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22 sedative hypnotic drugs

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22 sedative hypnotic drugs

  1. 1. SEDATIVE-HYPNOTIC DRUGS Anita Q. Sangalang, MD, FPOGS FACULTY OF PHARMACY UNIVERSITY OF SANTO TOMAS
  2. 2. SEDATIVE-HYPNOTIC DRUGS SEDATIVE-HYPNOTICS Benzodiazepines Barbiturates Miscellaneous agents Short Ultra action action Intermediate Short Buspirone action action Chloral hydrate Long Long Zaleplon action action Zolpidem
  3. 3. SEDATIVE-HYPNOTIC DRUGS SEDATION • Reduction of anxiety • Calming effect ANXIOLYTIC • Drug that reduces anxiety • Sedative HYPNOSIS • Induction of sleep
  4. 4. SEDATIVE-HYPNOTIC DRUGS • Lipid soluble • Absorbed well from the GIT • Good distribution to the brain • Metabolized before elimination from the body by hepatic enzymes
  5. 5. SEDATIVE-HYPNOTIC DRUGS BENZODIAZEPINES • Converted initially to active metabolites with long half-lives • Diazepam and flurazepam  After several days of therapy accumulation of active metabolites can lead to excessive sedation
  6. 6. SEDATIVE-HYPNOTIC DRUGS BENZODIAZEPINES • Lorazepam and oxazepam  Undergo extrahepatic conjugation and do not form active metabolites
  7. 7. SEDATIVE-HYPNOTIC DRUGS BENZODIAZEPINES • Bz receptors  Form part of GABAA receptor-chloride ion channel macromolecular structure  Binding facilitates the inhibitory actions of GABA  Increased GABA mediated chloride ion conductance
  8. 8. SEDATIVE-HYPNOTIC DRUGS BENZODIAZEPINES • Flumazenil  Reverses the CNS effects of benzodiazepines  Antagonist at the Bz receptor
  9. 9. SEDATIVE-HYPNOTIC DRUGS BENZODIAZEPINES • Beta-carbolines  High affinity for Bz receptors  Can elicit anxiogenic and convulsant effects  Inverse agonists
  10. 10. SEDATIVE-HYPNOTIC DRUGS BENZODIAZEPINES • Diazepam desmathyldiazepam active oxazepam metabolites conjugation
  11. 11. SEDATIVE-HYPNOTIC DRUGS BENZODIAZEPINES • Chlorazepam • Estazolam immediately converted to • Oxazepam inactive metabolites
  12. 12. SEDATIVE-HYPNOTIC DRUGS BARBITURATES • Extensively metabolized • Depress the neuronal activity • Facilitates and prolongs the inhibitory effects of GABA and glycine
  13. 13. SEDATIVE-HYPNOTIC DRUGS BARBITURATES • Bind to multiple isoforms of GABAA receptor but at different sites from those with which benzodiazepines interact
  14. 14. SEDATIVE-HYPNOTIC DRUGS BARBITURATES • Not antagonize by flumazenil • Increase the duration of GABA- mediated chloride ion channel opening
  15. 15. SEDATIVE-HYPNOTIC DRUGS BARBITURATES • Block the excitatory transmitter glutamic acid and at high concentration, sodium channels
  16. 16. SEDATIVE-HYPNOTIC DRUGS BARBITURATES • Thiopental  Drug with highest lipid solubility enter the CNS rapidly  Used as induction agents in anesthesia
  17. 17. SEDATIVE-HYPNOTIC DRUGS BARBITURATES • Thiopental  CNS effects are terminated by rapid redistribution of the drug from the brain to other highly perfused tissues (skeletal muscles)
  18. 18. SEDATIVE-HYPNOTIC DRUGS BARBITURATES • Thiopental  Metabolism occur via oxidation and glucoronidation  Converted to active metabolite
  19. 19. SEDATIVE-HYPNOTIC DRUGS BARBITURATES • Phenobarbital  Goes to the liver to be oxidized  Excreted partly unchanged in the urine  Alkalinizes the urine  Half-life of 4-5 days  Requires loading dose
  20. 20. SEDATIVE-HYPNOTIC DRUGS OTHER DRUGS • Buspirone  Partial agonist at serotonin receptor (5-HT receptor)  Impairment of mental activity  Psychomotor impairment  Selective with minimal depressant effects on the CNS
  21. 21. SEDATIVE-HYPNOTIC DRUGS OTHER DRUGS • Zolpidem and zaleplon  Exert their CNS effects via interaction with benzodiazepine receptors  Bind more selectively  Antagonize by flumazenil
  22. 22. SEDATIVE-HYPNOTIC DRUGS DRUG A - BARBITURATES dose = CNS depression DRUG B - BENZODIAZEPINES - flatter dose response curve - greater margin of safety DRUG A DRUG B
