Biological therapies barbiturates

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Biological therapies barbiturates

  1. 1. MARIA FE SALVADOR NAVARRETE MD BIOLOGICALTHERAPIES
  2. 2. Barbiturates and Similarly Acting Drugs  used as sedative-hypnotic agents in 20th century  high abuse and addiction potential,  a narrow therapeutic range with low therapeutic index,  and unfavorable side effects.  The use of barbiturates and similar compounds such as meprobamate (Miltown) has been practically eliminated by the benzodiazepines,  buspirone (BuSpar), and hypnotics such as zolpidem (Ambien) and zaleplon (Sonata), which have a lower abuse potential and a higher therapeutic index than the barbiturates.  the barbiturates and similarly acting drugs still have a role in the treatment of certain mental disorders.
  3. 3. Pharmacologic Actions  well absorbed after oral administration.  The binding of barbiturates to plasma proteins is high, but lipid solubility varies.  metabolized by the liver and excreted by the kidneys.  The half-lives of specific barbiturates range from 1 to 120 hours (Table 36.8-1).  Barbiturates may also induce hepatic enzymes (cytochrome P450), thereby reducing the levels of both the barbiturate and any other concurrently administered drugs metabolized by the liver.  The mechanism of action of barbiturates involves the γ- aminobutyric acid (GABA) receptor–benzodiazepine receptor–chloride ion channel complex.
  4. 4. Therapeutic Indications: Electroconvulsive Therapy  Methohexital (Brevital) is commonly used as an anesthetic agent for electroconvulsive therapy (ECT).  It has lower cardiac risks  Used intravenously, methohexital produces rapid unconsciousness and, because of rapid redistribution, it has a brief duration of action (5 to 7 minutes)  Typical dosing for ECT is 0.7 to 1.2 mg/kg. Methohexital can also be used to abort prolonged seizures in ECT or to limit postictal agitation.
  5. 5. Seizures  Phenobarbital (Solfoton, Luminal), the most commonly used barbiturate for treatment of seizures, has indications for the treatment of generalized tonic-clonic and simple partial seizures.  Parenteral barbiturates are used in the emergency management of seizures independent of cause. Intravenous (IV) phenobarbital should be administered slowly, 10 to 20 mg/kg for status epilepticus.
  6. 6. Narcoanalysis  Amobarbital (Amytal) has been used historically as a diagnostic aid in a number of clinical conditions,  including conversion reactions,  catatonia,  hysterical stupor,  and unexplained muteness,  and to differentiate stupor of depression,  schizophrenia, and structural brain lesions.
  7. 7. SLEEP  The barbiturates reduce sleep latency and the number of awakenings during sleep, although tolerance to these effects generally develops within 2 weeks.  Discontinuation of barbiturates often leads to rebound increases on electroencephalogram (EEG) measures of sleep and a worsening of the insomnia.
  8. 8. Withdrawal from Sedative- Hypnotics  used to determine the extent of tolerance to barbiturates or other hypnotics to guide detoxification.  a test dose of pentobarbital (200 mg) is given orally.  An hour later the patient is examined.  Tolerance and dose requirements are determined by the degree to which the patient is affected  If the patient is not sedated, another 100 mg of pentobarbital can be administered every 2 hours, up to three times (maximum, 500 mg over 6 hours).  The amount needed for mild intoxication corresponds to the approximate daily dose of barbiturate used.  Phenobarbital (30 mg) may then be substituted for each 100 mg of pentobarbital.  daily dose requirement can be administered in divided doses and gradually tapered by 10 percent a day, with adjustments made according to withdrawal signs (Table 36.8-2).
  9. 9. Precautions and Adverse Reactions  paradoxical dysphoria,  hyperactivity,  and cognitive disorganization.  Rare adverse effects associated with barbiturate use include the development of Stevens-Johnson syndrome,  megaloblastic anemia, and neutropenia.
