Unit IV, week 2 Flashcards
1
Q
General Anesthesia is a ___________ depression with progressive loss of function from ________ to ____________ levels within the CNS
A
DESCENDING depression: progressive loss of function from HIGHER (cognition, consciousness) to LOWER (respiratory control) levels within the CNS
2
Q
Stages of general anesthesia (1-4)
A
Stage I =analgesia
Stage II = excitement, delirium
Stage III = surgical anesthesia
Stage IV = medullary paralysis
-Respiratory failure, vasomotor collapse and resulting circulatory failure lead to death within minutes
3
Q
Time course of anesthesia (3)
A
1) Induction
2) Maintenance
3) Recovery
4
Q
Induction
A
time between initiation of administration and attainment of surgical anesthesia (until stage III reached)
5
Q
Maintenance
A
time during which surgical anesthesia is in effect (surgery)
6
Q
Recovery
A
time following termination of administration, complete recovery of patient from anesthesia
7
Q
Inhaled anesthetics enter _____________ in various membrane proteins (such as what?) –> what effects?
Is this specific binding?
A
hydrophobic pockets
such as GABA-A receptors
→ overall CNS depression
**Hydrophobic protein pockets within which volatile anesthetics bind are NOT specific binding sites
8
Q
Rate an effective concentration of anesthetic is reached in brain depends on 5 factors:
A
1) Concentration of anesthetic in inspired air
2) Alveolar ventilation rate (Respiratory depression can prolong recovery time)
3) Pulmonary blood flow (cardiac output)
4) Blood:gas partition coefficient
5) Potency (oil:gas partition coefficient)
9
Q
Uptake by blood from alveoli determined by…
how is rate of approach to stage III related to these two factors?
A
solubility of anesthetic in blood and cardiac output
rate of approach to stage III is INVERSELY PROPROTIONAL to pulmonary blood flow and solubility of anesthetic in blood
10
Q
Solubility of General Anesthetic
How does solubility of GA in blood effect approach to equilibrium?
A
rate of rise in partial pressure ratio is faster for gas with low solubility
Highly soluble GA (halothane)→ slower approach to equilibrium because a larger amount must be dissolved in blood
Low-solubility GA (nitrous oxide) exhibits more rapid increase in partial pressure in blood
11
Q
Faster pulmonary blood flow effects anesthetic uptake how?
A
Faster pulmonary blood flow → less time for anesthetic to diffuse into blood
12
Q
Uptake from arterial blood to body tissues depends on (3)
A
1) anesthetic gas solubility in body tissues
2) tissue blood flow (Higher tissue blood flow = faster delivery)
3) partial pressure of anesthetic in blood/tissues
13
Q
Tissue distribution of general anesthetics (3)
A
1) Vessel-rich groups: highly vascularized tissues (brain, heart, kidney, liver, endocrine glands) → high uptake
2) Muscle groups: muscle and skin → slower uptake, 2-4 hours
3) Fat group: very slow uptake due to high ability to dissolve anesthetic
Equally soluble in blood and lean tissues but more soluble in fatty tissue = large reservoir for anesthetic
14
Q
Oil:gas partition coefficient vs. Blood:gas partition coefficient
A
Oil:gas partition coefficient = anesthetic potency
-Potency = 1/MAC (minimum alveolar concentration)
Blood:gas partition coefficient = anesthetic uptake and elimination kinetics
15
Q
Metabolism and excretion of volatile anesthetics
A
Clearance of inhaled anesthetics primarily by lungs
Metabolism in liver of volatile anesthetics is not important in terminating anesthetic action BUT is important for adverse drug reactions and interactions
16
Q
Xenon
A
not used clinically, equivalent potency to Nitrous oxide
17
Q
Nitrous oxide
- potency?
- use?
- onset?
