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What are different kinds of partial seizures?
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)
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What seizures can Valproic acid treat?
Carbamazepine?
Phenytoin?
-All Partial and Generalized types
- -All Partials
- -All partials
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What drugs are good for the treatment of Partial seizures?
- NEWER
- Gabapentin
- Lamotrigine
- Levetiracetam
- Tiagabine
- Zonisamide
- Lacosamide
- Pregabalin
- CONVENTIONAL
- Carbamazepine
- Phenytoin
- Valproic acid
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What is Lennox Gastaut syndrome?
What is the best treatment?
(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 c haracterized by frequent seizures and different seizure types; itis often accompanied by mental retardation and psychological and behavioral problems.
-lamotrigine- -felbamate
- -topiramate
- -rufinamide
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What are Seizures induced by?
What are seizures inhibited by?
- 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
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Name two Barbiturates and what they are used for.
What are some of their adverse effects?
When is it contraindicated?
What is their Mech of action?
- 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
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Name the Hydantoins
When are they used?
Which have good solubility?
What are some side effects?
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
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Name the Iminostilbenes
What are they used for?
What us the mechanism of action?
- 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
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How is Carbamazepine metabolized?
Oxcarbamazepine?
- 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
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Name the Succinimides
What are they used for?
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What is Ethosuximide Mech of action?
What are some Adverse effects?
-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
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Valproic acid
What is it used for?
What is its Mech of action?
What are some Adverse effects?
used to treat all seizure types (also migrains, and bipolar disorders)
– Prolongs recovery (from inactivation) o f 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
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What is Gabapentin used for?
What is its Mech of action?
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
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What is Lamotrigine used for?
What is its mech of action?
- –All seizure types
- –Lennox-Gastaut syndrome
- –Bipolar Disorder
- –Use dependent Na+ channel inhibitor
- –Reduces glutamate release
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What happens if you combine Valproate and Lamotrigine?
What happens if you add Phenobarbital and carbamazepine to LTG?
-Increase Lamotrigine concentrations by 2X
-Decreases its concentrations by 40%
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What is Felbamate useful for?
Why is it not 1st line?
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
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Levetiracetam
What is it used for?
- -partial seizures, with and without generalization
- -myoclonic seizures in Juvenile Myoclonic Epileps
- -Tonic-Clonic seizures in Idiopathic Generalized Epilepsy
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What is Tiagabine used for?
What is its Mech of action?
-Partial seizures, with and without generalization
-Inhibits GABA transporter (GAT-1), thus increasing duration of action of GABA.
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What is Topiramate used for?
What is its Mech of action?
- -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
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What is Zonisamide?
What is its Mech of action?
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)
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What is Vigabatrin used for?
What is its Mech of action?
What is an important side effect?
- -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
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What is Lacosamide used for?
-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
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What is Pregabalin used for?
What is its MOA?
-Partial seizures (also: Neuropathic pain due to Diabetes, Fibromyalgia, Post herpetic meuralgia)
-Binds voltage gated Ca++ channels
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What is Rufinamide?
- –Lennox-Gastaut syndrome
- –Na+ channel modulation
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