Block 5 - Antiseizure Drugs 2012 - done by me

DOC: Carbamazepine, Phenytoin, Valproic Acid (Valproate)

Alternatives: Phenobarbital/Primidone (infants), Lamotrigine, Gabapentin, Topiramate, Vigabatrin, Tiagabine

DOC: Ethosuximide, Valproic Acid, Clonazepam

Alternatives: Clonazepam, Lamotrigine, Topiramate

DOC: Valproic Acid, Clonazepam

Alternatives: Felbamate, Iamotigine, Levetiracetam, Zonisamide

Felbamate
Gabapentin
Lamotrigine
Tiagabine
topiramate
vigabatrin
Zonisamide

Barbiturate -- Phenobarbital
Benzodiazepine -- Diazepam
Carboxylic Acids -- Valproic Acid
Hydantoins -- Phenytoin
Succinimides -- Ethosuzimide
Tricyclics -- Carbamazepine
Newer Agents -- many

Anticonvulsants and Antiepileptics
-Well absorbed orally
-Good bioavailability
-Most drugs metabolized by hepatic enzymes --> active metabolites
-Adjust dose with liver disease

Drugs that inhibit antiseizure drug metabolism (CYP inhibitors) --> Toxic levels of drug in body

Drugs that induce hepatic enzymes (Rifampicin) --> inadequate levels of drug in body

Hydantoin type Antiseizure drug
-Blocks sodium channels --> blocks action potential
-Non-sedating = advantage
-High doses --> toxic
-Treats tonic-clonic and partial seizures and bipolar disorder

Drug interactions:
Sulfonamides and Valproic Acid - both displace phenytoin from its protein binding site (where its inactive) --> toxic levels

Decrease phenytoin levels by inducing liver metabolism: Phenobarbital, Rifampicin

Increase Phenytoin levels by inhibiting liver metabolism: Cimetidine, Isoniazid

Gingival hyperplasia (gums swelling) - clear indicator of toxic levels
Diplopia, Ataxia, hirsutism, rash, hematologic complications

Tricyclic type Antiseizure drug
-Blocks sodium channels
-Used for tonic-clonic and partial seizures

-Non-sedating
It's a liver enzyme inducer so it increases its own metabolism. As you give it you have to keep increasing the dose.
Drug interactions:
Increases metabolism of many other anticonvulsants
Propoxyphene and Valproic Acid inhibit its metabolism

Toxic Effects:Diplopia, Ataxia, Rashes, Blood dyscrasia

Carboxylic Acid type Antiseizure
-Activates potassium channels --> maintains the resting potential more --> makes it harder for neuron to fire

-Used specifically for tonic-clonic seizures (best) but also used for absence and myoclonic seizures
Competes for phenytoin plasma protein binding sites so increases levels of phenytoin

Drug interactions: inhibits metabolism of Phenytoin, Phenobarbital, Lamotrigine

Toxic Effects: Hepatoxicity in kids <2

Succinimide type Antiseizure drug
-Inhibits calcium channels --> block action potential

-Used for Absence seizures
Valproic acid increases level of drug
Toxic effects: Gastric issues (lose weight, not eating), hematological abnormalities, Skin rashes

Barbiturate type Antiseizure
-Mechanism = sedation
-enhances the inhibitory actions of GABA. Increased duratin of chloride channel opening
Being replaced by Primidone

Barbiturate type Antiseizure
-Replacing Phenobarbital
-mechanism = sedation
Prodrug metabolized into phenobarbital
-Used often for Infants!!

Lorazepam --> Xanax
Clonazepam --> used as alternative drug in absence seizures and myoclonic seizures. Can cause drowsiness
Clorazepate
Nitrazepam

-Mechanism: Interact with specific GABA receptor-chloride ion channel macromolecular complex. Frequency of Cl- channel opening increases --> facilitates the inhibitory effects of GABA.

Gives a calming effect. Used as an antianxiety med

All Benzodiazepines can be used for Status Epilepticus and infantile spasms

Newer Antiseizure drug
-Structural analog of GABA. How is works is unknown
-Uses: used when nothing else is working. In generalized tonic-clonic and partial seizures if refractory cases.

Drug of choice for Trigeminal neuralgia ***** know for test

Newer Antiseizure Drug
-Irreversibly inactivates GABA transaminase so GABA is not degraded --> inhibitory effects of GABA

-Used as a back-up drug in tonic-clonic and partial seizures

Newer Antiseizure Drug
-Block voltage gated sodium channels
-Used as alternative in generalized tonic-clonic and partial seizures, absence and myoclonic seizures
-Usefulness is limited by its toxic potential --> skin rashes and Steven-Johnson Syndrome

Newer Antiseizure Drug
-Blocks sodium channels and potentiates the action of GABA
-Used as back up drug for tonic-clonic and partial and absence seizures.

Phenytoin, Carbamazepine, Lamotrigine

Vigabatrin
Valproic acid also does but only at very high doses

Newer Antiseizure drug
-Inhibits reuptake of GABA transporters in neurons and glia

-Used for partial seizures

Newer Antiseizure Drug
-Blocks glutamate NMDA receptors

-Used as adjunct drug in myoclonic seizures

-Toxic effects: aplastic anemia and acute hepatic failure

Consciousness preserved

Convulsive jerking, paresthesia, psychic symptoms (altered sensory perceptoin, illusions, hallucinations), autonomic dysfunction

Impaired consciousness

Preceded, accompanied or followed by psychological symptoms (aura)

Tonic Phase: very rapid (< 1min), Abrupt loss of consciousness, Muscle rididity (arched back), respiratory arrest

Clonic Phase: 2-3 min, Jerking of body muscles, lip or tongue biting, fecal and urinary incontinence

Impaired consciousness
-Often abrupt onset and brief
-sometimes with automatism
-Loss of postural tone
-Enuresis (pee pants)
-Begin in childhood. Usually stop by 20 yo.

Single or multiple myoclonic muscle jerks

Series of seizures
-usually tonic-clonic
-Without recovery of consciousness between attacks
-Life threatening emergency

IV diazepam or Lorazepam
-effective in terminating attacks
-Short-term control

IV Phenytoin
-prolonged therapy
-Very effective, less sedating
-May cause cardiotoxicity
-Fosphenytoin much safer in emergency situation

Phenobarbital - in children

General Anesthesia - very severe status epilepticus.

Corticotropin and corticosteroids
-cushingoid side effect

Benzodiazepines

Phenytoin

Gabapentin

Valproic acid, carbamazepine, phenytoin and gabapentin

Phenytoin --> fetal hydantoin syndrome

Valproic acid --> Neural tube defect (spina bifida)

Respiratory depression
CNS depression

Give Flumazenil for bendodiazepine overdose