- contraindications (2)
A
low potency anesthetic, cannot reach surgical dose
Adjunctive agent due to analgesic and anxiolytic properties
Rapid onset
Contraindications: respiratory obstruction (COPD), pregnancy
18
Q
Diethyl ether
A
no longer used
Flammable and explosive
Produces excessive respiratory tract excretions → choking patient
Good analgesic
19
Q
Chloroform
A
no longer in common use
Can cause cardiac arrhythmias and hepatotoxicity
20
Q
Halothane
A
was most widely used inhalational anesthetic until recently
Highly potent
Induction and recovery not prolonged (low blood:gas coefficient)
non explosive
21
Q
Halothane negatives (4)
A
1) Not a good analgesic
2) Can easily produce respiratory and cardiovascular failure (arrhythmias)
3) Hepatotoxic (increased risk with repeated exposure)
4) Can trigger malignant hyperthermia
22
Q
Malignant hyperthermia
A
Muscle rigidity, fever
TX = dantrolene (muscle relaxant), blocks Ca2+ release via ryanodine receptor
Can be triggered by halothane
23
Q
Enflurane
-uses? (4)
negatives? (1)
A
- Excellent analgesic
- Fast induction and recovery
- Good muscle relaxant
- Less CV effects, less hepatotoxicity
Negatives: Can trigger seizures during induction/recovery
24
Q
Isoflurane
A
most widely used inhalational anesthetic
- More potent than enflurane
- Minimal hepatotoxicity or renal toxicity
- No seizure triggering
- Rapid and smooth induction and recovery
- Minimal CV depression
- Good muscle relaxant
Negative: has pungent odor → can cause coughing
25
Desflurane
- Low blood and fatty tissue solubility → faster recovery
- Pungent odor
- Not hepatotoxic
Contraindicated for malignant HTN patients
26
Sevoflurane
High potency, low blood:gas coefficient → rapid onset and recovery
Pleasant odor → can be used for induction
Chemically unstable → toxic to kidneys
27
Thiopental
- mechanism?
- onset?
- use?
ultra-short acting barbiturate
Used for induction of general anesthesia
Rapid onset of action - LOC within 15-20 seconds, reawaken in 3-5 minutes
28
Propofol
- mechanism?
- use?
- 2 benefits?
potentiates GABA-A receptor
Rapid onset induction anesthetic, fast recovery
Less nausea post-op
No involuntary movements
29
Etomidate
- mechanism?
- use?
- benefit?
- onset?
- drawback?
potentiates GABA-A receptor
-Used for induction of general anesthesia
Larger safety margin - minimal depression of CV and respiratory function
LOC in seconds, recovery in 3 min
Can cause involuntary patient movements during induction
30
Ketamine
glutamate receptor antagonist, no action on GABA-A receptor
Catatonia, amnesia, analgesia
Potent bronchodilator
31
d-Tubocurarine
neuromuscular blocking agent (competitive ACh antagonist)
Relaxes skeletal muscle
32
Ondansetron
antiemetic
Postop nausea and vomiting
33
Glycopyrrolate
anticholinergic, given to combat HTN and bradycardia
34
Main mechanism of general anesthetics
Depress neuronal excitability in CNS via potentiation of GABA-A receptor activity
→ potentiate GABAergic IPSPs in CNS
→ greater inhibition of CNS and depression of neuronal excitability
35
Main brain regions involved in general anesthesia (3)
Hypothalamic nuclei involved in sleep
Reticular formation of brainstem → control of pain, alertness, sleep
Hippocampus → amnesia of post-op patients
36
Ideal characteristics of general anesthetics
rapid and smooth onset of action, rapid recovery from anesthesia upon termination of drug administration, and drug has wide margin for safe use
No drug has all these → use combination of drugs
**Specific drug combinations designed to take advantage of desirable properties of individual drugs while attenuating undesirable side effects
37
Identification of attentional dysfunction
Gold standard = good history and exam - screens supportive, but not sufficient
NOT a learning disorder, intellectual disability, or oppositional behavior
38
Types of ADHD (3)
1) Inattentive type
2) Hyperactive type
3) Combined type
39
Inattentive type
Frequently undiagnosed, more common in girls
Fails to give close attention to details, difficulty sustaining attention
Doesn’t appear to listen, struggles to follow instructions
Difficulty with organization, avoids tasks with lots of thinking
Loses things, easily distracted, forgetful
40
Hyperactive type
Diagnosed earlier (bothersome to others), frequently confused with oppositionality
Fidgets, squirms, difficulty remaining seated
Difficulty engaging in activities quietly, talks excessively
Blurts out answers before questions have been completed, interrupts others, difficulty waiting or taking turns
41
Combined type ADHD
meets criteria for both (6 symptoms from each category)
42
Functional impact of ADHD
Less likely to graduate from high school, get a higher education, and work in a professional environment.
