Lecture 3-Antiepileptics

Question 1

For antiepileptic drugs we want to ______ neuroexcitability.

To Limit Excitability we _____ activity in:

Voltage-gated Sodium Channel

Voltage-gated Calcium Channel

Glutamate Receptors

Or we can _____ Inhibition via the GABA system

Answer 1

decrease; decrease; increase

Question 2

Drugs that stabilize inactive state inhibiting recurrent depolarization?

Answer 2

Phenytoin, Carbamazepine, Oxcarbamazepine, Lamotrigine

Question 3

Voltage-gated Calcium Channels are Presynaptic membrane channels. For epilepsy we can block the influx of Ca, which leads to ____ neurotransmitter release.

What drugs block seizures in the thalamus due to Ca channels?What drugs block the high voltage type channels due to Ca channels?

Answer 3

less;

Ethosuximide – T-type in thalamus (T for thalamus);

Gabapentin, Pregabalin – high voltage type

Question 4

Glutamate Receptors are _____ synaptic membrane of excitatory synapses (so we dampen neurotransmitter potency). They are Ligand-gated cation channels (Ca, Na). What drugs block the NMDA receptors? What drugs block the AMPA & Kianate receptors?

Answer 4

Post ;

Felbamate – NMDA receptor blocker

Topiramate – partially active as AMPA and Kainate receptor blocker

Question 5

GABA – A receptors are found on _____ synaptic membranes of inhibitory synapses. They are ligand gated Cl channels. What drugs activate GABA-A receptors (2)?

Answer 5

post;

Phenobarbitol, Benzodiazepnes activate GABA-A receptors

Question 6

Drugs that block Voltage-gated Sodium Channels stabilize inactive state inhibiting recurrent depolarization
Similar efficacy, Similar metabolism, Similar toxicities. What are the general sodium channel blocker toxicities? What do they do to Hepatic P450 enzymes? Name the 4 sodium channel blockers. Useful in treating what 2 disorders other than seizure?

Answer 6

Sedation, Ataxia, Diplopia (dizzy, drunk, double vision) & contraceptive failiure;

Hepatic enzyme inducers, so increases P450s

Phenytoin, Carbamazepine, Oxcarbamazepine, Lamotrigine

Useful in Bipolar Affective disorder & Useful in treating in neuropathic pain

Question 7

What kind of drug is Carbamazepine? What is it used for? Distingishing side effects?

Answer 7

sodium channel blocker; More effective for Complex Partial Epilepsy than Primary Generalized (everywhere seizures). Complex partial = start in 1 place;

Rash 15%, rarely Stevens-Johnson

Question 8

What kind of drug is Phenytoin? Distinguishing side effects? What is it used for?

Answer 8

Sodium Channel Blocker;

Gingival hyperplasia, rash, hirsutism, Lups-like reaction;

IV infusion limited by hypotension (so useful for status epilepticus). Effective against Tonic-Clonic seizures of Primary Generalized Epilepsy or Partial onset and Secondarily Generalized seizures
Effective for acute seizures, even those that may not be related to epilepsy

Question 9

What kind of drug is Oxcarbamazepine? Distinguishing side effects? What is it used for?

Answer 9

(metabolite of Carbamazepine Designed to bypass cabamazepine epoxide) so sodium channel blocker;

less side effects;

seizures

Question 10

What kind of drug is Lamotrigine? Distinguishing side effects? What is it used for?

Answer 10

Sodium Channel Blocker;

Rash 3%, rarely Stevens-Johnson; Synergistic action with Depakote (dizzy, drunk, double vision). Lamotrigine will increase Depakote and vice versa.

Effective for Primary Generalized Epilepsy, Partial Complex Epilepsy and secondary generalization, Absence seizures

Indication for use in children

Question 11

Benzodiazepines are used in? Short or long acting?

Answer 11

Status epilepticus;

Short acting due to redistribution (minutes)
Lorazepam (more potent) vs. Diazepam

Status epilepticus (SE) is an epileptic seizure of greater than five minutes or more than one seizure within a five minute period without the person returning to normal between them.

Question 12

Valproate acts on? What does it do? How does it treat status epilepticus?

Answer 12

Na Channels and GABA system;

Effective against Absence, Myoclonic and Tonic-Clonic seizures of Primary Generalized Epilepsy as well as Partial onset and secondarily generalized seizures
Used in treatment of Bipolar Affective disorder, Used in Migraine prophylaxis

IV route useful in Status Epilepticus

Question 13

Gabapentin and Pregabalin are? What are they used in? Toxicity?

Answer 13

GABA analogs, inhibits Ca currents;

Used as adjunctive treatment for partial complex epilepsy. More commonly used for neuropathic pain

No major toxicity, mostly sedation

Question 14

Ethosuximide is useful vs what type of seizure? What does it block?

Answer 14

Effective against Absence Seizures only;

Blocks T-type Calcium currents in thalamo-cortical circuits

Question 15

What does topiramate block? What does it treat? Side effects?

Answer 15

AMPA and Kaniate Ca channel blocker. Also activity at Na channels and GABA;

Effective against Partial onset and secondarily generalized seizures as well as Primary Generalized Epilepsy. Effective for Migraine prophylaxis

Carbonic anhydrase activity gives alkalosis & tingling, word finding becomes difficult, weight loss.

Question 16

Levetiracetam uses & mechanism. Adverse rxns?

Answer 16

Effective against Partial onset and secondarily generalized seizures. Some evidence of activity against Primary Generalized Epilepsy;

Binds to synaptic vesicle protein 2 resulting in less neurotransmitter release;

irritability

Question 17

Lithium is an antiepileptic drug also used to treat? Mechanism? Contraindications? Major side effects?

Answer 17

Used to treat Bipolar Affective Disorder; Used in Cluster Headache;

Alters Sodium transport.
Inhibits Sodium re-absorption proximal tubule;

Contraindicated in those with arrhythmia or prone to dehydration;

Brugada syndrome (sudden cardiac death—abnormal EKG), arrythmia, ask family Hx of sudden death <45