  10. 10.  A major difference between the barbiturates and the benzodiazepines is the low therapeutic index of the barbiturates. An overdose of barbiturates can easily prove fatal
  11. 11.  Barbiturate intoxication is manifested by confusion, drowsiness, irritability, hyporeflexia or areflexia, ataxia, and nystagmus.
  12. 12.  Because of some evidence of teratogenicity, barbiturates should not be used by pregnant women or women who are breast-feeding.  Barbiturates should be used with caution by patients with a history of substance abuse, depression, diabetes, hepatic impairment, renal disease, severe anemia, pain, hyperthyroidism, or hypoadrenalism
  13. 13. Drug Interactions  The primary area for concern about drug interactions is the potentially additive effects of respiratory depression.  Barbiturates should be used with great caution with other prescribed central nervous system (CNS) drugs (including antipsychotic and antidepressant drugs) and nonprescribed CNS agents (e.g., alcohol)
  14. 14. Paraldehyde  Paraldehyde is a cyclic ether, first used in 1882 as a hypnotic. It has also been used to treat epilepsy, alcohol withdrawal symptoms, and delirium tremens. Because of its low therapeutic index, it has been supplanted by the benzodiazepines and other anticonvulsants
  15. 15.  Precautions and Adverse Reactions  Paraldehyde frequently causes foul breath because of expired unmetabolized drug. It can inflame pulmonary capillaries and cause coughing. It can also cause local thrombophlebitis with IV use. Patients may experience nausea and vomiting with oral use. Overdose leads to metabolic acidosis and decreased renal output.There is risk of abuse among drug addicts.
  16. 16. Drug Interactions  Disulfiram (Antabuse) inhibits acetaldehyde dehydrogenase and reduces metabolism of paraldehyde, leading to possible toxic concentration of paraldehyde. Paraldehyde has addictive sedating effects in combination with other CNS depressants such as alcohol or benzodiazepines.
  17. 17. Meprobamate  Meprobamate, a carbamate, was introduced shortly before the benzodiazepines, specifically to treat anxiety. It is also used for muscle relaxant effects.
  18. 18.  Chloral Hydrate  Chloral hydrate is a hypnotic agent rarely used in psychiatry because numerous safer options, such as benzodiazepines, are available.
  19. 19. Benzodiazepines and Drugs Acting on Benzodiazepine Receptors  modulate γ-aminobutyric acid (GABA) activity.  Nonbenzodiazepine agonists, such zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta)—the so-called “Z drugs―— interactions with GABA-receptor complexes at binding domains located close to or coupled to benzodiazepine receptors.  Flumazenil (Romazicon), a benzodiazepine receptor antagonist used to reverse benzodiazepine-induced sedation and in emergency care of benzodiazepine overdosage
  20. 20.  With the exception of clorazepate (Tranxene), all the benzodiazepines are completely absorbed unchanged from the gastrointestinal (GI) tract.  The absorption, the attainment of peak concentrations, and the onset of action are quickest for diazepam (Valium), lorazepam (Ativan), alprazolam (Xanax), triazolam (Halcion), and estazolam (ProSom).
  21. 21.  rapid anxiolytic sedative effect, they are most commonly used for immediate treatment of insomnia, acute anxiety, and agitation or anxiety associated with any psychiatric disorder.  used as anesthetics, anticonvulsants, and muscle relaxants.  Because of the risk of psychological and physical dependence, long-term use of benzodiazepines should be in conjunction with psychotherapy and in cases where alternative agents have been tried and proved ineffective or poorly tolerated.
  22. 22.  Diazepam, chlordiazepoxide, clonazepam (Klonopin), clorazepate, flurazepam (Dalmane), prazepam (Centrax), quazepam (Doral), and halazepam (Paxipam) have plasma half-lives of 30 to more than 100 hours and, therefore, are the longest-acting benzodiazepines
  23. 23.  Gaboxatal  This is a new hypnotic agent which works on the α-4 GABA receptor subtype rather than on the α-1 GABA subtype which the other benzodiazepines effect. α-4 GABA is expressed at high levels in the thalmus.