More likely to use drugs/alcohol/tobacco and be incarcerated
43
Common comorbidities with ADHD
substance abuse, anxiety disorders, depression, learning disorders, oppositional behavior
44
Why is comorbidity so high with ADHD (5)
Underlying genetic vulnerability
Developmental changes
Psychological effects of having ADHD
Living with others who are irritated by the ADHD
Self-treating the problem
45
Treatment of ADHD (4)
1) Stimulants
2) Atomoxetine
3) Bupropion (Wellbutrin)
4) Alpha agnoists (guanfacine, clonidine)
- Mostly affect hyperactive symptoms
46
Stimulants used for treatment of ADHD (2 types)
standard of care
Amphetamines: Adderall, Vyvanse
Methylphenidates: Ritalin, Concerta
47
ADHD Long term
lifelong disorder that frequently requires chronic treatment
65% continue to have ADHD symptoms into adulthood
Hyperactivity tends to decrease with time
Inattentive symptoms, restlessness and impulsivity remain
48
Long term treatment of ADHD
Focus on quality of life, treatment can decrease burden on partner
May still need stimulants as adults
49
Epilepsy
tendency for recurrent seizures because of an underlying brain abnormality
disorder of recurrent spontaneous seizures
Generalized or partial
50
post ictal and during seizure
Postictal period: negative symptoms, loss of function in areas of brain involved
-Due to neuronal exhaustion or inhibitory inputs to that area
During seizure → positive symptoms
51
Signs of epileptic seizures
paroxysmal change in behavior or movement, or an alteration of consciousness
52
Focal (partial) seizures vs. Generalized seizures
Focal: begin in one area of cortex, remains localized or spreads
Generalized seizures: begins because cortex as a whole is hyper-irritable
53
Focal (partial) seizure with consciousness preserved
SIMPLE seizure
not effecting awareness or memory
54
Focal (partial) seizure with loss or impairment of consciousness
COMPLEX seizure
Partial onset followed by impairment of consciousness
affecting awareness or memory of events before, during, and immediately after the seizure and affecting behavior
Focal seizures can evolve (spread like a brush fire to “bigger seizure” including convulsive seizure)
55
Absence seizures
Generalized seizure
Involve widespread areas of cortex, but not all layers of neurons
Period of AMS unaccompanied by major motor manifestations
56
Partial complex seizures
followed by postictal state (most absence seizures are not)
Period of AMS unaccompanied by major motor manifestation
Often hard to distinguish from absence seizures
57
Seizures
episodic events which are unexpected and sudden resulting from abnormal and excessive activity of neurons
Involves electrical functions of brain
58
Intractable epilepsies
do not respond to trial of at least 3 anticonvulsants
30% of new onset seizure patients may develop intractable epilepsy
59
Febrile Seizures
Event in infancy/childhood occurring between 3 mos and 5 yrs, associated with fever but without evidence of intracranial infection or defined cause
Most common childhood seizure
No proof of occurrence with rise in fever
Usually within first 24hrs of illness
60
Simple vs. Complex febrile seizure
Simple: generalized, last 10-15 minutes, do not recur within 24 hrs
Complex: focal in nature, at onset, or during, longer than 10-15 min, recur in less than 24 hours
20-30% of febrile seizures are complex
61
What is the likelihood of future seizures after a febrile seizure?
25-40% will have recurrent febrile seizure
62
Future impact of febrile seizures on sleep, cognition, and risk of epilepsy
Cognition: almost all will have normal cognition, prolonged/complex than may have increased risk of cognitive problems
Sleep: tendency to have sleep problems, nightmares
Increased risk of epilepsy with complex seizure, neurological abnormality, or family history of afebrile seizures
63
Mechanisms of Seizure Pathophysiology (2 main ways neuronal membrane is made unstable)
unstable neuronal membrane (focal epileptogenesis → initiation)
1) Paroxysmal discharges can recruit and synchronize a large population of cortical neurons or neurons in thalamic region
2) Enhancement of excitatory neurotransmitters (primarily glutamate) or deficiency of inhibitory neurotransmitters (primarily GABA) can promote spread or propagation of abnormal activity as can metabolic causes.
64
Common causes of seizure: primary and secondary
Primary: hereditary or idiopathic causes
Secondary: mechanical (trauma, brain tumor), metabolic (hypoxia, hypoglycemia, hypocalcemia, alkalosis), withdrawal of CNS depressant drugs, toxins
65
Consequence of seizure
seizure activity → increased O2 demand of CNS → insufficient O2 supply → ischemia → brain damage (neuronal destruction)
Seizures beget seizures
66
3 drugs used to treat Grand mal (tonic clonic) seizures
valproate, lamotrigine, levetiracetam
67
Mechanism of grand mal seizure (4)
1) Loss of GABA inhibitory tone
2) Propagation due to decreased GABA tone over large area
3) Increased response to glutamate
4) Na+ channel excitation
68
Features of a grand mal (tonic clonic) seizure
loss of postural control, LOC, tonic phase (rigid extension of trunk and limbs), clonic phase (rhythmic contraction of arms and legs)
69
2 drugs used to treat a petit mal (absence) seizure
Ethosuximide, Valproate
70
Mechanism of petit mal (absence) seizure
inappropriate activation of low-threshold T-type Ca2+ channels
71
Features of petit mal (absence) seizure
normal muscle tone, impaired consciousness with staring spells (with/without eye blinks), function normal after seizure
72
Mechanism of partial seizures
involves initiation (Rather than propagation) → more difficult to treat
73
3 drugs used to treat partial seizures
carbamazepine, lamotrigine, levetiracetam
74
Treatment of status epilepticus (inpatient vs. outpatient)
BDZS → diazepam, lorazepam, midazolam
Inpatient → Fosphenytoin, Levetiracetam
75
Treatment of Atonic Myoclonic seizures (3 drugs)
Valproate, Levetiracetam, Lamotrigine
*same drugs that treat tonic clonic grand mal seizure!
