Unit 4 Flashcards
3 transmitters with ascending regulation of thalamus
NE, ACh, and 5HT
NE on Thalamus
Release from LC causes fight/flight
ACh on Thalamus
Release from Reticular Activating System causes awakening
5HT on Thalamus
Release from Raphe Nuclei causes sleep and wakefullness
Two drugs that inhibit T-type Ca channels
Valproate and Ethosuximide
Declarative Memory
recalling events/facts with temporal and spatial components
Where is declarative memory formed?
Hippocampus
Procedural Memory
learning motor skills
Where is procedural memory formed?
Cerebellum, Striatum, frontal cortex
Short Term Memory
Seconds, sensory input, sensory cortex
Working Memory
Minutes, frontal lobes (executive function region)
Long Term Memory
Days+, stored in neocortex, different types in different places
Which Hippocampal Fibers are important for associative memory?
CA3
Describe Condition Flavor Aversion
Novel food causes cholinergic activation in the forebrain. ACh is released in insular cortex (taste response) and NMDAs are phosphorylated. IF amygdala receives vagal input of malaise while NMDAs are phosphorylated, stimulation of the insular cortex from amygdala produces conditioned flavor aversion.
Criteria for SCZ
2+ symptoms for 1+ month each, total of 6 months
- Delusions, hallucinations, disorganized speech, catatonic behavior, negative symptoms
SCZ prevalence
1% of general population
10% with 1st degree relative
Typical SCZ onset
Late Adolescence - Early Adulthood
How to generally think of SCZ
Sensory gating disorder and difficulty processing short term memory
All caused by NT imbalances
DA theory of SCZ
Increased mesolimbic system of VTA onto NA, increasing reward pathway and causing positive smptoms
Decreased mesocortical of VTA to PFC (executive functioning in DLPFC) and from SN to basal ganglia for motor control causing negative symptoms
What causes positive symptoms of SCZ?
Mesolimbic Hyperactivity
What causes negative symptoms of SCZ?
Mesocortical Hypoactivity
Glutamate model of SCZ
Similar to DA but w/ NMDA effects.
NMDA antagonism chronically increases DA in NA and reduces DA in PFC. Suggests glutamate hypoactivity might cause both positive and negative symptoms
Association Cortex in SCZ:
all cortical areas other than primary sensory (includes DLPFC), atrophy in SCZ w/ abnormal blood flow, physiological inefficiency
Medial Temporal and Hippo in SCZ
MTL is needed for sensory integration and attaching limbic value, atrophied in SCZ.
Hippo has reduction of pyramidals, increased flow during positive symptoms
Thalamus in SCZ
atrophy in SCZ, reduced sensory filtering
Basal Ganglia in SCZ
caudate atrophy, reduced integration of cortical inputs
Final common pathway of drug-reward reinforcement?
VTA releasing DA onto NA
This integrates emotional response to motor
Addiction potential is proportional to…..
DA release in NA
3 parts of reflective reward system
All in PFC:
OFC (impulses)
VMPFC (emotions)
DLPFC (analysis)
Pharmocokinetics of Drug Addiction
Faster rate of onset: inhalation > IV > mucous membranes > oral
Shorter Half Lives: frequent use, more withdrawal
Genetics: ex ADH in Asians
Catecholamie Hypothesis in Depression
Increasing NE and 5HT reduces depression
BUT: effects take 2-3 weeks……
High potency typical anti-psychotic effects
Extrapyramidal side effects
Low potency typical anti-psychotic effects
No extrapyramidal but higher concentrations produce anti-muscarinic effects
Atypical anti-psych side effects
Agranulocytosis, weight gain, cholesterol, diabetes
4 main brain dopamine pathways
Mesolimbic (hyperactivity = positive SCZ)
Mesocortical (hypoactivity = negative SCZ)
Nigrostriatal (coordinated/planned movement, PD)
Tuberoinfundibular (hypothalamic, prolactin inhibition)
Disability worldwide form neuropsych and mood disorders
50% is neuropsych; half of neuropsych are mood disorders
What percent of depressed patients are treated?
