PUBH 3003 1st Edition Lecture 14Outline of Last Lecture I. Drugs and birth defectsa. Effects on pregnant motherII. Fetal Alcohol DisordersIII. Brain changesIV. Alcohol and PregnancyV. PreventionOutline of Current Lecture I. What are CNS depressants and how do they work?a. Pharmacologyb. Classesi. Barbituratesii. Benzodiazepines iii. Sleep agentsiv. Opiate II. How are these drugs abused?III. Other Depressants Current Lecture:What is a CNS Depressant?- A drug that slows brain activity o Usually causes relaxation and a sense of calm- Most work on GABA receptors in the braino Barbiturates, benzos, non- benzo sleep agents - Opioids work on opiate receptors, not GABA- Ethanol works on GABA and glutamate receptors What Is GABA?- Inhibitory neurotransmittero Slows neurons downBarbiturates - First developed in the early 20th century by Bayer companyThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.o Veronal (barbital) – used as a sleep aid- Many derivatives synthesized o Ultra short actingo Short/ intermediate acting o Long acting - 1950’s people began to recognize potential for addiction and dependence - Commonly used Barbiturates o Phenobarbital  Used primarily for epilepsyo Amobarbital Used as “truth serum” o Sodium Thiopental/ Pentobarbital Used in anesthesia for surgery Euthanasia  Capital punishment - Abuse of Barniturates:o Recreational use produces similar effects to ethanol Relaxed contentment o Main concern is overdose, which would cause respiratory depression o Not used very much at all anymore…. Because we have benzos!Benzodiazepines - First discovered in 1955, marketed in 1960 by Hoffman- LaRocheo Librium (chlordiazepoxide) - Many derivatives synthesized o Short acting (sleep)o Intermediate acting (sleep/anxiety)o Long acting (Anxiety/ alcohol withdrawal)- Development of benzodiazepines drastically decreased the use of barbituates- Commonly used Benzoso Short Acting Versed (Midazolam)o Intermediate acting Xanax (alprazolam) Ativan (lorazepam) Rohypnol (flyintrazepam)o Long Acting  Valium (diazepam)  Librium (Chloediazepoxide) - Abuse of Benzodiazepineso Recreational use causes the same calm feeling as barbiturates, but does not suppress breathing at all o Generally, abusers of benzodiazepines also abuse other substances as Wello Recreational (even therapeutic) doses cause amnesia - Non- benzo Sleep Agents o First marketed in 1992  Ambien (zolpidem)o Work on GABA receptors, but not at the same site as benzoso Short Acting- used for initiation of sleep Ambien CR is extended – release product for sleep and onset durationEffects of Sleep Agents - Recreational use causes decreased anxiety, euphoria, hallucinations, and perceptual changes - Therapeutic use can cause amnesia and unusual “sleep-related behaviors”- Dangers of Abuse/ Overdose o Barbiturates High doses can cause respiratory depression o Benzodiazepines  Amnesiao Non Benzo Sleep Agents  Amnesia Behavior changes - Withdrawalo All of these agents increase the action of GABAo Sudden withdrawal of these drugs will cause unregulated neuron firing, which can lead to seizures o Withdrawal of these agents should be done slowly under medical supervisionOpiates- Opiates work on some combination of three main receptorso MU (causes release of GABA indirectly) Analgesia, sedation, itching, nausea, euphoria, decreased respiration, and pinpoints pupils (miosis)o Kappa  Hallucinations, sedation, deliriumo Delta Analgesia, convulsant effects, physical dependence - Derived from opium poppies - Has been used since prehistoric times (tea smoking, ingesting)- Morphine was purified in 1805o Was used extensively in the Civil War - Bayer marketed a new OTC opiate in 1895o Heroin (diacetylmorphine) o Marketed as a “non- addictive cough medicine”- Commonly used opiateso Natural Opiates  Morphine Codeine o Semi- synthetic opiates Hydrocodone Hydromorphine Oxycodone Oxymorphoneo Synthetic Opiates Fentanyl Methadone - Abuse of opiateso Can be administered virtually any way possible Injection, inhalation, ingestion, topical, sublingual, etc.o Causes euphoria, calm and decreased pain sensationo Most concerning is respiratory depression- Overdose of Opiateso In overdose, opiates cause Respiratory depression*** Mitosis  Hypotension (low blood pressure)o There is a way to reverse opiate induced respiratory failure  Narcan (naloxone)- Withdrawal of Opiateso Flu-like symptoms o Diarrhea o Restlessness o Difficulty sleeping o Dysphoriao Withdrawal is very unpleasant, but not life threatening o Medications can help (hydroxyzine, clonidine)- Long term abuse of opiates o Use of opiates recreationally causes a rush of dopamine Brains reward center o Soon there is an increase in dopamine receptors Need more drug for the same effecto When you stop, the receptors don’t go away and you have less dopamine released Causes a feeling of depressionOther Depressants - Diprivan (propofol) - Inhaled Anesthetics o Sevoflurane, desflurane, isoflurane, nitrous oxide - Antihistamines o Benadryl