of opioids -> may cause .. depression
How do Cimetidine (H2 blocker) and Erythromycin affect the metabolism (CYP) of antiseizure drugs?
they are potent CYP inhibitors
-> increases serum concntration of antiseizure drugs
-> REMINDER: Valproic acid is CYP inhibitor
What alteration has to be done if a woman gets pregnant while on antiseizure drugs?
the metabolism increases significantly during the third trimester
-> may increase the dose
Which antiseizure should NOT be used while breastfeeding?
-Phenobarbital
-will be absorbed by the baby in high concentration -> sedation
Recommended antiseizure drug for pregnant women?
-Lamotrigine, but recently tetratogenicity seen
-might use Keppra
Guidelines for women with seizure disorder who would liek to become pregnant
-seizure fee for 2-5 years
-only 1 seizure type
-normal neurologic exam
-normal IQ
-normal EEG
-> taper them off and see if they have seizure for 6 months
Considerations for antiseizure therapy during pregnancy
-measure levels each trisemester to see if they are therapeutic (metabolism of pregnant women goes up)
-if they are on 2 meds, try to get them on 1 before pregnancy -> should not change antiseizure meds during pregnancy if they are controlled
What should be the dose for folic acid for women who want to become pregnant?
4 mg -> if teratogenic drugs
1 mg -> with newer and less teratogenic antisezure drugs
What should be considered if a patient decides to continue using an estrogen contraceptive despite the DDI?
the OC should have at least 50 mg of estrogen to be effective
-> consider using an IUD
Does seizure disorder affect fertility?
Yes, it causes less progesterone secretion -> may not ovulate
-> patients may be treated with progesterone
Which Vitamin is recommended in patients with a seizure disorder?
Vitamin K
Carbamazepine, Phenytoin increase the metabolism of Vitamin K
What is the therapeutic range of Phenytoin?
10-20 mg/L
free concentration: 1-2 mg/L
for Carbamaezpein: 4-12 mg/L
Idiosyncratic side effects of Phenytoin
-gingival hyperplasia (can be irreversible)
-hirsutism
-anemia, lymphadenopathy
-hepatitis
-osteoporosis
-rash
How should Phenytoin be tapered when considering D/C?
Yes, slowly at least 6 months
criterias that have to be met:
-no seizures for 2-5 years
-normal neuro exam
-normal IQ
-normal EEG during treatment
-a single type of partial or generilzed seizure
Why must seizures in children be controlled ASAP?
because development changes occur rapidly in children
-choose drugs that are less likely to interfere with cognitive function and development
Patient population who are at risk for Status epilepticus
-under the age of 2 yo and older than 60 yo
-considered status epillepticus when they have a seizure for more than 5 minutes -> call 911
-recurrent (they do not regain consciousness in between) or continuous seizure
Treatment options for Status epilepticus
-intranasal or IM midazolam
-intransal diazepam
Why is thiamine administered in adults with status epilepticus in the ER?
alcohol cause thiamin (vitamin B1) deficiency
-thiamine is a cofactor of dextrose metabolism
-if its inot replaced before given dextrose it can cause Wernicke encepohlopathy (can be irreversible)
What might be given to patients in the ER when they are having status epilepticus
-thiamin (vitamin B1) - adults
-Glucose - adults, infants
-Pyridoxine (in case they have a pyridoxine dependent epilepsy - infants
-Naloxone if narcotic overdose suspected
-Antibiotics if infection is suspected
Which labs to check in the ER (status epilepticus)
-CBC: infection
-serum chemisty: electrolytes, glucose, renal/hepatic function, calcium, magnesium
-arterial blood gas: they may have been without O2 during epilepsy; also to see if they have alkalosis or acidosis
-serum anticonvulsant (to see if they are on meds)
-alcohol screen
Which drug is preferred in the first 30 minutes?
Benzodiazepines, bc they work quickly
-IV lorazepam OR midazolam
Why is diazepam not the drug of choice to stop seizures?
-it goes to the brain quickly (highly lipophilic), but also redistributes out of the brain quickly -> risk of seizing again
-the half-life? is less than 1 hour -> its effect may last for 30 min
-another long-acting antiseizure drug has to be used: Phenotoyin, Fosphenytoin or Keppra
-> Diazepam is not used anymore unless there is no other benzodiazpane available
-> Lorazepam is #1 because it is not as lipophilic, so it doesn’t redistribute out of the brain as quickly -> effective for up to 24 hr
How would Midazolam (Versed) be used for rapid seizure treatment?
it has a short half-life, it has to be administered through continuous infusion
How to treat status epileptic at 30-60 minutes
drug of choicce: Fosphenytoin, Phenytoin
IV Valproic acid
Keppra
What is Phenytoin formulation mixed with?
-can only be mixed with normal saline
-40% propylen glycol
-if infused too fast it can cause purple glove syndrome
-> Fosphenytoin is more water-soluble -> and it will be converted to Phenytoin as soon it hits the tissue (can be administered faster)
Generalized convulsive status epilepticus (GCSE) for over 120 minutes
-continous EEG monitoring, check blood volume, end brain perfusion
often seen Propofol used
OR midazolam, Pentobarbital
Super Refractory GCSE over 24 hours
Ketamine
Hypothermia (lower body temperature)
Lidocaine
Topiramate
