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Epilepsy
Disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of the condition. Requires the occurrence of atleast one epileptic seizure
Sudden imbalance between excitatory and inhibitory forces in the cortical neurons... too much excitation
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Aura
subjective disturbance of perception that represents the start of certain seizures
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Ictal Phase
the actual seizure
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Post-Ictal Phase
the period after the seizure when the individual is amnesic confused and disoriented
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Generalized Seizures
- LOSS of consciousness
- Entire cortex affected at once
- EEG shows general spike and wave pattern
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Partial (focal) Seizures
- Consciousness is NOT lost
- Seizures in specific part of the brain
- EEG is focal
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Tonic-Clonic Seizures (Primary)
Grand Mal
last 2-5 minutes
- Loss of consciousness - no warning
- Tonic Stage - patient falls and cries out
- Clonic Stage - generalized bisynchronous rhythmic forceful jerking movements
- Post-Ictal Stage - exhaustion, sleep, disorientation, amnesia
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Absence Seizures
Petit Mal seizures
- may occur up to 100 times a day
- can be provoked
- EEG - 3 Hz "spike and wave" pattern
- 2-20 sec
- Abrupt loss of consciousness-no warning or loss of posture
- Clonic Movements-Twitching of the eyes and hands
- Abrupt consciousness
- Resumption of normal activities
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Simple Partial Seizure
- Focal, Cortical
- Aura - Altered sensations, illusions/hallucinations
- can become tonic clonic
- no loss of consciousness
- asymmetrical convulsion, localized sensory disturbances
- no postictal stage
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Complex Partial Seizure
- Psychomotor/temporal lobe
- impairment of consciousness
- differentiate from psychosis and night terrors
- can become tonic clonic
- 4 A's
- Aura -often olfactory or epigastric
- Alteration of consciousness
- Automatisms/strange behavior
- Amnesia
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Status Epilepticus
two or more seizures without recovery of consciousness
single seizure lasting more than 20-30 minutes
life threatening... must stop as soon as possible
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How to stop Epilepsy
AED's try to stop the spread of seizures.
- Prevent post-tetanic potentiation
- Prolong refractory period
- Potentiate inhibitory activity
- Reduce excitatory activity
- Increase excitatory synaptic threshold
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Antiepileptic drugs that block sodium channels
Phenytoin, Carbamazepine, Valproate
Stops the action potential and therefore stops the spread
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Antiepileptic Drugs that Potentiate GABA
Barbiturates, Benzodiazepines, Valproate
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Antiepileptic drugs that block calcium channels
Ethosuximide
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Drugs to treat Tonic Clonic seizures and Partial seizures
- Phenytoin
- Phenobarbital
- Primidone
- Carbamazepine
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Drugs that treat Absence seizures
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Drugs that treat both tonic clonic and absence
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Phenytoin
Uses and mechanism and pharmacokinetics
partial, tonic clonic, status epileptics
also used for treatment of trigeminal neuralgia
Digoxin-induced AV-block
blocks sodium channels to prevent spread
- eliminated by zero-order kinetics
- narrow therapeutic window
- mostly bound to albumin
- inactivated by P-450
- no half life
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Penytoin
Side Effects
- CNS
- Nystagmus, ataxia, dysarthria, decreased coordination, mental confusion
- Hypersensitivity Reactions
- rash, t cell mediated, type 4- not dangerous but lets you know that the patient could possibly go to Steven's Johnson Syndrome... if SJS occurs then take them off the drug immediately
Hirsutism
- Connective Tissue
- Gingival Hyperplasia
- Coarsening of facial features
- Folic Acid Deficiency (blocks deconjugases)
- macrocytic anemia, teratogenic
Osteomalacia
- Pregnancy
- folic acid deficiency
- fetal hydantoin syndrome
- hemorrhagic disease in the newborn
- reduced efficacy of OC's
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Phenobarbital
Uses, mechanism, pharmacokinetics
Partial, tonic clonic, status epilepticus
