Seizures/Epilepsy Flashcards
What is Epilepsy?
Chronic Seizure
Classification of Seizures
1) Focal (one side of the brain)
2) Generalized (Both sides of the brain)
Tonic - rigid, tense muscles
Clonic - uncontrolled jerking movements
What is a Seizure?
This is a sudden, uncontrolled surge of excitatory neuronal activity within the brain.
Causes of seizures?
1) Alcohol withdrawal
2) Electrolyte abnormality
3) Fever or infection
4) Head injury
5) Hypoglycemia
6) Drug-induced
What are some drugs which can lower the seizure threshold and cause seizures?
1) Opioids (tramadol, meperidine)
2) Antibiotics (Quinolones, Carbapenems, Cephalosporins, Penicillins)
3) Psych (Bupropion, Clozapine, Lithium, TCAs)
Seizure Classification
1- Seizures (<5 mins)
2- Status Epilepticus (> 5 mins)
Acute Treatment of Status Epilepticus
0-5 mins: Oxygen, monitor labs
5-20 mins: Injectable Benzodiazepines (IV lorazepam, IV diazepam, IM midazolam)
20-40 mins: IV Antisezure Meds (Fosphenytoin, Valproic Acid, Levetiracetam)
Diastat AcuDial Dispensing
Pharmacist MUST dial and lock correct prescribed dose.
*This is a rectal diazepam
Chronic Seizure Management
Primary Treatment: Lamotrigine, Valproate, Levetiracetam
Adjuvant Treatments: Cannabis-derived products, Neurostimulation, Keto Diet (4:1 ration of fats to combined protein and carb. High-fat, Low-Carb & Protein)
Note: discontinuing any anti-seizure medication abruptly can cause seizures to re-occur. Taper off.
What medications are used to treat Broad Spectrum seizures (Focal and Generalized seizures)?
1) Lamotrigine
2) Levetiracetam
3) Topiramate
4) Valproate
What medications are used primarily to treat Focal Seizures?
1) Carbamazepine
2) Phenytoin
What medication is primarily used to treat Absense seizures?
Ethosuximide
What are the neurotransmitters involved in seizures?
1) Glutamate (Excitatory)
2) GABA (Inhibitory)
*Blocking Na channels, decrease excitatory transmission (glutamate)
MOA of Benzodiazepines and Phenobarbital?
Enhances GABA effect
MOA of Valproate?
Blocks Na channels and increases GABA
MOA of Levetiracetam?
Inhibits vesicle fusion by binding SV2A proteins
MOA of Carbamazepine, Phenytoin/Fosphenytoin, Topiramate?
Blocks Na channels
MOA of Ethosuximide?
Blocks T-type Ca channels
MOA of Lamotrigine?
Blocks Na channels and decreases glutamate
Common side effects of common ASM?
1) CNS Depression (Confusion, sedation, poor coordination, falls)
2) Suicide risk (Changes in mood)
3) Bone loss (increase risk of fractures)
4) Rash (SJS, TEN, DRESS)
SJS - Stevens-Johnson syndrome
TEN - Toxic Epidermal Necrolysis
DRESS - Drug-reaction with Eosinophilia and Systemic Symptoms
Lamotrigine
- Also used in Bipolar Disorder
Brand - Lamictal
Boxed Warning - SJS and TEN (both are life threatening) - it is important to report any rash development with Lamotrigine. There is increased risk with higher dosing, dose escalation and valproate use.