76
Two goals of anticonvulsants
elevate seizure threshold (Stabilize membrane) and limit propagation (reduce synaptic transmission or nerve conduction)
77
Mechanism of action of anticonvulsant drugs (4)
1) Inhibition of sodium channel (VSSC)
2) Decrease T-type Ca2+ current
3) Inhibition of high-voltage activate Ca2+ channels (VSCC)
4) Enhance GABA action
78
Anticonvulsant drugs: Inhibition of sodium channels
what does this accomplish?
5 drugs that do this
use dependent block that stops sustained high-frequency repetitive firing of APs that can initiate seizure formation
Drugs: Phenytoin (class IB antiarrhythmic), Carbamazepine, Lamotrigine, Topiramate, Valproic acid
79
Anticonvulsant drugs: Decrease T-type Ca2+ current
what does this accomplish?
2 drugs that do this?
control oscillatory firing of thalamic neurons
Drugs: Ethosuximide (absence seizures), Valproic acid
80
Each of these four drugs has a different mechanism to enhance GABA action. How?
1) Benzodiazepines and Phenobarbital
2) Vigabatrin
3) Tiagabine
4) Gabapentin
1) Benzodiazepines and Phenobarbital → facilitate GABA-Cl- channel opening
2) Vigabatrin → inhibit inactivation of GABA by GABA-transaminase
3) Tiagabine → block reuptake of GABA at synapse
4) Gabapentin → increase GABA levels in brain
81
Valproate
Mechanism of action
VSSC block and T-type Ca2+ block
82
Valproate
**Side effects (5)
GI complaints
hepatotoxicity**
weight gain common
CONTRAINDICATED IN PREGNANCY
DO NOT USE IN PATIENT UNDER 2 YEARS OLD
83
Valproate
Use (3)
broad spectrum agent with efficacy against most seizure types
1) First line for generalized tonic-clonic seizures
2) Also very effective against absence seizures, BUT hepatotoxicity → use ethosuximide instead
3) Also can be used in mania
84
Valproate
Drug interactions (3)
Alcohol/CNS depressants → additive effects
Anticonvulsants → inhibit metabolism of phenobarbital, phenytoin, lamotrigine, carbamazepine, ethosuximide
ASA/Warfarin → can inhibit platelet aggregation
85
Lamotrigine
mechanism
binds to and disrupts function of SV2A
no one really knows!
86
Lamotrigine
Side effects (4)
fatigue, somnolence, dizziness
**Minimal drug interactions, no CYP450 metabolism
87
Lamotrigine
Use (1)
first line for generalized tonic-clonic seizures
88
Ethosuximide
mechanism
T-type Ca2+ channel blocker
89
Ethosuximide
side effects (4)
Metabolized (primarily hydroxylation) by CYP3A4→ DDIs with inducers or inhibitors possible
Gastric distress, headache, dizziness
90
Ethosuximide
use (1)
drug of choice in absence (petit mal) seizures
91
Carbamazepine
Mechanism
bind and block VSSC → suppress repetitive AP
92
Carbamazepine
Use
partial seizures and generalized tonic-clonic
Inhibit peripheral sensitization in treatment of chronic pain (trigeminal neuralgia)
93
Carbamazepine
Side effects (6)
1) P450 enzyme inducer**
2) Diplopia, ataxia, nausea-vomiting, drowsiness
3) Hyponatremia
4) Stevens-Johnson syndrome
5) Idiosyncratic blood dyscrasias (fatal cases of aplastic anemia, agranulocytosis), rare
6) Hepatotoxicity → monitor CBC, platelets, liver function
94
Phenytoin
Mechanism
bind VSSC→ suppress repetitive AP
95
Phenytoin
Side effects (5)
1) Strong P450 inducer**
2) Zero order rate of elimination
3) Nystagmus, ataxia, sedation (additive with other CNS depressants)
4) Rash, gingival hyperplasia, hirsutism
5) OD → death from respiratory/circulatory depression
96
Phenytoin
Use (2)
no longer considered drug of first choice to to adverse effects
Partial seizures and generalized tonic-clonic seizures
97
Phenobarbital
Mechanism
enhance GABA inhibition and antagonize glutamate excitation
98
Phenobarbital
Side effects (3)
CYP450 enzyme inducer → significant DDIs
Sedative effect, interfere with learning
CONTRAINDICATED IN PREGNANCY (along with valproate)
99
Phenobarbital
Use (3)
excessive sedation limits use to adjunctive role
Partial seizures and generalized tonic-clonic seizures
Neonatal status epilepticus
100
Dorsolateral PFC
contributes to the representation, planning, and selection of goal-directed behaviors
101
Input to DL PFC
somatosensory, visual and auditory cortical association areas (parietal, occipital, and temporal lobes)
Also involved in basal ganglia-thalamocortical circuit
102
Output from DLPFC
premotor cortex and somatosensory association cortex
Also deep brainstem structures (superior colliculus, midbrain tegmentum, PAG)
103
Lesion to DLPFC results in what symptoms?