Binds to the barbiturate binding site on GABAA receptors and prolongs the chloride channel opening
induces P-450 enzymes in the liver
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Phenobarbital
Side Effects and Contraindications
- CNS
- sedation, ataxia, nystagmus, impaired cognition, hyperactivity in children
folate deficiency
- Pregnancy (Category D)
- teratogenic
- hemorrhagic disease in the newborn
- reduced efficacy of OC's
- Contraindications
- acute intermittent porphyria
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Carbamazepine
Uses, mechanism, pharmacokinetics
- Partial seizures, tonic clonic
- trigeminal neuralgia (drug of choice)
- Bipolar disorder (alternative to lithium)
- Neurogenic Diabetes Insipidus (stimulates ADH)
- Mechanism
- blocks sodium channels to prevent spread
- Pharmacokinetics
- 80% bound to plasma proteins
- induces P-450 enzymes
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Primidone
Partial and tonic clonic seizures
metabolized to phenobarbital and PEMA
- main action is through the phenobarbital
- reduces seizure spread by enhancing GABA
- SE, CI, DI
- Intense sedation, dizziness, and nausea - transient
- also any side effects of phenobarbital
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Carbamazepine
Side Effects
- CNS
- dizziness, ataxia, vertigo, nystagmus, blurred vision
- Hemopoietic complications
- thrombocytopenia, agranulocytosis, aplastic anemia
- Liver toxicity
- cholestatic jaundice
SIADH
- Pregnancy (category D)
- teratogenic (craniofacial and limb abnormalities)
- Hemorrhagic Disease of the Newborn
- Reduced efficacy of OC's
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Ethosuximide
Absence seizure (drug of choice)
blocks calcium channels to prevent the spike and wave
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Clonazepam
- Absence Seizures
- Anxiety Disorders
blocks seizure spread by enhancing GABA A
- Side Effects
- drowsiness, ataxia, impaired cognition, memory and behavioral changes,
Tolerance develops
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Valproic Acid
Divalproex Sodium
USES and MECHANISM
tonic clonic, absence, complex partial seizures
- Other uses
- Bipolar disorder
- Migraine prophylaxis
- Mechanism
- increases the synthesis of GABA
- blocks sodium channels
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Valproic Acid
Side Effects
- Hypersensitivity reactions
- hepatitis, pancreatitis
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Alopecia - treat with baby shampoo
Tremor - fine action tremor of hand
- GI
- nausea, vomiting (give sodium salt to combat this)
Pregnancy (Category D)
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Lamotrigine
tonic clonic, absence, complex partial seizures
Bipolar disorder
- Mechanism
- blocks sodium channels
- Suppresses release of glutamate
- Side Effects
- Rash - Stevens-Johnson Syndrome
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Narrow Spectrum new AED's
- Gabapentin
- partial seizures
- Secondarily generalized tonic clonic
- commonly used for neuropathic pain
- enhances GABA
- reduces glutamate levels
- Tiagabine
- Inhibits GABA uptake
- rerefractory partial and secondarily generalized seizures
- Oxcarbazepine
- Analogue of carbamazepine
- Refractory partial and generalized tonic clonic
- Levetiracetam
- Mechanism unknown
- Refractory partial seizures
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New Broad Spectrum AED's
- Felbamate
- Refractory complex partial epilepsy
- Refractory Lennox-Gastaut syndrome
- blocks NMDA receptors and calcium channels
- blocks sodium channels to prevent spread
- Aplastic anemia
- Hepatic Failure
- Topiramate
- Multiple mechanisms of
action - migraine prophylaxis
- Angle Closure glaucoma and renal stones
- Zonisamide
- blocks sodium and calcium channels
- CI in pts with sulfa allergies
- Vigabatrin
- increases GABA levels
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Status Epilepticus Treatment Strategy
Lorazepam or Diazepam (IV)
if that doesnt work then try phenytoin or Fosphenytoin(iv version)
if that doesnt work then Phenobarbital (IV)
if that doesnt work put them into a coma
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When to discontinue AED's
seizure freedom for more than 2 years
- Favorable factors
- control achieved easily on one drug at low dose
- no previous attempts and withdrawal
- normal neurologic exam and EEG
- primary generalized seizures
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Epilepsy and pregnancy
- Teratogenic Effects (first trimester)
- Valproate
- Phenytoin
- Acute Hemorrhagic Disease of the Newborn
- Phenobarbital
- Primidone
- Phenytoin
- Carbamazepine
- Failure of OC's
- Carbamazepine
- Phenobarbital
- Primidone
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