Pharmacology-Anti-Epileptic Drugs

Question 1

What is the difference between a seizure and epilepsy?

Answer 1

Seizure: brain dysfunction from abnormal synchronous neuronal discharge. Epilepsy: disorder characterized by recurrent seizures.

Question 2

How effective are anti-seizure drugs?

Answer 2

36% of patients are not seizure free (refractory).

Question 3

What is the most prevalent etiology of epilepsy?

Answer 3

Idiopathic (genetic) epilepsy

Question 4

What types of epilepsy are responsible for most adult onset epilepsies?

Answer 4

TBI, Infection, Tumor, Degenerative, Developmental abnormalities, Metabolic disorder, Cardiovascular disease, Substance toxicity.

Question 5

What types of seizures are more difficult to control?

Answer 5

Symptomatic epilepsies caused by adult onset epilepsy.

Question 6

Types of seizures

Answer 6

Partial: Simple, Complex, Secondarily Generalized. Generalized: Tonic-clonic, Absence.

Question 7

What differentiates an absence seizure from a complex partial seizure?

Answer 7

*

Question 8

Off-label

Answer 8

FDA approval is only for adjunct therapy (levetiracetam)

Question 9

Refractory

Answer 9

Use is restricted

Question 10

What drugs play a role in inhibiting high frequency action potential firing?

Answer 10

Na+ channel inhibitors. These slow recovery from the inactivated state and decrease frequency of action potentials.

Question 11

How does lacosamide differ from the other sodium channel blocking anti-seizure drugs?

Answer 11

Lacosamide stabilizes slow inactivation of sodium channels and is not overcome by repolarization. The others target fast inactivation during the refractory period.

Question 12

What anti-seizure drugs would cause the change seen below?

Answer 12

They modulate K+ channels to allow more K+ to exit the cell. This makes the resting membrane potential more negative.

Question 13

What drugs play a role in inhibiting the pattern seen below?

Answer 13

T-type Ca2+ channel blockers inhibit synchronization of thalamocortical activity into spike and wave patterns.

Question 14

What drugs play a large role in inhibiting neurotransmitter release?

Answer 14

Ca2+ VGC blockers. No Ca2+ entry means no excitatory neurotransmitter release to propagate seizures.

Question 15

What drugs play a large role in inhibiting EPSPs?

Answer 15

Levetiracetam hits SV2A vesicular protein that packages glutamate. High doses of phenobarbital inhibit AMPA receptors.

Question 16

What drugs play a large role in enhancement of IPSPs?

Answer 16

Phenobarbital enhances Cl- entry. Valproate enhances Glutamic Acid Decarboxylase (GAD) and inhibits GABA-Transaminase (GABA-T). Vigabatrin irreversibly inhibits GABA-T.

Question 17

Most anti seizure drugs have a low therapeutic index, what are very common side effects you see with these drugs?

Answer 17

Rash and suicide.

Question 18

What anti seizure drug can cause this side effect?

Answer 18

This is gingival hyperplasia. It is a side effect of phenytoin.

Question 19

What drug is the sporadic rapid increase in plasma drug concentration seen in the patient population below characteristic of?

Answer 19

Phenytoin. The dose relationship is not linear because liver enzymes can become saturated.

Question 20

You put a patient on an anti seizure drug and after a few days she becomes hyponatremic. She is also at high risk for Stevens-Johnson syndrome. What drug was prescribed?

Answer 20

Carbamazepine. It increases ADH secretion, increases water retention and can cause hyponatremia.

Question 21

Why screen HLA-B screen patients before prescribing them carbamazepine?

Answer 21

Stevens-Johnson syndrome (toxic epidermal necrolysis). Asians with a specific HLA-B gene have a high incidence of these conditions with use of carbamezapine.

Question 22

You put a patient on an anti seizure drug and after a few days she becomes hyponatremic. She is also at lower risk for Stevens-Johnson syndrome compared to being on carbamazepine. What drug was prescribed?