  24. 24. Therapeutic Indications Insomnia  Because insomnia can be a symptom of a physical or psychiatric disorder, hypnotics should not be used for more than 7 to 10 consecutive days without a thorough investigation of the cause of the insomnia.
  25. 25.  Anxiety Disorders  Generalized Anxiety Disorder  Benzodiazepines are highly effective for the relief of anxiety associated with generalized anxiety disorder.  Because generalized anxiety disorder is a chronic disorder with a high rate of recurrence, some persons with generalized anxiety disorder may warrant long-term maintenance treatment with benzodiazepines.
  26. 26.  Panic Disorder  Alprazolam and clonazepam, both high-potency benzodiazepines, are commonly used medications for panic disorder, with or without agoraphobia.  Although the selective serotonin reuptake inhibitors (SSRIs) are also indicated for treatment of panic disorder, benzodiazepines have the advantage of working quickly and of not causing significant sexual dysfunction and weight gain.
  27. 27.  Social Phobia  Clonazepam has been shown to be an effective treatment for social phobia. In addition, several other benzodiazepines (e.g., diazepam) have been used as adjunctive medications for treatment of social phobia.
  28. 28.  OtherAnxiety Disorders  Benzodiazepines are used adjunctively for treatment of adjustment disorder with anxiety, pathological anxiety associated with life events (e.g., after an accident), OCD, and posttraumatic stress disorder.
  29. 29.  Mixed Anxiety–Depressive Disorder  Alprazolam is indicated for the treatment of anxiety associated with depression.
  30. 30.  Bipolar I Disorder  Clonazepam, lorazepam, and alprazolam are effective in the management of acute manic episodes and as an adjuvant to maintenance therapy in lieu of antipsychotics. As an adjuvant to lithium (Eskalith) or lamotrigine (Lamictal), clonazepam may result in an increased time between cycles and fewer depressive episodes.
  31. 31.  Akathisia  The first-line drug for akathisia is most commonly a β-adrenergic receptor antagonist. Benzodiazepines are also effective in treating some patients with akathisia
  32. 32.  Parkinson's Disease  A few persons with idiopathic Parkinson's disease will respond to long-term use of zolpidem with reduced bradykinesia and rigidity. Zolpidem dosages of 10 mg four times daily may be tolerated without sedation for several years.
  33. 33.  Precautions and Adverse Reactions  The most common adverse effect of benzodiazepines is drowsiness, which occurs in about 10 percent of all persons.
  34. 34. Signs and Symptoms of Benzodiazepine Withdrawal  Anxiety  Tremor  Irritability  Depersonalization  Insomnia  Hyperesthesia  Hyperacusis  Myoclonus  Nausea  Delirium Difficulty concentrating Seizures
  35. 35. Drug Interactions  The most common and potentially serious benzodiazepine receptor agonist interaction results in excessive sedation and respiratory depression occurring when benzodiazepines, zolpidem, or zaleplon are administered concomitantly with other CNS depressants, such as alcohol, barbiturates, tricyclic and tetracyclic drugs, dopamine receptor antagonists (DRAs), opioids, and antihistamines.
  36. 36. RAMELTEON  Ramelteon (Rozerem), a new treatment for insomnia, was approved by the US Food and DrugAdministration (FDA) in 2005.
  37. 37. Pharmacologic Actions  Unlike the other hypnotic agents discussed in this section, ramelteon does not act on the benzodiazepine or GABA system.  It specifically targets the melatonin MT1 and MT2 receptors in the brain's suprachiasmatic nucleus (SCN).The SCN regulates 24-hour, or circadian, rhythms including the sleep–wake cycle.
  38. 38.  THANKYOU  POWER!!!!!!!!!!!!!!!!

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