Block 6 IPC - Week 1
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- Name the two functional types of neurotransmitter receptors and specify their relative speed:
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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
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Degraded by acetylcholinesterase in synaptic cleft.
Reuptake of resulting choline into presynaptic neuron. - Acetylcholine - pathways in CNS
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**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
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Nicotinic (ionotropic)
Muscarinic (metabotropic) - Acetylcholine - full metabolic pathway
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See image. - Acetylcholine - related disease states
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Alzheimer's -- Loss of ACh projections to cortex and hippocampus
Down's syndrome
Movement disorders - Dopamine - reuptake and degradation
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Reuptake into presynaptic cell --> repackaged OR broken down by MAO.
Degradation by COMT in synaptic cleft.
End product is HVA (homovanillic acid). - Dopamine - pathways
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Ventral tegmental area --> prefrontal cortex, temporolimibic regions
Substantia nigra --> caudate and putamen (D1, D2)
Arcuate nucleus --> pituitary gland - Dopamine - receptors
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Both G protein linked.
D1 - increases adenylyl cyclase activity
D2 - decreases adenylyl cyclase activity - Dopamine - related disease states
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Parkinson's -- loss of inhibitory input to neurons of caudate and putamen
Schizophrenia -- functional excess of dopamine with D2 receptor activation - Dopamine - related drugs
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Typical antipsychotics (block D2)
Atypical antipsychotics (weak D2 blockage)
Bupropion inhibits dopamine/NE reuptake pump.
Various stimulants, antidepressants, !parkinson meds. - Norepinephrine - reuptake, degredation
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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
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See image. - Norepinephrine - pathways
- Locus ceruleus --> entire brain (cortex, midbraine, temporal lobe, hypothalamus, cerebellum, brainstem)
- Norepinephrine - receptors
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Alpha-1, Alpha-2, Beta-1, Beta-2
All G protein linked. - Norepinephrine - related disease states
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Depression - low NE
Mania - high NE
Panic attacks - paroxysmal discharge of locus ceruleus - Norepinephrine - related drugs
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Some antidepressants
Cocaine
Amphetamines - Serotonin (5-HT) - reuptake & degradation
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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
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7 subtypes, 5-HT 1 through 7.
All but one of them (5-HT3) are metabotropic. - Serotonin (5-HT) - related disease
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Depression
Anxiety - Serotonin (5-HT) - related drugs
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SSRIs
Atypical antipsychotics, some antidepressants (MAO inhibitors) - Serotonin (5-HT) - Synthesis pathway
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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
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Reuptake pump into presynaptic cell for recycling.
Reuptake pump into glial helper cell & glutamine is regenerated. - Glutamate - related pathways
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Cerebral cortex efferents (corticospinal, corticobulbar, etc.) -- pyramidal cells of cortex -> striatum
Granule cells in cerebellar cortex.
Nociceptive afferent fibers entering brainstem, cord. - Glutamate - receptors
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1 metabotropic receptor
3 ionotropic receptors (kainate, AMPA, NMDA) - Glutamate - related disease
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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
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Phencyclidine (PCP) blocks NMDA activity.
Namenda is an NMDA receptor inhibitor used in Alzheimer's. - Glutamate and GABA synthesis pathways.
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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
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Reuptake into presynaptic cell and degradation by GABA transaminase.
Reuptake into glial cell and regeneration of glutamine by GABA shunt. - GABA - related pathways
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Purkinje, stellate, basket and golgi cells in the cerebellum.
Striatum.
Local circuit GABA neurons in neocortex originating from stellate cells. - GABA - receptors
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GABA-A Cl- channel (inotropic)
GABA-B channel (metatropic) - GABA - related disease
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Anxiety and seizures
Huntington's disease
Parkinson's disease - GABA - related drugs
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Antianxiety drugs (barbiturates, benzodiazepines)
Alcohol - Schizophrenia: associated neurotransmitter(s)
- dopamine
- Depression: associated neurotransmitter(s)
- NE, 5-HT, Dopamine
- Anxiety: associated neurotransmitter(s)
- GABA, NE, 5-HT
- Alzheimer's: associated neurotransmitter(s)
- ACh
- Dopamine metabolites measured in research: name, diseases, and direction of change
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HVA
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
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MHPG
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
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5-HIAA
CSF levels decreased in severe depression, aggressiveness, impulsiveness, violence. - Mental status examination (MSE): 5 sub categories
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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:
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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:
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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:
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Speech patterns
Goal directedness
Organization - Some descriptors of speech patterns?
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Pressured (can't interrupt)
Rapid
Underproductive (1-2 word answers)
Overproductive
Slurred
Dysarthric (impaired motor)
Aphasic - Three levels of goal directedness?
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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?
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Thought blocking
Racing thoughts
Perseveration
Flight of ideas
Loose associations
Word salad
Clanging
Neologisms - 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?
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Suicidal
Homicidal
Phobia
Preoccupation
Flashbacks
Illusions
Hallucinations
Delusions - Questions to ask about suicidal thoughts?
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Passive deathwish?
Actively suicidal OR homicidal?
Have a plan?
Have means?
Has a note?
Determine if in imminent danger. - Hallucinations: definitions and signs
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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:
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Auditory: psychiatric
Visual: medical, organic, substance. Get CT/MR!
Olfactory/gustatory: organic, get CT/MR!
Tactile: withdrawal - Two types of auditory hallucations and characteristics:
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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
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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
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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
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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
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Jealousy
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
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Consciousness
Orientation
Concentration
Memory
Intellect
Abstraction - Consciousness: some descriptors?
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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
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Serial 7s
Spell world
months of the year - S&C - Memory: tests
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Remember 3 objects
Immediate memory vs STM vs LTM
Current events, past events - S&C - Intellect: things to test
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IQ
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?
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Pose imaginary situations.
Also use history to determine past social judgement.