Inability to employ intention (goals) to modulate attention (task at hand)
Perseveration: failure to switch attention appropriately
Environmental dependency: lack of internally generated goal direction → big requirement for environmental cues to accomplish a task
104
Ventromedial PFC aka “orbitofrontal”
central role in assessing positive and negative valence of stimuli and (with dopaminergic VTA/nucleus accumbens input) computes potential gains/losses of potential actions
105
Input to VM PFC
Somatosensory, visual, auditory assoc. areas (less than DLPFC)
Strong olfactory, gustatory, and visceral inputs
Amygdala and parahippocampal cortices
106
Output from VM PFC
Cortical and subcortical regions of forebrain
Lateral and posterior hypothalamus → stress/autonomic centers
PAG, solitary nucleus tract, dorsal motor nucleus of vagus
107
Lesion to VM PFC results in what symptoms
impair ability to estimate risk/reward of certain behaviors and impair suppression of excessively risky behaviors (esp. in context of social function)
Characteristic performance on Iowa Gambling Task
- Continue to draw from “bad” decks even though they know they are losing
- Don’t develop physiologic reaction to an impending punishment
- Inadequate inhibition of aggression, sexual behavior, anxiety, and appetitive functions
108
Anterior cingulate cortex
detects conflicts between current attention/behavior and desired results, promotes action towards goal (motivation)
109
Anterior cingulate cortex input/output
Extensive reciprocal relationships with limbic and autonomic structures
Stimulation → autonomic and limbic responses (change HR, BP, respiration, vocalizations, and facial expressions)
110
Lesion to Anterior Cingulate Cortex results in what symptoms?
syndrome of poor motivation, apathy, or lack of will
Abulia (lack of will), akinesia and mutism in some cases
Impaired attentional conflict and focused mental effort
Stroop test - active during the switching required to perform task
111
Function of PFC
modulatory rather than transmissive
PFC guides activity flow along task-relevant pathways in more posterior and/or subcortical areas
112
Bilateral hippocampal dysfunction --> ??
(patient HM)→ lose declarative or episodic memory as well as spatial memory
113
Neurotransmitters involved in bottom up processing (2)
Acetylcholine: ACh released diffusely throughout cerebral cortex when something novel happens
Norepinephrine: projects diffusely throughout cortex, important for attention, learning, anxiety, and arousal
Both are important modulators for what our brains are tuned to
114
Grid cells
cells of entorhinal cortex, principal input to hippocampus
Dynamic computation of self-position based on continuously updated info about position and direction
Send output to “place cells”
115
Two main inputs to hippocampus
1) Entorhinal cortex
| 2) Septal nuclei
116
Circuit of hippocampus:
1) Entorhinal cortex via _________ path --> _________
2) Dentate gyrus _________ cells send axons via _______ fibers to _______
3) _________ from CA3 neurons form __________ with other CA3 neurons and CA1 via ____________
4) _________ cells send projections to _______ field --> ____________ --> ___________ --> ____________
1) Entorhinal cortex via perforant path→ dentate gyrus
2) Dentate gyrus granule cells send axons via mossy fibers to CA3 field
3) Axon collaterals from CA3 neurons form auto-associations with other CA3 neurons and CA1 via Schaffer collaterals
4) → pyramidal cells send projection to CA1 field → subiculum (transition from 6 layered cortex to 3 layered hippocampus) → entorhinal cortex → cortical association areas
117
Perforant path
entorhinal cortex → dentate gyrus and hippocampus
118
Mossy fibers
granule cell axons that project to CA3
119
Schaffer collaterals
axons from CA3 → CA1 neurons
120
What role does synaptic plasticity play in the hippocampal circuit?
