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Block 6 IPC - Week 1


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Name the two functional types of neurotransmitter receptors and specify their relative speed:
Ionotropic (ion channel) -- fast acting
Metabotropic (G-protein coupled) -- slower acting
What are the criteria for a classical neurotransmitter?
Neuron contains, synthesizes and releases upon depolarization the substance. The exogenous substance exerts the same response post-synaptically as that released by the neuron.
Acetylcholine - degredation and reuptake
Degraded by acetylcholinesterase in synaptic cleft.
Reuptake of resulting choline into presynaptic neuron.
Acetylcholine - pathways in CNS
**Nucleus basalis of Meynert --> Cortex
Broca and Septal nucleus --> hippocampus, cingulate gyrus
Local circuit neurons that enter the basal ganglia
Acetylcholine - receptor types and functional class of each
Nicotinic (ionotropic)
Muscarinic (metabotropic)
Acetylcholine - full metabolic pathway

See image.
Acetylcholine - related disease states
Alzheimer's -- Loss of ACh projections to cortex and hippocampus
Down's syndrome
Movement disorders
Dopamine - reuptake and degradation
Reuptake into presynaptic cell --> repackaged OR broken down by MAO.

Degradation by COMT in synaptic cleft.

End product is HVA (homovanillic acid).
Dopamine - pathways
Ventral tegmental area --> prefrontal cortex, temporolimibic regions

Substantia nigra --> caudate and putamen (D1, D2)

Arcuate nucleus --> pituitary gland
Dopamine - receptors
Both G protein linked.
D1 - increases adenylyl cyclase activity
D2 - decreases adenylyl cyclase activity
Dopamine - related disease states
Parkinson's -- loss of inhibitory input to neurons of caudate and putamen
Schizophrenia -- functional excess of dopamine with D2 receptor activation
Dopamine - related drugs
Typical antipsychotics (block D2)
Atypical antipsychotics (weak D2 blockage)
Bupropion inhibits dopamine/NE reuptake pump.
Various stimulants, antidepressants, !parkinson meds.
Norepinephrine - reuptake, degredation
Reuptake into presynaptic cell --> repackaged OR broken down by MAO.

Degradation by COMT in synaptic cleft.

End product is MHPG (3-methoxy-4-hydroxyphenylglycol) & VMA (vanillylmandelic acid)
Dopamine, Norepinephrine, Epinephrine - synthesis pathway

See image.
Norepinephrine - pathways
Locus ceruleus --> entire brain (cortex, midbraine, temporal lobe, hypothalamus, cerebellum, brainstem)
Norepinephrine - receptors
Alpha-1, Alpha-2, Beta-1, Beta-2
All G protein linked.
Norepinephrine - related disease states
Depression - low NE
Mania - high NE
Panic attacks - paroxysmal discharge of locus ceruleus
Norepinephrine - related drugs
Some antidepressants
Serotonin (5-HT) - reuptake & degradation
Reuptake pump to presynaptic cell where MAO degrades.
End product is 5-HIAA (5-hydroxyindolacetic acid)
Serotonin (5-HT) - pathways
Raphe nuclei --> large portion of CNS (neocortex, basal ganglia, temporolimbic area, hypothalamus, cerebellum, brain stem, spinal cord)
Serotonin (5-HT) - receptors
7 subtypes, 5-HT 1 through 7.

All but one of them (5-HT3) are metabotropic.
Serotonin (5-HT) - related disease
Serotonin (5-HT) - related drugs
Atypical antipsychotics, some antidepressants (MAO inhibitors)
Serotonin (5-HT) - Synthesis pathway

See image.
Glutamate - synthesis
Glutamine produced in glial helper cells and transported to presynaptic neuron, where it is converted into glutamate and packaged into vesicles.
Glutamate - reuptake & degradation
Reuptake pump into presynaptic cell for recycling.
Reuptake pump into glial helper cell & glutamine is regenerated.
Glutamate - related pathways
Cerebral cortex efferents (corticospinal, corticobulbar, etc.) -- pyramidal cells of cortex -> striatum
Granule cells in cerebellar cortex.
Nociceptive afferent fibers entering brainstem, cord.
Glutamate - receptors
1 metabotropic receptor
3 ionotropic receptors (kainate, AMPA, NMDA)
Glutamate - related disease
Neurodegenerative diseases (Huntington's): hyperactivity of NMDA --> increase Ca influx and cell death.
Excess causes mania, panic... excitotoxicity causes neuronal damage and cell death.
Possible role in psychotic diseases.
Glutamate - related drugs
Phencyclidine (PCP) blocks NMDA activity.
Namenda is an NMDA receptor inhibitor used in Alzheimer's.
Glutamate and GABA synthesis pathways.

