Test 4 Pharm

Dopamine, Norepinephrine, Serotonin

GABA, Glutamate

• Motor activity (involuntary)
• Memory and cognition
• Motivation and Reward
• Emotional Responses
• Regulation of milk production
• Emesis

• Substantia Nigra
• Ventral Tegmental Area
• Arcuate Nucleus of the Hypothalamus

• 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)

• 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

Ventral Tegmental Area - Prefrontal Cortex

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

Dysfunction leads to psychosis and negative symptoms of schizophrenia

Arcuate Nucleus - Pituitary (median eminence)

tonic inhibitory control of prolaction secretion from anterior pituitary gland

can lead to increase in prolactin secretion

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

• Arousal
• Attention
• Affect
• Appetite

Disruption leads to anxiety and depression

Locus Coeruleus and Lateral Tegmental Area

Projects to

Hippocampus, Thalamus, Cortices, Amygdala, Hypothalamus

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

• 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

Raphe Nuclei

projects to

• Most of the brain including the 
•    amygdala
•    hippocampus
•    hypothalamus
•    septum
•    CTZ

Na/K ion channel

converted to 5-HIAA by MAO-A

MT1 and MT2 agonist used for insomnia

• Emotion - Limbic System
• Memory/Cognition - Hippocampus
• EPM - Striatal Interneurons
• Emesis - Vomiting Center

Disruption associated with Alzheimer's, Parkinsonism, psychosis, emesis

Basal Forebrain and Pedunculopontine nucleus

project to 

most of the brain including amygdala, hippocampus, thalamus, cortices, CTZ

• 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

endorphins

• involved in:
•   motivation
•   emotion
•   response to stress and pain
•   control of food intake

• Promotes sleep and suppresses arousal
• caffeine's stimulatory effects due in part to antagonism of adenosine leading to increases in dopamine and glutamate

• 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)

serotonin 3

H1 and M1

• Serotonin 3
• Dopamine 2
• M1
• H1

• M1
• D2
• Serotonin 3
• NK1

Ondansetron, Granisetron, Dolasetron

• USES
• Acute CINV
• Post-op and Post-rad N&V
• Little use for motion sickness

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

Aprepitant

Acute and Delayed CINV

Scopolamine

Motion Sickness and Prophylaxis of PONV

• Side Effects: Anti-muscarinic side effects
•      Sedation
•      dry mouth
•      etc.

Diphenhydramine, Promethazine, Miclizine

PONV and motion sickness

Side Effects: anti muscarinic side effects

Lorazepam, Alprazolam

Premed for CINV and PONV

sedative, anxiolytic and amnestic properties

• Dronabinol (THC)
• Nabilone (regulated THC analogue)

CINV (also appetite stimulation