Answer 22

Oxcarbazepine. It still increases ADH levels, but has a different intermediate in metabolism which reduces incidence of Stevens-Johnson syndrome.

Question 23

What anti seizure drug is commonly used in infants?

Answer 23

Infants

Question 24

What anti seizure drugs are often used for chronic pain and have little drug interactions?

Answer 24

Gabapentin & Pregabalin. They are excreted unchanged by the kidneys.

Question 25

What anti seizure drug has negligible drug interactions, but has been shown to cause behavioral changes, irritability and psychosis?

Answer 25

Levetiracetam.

Question 26

What drug limits axonal sprouting and has adverse effects of sedation, dizziness, ataxia, abnormal gait, diplopia & nystagmus? What other problems is this drug associated with?

Answer 26

Lacosamide. It blocks Na+ channels & CRMP-2, which limits axonal sprouting. These drugs can also cause problems in cardiac patients (atrial flutter, a-fib, heart block).

Question 27

What anti seizure drug is a schedule V controlled substance?

Answer 27

Lacosamide. The side effects of sedation and dizziness make it abusable.

Question 28

Use of ethosuximide

Answer 28

Only clinical use is for absence seizures.

Question 29

What anti seizure drug absolutely requires liver tests before taking it?

Answer 29

Valproate. It inhibits hepatic enzymes and can cause idiosyncratic hepatotoxicity, pancreatitis and hyperammonemia.

Question 30

What anti seizure drug is used exclusively in adults due to increased risk of Stevens-Johnson syndrome in children (especially those comedicated w/valproate as the patient seen below)?

Answer 30

Lamotrigine. Valproate inhibits CYP450, which is responsible for lamotrigine metabolism.

Question 31

What anti seizure drug is the only drug that causes dramatic weight loss and is associated with metabolic acidosis and renal calculi?

Answer 31

Topiramate. It is also a carbonic anhydrase inhibitor, which explains metabolic aciosis and renal calculi.

Question 32

What anti seizure drug is reserved for severe refractory use, complex partial seizures or infantile spasms?

Answer 32

Vigabatrin. It is associated with permanent vision loss in 1/3 of patients and can cause psychosis, hence its status as a refractory drug.

Question 33

Why do carbamazepine, phenobarbital and phenytoin all have lots of drug interactions? What about valproic acid?

Answer 33

Carbamazepine, phenobarbital and phenytoin all induce hepatic enzymes and valproate inhibits hepatic enzymes.

Question 34

What special P450 interactions do you need to consider when you prescribe carbamazepine, felbamate, phenytoin, phenobarbital, oxcarbazepine or topiramate?

Answer 34

They reduce oral contraceptive levels so dosing will need to be increased and they may cause osteoporosis.

Question 35

Off label uses for anti seizure drugs

Answer 35

*

Question 36

A patient comes to the ED after 10 minutes of continuous tonic-clonic seizure activity without any recovery in between. How do you treat this patient?

Answer 36

This patient is in status epilepticus. If you can treat within 30 minutes you can save their life. You want to give them diazepam or lorazepam ASAP to stop the seizure. You then load with a long-acting anti seizure drug like phenytoin. If that doesn’t work you induce iatrogenic coma to stop the seizure with propofal, midazolam or pentobarbital.

Question 37

What people are at high risk for status epilepticus?

Answer 37

*

Question 38

A mother brings her baby in complaining of brief, shock-like muscle contractions. How do you treat this baby?

Answer 38

The child is having myoclonic spasms characteristic of infantile spasms. ACTH (corticotropin) and prednisone are first line therapy.

Question 39

A mother brings her baby in complaining of seizures in her 1 year old. He has a fever. How do you treat this child?

Answer 39

Normally you don’t. If the child is prone to febrile seizures you give rectal diazepam during fever. However, if there is family history you may consider medication.