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What are the three Monoamines
Dopamine, Norepinephrine, Serotonin
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Two main nuerotransmitters in the brain
GABA, Glutamate
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What does Dopamine do
- Motor activity (involuntary)
- Memory and cognition
- Motivation and Reward
- Emotional Responses
- Regulation of milk production
- Emesis
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Where are Dopaminergic neurons located
- Substantia Nigra
- Ventral Tegmental Area
- Arcuate Nucleus of the Hypothalamus
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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)
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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
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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
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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
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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
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Norepinephrine functions
- Arousal
- Attention
- Affect
- Appetite
Disruption leads to anxiety and depression
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Norepinephrine Pathways and Locations in the brain
Locus Coeruleus and Lateral Tegmental Area
Projects to
Hippocampus, Thalamus, Cortices, Amygdala, Hypothalamus
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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
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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
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Serotonin Brain locations
Raphe Nuclei
projects to
- Most of the brain including the
- amygdala
- hippocampus
- hypothalamus
- septum
- CTZ
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Serotonin 3 receptor
Na/K ion channel
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Serotonin metabolism
converted to 5-HIAA by MAO-A
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Ramelteon
MT1 and MT2 agonist used for insomnia
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Acetylcholine Functions
- Emotion - Limbic System
- Memory/Cognition - Hippocampus
- EPM - Striatal Interneurons
- Emesis - Vomiting Center
Disruption associated with Alzheimer's, Parkinsonism, psychosis, emesis
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Acetylcholine Brain Pathways
Basal Forebrain and Pedunculopontine nucleus
project to
most of the brain including amygdala, hippocampus, thalamus, cortices, CTZ
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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
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Opioid peptides
endorphins
- involved in:
- motivation
- emotion
- response to stress and pain
- control of food intake
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Adenosine
- Promotes sleep and suppresses arousal
- caffeine's stimulatory effects due in part to antagonism of adenosine leading to increases in dopamine and glutamate
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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)
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Receptor types in Stomach and Small intestines that induce N&V
serotonin 3
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Receptor types in Cerebellum that induce N&V
H1 and M1
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Receptor types in STN that induce N&V
- Serotonin 3
- Dopamine 2
- M1
- H1
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Receptor types in CTZ that induce N&V
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Serotonin Receptor Antagonist
Ondansetron, Granisetron, Dolasetron
- USES
- Acute CINV
- Post-op and Post-rad N&V
- Little use for motion sickness
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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
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Neurokinin Receptor Antagonist
Aprepitant
Acute and Delayed CINV
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Muscarinic Receptor Antagonists
Scopolamine
Motion Sickness and Prophylaxis of PONV
- Side Effects: Anti-muscarinic side effects
- Sedation
- dry mouth
- etc.
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Histamine Receptor Antagonists
Diphenhydramine, Promethazine, Miclizine
PONV and motion sickness
Side Effects: anti muscarinic side effects
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Benzodiazepines
Lorazepam, Alprazolam
Premed for CINV and PONV
sedative, anxiolytic and amnestic properties
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Cannabinoids
- Dronabinol (THC)
- Nabilone (regulated THC analogue)
CINV (also appetite stimulation
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