Synaptic plasticity in this circuit is crucial for forming memories and associations between places and actions, and associations between events
121
Function of hippocampus (4)
1) Formation of declarative memories
2) Memory consolidation to neocortex
3) “Search engine” - search among deposited memories in neocortex
4) “GPS of brain” = spatial memory
122
Place cells
firing of each cell indicates specific location in environment → space encoded in firing pattern of hippocampus
123
Dentate gyrus
Contain granule cells and local circuit neurons (interneurons)
124
Ammon’s Horn
Contain pyramidal cells and local circuit neurons (interneurons)
CA3 + CA2 + CA1 field
125
CA3 field
next to dentate gyrus
CA3 neurons have recurrent collaterals to other CA3 cells → allows arbitrary associations between inputs from very different parts of cerebral cortex to be formed = Autoassociative memory
126
CA2 field
follows CA3 field
127
CA1 field
merges with subiculum
128
Subiculum
transition zone between three layered hippocampus and 6 layered entorhinal cortex
129
Sleep and memory consolidation
Hippocampus and neocortex interact during sleep → representations of recent experiences are transferred from hippocampus to neocortex via consolidation to form long-term memories
Hippocampus only has limited capacity storage of memories → teaches cortex about information when info is recalled → make memory hippocampus-independent
Hippocampus and cortical neurons synchronously active during sleep
130
6 Layered cortex
Layer 4 = “inbox”, Layer 5/6 = “outbox”, Later 2/3 = interoffice mail
Layer 5 = motor output layer over entire cortex
Layer 4 contains granule cells
131
Ascending pathway in cerebral cortex
= input into layer 4 from primary (first order) relay nucleus of thalamus
Bottom up attention: activity generated by sensory inputs, relayed through hierarchy of progressively more sophisticated processors
Driving in character - initiates activities
132
Descending pathway in cerebral cortex
= feedback issuing from layers 5 and 6 and terminating in layers 6,5,1
Top down attention
Modulatory rather than driving in action - capable of modifying ascending activity, but not of initiating activity de novo
133
Neural network models
assume that neural circuit function arises from activation of groups or ensembles of neurons
Ensembles generate emergent functional states that cannot be identified by studying one neuron at a time
Gene expression pattern reflects a state of the network
134
EEG
measures electrical potential fluctuations at scalp surface
Fluctuations produced by temporal and spatial summation of electrical currents caused by relatively slow postsynaptic potentials (EPSPs and IPSPs) in cerebral cortex (may or may not lead to AP, represent fluctuations in resting potential)
135
Pyramidal cells
(vertically oriented cells) sum the electrical potential changes in the cerebral cortex
136
Distinct patterns of EEG
generated by simultaneous depolarization/ hyperpolarization of a large number of neurons → distinct continuous oscillations on EEG
137
“Functional Connectivity”
maps of brain constructed based on synchrony observed in EEG, MEG, or fMRI signals
Connectivity is based on physiological synchrony, not anatomical connectivity
Alterations in structural and functional connectivity observed in wide variety of neurologic and psychiatric conditions
138
Thalamic reticular nucleus
controls thalamocortical information flow = conductor entraining diverse cortical members in a concerted rhythm
Slow wave sleep, absence seizures, deep anesthesia → delta wave pattern representing temporary detachment of thalamic relay cells from sensory inputs
139
Cholinergic input from brainstem
ACh depolarizes thalamic relay neurons → inhibit thalamic reticular nucleus → steady train of thalamic relay activity
ACh acts to open thalamocortical gate to sensory information → attention and arousal = conductor of a conductor
140
Reticular formation of brainstem
stimulation → awaken from sleep
“Ascending reticular activating system”
141
__________ learns drug and cues cause pleasure - may signal relief from craving
Amygdala
142
Drug cues lead to ________ release in _______ --> trigger output to _______ and ________
DA release in nucleus acumbens
thalamus and cortex
143
In absence of activity from _____________ system --> drug seeking initiated
reflective reward system
144
Tolerance and ________ do not necessarily coexist, nor do addiction and ______________
dependence
physical dependence
145
1) Increased dopamine release in the hypothalamus via the tuberoinfundibular pathway --> ?
2) Increased dopamine release in the nucleus accumbens via the mesolimbic pathway --> ?
