antiepileptic

• Drug interactions involving phenytoin can occur due to its induction or inhibition of these cytochrome P450 enzymes.
• Phenytoin has a narrow therapeutic index, which means it must be carefully monitored to avoid toxicity or subtherapeutic levels.
• Phenytoin is an anti-epileptic drug that can be used to treat seizures
• Phenytoin is also known as Dilantin
• Seizures


  Episodes of abnormal electrical activity in the brain that cause involuntary movements, sensations, or thoughts

  
• Seizures


  • Caused by depolarization increases more (overactivity) in neurons in the central nervous system

  
• Seizures can result from head trauma, stroke, brain tumors, hypoxia, hypoglycemia, fever, chronic alcohol withdrawal and other conditions that alter neuronal function

  
• Seizures


  • Self-limiting
  • Last for 1 second to 5 minutes
  • Preceded by an aura (sensation or feeling that can indicate an upcoming seizure)

  
• Epilepsy


  Recurrent seizures that happen time after time

  
• Epilepsy


  • Appears to have a genetic basis
  • Also develops from environmental perturbations (temperature, light, sound, nutrition, maternal effects, infectious agents, and brain trauma)
• Having a single seizure doesn't mean that you have epilepsy, at least 2 seizures with an unknown or unprovoked seizure that happens at least 24 hours apart are generally required to diagnose that the patient is epileptic

  
• Treatments for seizures/epilepsy


  • Medications
  • Surgery (to control seizures)

  
• Neurobiology of seizures


  1. Depolarization of neuron

  2. Influx of sodium and calcium into neuron

  3. Release of neurotransmitter glutamate

  4. Glutamate binds to AMPA and NMDA receptors on other cells, causing further depolarization and excitation
• Seizures


  • Caused by overexcitation of neurons in the central nervous system

  
• GABA


  Major inhibitory neurotransmitter, promotes influx of chloride ions which causes hyperpolarization and decreased excitability
• Types of seizures


  • Partial seizures (focal onset)
  • Generalized seizures (affecting the whole brain)
• Partial seizures


  • Simple partial seizure (focal onset aware)
  • Complex partial seizure (focal onset impaired awareness)
  • Secondary generalized seizure (focal seizure becoming generalized)
• Generalized seizures


  • Generalized tonic-clonic seizure (grand mal)
  • Absence seizure (petit mal)
  • Atonic seizure (drop attacks)
  • Myoclonic seizure (rhythmic jerking spasms)
• Stages of seizures


  • Prodrome
  • Pre-ictal
  • Ictal
  • Postictal
• Drugs for partial and generalized tonic-clonic seizures

  • Carbamazepine
  • Oxcarbazepine
  • Phenytoin
  • Fosphenytoin
• Carbamazepine and oxcarbazepine


  First line agents for partial and generalized tonic-clonic seizures, mechanism of action is blocking voltage-sensitive sodium channels to inhibit spread of abnormal electrical discharges
• Carbamazepine


  • Additional mechanisms: converted to carbamazepine epoxide which also blocks sodium and calcium channels, blocks adenosine receptors which can cause sleepiness
• Adverse effects of carbamazepine and oxcarbazepine

  • Drowsiness
  • Ataxia
  • Other CNS depression symptoms
  • GI reactions
  • Aplastic anemia
• Phenytoin and fosphenytoin


  Hydantoin derivatives, fosphenytoin is more soluble in water and prevents precipitation after IV/IM administration
• Patients taking phenytoin and fosphenytoin need to be closely monitored as these drugs have a narrow therapeutic index
• Erythropoiesis


  Formation of blood cells
• Erythropoiesis can cause


  Aplastic anemia
• Aplastic anemia


  Stop producing enough blood cells
• Carbamazepin produces fewer adverse effects than Phenytoin
• Carbamazepin

  Potent inducer of CYP450 enzymes
• Erythropoiesis induces CYP450 enzymes


  Decreased serum level of Lamotrigine, Phenytoin, Topiramate, and Valproate
• Drugs above can eliminate earlier and result in under dosage
• Carbamazepine (CBZ)


  Drug of choice for Trigeminal Neuralgia (intense pain in both side or one side of face) usually upper side of ear
• Carbamazepine (CBZ)


  Alternative to Lithium in the treatment of Bipolar Disease
• Carbamazepine inhibits the influx of sodium


  Leads to increase of lithium
• If patient have seizure & bipolar disorder needs lithium bromide it may lead to toxicity
• Phenytoin


  Hydantoin derivative
• Phenytoin


  Poorly soluble in water
• Fosphenytoin


  More soluble in water
• Fosphenytoin


  Prevents precipitation after IV, IM, administration