See image.
GABA - general role
Major inhibitory neurotransmitter of the brain. ~8 billion neurons produce GABA.
Glutamate - general role
Major excitory neurotransmitter of the brain. ~20 billion neurons produce Glutamate.
Serotonin (5-HT) - general role
Can be inhibitory or excitory, only ~250,000 neurons produce 5-HT.
Norepinephrine - general role
Inhibitory neurotransmitter.
Dopamine - general role
Important in cognition and emotion. Only ~250,000 neurons produce dopamine.
Acetylcholine - general role
Major role in encoding memory.
GABA - synthesis
Glutamine produced in glial helper cells from glutamate and transported to presynaptic neuron --> converted to glutamate --> converted to GABA.
GABA - reuptake/degradation
Reuptake into presynaptic cell and degradation by GABA transaminase.
Reuptake into glial cell and regeneration of glutamine by GABA shunt.
GABA - related pathways
Purkinje, stellate, basket and golgi cells in the cerebellum.
Local circuit GABA neurons in neocortex originating from stellate cells.
GABA - receptors
GABA-A Cl- channel (inotropic)
GABA-B channel (metatropic)
GABA - related disease
Anxiety and seizures
Huntington's disease
Parkinson's disease
GABA - related drugs
Antianxiety drugs (barbiturates, benzodiazepines)
Schizophrenia: associated neurotransmitter(s)
Depression: associated neurotransmitter(s)
NE, 5-HT, Dopamine
Anxiety: associated neurotransmitter(s)
Alzheimer's: associated neurotransmitter(s)
Dopamine metabolites measured in research: name, diseases, and direction of change
Plasma levels increased in schizophrenia.
CSF, plasma levels decreased in Parkinsons, ADHD, Tourette's
Norepinephrine metabolites measured in research: name, diseases, and direction of change
CSF, urine levels decreased in severe depression, attempted suicide.

VMA, CSF levels increased in pheochromocytoma (adrenal medulla tumor)
Serotonin metabolites measured in research: name, diseases, and direction of change
CSF levels decreased in severe depression, aggressiveness, impulsiveness, violence.
Mental status examination (MSE): 5 sub categories
General appearance, behavior and attitude (GABA)
Mood and Affect (M&A)
Thought Process (TP)
Thought Content (TC)
Sensorium and Cognition (S&C)
Definition of patient Mood and some descriptors:
Pervasive, sustained emotinoal state often calculated by simply asking the patient to describe their mood. Subjective.

Depressed, happy, sad, anxious, angry.
Definition of patient Affect and some descriptors:
Expression and expressivity of emotions. Objective.

Range: full, constricted, flattened
Intensity: intense, normal, blunted
Stability: stable, labile
Appropriate to mood?
Check 3 general things while determining the patient's thought process:
Speech patterns
Goal directedness
Some descriptors of speech patterns?
Pressured (can't interrupt)
Underproductive (1-2 word answers)
Dysarthric (impaired motor)
Three levels of goal directedness?
Goal directed... normal.
Circumstantial... too much detail but answers questions.
Tangential... will never return to the topic of the question!
8 descriptors of poor thought organization?
Thought blocking
Racing thoughts
Flight of ideas
Loose associations
Word salad
Word Salad
Single sentances, even out of context, make no sense.
Loose associations
The logic from one sentance to the next is not entirely clear... but slower than flight of ideas.
Flight of ideas
Logical disconnects between sentances due to a rapid, manic, and rushing flood of ideas.
Thought content, some general categories of abnormal thought?
Questions to ask about suicidal thoughts?
Passive deathwish?
Actively suicidal OR homicidal?
Have a plan?
Have means?
Has a note?
Determine if in imminent danger.
Hallucinations: definitions and signs
sensory perception in abscense of stimulus.

Patient may be picking at things, or distracted and hypervigilant... looking around at imaginary things.
4 sensory types of hallucinations and the usual causes:
Auditory: psychiatric
Visual: medical, organic, substance. Get CT/MR!
Olfactory/gustatory: organic, get CT/MR!
Tactile: withdrawal
Two types of auditory hallucations and characteristics:
Schizophrenia: clear voice, commanding tone, running commentary, arguing, insulting or possibly complimentary.
Mood disorder or borderline personality disorder: brief, hears name being called
Delusions: definition and examples
Fixed, false belief, usually either grandiose or paranoid.

Do not try and talk the patient out of it, risk becoming party of delusional system.

Ex. the "dead" patient.
Grandiose delusions: examples
Special powers
Extrodinary accomplishments
Hyperreligous or god-like
Connected to computers that confer powers (transmitters)
Erotomanic (thinks someone wants them when they clearly do not)
Paranoid delusions: ideas of reference
Casual events that have a special significance in relation to patient.

IE, people talking about patient or TV or radio program with "messages" for the patient.
Paranoid delusions: delusions of control or influence
Patient or others are controlled by an outside force
Paranoid delusions: some examples
Somatic (being poisoned)
Passivity (thought insertion by outside agency)
Paranoid delusions: Capgras' syndrome
Patient believes that a person known to them, usually a friend or a relative, has been replaced by an imposter or a double.
Sensorium & cognition (S&C): 6 subtypes
Consciousness: some descriptors?
Clouding, coma, stupor, lethargic, alert, somnolent, hyperalert.

Stable, fluctuating.
Delerium vs. dementia.
S&C - Orientation: things to check
Pt knowledge of person, place, time, date, situation.
S&C - Concentration: tests
Serial 7s
Spell world
months of the year
S&C - Memory: tests
Remember 3 objects
Immediate memory vs STM vs LTM
Current events, past events
S&C - Intellect: things to test
Fund of knowledge
Paucity of knowledge
S&C - Abstraction: how to test?
Posit proverbs ("grass is always greener")
Insight: how to test?
Try and determine if the patient is aware of their sickness and that they might need help...
Judgement: how to test?
Pose imaginary situations.

Also use history to determine past social judgement.

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