Anticonvulsants

Front 1

Carbamazepine:Mechanism

Back 1

- blocks Na channels
- blocks catecholamine reuptake
- clonidine blocks anticonvulsant effect

Front 2

Carbamazepine: Uses

Back 2

- generalized tonic-clonic
- complex partial
- trigeminal neuralgia
- bipolar depression
- neuropathic pain

Front 3

Carbamazepine: Toxicity

Back 3

- increased ADH: water retention
- considered less toxic/sedative; used more safely in pregnant women
- Steven-Johnson syndrome (dermatitis)
- stimulates own metabolism; shorter half-life
- active metabolite in toxicity

Front 4

Phenytoin: Mechanism

Back 4

- Na channel block
- dose-dependent elimination: at first is first order but once metabolic enzyme is saturated, becomes zero order

Front 5

Phenytoin: Uses

Back 5

- partial
- tonic-clonic
- psychomotor

Front 6

Phenytoin: Toxicity

Back 6

- skin rash, bone marrow suppression, liver toxicity
- gingival hyperplasia, folic acid deficiency, decrease Ca and Vit. K absorption

Front 7

Phenobarbital (primadone): Mechanism

Back 7

- enhance GABA
- Ca channel block

Front 8

Phenobarbital (primadone): Uses

Back 8

- tonic-clonic, partial and some complex partial
- recurrent febrile convulsions of children
- withdrawal convulsions

Front 9

Phenobarbital: Toxicity

Back 9

- pH dependent excretion
- sedative
- long half-life makes it less toxic

Front 10

Valproic Acid: Mechanism

Back 10

- T-type Ca channel block
- Na channel block
- stimulates GABA synthesis & inhibits breakdown

Front 11

Valproic Acid: Uses

Back 11

- absence, myoclonic, atonic
- drug of choice for partial/secondary generalization

Front 12

Valproic Acid: Toxicity

Back 12

Idiosyncratic Hepatotoxicity

Front 13

Ethosuximide: Mechanism

Back 13

blocks T-type Ca channel

Front 14

Ethosuximide: Uses

Back 14

Absence

Front 15

Ethosuximide: Toxicity

Back 15

- aplastic anemia
- NO renal or hepatic toxicity - no drug interactions

Front 16

BZDs: Mechanism

Back 16

- allosteric modulator of GABA receptor: enhances binding of GABA --> keeps channel open longer --> results in greater entry of Cl ions
- increased frequency of channel openings produced by GABA

Front 17

BZDs: Uses
Diazepam
Lorazepam
Clonazepam
Chlorazepate

Back 17

Diazepam: status epilepticus (IV); 30-minute effective duration
Lorazepam: longer duration
Clonazepam: absence (oral)
Chlorazepate: complex partial

Front 18

BZDs: Toxicity

Back 18

- tolerance
- sedative
- ataxia

Front 19

Group I Na channel block/mixed:
Lamotrigine
Felbamate
Topiramate

Back 19

Lamotrigine:
Mechanism - Na channel block; anti-folate activity
Uses - partial w/ secondary generalization

Felbamate:
Mechanism - Na channel block; inhibits NMDA; enhances GABA
Uses - partial seizures
Toxicity - aplastic anemia

Topiramate:
Mechanism - Na channel block; enhances GABA; inhibits AMPA; weak carbonic anhydrase inhibitor
Uses - intractable partial seizures; secondary agent in partial seizures
Toxicity - weight loss

Front 20

Group II - not Na channel blockers:
Vigabatrin
Tiagabine
Gabapentin
Levetiracetam

Back 20

Vigabatrin:
Mechanism - inhibits GABA-transaminase
Uses - partial seizures
Toxicity - agitation, psychosis, weight gain, sedation

Tiagabine:
Mechanism - inhibits GABA transporter
Uses - adjunctive partial seizures
Toxicity - abnormal thinking (mental lethargy, difficulty concentrating)

Gabapentin:
Mechanism - controversy
1. binds GABA B heterodimer linked to K and N-type VGCC
2. alpha2delta subunit of Ca channel (overexpressed in nerve injury); N, L, P/Q-type VGCC
3. may interact at presynaptic NMDA receptors
4. non-vesicular GABA
Uses - partial seizures
Toxicity - less because not metabolized by liver; there are no drug interactions

Levetiracetam:
Mechanism - selective blockade of N-type Ca channels; reduction of voltage-operated K current channels; does not modulate neuronal Na+ and t-type Ca channels
Uses - refractory partial seizures