Anticonvulsants

• CNS Drugs (Anti-convulsants)


  • Sedative-hypnotic Drugs
  • Barbiturates
  • Benzodiazepines
  • Other sedative-hypnotics
• Sedative


  A substance that moderates activity and excitement while inducing a calming effect (subdues excitement> calmness)
• Hypnotic


  A substance that causes drowsiness and facilitates the onset and maintenance of natural sleep
• Sedative-hypnotic drugs


  • Barbiturates
  • Benzodiazepines
  • Other sedative-hypnotics
• Uses of sedative hypnotics

  • Relief of anxiety
  • Insomnia
  • Sedation and amnesia before medical and surgical procedures
  • Treatment of epilepsy and seizure states
  • Component of balanced anesthesia
  • Control of ethanol or other sedative-hypnotic withdrawal states
  • Muscle relaxation in specific neuromuscular disorders
  • Diagnostic aids or for treatment in psychiatry
• Barbiturates


  • Used as hypnotic and sedative
  • For induction of anesthesia and for the treatment of epilepsy and status epilepticus
• Barbiturate groups based on duration of action

  • Ultrashort-acting
  • Short-acting
  • Intermediate-acting
  • Long acting
• Ultrashort-acting barbiturates


  • Preanesthetic agents (before inducing gen anesthesia)
• Short-acting barbiturates


  • For sedation
• Intermediate-acting barbiturates


  • Anticonvulsant, insomnia, sedative-hypnotic
• Long-acting barbiturates


  • More common, DOC for Febrile Seizure
  • Used to prevent withdrawal symptoms in people who are alcohol dependent
• Mechanism of action of barbiturates

  They appear to increase the duration of the GABA-gated chloride channel openings
• Mechanism of toxicity of barbiturates

  • All barbiturates cause generalized depression of neuronal activity in the brain achieved through enhanced GABA-mediated synaptic inhibition
  • Depression of central sympathetic tone and depression of cardiac contractility cause hypotension
  • Affects Glutamate, Adenosine, and ACh receptors
• Toxic dose of barbiturates

  Generally, toxicity is likely to happen when the dose exceeds 5-10 times the hypnotic dose
• Fatal dose of shorter-acting barbiturates is > 2-3 g, Phenobarbital is > 6-10 g, Methohexital IV injections of 1-3 mg/kg have been reported to cause death in young women undergoing abortion
• Clinical presentation of mild to moderate barbiturate intoxication

  • Lethargy
  • Slurred speech
  • Ataxia
  • Nystagmus
• Clinical presentation of higher dose barbiturate intoxication

  • Hypotension
  • Coma
  • Respiratory arrest
• With deep coma, the pupils are usually small or mid-position and hypothermia may occur
• Diagnosis of barbiturate intoxication

  • Usually based on a history of ingestion
  • Specific levels: >60-80 mg/L are usually associated with coma, >150-200 mg/L with severe hypotension upon use of Phenobarbital, for short-acting barbiturates, coma is likely when serum concentration exceeds 20-30 mg/L
• Other useful laboratory studies for barbiturate intoxication

  • Electrolytes, glucose, BUN, creatinine, arterial blood gases or oximetry, chest x-ray
• Treatment for barbiturate intoxication

  • Emergency and supportive measures
  • Specific drugs and antidotes (no specific antidote, only symptomatic)
  • Decontamination (prehospital: activated charcoal and ipecac-induced emesis, hospital: activated charcoal and cathartic)
  • Enhanced elimination (alkalinization of urine increases elimination of phenobarbital, repeat-dose activated charcoal decreases half-life of phenobarbital, hemoperfusion for severely intoxicated patients)
• Benzodiazepines


  • Drug class that varies widely in potency, duration of effect, presence or absence of active metabolites, and clinical use
  • Death from overdose is rare, unless combined with other CNS depressant agents
• Mechanism of action of benzodiazepines

  They appear to increase the FREQUENCY of the GABA-gated chloride channel openings
• Mechanism of toxicity of benzodiazepines

  Cause generalized depression of spinal reflexes and the reticular activating system, which may cause coma and respiratory arrest
• Benzodiazepines that can cause respiratory arrest


  • Short-acting triazolobenzodiazepines such as Triazolam, Alprazolam and Midazolam
• Benzodiazepines that can cause cardiopulmonary arrest

  Rapid injection of Diazepam
• The toxic therapeutic ratio for benzodiazepines is very high, prone to dependence
• Clinical presentation of benzodiazepine intoxication

  • Lethargy
  • Slurred speech
  • Ataxia
  • Coma
  • Respiratory arrest
  • Hypothermia may occur
  • Hyporeflexia and midposition or small pupils
• Diagnosis of benzodiazepine intoxication


  • Usually based on the history of ingestion or recent injection
  • Serum drug levels, urine and blood qualitative screening
  • Glucose, arterial blood gases or pulse oximetry
• Flumazenil


  • A specific benzodiazepine receptor antagonist that can rapidly reverse coma
  • Administered intravenously with a starting dose of 0.1-0.2 mg, repeated as needed up to a total of no more than 3 mg
• Potential drawbacks of using flumazenil include inducing seizures in patients with cyclic antidepressant overdose, inducing acute withdrawal, and common resedation when the drug wears off after 1-2 hours
• Decontamination for benzodiazepine intoxication

  • Prehospital: activated charcoal and ipecac-induced emesis
  • Hospital: activated charcoal and cathartic
• There is no rule for diuresis, dialysis, or hemoperfusion, and repeat dose charcoal has not been studied for enhanced elimination of benzodiazepines
• Benzodiazepines with no active metabolites

  • Alprazolam
  • Clonazepam
  • Estazolam
  • Halazepam
  • Lorazepam
  • Oxazepam
  • Temazepam
  • Triazolam
• Benzodiazepines with active metabolites

  • Chlordiazepoxide
  • Clorazepate
  • Diazepam
  • Flurazepam
  • Midazolam
  • Quazepam
• Chloral hydrate


  Metabolized to trichloroethanol, which also has CNS-depressant activity and may sensitize the myocardium to catecholamines, resulting in cardiac arrhythmias
• Glutethimide


  Sedative introduced as a safe alternative to barbiturates for insomnia, often produces anticholinergic effects and prolonged/cyclic coma
• Meprobamate


  Hypotension is more common with this agent than with other sedative hypnotics, used for anxiety
• Methaqualone


  Unusual among sedative-hypnotics in frequently causing muscular hypertonicity, clonus, and hypereflexia, overdose can cause delirium, convulsion, vomiting, kidney failure and death
• Seizure


  Excessive abnormal electrical discharge from the cortical neurons, can be a single occurrence or recurrent (epilepsy)