  23. 23. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 1. Sedation 2. Hypnosis • Promote sleep onset • Increase the duration of the sleep state STAGES OF SLEEP a. REM (Rapid eye movement) • Dream • Decreases at high doses b. Non-REM • 70-75%
  24. 24. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 3. Anesthesia • Thiopental (barbiturate) • Midazolam (benzodiazepine) • Loss of consciousness, amnesia and suppression of reflexes
  25. 25. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 4. Anticonvulsant actions • Phenobarbital, clonazepam  Suppression of seizure activity  Selective because they do not cause severe sedation
  26. 26. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 4. Anticonvulsant actions • Diazepam, lorazepam and phenobarbital  Given IV  Used in status epilepticus  Heavy sedation is needed
  27. 27. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 5. Muscle relaxation • Diazepam  Spasticity states  Cerebral palsy
  28. 28. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 6. Medullary depression • High doses can lead to  Respiratory arrest  Hypotension  CVS collapse  Death in suicidal overdose
  29. 29. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 7. Tolerance and dependence • Tolerance  Decrease in responsiveness  Used chronically or in high dosage
  30. 30. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 7. Tolerance and dependence • Tolerance  Metabolic tolerance  Occurs with phenobarbital  Induces its own metabolism  Decreases CNS response to the drug itself
  31. 31. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 7. Tolerance and dependence • Dependence Physiologic  State of response to a drug  Removal of the drug evokes unpleasant symptoms  Opposite of the drug’s effects
  32. 32. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 7. Tolerance and dependence • Dependence Physiologic  Leads to abstinence syndrome (withdrawal state) when the drug is discontinued
  33. 33. SEDATIVE-HYPNOTIC DRUGS ORGAN –SYSTEM EFFECTS 7. Tolerance and dependence • Dependence Physiologic  Withdrawal signs  Anxiety  Tremors  Hyperreflexia  Seizures
  34. 34. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 7. Tolerance and dependence • Dependence Physiologic  Occur more commonly with short- acting drugs  Pentobarbital and secobarbital  Dependence is unlikely to occur with buspirone
  35. 35. SEDATIVE-HYPNOTIC DRUGS ORGAN SYSTEM EFFECTS 7. Tolerance and dependence • Dependence Psychological  State of response to a drug  Drug taker feels compelled to use the drug  Suffers anxiety when separated from the drug
  36. 36. SEDATIVE-HYPNOTIC DRUGS CLINICAL USES 1. Anxiety states • Benzodiazepines with intermediate or long durations of action are favored • Buspirone  Used for generalized anxiety disorders • Alprazolam  Phobic and panic attacks
  37. 37. SEDATIVE-HYPNOTIC DRUGS CLINICAL USES 2. Sleep disorders • Used to treat primary insomnia and other sleep disorders
  38. 38. SEDATIVE-HYPNOTIC DRUGS CLINICAL USES 3. Sedation • Prior to medical/surgical procedures • Conscious sedation-anterograde amnesia 4. Treatment of seizures and convulsions
  39. 39. SEDATIVE-HYPNOTIC DRUGS CLINICAL USES 4. Detoxification of alcoholics • Chlordiazepoxide • Diazepam 6. Muscle relaxation 7. Manias, major depression, phobias
  40. 40. SEDATIVE-HYPNOTIC DRUGS TOXICITY 1. Psychomotor dysfunction • Cognitive impairment • Decreased psychomotor skills • Unwanted daytime sedation
  41. 41. SEDATIVE-HYPNOTIC DRUGS TOXICITY 2. Additive CNS depression • When used with  Alcoholic beverages  Antihistamines  Antipsychotic drugs  Opioid analgesics  Tricyclic antidepressants
  42. 42. SEDATIVE-HYPNOTIC DRUGS TOXICITY 3. Overdosage causes severe respiratory and cardiovascular depression 4. Terratogenic
  43. 43. SEDATIVE-HYPNOTIC DRUGS TOXICITY 3. Induce formation of liver microsomal enzymes • Metabolize drugs multiple drug interactions • Chloral hydrate displaces coumarin from protein binding sites and increases anticoagulant effects

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