Antiepileptic Drugs

Question 1

How do drugs act on voltage gated sodium channels to tx epilepsy?

Answer 1

they stabilize the inactive state to inhibit recurrent depolarization

Question 2

How do drugs act on voltage gated calcium channels to tx epilepsy?

Answer 2

they act on presynaptic membrane channels and block influx of calcium; thus leading to less excitatory neurotransmitter release.

Question 3

Where are glutamate and Gaba receptors found?

Answer 3

Glutamate–>post synaptic membrane of excitatory synapses (Ca and Na ligand gated channels)

Gaba —>post synaptic membrane of inhibitory synapses (Cl ligand gated channels)

Question 4

What are the 4 voltage gated Na channels used to tx epilepsy and how do they all act?

Answer 4

Phenytoin, Carbamazepine, Oxcarbamazepine, Lamotrigine; all stabilize the inactive conformation of the Na channel

Question 5

What are Carbamazepine and Oxcarbamazepine useful in treating?

Answer 5

More effective for complex partial epilepsy than primary generalized; tx bipolar affective disorder, tx neuropathic pain

Question 6

What are some of the pharmacologic considerations with Carbamazepine and Phenytoin?

Answer 6

highly protein bound, hepatic metabolism (both autoinducer and heteroinducer) thus effects on other hepatically metabolized meds, can cause contraceptive failure, short half life (Carbazepine)/ variable but longer half-life (Phenytoin)

Question 7

What are some symptoms of Carbamazepine (and all sodium channel stabilizers) toxicity?

Answer 7

sedation, ataxia and diplopia “dizzy, drunk, double vision” possibly due to epoxide metabolite

Question 8

What are some adverse reactions to taking Carbamazepine?

Answer 8

rash, Steven-Johnson (rare), mile hepatic enzyme elevation, mild myelosuppression

Question 9

What is Phenytoin effective at treating?

Answer 9

Tonic-Clonic seizures of primary generalized epilepsy or partial onset and secondarily generalized seizures; effective for acute seizures (even those not related to epilepsy)

Question 10

Explain the pros and cons of Phenytoin administration by IV

Answer 10

IV is useful to treat Status Epilepticus; IV infusion is limited by hypotension

Question 11

What are some adverse reactions to taking Phenytoin?

Answer 11

mild hepatotoxicity, myelosuppression, gingival hyperplasia, rash, hirsutism (excess hair in women), Lupus-like rxn

long term: cerebellar degeneration, peripheral neuropathy, osteoporosis

Question 12

What differentiates Oxcarbazepine from Carbamazepine?

Answer 12

it’s a prodrug designed to bypass carbamazepine epoxide (metabolite); thus is less protein bound, less autoinduction, fewer interactions, less toxic, and has a longer half life.

Question 13

What is Lamotrigine effective in treating?

Answer 13

effective for primary generalized epilepsy, partial complex epilepsy and secondary generalization and absence seizures; indicated in children!! (i.e. very safe), tx bipolar affective disorder, neuropathic pain.

**note it’s less effective for and may exacerbate myoclonic seizures

Question 14

What are some pharmacologic considerations when taking Lamotrigine?

Answer 14

hepatic metabolism, less protein bound, hepatic enzyme inducer, cause contraceptive failure, competes for excretion with Valproic Acid and as such has a synergistic action when both drugs taken together

Question 15

What are the adverse reactions to taking Lamotrigine?

Answer 15

rash that’s dose dependent, rarely steven-johnson, slow initial titration is important!!

Question 16

What does Valproate tx?

Answer 16

broad spectrum: absence, myoclonic, tonic-clonic seizures of primary generalized epilepsy and partial onset and secondarily generalized seizures; bipolar disorder and migraine prophylaxis

Question 17

What are some pharmacologic considerations when taking Valproate?

Answer 17

highly protein bound, hepatic metabolism, rapidly absorbed and metabolized, short half-life, extended release preparations (IV route useful in Status Epilepticus)

Question 18

What is the MOA for Valproate? What are signs of toxicity?

Answer 18

unsure of mechanism–>likely affects Na channels and GABA system.

toxicity signs include: sedation and tremor

Question 19

What are some adverse reactions to taking Valproate?

Answer 19

nausea, weight gain, hair turnover, hyperammonemia, teratogenic

Question 20

How do Benzodiazepines act to tx status epilepticus?

Answer 20

Binds to GABA-A receptors to help hyperpolarize the cell membrane; dose limited by sedation and long term usefulness limited by tolerance; short acting due to redistribution (w/in minutes)

Question 21

What type of benzodiazepine is used for anesthesia or to tx refractory status epilepticus?

Answer 21

Midazolam (IV 1/2 life in minutes, orally ~1hr)

Question 22

What is the MOA of Vigabatrine?

Answer 22

GABA transaminase binder that slows down intracellular breakdown of GABA (thus increasing GABA)

Question 23

What is the MOA of Tiagabine?

Answer 23

GABA reuptake inhibtor (thus increasing GABA)

Question 24

What are the MOA of Gabapentin and Pregabin and what are they used to treat?

Answer 24

GABA analogs that inhibit Ca currents; they are used as adjunctive treatment for partial complex epilepsy; more commonly used for neuropathic pain

Question 25

What are the pharmacologic considerations when taking Gabapentin?

Answer 25

absorption limited at intestinal amino acid transporter, limited protein binding, no evidence of metabolism in humans (so few side effects), no interaction with other meds, eliminated unchanged in urine, no serious organ toxicity (toxicity related to sedation)

Question 26

What type of drug is Ethosuximide and what's it used to treat

Answer 26

it's a voltage gated calcium channel blocker that blocks T-type calcium currents in thalamo-cortical circuits; used to treat Absence Seizures only

Question 27

What are some pharmacological considerations and side effects of Ethosuximide?

Answer 27

readily absorbed with minimal first pass metabolism, not protein bound, half life 40-60hrs; side effects: transient nausea, sedation and irritability

Question 28

What type of drug is Topiramate and what is it's MOA?

Answer 28

Glutamate receptor blocker that blocks AMPA and Kainate calcium receptors with secondary effects at Na channels and GABA

Question 29

What is Topiramate effectively treat?

Answer 29

partial onset and secondarily generalized seizures as well as primary generalized epilepsy; effective migraine prophylaxis too

Question 30

What are some of the adverse reactions and toxicities related to Topiramate use?

Answer 30

carbonic anhydrase activity-->mild metabolic acidosis-->resp compensation-->mild alkalosis--> calcium ionization-->tingling; modest weight loss, kidney stones, rare acute glaucoma toxicity includes sedation, and cognitive "word finding" problems

Question 31

What is Levetiracetam used to treat and what is its MOA?

Answer 31

binds synaptic vesicle protein 2 causing decreased NT release; tx partial onset and secondarily generalized seizures with some evidence of activity against primary generalized epilepsy

Question 32

What are the toxicities and side effects of Levetiracetam?

Answer 32

generally well tolerated, but reactions include irritability, aphasia, thrombocytopenia; toxicity signs include sedation

Question 33

What type of drug is Felbamate and what is it used to treat?

Answer 33

it's an NMDA receptor blocker with secondary effect at voltage-gated Na and Ca channels and GABA system; tx partial onset seizures with or w/out secondary generalization and for medically refractory epilepsy

Question 34

What are some potential side effects of taking Felbamate?

Answer 34

aplastic anemia and acute hepatic failure (requires monitoring)