EPILEPSY

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 Different seizure types & syndromes originating from several mechanism that have in

common sudden, excessive & synchronous discharge of cerebral neurons

3rd most common disease after CVS & Alzheimer



Idiopathic Epilepsy

when no specific anatomic cause for the seizure such as Trauma or Neoplasm, patient may be diagnosed with Idiopathic/Cryptogenic/Primary Epilepsy

Symptomatic Epilepsy

 Ano. Of cause such as Illicit drug use,tumor, head injury, hypoglycemia, meningeal infection, rapid withdrawl from Alchol can precipitate seizure

Classification of Seizure

1) Partial seizure: involve only a portion of brain,part of one lobe of one Hemisphere...

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I. Simple Partial: these seizures are caused by a group of hyperactive neuron exhibiting

abnormal electrical activity which confined to single locus in the brain

ll. Complex Partial: These seizures exhibit complex sensory hallucination & mental

distortion. Motor dysfunction involves Chewing movement, Diarrhea, Urination.

2) Generalized seizure: May begin locally & include abnormal electrical discharge throughout both Hemisphere of brain..

Immediate loss of consciousness

Tonic-Clonic

 Continuous contraction (tonic) & rapid contraction & relaxation (Clonic) loss of consciousness...depletion of Glucose 

Absence

Brief, abrupt and self-limiting loss of consciousness...Patient stares & rapid eye-blinking..3-5yr of age

Myoclonic

 Short episodes of muscle contraction that occur for several minutes... occur after Awakening & brief jerks of the limbs....at any age

Febrile Seizure

 young children develop seizure by high fever...

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V-Status Epilepticus

Two or more seizures occur without recovery of full consciousness b/w them.

Benzodiazepines (BZD)

bind to GABA inhibitory...Diazepam & Lorazepam as Adjunctive therapy for myoclonic as well as partial & generalized seizure

Carbamazeoine (CBZ)

block Na+ channel

T.E= Partial, Generalized tonic-clonic, Trigeminal neuralgia, Bipolar disorder... drugs that Θ UGT & UDP inhibit CBZ conc. Leads totoxicity

S.E

Hyponatremia...Contraindicated in Absence seizure

Ethosuximide

 inhibit T-type Ca++ channels...Effective only Primary Generalized Absence Seizure....Very Narrow Spectrum of Activity

Felbamate

Broad spectrum...Block Na+ channel..Competing with Glycine-Coagonist on the NMDA Glutamate...Block Ca++ channel...Increase action of GABA..inhibtor of drugs metabolized wuth CYP2C19 & Inducer ofdrugs metabolized by CYP3A4..

Used in Refractory Epilepsies...risk of Aplastic Anemia & Hepatic Failure



Gabapentin

 Analog of GABA..but does not act on GABA..unknown mechanism... Non- Linear P.K...good choice for elder Patients...used in Postheerpetic neuralgia

Lacosamide

 block Na+ channel..binds with Collapsin Response Mediator Protein-2 (CRMP-2)...cause EUPHORIA like Alprazolam labeled as Controlled substance V...

Lamotrigine

block Na+ channel & Ca++ channel...cause RASH...dosage reduced when used VALPROATE..

Levetiracetam

 high affinity for Synaptic Vesicle Protein (SV2A)...cause sleep.dizziness

OxyCarbazepine

 Prodrug...metabolite into10-MonoHydroxy (MHD)...have anticonvulsant block Na+ channel...modulate Ca++ channel..S.E; visual disturbance

Phenobarbital

 synthesized by 1912 by Bayer...activate GABA...used in Status Epilepticus

Phenytoin & Fosphenytoin 

block Na+ channel...block Ca++ channel....

used in status epilepticus,partial seizure, generalized tonic-clonic....90% P.B...follow Zero-order kinetics...not used by I.M cause tissue damage...cause Nystagmia & Ataxia

Gingival Hyperplasia caused by Phenytoin..Fosphenytoin is prodrug...used I/M

Pregabalin

bind to α2-δ site of Ca++ channel in CNS...inhibit its action...cause blurred vision, weight gain, peripheral edema

Rufinamide

block Na+ channel..Adjunct treatment of seizure with Lennox-Gastaut..not used in pregnancy...Increase QT interval , not used in short QT syndrome

Tiagabine

increase GABA by inhibiting uptake of GABA from presynaptic neuron..bind to Albumin & α1-acid glycoprotein 95%....cause GIT upset

Topiramate

inhbit NMDA 7L-type Ca++ channel...activate GABA...Carbonic Anhydrase Inhbitor...used for MIGRAINE...reduce Ethinyl Estradiol, women should use extra Birth control pills....Renal stones reported...cause Glaucoma, Hyperthermia, Oligohidrosiss

Valproic Acid & Divalproex

 valproic acid free acid...broad spectrum...block Na+, Ca++, ..Teratogenic drug...cause birth defects

Vigabatrin

irreversible inhibitor of GABA-Transaminase which metabolize GABA...available in “SHARE” program

Zonisamide

 Sulfonamide derivative, ...broad spectrum..block Na+ & Ca++..cause

Kidney stone, Hyperthermia

VAGAL NERVE STIMULATION(VNS)

For treatment of Depression & Seizure...surgical implant of pulse generator with battery

and Lead wire for stimulus..

DEEP BRAIN STIMULATION (DBS)

Pacemaker like device...for partial-onset seizure



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