sedative

• Sedatives


  • Cause sedation (reduce anxiety)
  • Treat anxiety states
• Hypnotics


  • Produce drowsiness and encourage sleep
  • Treat sleep disorders
• Anxiety states and sleep disorders are common problems
• World Sleeping Day


  3.21
• Effects of Sedative-Hypnotics


  • Anti-anxiety
  • Sedation-Hypnosis
  • Anti-convulsant effect
  • Antiepileptic
  • Anesthesia
  • Respiratory paralysis (death)
• Sedative-Hypnotics


  • Benzodiazepines (BZ/BDZ/BZD)
  • Barbiturates
  • Others
• Benzodiazepines (BZ/BDZ/BZD)


  • Short-acting (t1/2<6 h)
  • Intermediate-acting (t1/2= 6~20 h)
  • Long-acting (t1/2>20 h)
• Barbiturates


  • Long-acting
  • Intermediate-acting
  • Short-acting
  • Super short-acting
• Pharmacokinetics


  • Absorption: po; im; iv
  • Distribution: Enter CNS, Cross placental barrier, Enter breast milk
  • Biotransformation: Liver drug metabolizing, Enzyme inducer: Barbiturates
  • Excretion: Kidney
• Mechanism of Benzodiazepines


  Chloride ion channel, GABA-BZ receptor-chloride ion channel complex
• Benzodiazepines prolong the opening time of the chloride channel, enhancing the inhibitory effect of GABA
• Barbiturates bind to the barbiturate binding site, prolonging the opening time of the chloride channel to exert an inhibitory effect
• Pharmacological effects


  • Antianxiety
  • Sedation & Hypnosis
  • Anesthesia
  • Anticonvulsant effects and antiepileptic effects
  • Muscle Relaxation
  • Respiratory and cardiovascular depression
  • Tolerance and dependence
• Antianxiety


  Smaller than hypnotic dose, relieve anxiety, decrementaling psychomotor and cognitive functions, anterograde amnesic
• Sedation & Hypnosis


  Two phases of sleep: REM sleep and NREM sleep, decrease the latency of sleep onset, prolong duration of NREM sleep, shorten duration of REM sleep
• Anesthesia


  High lipid solubility, rapid tissue redistribution, use for induction of the anesthetic state
• Anticonvulsant effects and antiepileptic effects

  Inhibit development and spread of epileptiform activity, without marked CNS depression
• Muscle Relaxation


  Inhibit polysynaptic reflexes, inhibit internuncial transmission, depress transmission at the skeletal neuromuscular junction at high doses
• Respiratory and cardiovascular depression

  In patients with pulmonary disease, overdose, depressing the medullary respiratory and cardiovascular center
• Tolerance and dependence


  Mechanism of tolerance: Barbiturates - increased drug metabolism, changed responsiveness of CNS; Benzodiazepines - down-regulation of brain BZ receptors
• Clinical Uses


  • Anxiety states: first choice drug is BDZ
  • Sleep disorders: first choice drug is BDZ
  • Anticonvulsant and antiepileptic
  • Muscle relaxant
  • Inducing anesthesia
• Compared with Barbiturates, Benzodiazepines have a higher therapeutic index, less liver enzyme induction effect, less adverse effects, and less rebound reaction
• Newer drugs for sleep disorders like Zolpidem and Zaleplon have less change in sleep patterns, less rebound insomnia, and less risk of developing tolerance and dependence
• Anticonvulsant uses


  • Tetanus
  • Eclampsia
  • Intoxication and fever (children)
• Antiepileptic uses


  • Diazepam for status epilepticus (iv)
  • Phenobarbital for generalized tonic-clonic seizure (grand mal)
• Muscle relaxant uses


  Reduces muscle rigidity induced by CNS damage, relieves muscle spasm induced by joint pathological changes
• Inducing anesthesia


  Thiopental, iv
• Adverse Effects


  • After effect ('hang-over' effect)
  • Rebound reaction
  • Tolerance and dependence
  • Acute overdose poisoning
• After effect ('hang-over' effect)

  Dizziness, drowsiness, dysphoria, fatigue, impaired judgment, and diminished motor skills, more common with drugs with long t1/2
• Rebound reaction


  Insomnia, anxiety, tremor, rebounded prolonged REM sleep with nightmare
• Tolerance and dependence


  Long time use, more common with Barbiturates than Benzodiazepines
• Acute overdose poisoning


  Severe respiratory depression, more common with Barbiturates than Benzodiazepines