NEUR332 Final Exam

• Antipsychotics


  Medications used to treat schizophrenia
• Schizophrenia


  A mental disorder characterized by a range of symptoms
• Positive Symptoms ("addition of symptoms")


  • Hallucinations
  • Delusions
  • Movement disorders
• Negative Symptoms


  • Social isolation
  • Flat affect
• Cognitive Symptoms


  • Attention
  • Executive functioning
  • Loss of pleasure
• Glutamate Hypothesis

  Theory that altered glutamate levels contribute to schizophrenia
• Glutamate Hypothesis


  1. PCP blocks NMDAR + mimics schizophrenia

  2. Altered levels of Glu (too much)

  3. PCP + Schizophrenia increases levels of synaptic Glu, which leads to hypoglutamatergic function
• 1st generation antipsychotics


  D2 antagonists, only treated positive symptoms, caused extrapyramidal side effects
• 2nd generation antipsychotics


  Less specific to D2, but has affinity for D3 and D4 + serotonin receptors antagonists, only treats positive symptoms
• Possible future treatments for schizophrenia

  • Targeting glutamate (mGluR 2/3 autoreceptor agonists)
  • Targeting synaptic pruning
• Sedation


  Mechanism of tiredness
• Steps to initiate sleep

  1. GABA inhibits histamine and orexin (INITIATES NREM)

  2. Orexin normally excites serotonin and norepinephrine but can no longer

  3. SE, NE, and adenosine inhibit ACh, but in this pathway are inhibited. So, ACh is disinhibited (REM BEGINS)
• Sleep Disorders


  • Narcolepsy
  • Parasomnias (sleep paralysis, sleepwalking, night terrors, sleep apnea)
  • Primary insomnia
  • Primary hypersomnia
• Cocaine


  3 major mechanisms of action: local anesthetic, vasoconstrictor, psychostimulant
• Cocaine pharmacokinetics


  Coca leaf, cocaine HCl, cocaine base (crack), metabolized with alcohol
• Amphetamines


  Mechanisms of action: taken up by DAT, taken up by VMAT, reverse transport by DAT
• Examples of Amphetamines

  • Adderall, Dexedrine
• Examples of Methamphetamines


  • Desoxyn
• Examples of Methylphenidate


  • Ritalin
• Amphetamine pharmacokinetics


  Methyl group increases lipophilicity, similar kinetics to cocaine
• ADHD


  People with ADHD may have decreased DA transmission, seek stimulation to compensate
• Caffeine


  Adenosine receptor antagonist, absorbed fast, metabolized by CYP1A2, half-life 2.5-10 hours
• Nicotine


  Agonist at decreased concentration, antagonist at increased concentration, acts on nAChRs
• Nicotine absorption


  Easily through lungs, skin, buccal, nasal
• Nicotine metabolism


  Metabolized by CYP2A6, increases regulation of CYP1A2
• Considerations for special populations

  • Pregnant (fetal health, abuse potential, dose to fetus)
  • Children (weight, metabolism, learning/social impact, abuse potential)
  • Geriatric (substance use history, liver function, other medications, polypharmacy)
• Pain Medication


  Nociception via nociceptors, sensitization, COX2 synthesis of PGE2
• COX Inhibitors


  • Aspirin
  • Acetaminophen
  • NSAIDs (ibuprofen, naproxin)
• Opioid Receptors


  In the dorsal horn, release glutamate, overstimulation can lead to neuropeptide release and LTP-like effects
• Agonists at Opioid Receptors

  • Morphine
  • Fentanyl
  • Heroin
  • Oxycodone
• Depression


  MDD = major depressive disorder
• Monoamine Hypothesis


  Restoring levels of monoamines will help reduce depressive symptoms, but no consistent evidence of neurotransmitter deficiency
• How SSRI's work


  Serotonin increases survival rate of newly born neurons, slow compensation of neurons adjusting to new synaptic serotonin
• Diathesis-Stress Hypothesis


  Genetic predisposition + stressors = depression
• Treatments for depression


  • Psychotherapy
  • SSRI's/SNRI's (MAOIs, tricyclics)
  • Ketamine
  • Ketamine-inspired drug: Rapastinel
• Lithium Mechanism


  Reduces excitatory (Glu + DA) and increases inhibitory (GABA) neurotransmission
• Lamotrigine Mechanism


  Selectively binds/inhibits voltage-gated Na+ channels and inhibits presynaptic Glu + Asp release
• STAR*D Study


  Identify separate treatment strategies impacting them ______ with depressive disorder
• Alcohol


  Positive allosteric modulator for GABAA, allosteric inhibitor of NMDAR, affects memory, GABA inhibition may affect opioid & DA receptors
• Alcohol metabolism and elimination

  Mostly alcohol dehydrogenase (ADH), 85% metabolized through the liver, 5% diffused/exhaled by lungs, small amount in urine