Pharm II (AED)

1. Simple partial seizures (consciousness not impaired)

2.Complex partial seizures (with impairment of consciousness: may sometimes begin with simple symptomatology)

3.Partial seizures evolving to secondarily generalized seizures (this may be generalized tonic-clonic, tonic, or clonic)

-All Partial and Generalized types

• -All Partials
• -All partials

• NEWER
• Gabapentin
• Lamotrigine
• Levetiracetam
• Tiagabine
• Zonisamide
• Lacosamide
• Pregabalin

• CONVENTIONAL
• Carbamazepine
• Phenytoin
• Valproic acid

(LGS) is a difficult-to-treat form of childhood-onset epilepsy that most often appears between the second and sixth year of life, and is characterized by frequent seizures and different seizure types; itis often accompanied by mental retardation and psychological and behavioral problems.

• -lamotrigine
• -felbamate
• -topiramate
• -rufinamide

• Seizures induced by
• –GABAA antagonists
• –Glutamate receptor agonists
• NMDA
• AMPA (amino methyl propionic acid)
• kainic acid

• Seizures are inhibited by
• -GABA agonists
• -Glutamate receptor antagonists

• 1.Phenobarbital
• 2.Primidone

• Used to treat
• –Partial seizures
• –Generalized tonic-clonic seizures

Folate deficiency, Irritability, Agitation, Confusion, Sedation

May indice fatal attacks of porphyria in patients with acute intermittent porphyria

-inhibition via GABA-A receptor

• Phenytoin
• Fosphenytoin

Used to treat all types of partial seizures and tonic-clonic seizures, but NOT absence seizures

• -phenytoin – poor aqueous solubility
• -fosphenytoin –good solubility
• _________________
• -Folate deficiency
• -Vitamin D deficiency
• -Teratogenic effects
• -Drug interactions

• Carbamazepine
• Oxcarbazepine

• -Used to treat most types of seizures, except myoclonic and absence
• -Also used for Trigeminal Neuralgia and Bipolar disorder

-Na+ channels, by prolonging recovery from inactivation

• Induces its own metabolism by Cyp3A4, thus requires adjustment after about 2-3 weeks
• _________________________
• -Less potent
• -Can result in elevated levels of other Anti epileptic drugs like:phenytoin, valproic acid, lamotrigine

• Ethosuximide
• Phensuximide

Treat Absence Seizures

-Inhibition of low threshold Ca2+ currents (T currents) in thalamic neurons which play a role in 3-Hz spike-wave rhythms typical of absence seizures.

-SJS

used to treat all seizure types (also migrains, and bipolar disorders)

– Prolongs recovery (from inactivation) of voltage-activated Na+ channels [similar to carbamazepine]

• -Reduces low-threshold Ca2+ currents
• (T currents) in nodose ganglion [Similar to ethosuximide effects in thalamic neurons]

• -Transient hair loss
• -Weight gain
• -Elevated hepatic enzymes

Used in partial seizures with or without secondary generalizations

-Not a GABA agonist (despite structure)

• -Increase the release of GABA-->Inhibition of
• L-type Ca2+ channels

• –All seizure types
• –Lennox-Gastaut syndrome
• –Bipolar Disorder

• –Use dependent Na+ channel inhibitor
• –Reduces glutamate release

-Increase Lamotrigine concentrations by 2X

-Decreases its concentrations by 40%

Useful for the treatment of:

• –Partial seizures, with and without generalization
• –Lennox-Gastaut syndrome

-Not first line therapy due to significant increased risk of aplastic anemia and hepatic failure

• -partial seizures, with and without generalization
• -myoclonic seizures in Juvenile Myoclonic Epileps
• -Tonic-Clonic seizures in Idiopathic Generalized Epilepsy

-Partial seizures, with and without generalization

-Inhibits GABA transporter (GAT-1), thus increasing duration of action of GABA.

• -Adjunctive therapy for refractory partial or generalized seizures
• -Lennox-Gastaut syndrome

• –Blockade of use dependent Na+ channels
• –Inhibition of L-type Ca2+ channels
• –Enhancement of GABA activity
• –Glutamate antagonism

Adjunctive therapy for partial seizures

• –Inhibits low threshold Ca2+ currents (T currents)
• –Probably also via Na+ channels, by prolonging recovery from inactivation (like carbamazepine and phenytoin)

• -Approved as monotherapy for infantile spasms
• -adjunctive therapy for refractory epilepsy
• -Used for partial seizures with or without secondary generalization
• __________________________
• -Irreversible inhibitor of GABA transaminase (GABA-T), thus increasing GABA levels

Severe Peripheral Visual Field defects

-Adjunctive treatment in partial onset seizures

• MOA:
• –Enhances slow inactivation of voltage-gated Na+ channels
• -Stabilization of hyperexcitable neuronal membranes
• -Inhibition of repetitive neuronal firing

-Partial seizures (also: Neuropathic pain due to Diabetes, Fibromyalgia, Post herpetic meuralgia)

-Binds voltage gated Ca++ channels

• –Lennox-Gastaut syndrome
• –Na+ channel modulation