3) Dopamine release in the striatum via the nigrostriatal pathway --> ?
4) Decreased dopamine release in the tegmentum via the mesocortical pathway --> ?
1) decreased prolactin release
2) Positive symptoms (Delusions, hallucinations, disordered thoughts)
3) movement
4) Negative symptoms (blunted affect, anhedonia, alogia, asociality)
146
What's the main difference between between typical and atypical antipsychotics?
Typical psychotics: Haloperidol, Chlorpromazine
-High D2 block, low 5HT2A block (more extrapyramidal side effects)
Atypical antipsychotics: Clozamine, Olanzapine, Quetiapine
-High 5HT2A block, low D2 block
147
If you increase your dietary intake of salt what happens to your lithium levels?
decreased Li+ levels
148
3 drugs to treat partial seizures
Carbamazepine
Levetiracetam
Lamotrigine
149
3 drugs to treat Tonic-Clonic seizures
Valproate
Levetiracetam
Lamotrigine
150
3 drugs to treat atonic myoclonic seizures
Valproate
Levetiracetam
Lamotrigine
151
2 drugs to treat absence seizures
Ethosuximide
| Valproate
152
Ideal hypnotic
Rapidly induce sleep (absorption), duration sufficient to maintain sleep with no morning hangover (half-life)
No dependence/tolerance, no rebound insomnia with discontinued use
Normalize sleep without disturbing sleep
153
BDZs and Barbs in treatment of insomnia:
mechanism
facilitate action of GABA at GABA-A receptor-chloride channel complex → membrane hyperpolarization, decreased neuronal excitability
BDZs → sleep and anxiolysis use
154
BDZs and Barbs in treatment of insomnia:
Benefits
Useful for promoting sleep, and increasing duration of stage 2 sleep (maintenance of sleep state)
155
BDZs and Barbs in treatment of insomnia:
Drawbacks (5)
1) Decreases delta-sleep = BAD
2) Decrease REM duration = BAD
3) Use for longer than 1 week → tolerance = BAD
4) Rebound insomnia with discontinued use
5) Day time sedation (“hangover”)
156
NonREM stages of sleep
characterized by a reduction in physiological activity (70-75%)
Stage 1, stage 2, and slow wave sleep
157
Stage 1 sleep
transition phase from being awake to falling asleep
EEG like wakefulness (a-rhythm)
Falling sensations, sudden muscle jerks
158
Stage 2 sleep
light sleep, short fragmented thoughts
EEG slower with bursts of rapid waves
159
Slow wave sleep
deepest level of sleep, most difficult to arouse a person, people groggy several minutes after awakening
EEG has very slow delta waves
Night terrors, nocturnal enuresis can occur
160
REM sleep
active period of sleep with intense brain activity (25-30% of sleep)
EEG rapid and desynchronized (similar to waking state)
Rapid eye movements, decreased muscle tone, increased BP, pulse, and respirations
Most recallable dreams
161
Z drugs
schedule 4 controlled substances (like benzos)
Drug names: Zolpidem (Ambien), Zaleplon, Eszopiclone (Lunesta)
Z-drugs → non benzos that bind GABA-chloride channels with a1 subunit ONLY (found in cortex) → sleep WITHOUT anxiolysis, reduced potential for dependence
162
Zolpidem
effective for reducing sleep latency and nocturnal awakenings with an increase in total sleep time and efficiency
163
Zaleplon
decreases time to sleep onset but not number of awakenings
Best suited for use as a sleep aid for middle-of-the-night awakenings
Short half life, eliminated by morning
164
Eszopiclone
Longer half life
Safe long term use with no suggestion for development of tolerance or dependence
Help with sleep maintenance and onset
165
Side effects of Z drugs
less than benzos
Drowsiness, amnesia, dizziness, headache, GI complaints
Next day psychomotor (driving) impairment
Complex sleep-related behaviors
Rebound effects and withdrawal/tolerance minimal but possible
166
Use of Z drugs
first line agents for insomnia
Minimal effects on SWS and REM
167
3 benzodiazepines that are used to treat insomnia
Triazolam
Temazepam
Flurazepam
168
Side effects of benzos used for insomnia (5)
Fatal OD rare unless taken with other CNS depressants or alcohol
Daytime sedation and performance impairment
Anterograde amnesia
Rebound insomnia
Psychologic and physical dependence (Schedule 4 drug)
169
Drugs used to treat insomnia that don't act on GABA
Mirtazapine
Tricyclic antidepressants
Trazadone
Rameleteon/Melatonin
170
Mitazapine
antidepressant known for sedative effects
Mechanism: block 5HT2 receptors and Histamine H1 receptors
171
Tricyclic Antidepressants
amitriptyline
Mechanism: block reuptake of 5HT and NE, antagonist at histamine and muscarinic receptors