Starting dose 25 mg daily. titrate up
Common side effect - Alopecia (supplement with Selenium, Biotin and Zinc)
**IMPORTANT - Monitor for rash and/or fever development. D/c immediately
Lamotrigine Starting Kit
Orange Kit “Original” - Use if not taking any interacting drug
Blue Kit “Below” - Use if taking Valproate
Green Kit “Grow higher” - Use if taking an enzyme inducer, and would need a higher starting dose
E.g. enzyme inducer - Carbamazepine, Phenobarbital, Phenytoin/fosphenytoin, Primidone
Levetiracetam
Brand - Keppra
Warnings - Psych based. SJS/TEN
IV:PO - 1:1
*no significant drug interactions
**Preferred in:
1) Infants
2) Pregnancy
Topiramate
Brand: Topamax
Side Effects: CNS Effects ‘Dopa-max’, weight loss, anorexia
DO not use with oral contraceptives
Valproate
*Among all of the other anti-seizure medications, valproate has the highest incidence of fetal defects and lower IQ score
Valproate represents all the formulations, including valproic acid
*Side Effects: Somnolence, tremor, weight changes, nausea and vomiting, alopecia
*Hepatic failure can occur
Therapeutic Range: 50-100 mcg/mL
Indications: Epilepsy, bipolar, migraine
Valproate can INCREASE levels of Lamotrigine, Phenobarbital, Phenytoin and Warfarin
Carbapenems and estrogen-containing contraceptives can DECREASE levels of Valproate.
Lacosamide
Brand: Vimpat
Schedule 5 Controlled
Side Effects: Blurred vision, tremor, euphoria
IV:PO is 1:1
Carbamazepine & Oxcabazepine
CARBAMAZEPINE
Brand of Carbamazepine: Tegretol
Indications: Seizures, Trigeminal neuralgia
Boxed Warning: SJS [Increased risk for HLA-B*1502)
Contraindications: Myelosuppression
Warning: Fetal harm, hyponatremia (low Na)
Therapeutic Range: 4-12 mcg-mL
Carbamazepine is both a substrate and an inducer for CYP. Therefore it can induce its own metabolism (autoinduction). Oxcarbazepine is not an autoinducer.
Both Carbamazepine and Oxcarbazepine blocks Na channels.
Phenytoin
Brand: Dilantin
IV:PO is 1:1
Fosphenytoin is a prodrug to Phenytoin
Conversion is 1:1.5. That is 100 mg Phenytoin is 150 mg Fosphenytoin
Phenytoin MAX: 50mg/min
Fosphenytoin MAX: 150 mg PE/min
Boxed Warning: Hypotension and Cardiac Arrythmias with rapid infusion.
Side Effects:
-Acute: Ataxia(poor coordination), Diplopia (double vision), Nystagmus
-Chronic: Gingival hyperplasia, hair growth, hepatotoxicity
Phenytoin therapeutic range
Total: 10-20 mcg/mL
Free: 1-2 mcg/mL
Phenytoin and Fosphenytoin Administration Rate
IV Phenytoin: <= 50 mg/min
IV Fosphenytoin: <= 150 mg PE/min
Phenytoin is highly bound to albumin. Therefore patients with low albumin have higher levels of free phenytoin levels.
Corrected Phenytoin = [Total Phenytoin] / [(0.2 x albumin) + 0.1]
-This is used only in patients with albumin < 3.5 g/dL with CrCl >= 10 mL/min
Phenobarbital
This is an older medication which enhances GABA.
Schedule 4
-not first line
Warnings: Respiratory Depression, Fetal harm, Drug dependency
Side Effects: Residual sedation, dependence and tolerance.
Therefore, do not give to patients with a history of substance abuse.
Primidone is a prodrug for Phenobarbital!
Benzodiazepines in Seizures
Main ones: Diazepam, Lorazepam, Midazolam, Clobazam
These are used to stop an ACTIVE SEIZURE!
Which ASM has therapeutic levels for monitoring?
1) Phenytoin
2) Valproate
3) Carbamazepine
4) Phenobarbital
ASM Enzyme Inducers
1) Carbamazepine and Oxcarbazepine
2) Phenytoin and Fosphenytoin
3) Phenobarbital and Primidone
ASM Enzyme Inhibitor
1) Valproate
ASM in Pregnancy
Highest Risk: Valproate
Lowest Risk: Levetiracetam
HLA and ASM
HLA-B 1502 present?
Avoid Oxcarbazepine, Carbamazepine, Phenytoin, Fosphenytoin
