Seizures/Epilepsy

Question 1

What is Epilepsy?

Answer 1

Chronic Seizure

Question 2

Classification of Seizures

Answer 2

1) Focal (one side of the brain)
2) Generalized (Both sides of the brain)

Tonic - rigid, tense muscles
Clonic - uncontrolled jerking movements

Question 3

What is a Seizure?

Answer 3

This is a sudden, uncontrolled surge of excitatory neuronal activity within the brain.

Question 4

Causes of seizures?

Answer 4

1) Alcohol withdrawal
2) Electrolyte abnormality
3) Fever or infection
4) Head injury
5) Hypoglycemia
6) Drug-induced

Question 5

What are some drugs which can lower the seizure threshold and cause seizures?

Answer 5

1) Opioids (tramadol, meperidine)
2) Antibiotics (Quinolones, Carbapenems, Cephalosporins, Penicillins)
3) Psych (Bupropion, Clozapine, Lithium, TCAs)

Question 6

Seizure Classification

Answer 6

1- Seizures (<5 mins)
2- Status Epilepticus (> 5 mins)

Question 7

Acute Treatment of Status Epilepticus

Answer 7

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)

Question 8

Diastat AcuDial Dispensing

Answer 8

Pharmacist MUST dial and lock correct prescribed dose.

*This is a rectal diazepam

Question 9

Chronic Seizure Management

Answer 9

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.

Question 10

What medications are used to treat Broad Spectrum seizures (Focal and Generalized seizures)?

Answer 10

1) Lamotrigine
2) Levetiracetam
3) Topiramate
4) Valproate

Question 11

What medications are used primarily to treat Focal Seizures?

Answer 11

1) Carbamazepine
2) Phenytoin

Question 12

What medication is primarily used to treat Absense seizures?

Answer 12

Ethosuximide

Question 13

What are the neurotransmitters involved in seizures?

Answer 13

1) Glutamate (Excitatory)
2) GABA (Inhibitory)

*Blocking Na channels, decrease excitatory transmission (glutamate)

Question 14

MOA of Benzodiazepines and Phenobarbital?

Answer 14

Enhances GABA effect

Question 15

MOA of Valproate?

Answer 15

Blocks Na channels and increases GABA

Question 16

MOA of Levetiracetam?

Answer 16

Inhibits vesicle fusion by binding SV2A proteins

Question 17

MOA of Carbamazepine, Phenytoin/Fosphenytoin, Topiramate?

Answer 17

Blocks Na channels

Question 18

MOA of Ethosuximide?

Answer 18

Blocks T-type Ca channels

Question 19

MOA of Lamotrigine?

Answer 19

Blocks Na channels and decreases glutamate

Question 20

Common side effects of common ASM?

Answer 20

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

Question 21

Lamotrigine

Answer 21

• 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

Question 22

Lamotrigine Starting Kit

Answer 22

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

Question 23

Levetiracetam

Answer 23

Brand - Keppra

Warnings - Psych based. SJS/TEN

IV:PO - 1:1

*no significant drug interactions

**Preferred in:
1) Infants
2) Pregnancy

Question 24

Topiramate

Answer 24

Brand: Topamax

Side Effects: CNS Effects ‘Dopa-max’, weight loss, anorexia

DO not use with oral contraceptives

Question 25

Valproate

Answer 25

*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.

Question 26

Lacosamide

Answer 26

Brand: Vimpat Schedule 5 Controlled Side Effects: Blurred vision, tremor, euphoria IV:PO is 1:1

Question 27

Carbamazepine & Oxcabazepine

Answer 27

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.

Question 28

Phenytoin

Answer 28

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

Question 29

Phenytoin therapeutic range

Answer 29

Total: 10-20 mcg/mL Free: 1-2 mcg/mL

Question 30

Phenytoin and Fosphenytoin Administration Rate

Answer 30

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

Question 31

Phenobarbital

Answer 31

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!**

Question 32

Benzodiazepines in Seizures

Answer 32

Main ones: Diazepam, Lorazepam, Midazolam, Clobazam These are used to stop an ACTIVE SEIZURE!

Question 33

Which ASM has therapeutic levels for monitoring?

Answer 33

1) Phenytoin 2) Valproate 3) Carbamazepine 4) Phenobarbital

Question 34

ASM Enzyme Inducers

Answer 34

1) Carbamazepine and Oxcarbazepine 2) Phenytoin and Fosphenytoin 3) Phenobarbital and Primidone

Question 35

ASM Enzyme Inhibitor

Answer 35

1) Valproate

Question 36

ASM in Pregnancy

Answer 36

Highest Risk: Valproate Lowest Risk: Levetiracetam

Question 37

HLA and ASM

Answer 37

HLA-B 1502 present? Avoid Oxcarbazepine, Carbamazepine, Phenytoin, Fosphenytoin