50% are treated, 20% adequately
Depression Diagnosis
Sad mood AND 5+ of SIGECAPS for 2+weeks
- Sleep, Interest, Guilt, Energy, Concentration, Anhedonia, Psychomotor changes, SI
Bipolar Diagnosis
distinct period of elevated/irritable/expansive mood AND persistent goal directed activity for 1 week AND 3+ of DIGFAST
- Distractibility, Insomnia, Grandiosity, Flight of ideas, Activity, Speech, Thoughtlessness
Atypical Depression
mood reactive, leaden paralysis, increased weight gain and hypersomnia
Pyschotic Depression
auditory hallucinations, nihilistic delusions
Melancholic Depression
Worse in morning, anorexia, weight loss, guilt
Bipolar I vs II
I: depression and mania
II: major depression + hypomania
Depression recurrence?
50% after 1
60-70% after 2 episodes
90% after 3+
Other causes of mood symptoms
Mood disorder, medical illness, drugs, side effects, baseline personality
Are depression or bipolar chemical imbalances?
No, neural circuitry issues
Which is more heritable? Depression or Bipolar?
Bipolar, x10 RR
Neuroendocrine dysfunction in depression?
high hypothalamus stimulation for ACH release, high cortisol damages hippocampus (inhibitory of symptoms) and does not impact amygdala (excitatory)
Possible Bipolar etiology
Too much amygdala, not enough DLPFC
Possible MOA of anti-depressants
increased BDNF, replacing hippocamus
Response rate to anti-depressants?
2/3
Suicide Facts (COD, ages, genders, etc.)
11th COD, 2nd among 20-30s.
Genders: Male > Female, Females attempt 2-3x more
2/3 saw PCP w/in last month
Which anti-depressant has immediate effects?
Katamine, but has 1-2 week tolerance
4 domains for personality disorder
2+ of:
Cognition, affectivity, interpersonal functioning, impulse control
When does a personality style become a disorder
When it deviates markedly from culture, becomes inflexible, impairs social functioning, and is stable for long duration
ETOH absorption
GI tract, particularly small intestine, peak concentration reduced by 30% w/ meal
Distribution of ETOH
all body water, high blood flow faster than low blood flow (fat). CNS effects in 5 minutes, peak in 15-60
ETOH metablism
zero order by liver (7-10g/hr)
NADH and alcohol metabolism
Loss of NAD can cause acidosis, hypomagnesemia (convulsions), hyperuricemia, high acetyl CoA (fatty liver), hypoglycemia
What increases NADH to NAD?
Fructose, but causes diarrhea
Why does alcohol stimulate initially?
GABA neurons depressed first
Why no ETOH in epilepsy?
anti-convulsant by nature but rebound increases seizure liklihood
ETOH and sleep
somnolece but decreases REM sleep
ETOH and liver
reversible damage of increased fatty acids
irreversible when replaced by collagen in cirrhosis
- congestion, ascites, esophagela varices, clotting factors
ETOH and GI
Irritation, ulceration w/ aspirin, pancreatitis from increased secretions
ETOH and heart
vasodilation (HTN in heavy drinkers), protective at low doses (J curve)
ETOH and kidney
Diuresis from reduced ADH secretion (only when BAC is actively rising)
Withdrawal stages (EtOH)
6-48: seizures, agitation, anxiety, insomnia
12-48: hallucinations
48-96: delerium tremens (no seizure risk)
ETOH withdrawal treatment
benzos to prevent hyperexcitability, alpha2 agonists to reduce autonomic hyperactivity
ETOH intoxication treatment
Supportive: IVF, glucose, thiamine, electrolytes
Drugs for Alcoholism (3)
Disulfiram
Naltrexone
Acamprosate
Drugs for Opioid Disorders (3)
Methadone
Buprenorphine
Naltrexone
Nicotine disorder meds (3)
NRT (20mg/pack), rash and tachy
Buproprion: nAChR agonist, DA reuptake inhibitor
Varenicline: A4B2 agonist, black box SI and Dep
What determines GA potency?
oil:water coefficient
GA MOA?
