Pharmacology for Treatment of Seizures

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Pharmacology for Treatment of Seizures
2013-04-01 20:22:35
Seizures AED Antiepileptics

anti epileptic drugs
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  1. 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
  2. Aura
    subjective disturbance of perception that represents the start of certain seizures
  3. Ictal Phase
    the actual seizure
  4. Post-Ictal Phase
    the period after the seizure when the individual is amnesic confused and disoriented
  5. Generalized Seizures
    • LOSS of consciousness
    • Entire cortex affected at once
    • EEG shows general spike and wave pattern
  6. Partial (focal) Seizures
    • Consciousness is NOT lost
    • Seizures in specific part of the brain
    • EEG is focal
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. Antiepileptic drugs that block sodium channels
    Phenytoin, Carbamazepine, Valproate

    Stops the action potential and therefore stops the spread
  14. Antiepileptic Drugs that Potentiate GABA
    Barbiturates, Benzodiazepines, Valproate
  15. Antiepileptic drugs that block calcium channels
  16. Drugs to treat Tonic Clonic seizures and Partial seizures
    • Phenytoin
    • Phenobarbital
    • Primidone
    • Carbamazepine
  17. Drugs that treat Absence seizures
    • Ethosuximide
    • Clonazepam
  18. Drugs that treat both tonic clonic and absence
    • Valproic Acid
    • Lamotrigine
  19. 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
  20. Penytoin
    Side Effects
    • CNS
    • Nystagmus, ataxia, dysarthria, decreased coordination, mental confusion

    • GI
    • Nausea, vomiting

    • 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


    • Connective Tissue
    • Gingival Hyperplasia
    • Coarsening of facial features

    • Folic Acid Deficiency (blocks deconjugases)
    • macrocytic anemia, teratogenic


    • Pregnancy
    • folic acid deficiency
    • fetal hydantoin syndrome
    • hemorrhagic disease in the newborn
    • reduced efficacy of OC's
  21. 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
  22. 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
  23. 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
  24. 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
  25. Carbamazepine
    Side Effects
    • CNS
    • dizziness, ataxia, vertigo, nystagmus, blurred vision

    • Hemopoietic complications
    • thrombocytopenia, agranulocytosis, aplastic anemia

    • Liver toxicity
    • cholestatic jaundice


    • Pregnancy (category D)
    • teratogenic (craniofacial and limb abnormalities)
    • Hemorrhagic Disease of the Newborn
    • Reduced efficacy of OC's
  26. Ethosuximide
    Absence seizure (drug of choice)

    blocks calcium channels to prevent the spike and wave

    • CNS
    • drowsiness, lethargy

    • GI
    • nausea vomiting
  27. Clonazepam
    • Absence Seizures
    • Anxiety Disorders

    blocks seizure spread by enhancing GABAA

    • Side Effects
    • drowsiness, ataxia, impaired cognition, memory and behavioral changes, 

    Tolerance develops
  28. Valproic Acid
    Divalproex Sodium

    tonic clonic, absence, complex partial seizures

    • Other uses
    • Bipolar disorder
    • Migraine prophylaxis

    • Mechanism
    • increases the synthesis of GABA
    • blocks sodium channels
  29. Valproic Acid

    Side Effects
    • Hypersensitivity reactions
    • hepatitis, pancreatitis
    • (liver function test before treatment)

    Alopecia - treat with baby shampoo

    Tremor - fine action tremor of hand

    • GI
    • nausea, vomiting (give sodium salt to combat this)

    Pregnancy (Category D)
  30. Lamotrigine
    tonic clonic, absence, complex partial seizures

    Bipolar disorder

    • Mechanism
    • blocks sodium channels
    • Suppresses release of glutamate

    • Side Effects
    • Rash - Stevens-Johnson Syndrome
  31. 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
  32. 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
  33. 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
  34. 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
  35. 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