Test 4 Pharm

  1. What are the three Monoamines
    Dopamine, Norepinephrine, Serotonin
  2. Two main nuerotransmitters in the brain
    GABA, Glutamate
  3. What does Dopamine do
    • Motor activity (involuntary)
    • Memory and cognition
    • Motivation and Reward
    • Emotional Responses
    • Regulation of milk production
    • Emesis
  4. Where are Dopaminergic neurons located
    • Substantia Nigra
    • Ventral Tegmental Area
    • Arcuate Nucleus of the Hypothalamus
  5. Nigrostriatal Pathway
    • Substantia Nigra - Striatum
    • Dopamine
    • Involuntary motor movement... loss causes Parkinson's disease... too much causes Huntingtons and Tourette's

    can lead to Parkinsonism (side effect of too much dopamine onboard)(Extrapyramidal Motor Movement)
  6. Mesolimbic Pathway
    • Ventral Tegmental Area- Limbic System
    • (nucleus Accumbens and Amygdala and Hippocampus)

    • Pathway used in:
    • Memory
    • Emotional Responses
    • Reward and Desire
    • Addiction

    Dysfunction leads to psychosis and positive symptoms of schizophrenia and addiction
  7. Mesocortical Pathway
    Ventral Tegmental Area - Prefrontal Cortex

    • Used in
    • Cognition
    • Executive Function
    • Socialization
    • Motivation and Emotional Response

    Dysfunction leads to psychosis and negative symptoms of schizophrenia
  8. Tubero-Infundibular Pathway
    Arcuate Nucleus - Pituitary (median eminence)

    tonic inhibitory control of prolaction secretion from anterior pituitary gland

    can lead to increase in prolactin secretion
  9. Dopaminergic Pathway through the Neuro Junction
    Tyrosine goes into the neuron and is converted by tyrosine hydroxylase to Dopa

    Dopa converted via AAAD and Vit B6 to Dopamine and taken into the vesicular monoamine transporter

    released and acts on D1 and D2 receptors postsynaptically... and D2 (inhibitory) receptors on presynaptic neuron

    • Metabolized by COMT and MAO-B
    •  COMT creats 3-0-methyl DOPA which competes with L-Dopa
    • MAO-B creates HVA
  10. Norepinephrine functions
    • Arousal
    • Attention
    • Affect
    • Appetite

    Disruption leads to anxiety and depression
  11. Norepinephrine Pathways and Locations in the brain
    Locus Coeruleus and Lateral Tegmental Area

    Projects to

    Hippocampus, Thalamus, Cortices, Amygdala, Hypothalamus
  12. Norepinephrine Pathway in Neuron
    Tyrosine goes into the neuron and is converted by tyrosine hydroxylase to Dopa

    Dopa converted via AAAD and Vit B6 to Dopamine and taken into the vesicular monoamine transporter and converted to NE

    released and acts on a1 and b receptors postsynaptically... and a2 (inhibitory) receptors on presynaptic neuron

    Metabolized by COMT and MAO-A COMT creats inactive metabolites   MAO-A creates VMA
  13. Serotonin Functions
    • Affect
    • Anxiety / Depression
    • Appetite
    • Sleep
    • Emesis

    low levels of serotonin associated with anxiety and depression

    Most drugs used to treat depression increase serotonin levels in the brain
  14. Serotonin Brain locations
    Raphe Nuclei

    projects to

    • Most of the brain including the 
    •    amygdala
    •    hippocampus
    •    hypothalamus
    •    septum
    •    CTZ
  15. Serotonin 3 receptor
    Na/K ion channel
  16. Serotonin metabolism
    converted to 5-HIAA by MAO-A
  17. Ramelteon
    MT1 and MT2 agonist used for insomnia
  18. Acetylcholine Functions
    • Emotion - Limbic System
    • Memory/Cognition - Hippocampus
    • EPM - Striatal Interneurons
    • Emesis - Vomiting Center

    Disruption associated with Alzheimer's, Parkinsonism, psychosis, emesis
  19. Acetylcholine Brain Pathways
    Basal Forebrain and Pedunculopontine nucleus

    project to 

    most of the brain including amygdala, hippocampus, thalamus, cortices, CTZ
  20. GABA uses
    • Primary inhibitory transmitter in the brain
    • Ubiquitous in the CNS
    • GABA works together with glutamate to control many process, including the brains overall level of excitation
    • disruption of this balance leads to seizures and epilepsy
  21. Opioid peptides

    • involved in:
    •   motivation
    •   emotion
    •   response to stress and pain
    •   control of food intake
  22. Adenosine
    • Promotes sleep and suppresses arousal
    • caffeine's stimulatory effects due in part to antagonism of adenosine leading to increases in dopamine and glutamate
  23. nausea and vomiting centers
    • Labyrinth Apparatus (motion)
    • Stomach and small intestine
    • Solitary Tract Nucleus (STN)
    • Cerebellum
    • Vomiting Center (dorsal lateral reticular formation)
    • Chemoreceptor Trigger Zone (area postrema, 4th ventricle)
  24. Receptor types in Stomach and Small intestines that induce N&V
    serotonin 3
  25. Receptor types in Cerebellum that induce N&V
    H1 and M1
  26. Receptor types in STN that induce N&V
    • Serotonin 3
    • Dopamine 2
    • M1
    • H1
  27. Receptor types in CTZ that induce N&V
    • M1
    • D2
    • Serotonin 3
    • NK1
  28. Serotonin Receptor Antagonist
    Ondansetron, Granisetron, Dolasetron

    • USES
    • Acute CINV
    • Post-op and Post-rad N&V
    • Little use for motion sickness
  29. Dopamine Receptor Antagonists
    Prochlorperazine, Droperidol, Metoclopramide

    Prophylaxis and treatment of PONV and CINV

    Side Effects:  EPS

    • Droperidol cannot be used in pts. with QT prolongation
    • Metoclopramide is contraindicated in seizures
  30. Neurokinin Receptor Antagonist

    Acute and Delayed CINV
  31. Muscarinic Receptor Antagonists

    Motion Sickness and Prophylaxis of PONV

    • Side Effects: Anti-muscarinic side effects
    •      Sedation
    •      dry mouth
    •      etc.
  32. Histamine Receptor Antagonists
    Diphenhydramine, Promethazine, Miclizine

    PONV and motion sickness

    Side Effects: anti muscarinic side effects
  33. Benzodiazepines
    Lorazepam, Alprazolam

    Premed for CINV and PONV

    sedative, anxiolytic and amnestic properties
  34. Cannabinoids
    • Dronabinol (THC)
    • Nabilone (regulated THC analogue)

    CINV (also appetite stimulation
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