→ decrease REM and increase slow wave sleep
172
Trazodone
mechanism and side effects (4)
Mechanism: complex effects on 5HT neurons
-Decrease REM sleep, increase slow wave sleep
```
Side effects:
Oversedation
Orthostasis
Dangerous in elderly
Priapism
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173
Ramelteon/Melatonin
mechanism, side effects, use
Mechanism: agonist at melatonin MT1 and MT2 receptors
Regulates circadian rhythms in suprachiasmatic nucleus
Side effects: dizziness, somnolence, fatigue
Use: chronic or transient insomnia characterized by difficulty with sleep onset
174
Diphenhydramine
Mechanism: antihistamine H1 and muscarinic cholinergic antagonist
Use: NOT recommended for chronic use in adults or children
175
Delirium
fluctuating confusion, inattention, misperceptions (illusions or hallucinations)
176
Stupor
sleep-like state form which the patient can be aroused only by vigorous stimuli
177
Coma
sleep-like state where the patient is unresponsive to external stimuli, and there are no sleep-wake cycles
Usually lasts no more than 4 weeks
GCS definition: GCS 8 or less
Patients in coma if they are unable to: follow commands, speak any recognizable words, open either eye
178
Decerebrate (extension) posturing
UE extension with LE extension
Suggests lesion at upper brainstem
Prognosis worse in decerebrate than decorticate
179
Decorticate (flexion) posturing
upper extremity flexion with lower extremity extension
| Suggests lesion at hemispheres
180
Vegetative state
where sleep-wake cycles are re-established but there is no sign of cognitive function
Eyes open spontaneously
No evidence of perception of the outside world or purposeful motor activity
Considered permanent if 1 month after acute onset, 3 months after anoxic injury, and 12 months after trauma
181
Criteria for establishing brain death:
1) Unresponsive (GCS = 3)
2) Cerebrally modulated motor responses are absent during application of painful stimulus
- Spinal reflexes may be present
- Seizures or flexion/extension posturing may not
3) Brainstem reflexes are absent (pupils, corneals, oculocephalic, oculovestibular, cough, gag, respiratory effort/apnea test)
182
4 other things that must be present for coma
Core body temp of 90F
Toxicology tests find no explanation for low neurological state
Adequate BP and pulse (SBP > 90, P>50)
No voluntary movements or response to pain
183
Corneal blink reflex:
how do you do it, what CNs are involved?
What must not happen for brain death to be determined?
Touch cornea with tissue, there must be no blink response in either eye (CNs V and VII)
184
Oculocephalic Reflex
how do you do it, what CNs are involved?
What must not happen for brain death to be determined?
rotate head quickly to one side and observe eyes
CNs VIII, III, IV, and VI)
There must be no eye movements of any kind
185
Oculovestibular Reflex (Cold water calorics):
how do you do it, what CNs are involved?
What must not happen for brain death to be determined?
Flush each external auditory canal with 20 ml ice water x2 and observe
CNs VIII, III, IV, and VI
There must be no eye movements of any kind
186
Cough reflex:
how do you do it, what CNs are involved?
What must not happen for brain death to be determined?
suction trachea at the carina
CN X
There must be no cough response
187
Gag reflex:
how do you do it, what CNs are involved?
What must not happen for brain death to be determined?
tough oropharynx with Q-tip or suction
CNs IX and X
There must be no movement of the oral structures
188
Raphe nucleus
Locus coeruleus
Nucleus basalis of Meynert
Substantia nigra
Release what NT?
Raphe nucleus --> 5HT
Locus coeruleus --> NE
Nucleus basalis of Meynert --> ACh
Substantia nigra --> Dopamine
189
Minimally conscious state
eyes open spontaneously, sleep-wake cycles resume
Arousal level may be normal at times
Reproducible behavioral displays of perception comunication, or purposeful motor activity
190
Consciousness
derives from activation of intralaminar nuclei of thalamus by the reticular activating system projecting from reticular formation of brainstem
191
Unconsciousness
reflects diffuse or bilateral impairment of cerebral functions or failure of brainstem ascending reticular activating system or both
192
Loss of Consciousness, Paralytic Coma
must be witnessed by observer
Eyes are closed in a sleep-like state
Unresponsive to external stimuli
Lasts seconds-minutes-hours-days-weeks (lasts less than one month)
Length of coma correlated with outcome