Binding in pockets of GABAa receptors
General structure of GAs
No consistent structural motifs
Other targets of GAs
brainstem chloride Rs, nAChRs, background K channels
Major sits of GA action
Hypothalamus (sleep), Reticular Formation (pain, sleep), and Hippocampus (short term memory)
4 stages of anesthesia
I: analgesia
II: excitement, delerium
III: surgical anesthesia (muscle relaxation and respiratory depression increase through phase)
IV: medullary paralysis
What symptoms to watch for before stage IV GA?
dilated pupils and diaphragmatic breathing
Uptake factors for GAs
Lung factors: ventilation rate Solubility in blood Pulmonary blood flow Solubility in tissue (tissue:blood coefficient) Tissue blood flow partial pressures in blood/tissues
Potency vs solubility
Potency = oil:water Solubility = blood:gas (uptake)
Major route of elimination of GAs
Lungs: function of CA and respiration, liver is negligible, fat reservoirs are important
Xenon
Noble gas, similar to N2O, not used
Nitrous Oxide (MAC, uses, etc)
Only gas agent used
MAC 105%, must be used in combo for balanced anesthesia, rapid onset and recovery
N2O Weird Stuff (3)
Concentration Effect: Uptake faster than predicted as 1L/min inspired volumes rapidly enter blood and pull more with it.
Diffusion Hypoxia: Large volume leaving blood dilutes alveolar O2
Second gas effect: high concentration of N2O uptake pulls any combo anesthetic with it faster too
N2O contraindications
obstructive disease and pregnancy
Diethyl Ether
Liquid, complete anesthetic (all stages), flammable so no longer used
Respiratory secretions might choke patient
Slow induction and recovery (high blood:gas)
Chloroform
Not used, cardiac arrhythmia risk, hepatotoxic
Halothane
Highly potent, low blood:gas, poor analgesic.
High respiratory/cardio failure potential
Liver damage, potentially from immune reponse
Can cause malignant hyperthermia
What do you give for malignant hyperthermia?
Danrolene
Enflurane
Good analgesic, good muscle relaxant
USE FOR MAINTENANCE
can trigger seizures, less toxic than halothane
Isoflurane
More potent than enflurane, little hepato/renal toxicity
NO SEIZURES
Pungent odor can cause coughing
MOST WIDELY USED INHALANT
Desflurane
New, minimal solubility, also pungent, can be complete anesthetic, needs special vaporizer
Sevoflurane
High potency, low blood-gas, pleasant odor
RENAL TOXIC
Thiopental
short acting barbituate, GABAa potentiation
Common for induction
Propofol
GABAa potentiation, rapid onset and fast recovery
Etomidate
No analgesia, induction, larger safety margin than theopental
Ketamine
NMDA antagonist, potent bronchodilator
Adjuvants (5 categories)
D-tubocurarine (neuromuscular blocker, non-depolarizing, don’t cross BBB)
Anxiolytics (Benzos and Barbs)
Analgesics (opioids)
Antiemetics (odansetron)
Anticholinergics (hypotension and bradycardia treatment, glycopyrrolate)
What part of the brain atrophies in MS?
Corpus Collosum
3 types of ADHD
Inattentive, Hyperactive, Combined
Which type of ADHD is most common in girls?
Inattentive
Major comorbities with ADHD? (5)
Substance Abuse Anxiety Disorders Depression Learning Disorders Oppositional Behavior
Prevalence of ADHD
3-8% in kids
Gender of ADHD
Male > Female (gender bias based on type?)
ADHD diagnostic criteria
6+ symptoms of 1 or both disorder types, before age of 12, present in 2+ settings
2 types of ADHD stimulant medications
Amphetamines and Methylphenidates
Are stimulants effective?
80-90% reduction in symptom burden
What percentage of ADHD persist into adulthood?
65%
Which ADHD types decrease with time?
Hyperactivity
Why are psych co-morbidities high? (5)
Genetics Developmental influences of ADHD Psychiatric effects Living Situation Self Treating
Prevalence of epilepsy and etiology
0.7%; 50% unknown cause
Differentiating complex partial and absence seizures?
Complex partial are followed by post-ictal
What percent of epilepsy is intractable?
36%
47% respond to 1st med, +13% to 2nd, +4% to 3rd
Most common childhood seizure?
Febrile, 2-4%
What percent of febrile seizures are complex?
20-30%
Risk factor for recurrent febrile seizures (6)
Age <1 year Family history Low grade fever at onset brief fever complex seizure day care
DLPFC Lesion Symptoms
Perseveration and environmental dependency
VMPFC Lesion Symptoms
Iowa Gambling Task issue, lack of inhibition.
Overall an inability to estimate risk/reward behavior
Anterior Cingulate Cortex Lesion Symptoms
Lack of will; issues with mental effort
Granular vs Agranular cortex
Granular = input (primary sensory) Agranular = output
Frequency of EEG rhythms
Beta > Alpha > Theta > Delta
