Week 6 Flashcards
(135 cards)
1
Q
General anesthesia (balance)
A
balance btw hypnosis, analgesia (autonomic, somatic), and areflexia.
2
Q
Modern inhaled anesthetics
A
Fluorinated ether derivatives
3
Q
clinically relevant differences between inhaled anesthetics
A
potency, solubility, pungency, cost
4
Q
distribution, elimination of inhaled anesthetics
A
uptake into blood and distributed 1) VRG (brain, liver, kidney) 2) fat 3) muscle. eliminated by ventilation (almost no metabolic breakdown)
5
Q
solubility of inhaled anesthetics
A
low blood solubility = less potent, faster onset/offset, less accumulation in tissue/fat
6
Q
MAC inhaled anesthetics
A
minimum alveolar concentration at which 50% patients will not move in response to surgical incision (hypnosis more important now)
7
Q
MOA inhaled anesthetics
A
promiscuous binders allosterically and competitively. GABA-A.
8
Q
Respiratory effects inhaled anesthetics
A
bronchodilation, inc rate, dec tidal volume, dec reflexes to maintain oxygenation/ventilation
9
Q
CV effects inhaled anesthetics
A
Decrease blood pressure, redistribute blood from core to periphery. Impair autonomic reflexes, impaired contractile strength of heart.
10
Q
pharmacokinetics of IV anesthetics
A
Redistribution terminates drug effect–not elimination! order of peaks: Plasma–>VRG–>muscle–>fat
11
Q
Context-sensitive half time
A
longer you infuse a drug, the longer it takes to eliminate. Very fat-soluble drugs never get to steady state.
12
Q
Propofol (mechanism, onset, use, metabolism, contraindications)
A
potentiates GABA (no effect on pain!), fast onset/offset, used for induction, TIVA, ICU sedation, partially metabolized in extrahepatic tissues. Redistribution > elimination! Egg allergy.
13
Q
Etomidate (use, MOA, adverse effects)
A
induction drug of choice for hemodynamically compromised patients, potentiates GABA, causes adrenocortical suppression = reduced ability to compensate for shock!
14
Q
Thiopental (general properties, contraindications)
A
similar to propofol, contraindicated in porhpyria
15
Q
CV effects of IV anesthetics
A
hypotension!
16
Q
Ketamine (autonomic effects, anesthetic advantages, disadvantages)
A
sympathetic stimulation, potent analgesic, causes dissociative anesthesia and dysphoria, no IV access required.
17
Q
MOA local anesthetics
A
Cross membrane, bind intracellularly to Na+ channels in open and inactivated states. Acid reduces ability to cross membrane
18
Q
amide local anesthetics
A
two “i”s in generic name. metabolized in hepatocytes, greater toxicity
19
Q
ester local anesthetics
A
one “i” in generic name, metabolized in plasma to PABA (potential allergen), less toxic, OTC meds are esters.
20
Q
pharmacology local anesthetics (solubility, pKa)
A
greater lipid solubility –> more potent, longer duration. Lower pKa–> more un-ionized–> more rapid onset.
21
Q
toxicity and Tx of local anesthetics
A
tongue numbness, lightheadedness –> visual disturbance –> muscle twitching –> unconsciousness –> convulsion –> coma –> respiratory arrest. Ventricular arrhythmias. Intralipids given to absorb LA. Hyperventilate to generate acidosis
22
Q
S vs R isomer local anesthetics
A
S preferred – reduced cardiotoxicity
23
Q
Multi-Axial biopsychosocial model
A
I: clinical disorder (pervasive across all social interaction)
II: personality disorders, mental retardation, maladaptive personality features, defense mechanisms
III: general medical conditions
IV: psychosocial and environmental problems
V: global assessment of functioning
24
Q
Organizational vs activational effects of gonadal hormones (and examples)
A
organizational = development, fetal exposure, considered permanent (eg high CAH in girls leads to "masculinization"). Activational = re-exposure later in development, transient and super-imposed on organizational effects
25
sex hormone effects on NTs
estrogen is pro-5HT. progesterone acts on GABA
26
attachment behavior
behavior that promotes proximity to or contact with person(s) to whom an individual is attached
27
neurobiology of attachment (voles)
oxytocin mediates partner attachment/preference as well as mother-child attachment
28
Stages of normal infant attachment
```
Indiscriminate sociability (2 mos)
Attachments in the making -- differentiating caregivers, developing internal representation. (2-7mos)
Clear Cut Attachment -- Still Face test. Stranger/Separation anxiety (7-24mos)
Goal Oriented Partnerships (>24 mos)
```
29
Healthy vs disturbed attachement cycle
Healthy: Need--> Cry --> Response --> Trust
Disturbed: Need--> Cry--> No Response --> Rage
30
Reactive attachment disorder (definition, subtypes, consequences, treatment)
Absence of the ability to be genuinely affectionate toward others.
Inhibited type: Fearful and restricted in caregiver interest
Disinhibited type: indiscriminate interest, shallow relationships
Consequences: poor mental and emotional health, social difficulties, substance abuse, adolescent problems, abusive behavior, cruelty, superficiality.
Interventions: support groups, relationship therapy
31
Temperament
in-born differences in reactivity (response to environment) and self-regulation (processes modulating reactivity) vis-a-vis emotion, motor activity, attention.
32
Key dynamic mediating link between temperament and developmental outcomes
"Goodness of fit"(!)
33
Neurobiology of vulnerability
short allele of SERT (5-HTT) conferred greater vulnerability to stressful events/poor rearing (rhesus and human). Exaggerated cortisol levels, MDD
34
stress diathesis model of psychopathology
inborn vulnerability x stress --> outcome
35
Stress and mothering in rats
Good moms have more GCRs in hippocampus, lower stress response. Offspring of bad moms are more promiscuous, more aggressive, reach puberty earlier (makes sense evolutionarily).
36
HPA axis and early experience
Stress--> CRH, AVP increase --> cognitive and affective disorders
37
psychological trauma
dysregulated neuropsychological functioning in response to experience (subjective experience more important than objective)
38
Symptoms of traumatic response in children
memory problems, poor concentration, anxiety, impulsiveness, aches, inc HR, obesity, sleep disturbance, procrastination, fighting, sexualized behaviors.
39
public health of trauma
higher ACE scores --> heart disease, cancer, lung disease, liver disease, early pregnancy, eating disorder, MDD, smoking, drugs
40
Treatment approach to childhood trauma
build resilience
41
Growth routes during adolescence
Continuous: tends to be more resilient
Surgent: uneven, usually not clinically significant
Tumultuous: turmoil, frequent crises, intense emotion. Most clinically significant: susceptible to acting out, getting overwhelmed.
42
CNS maturation during adolescence
linear increases in white matter, inverted- U in gray matter (arborization, pruning). Different lobes peak at different times. Frontal last!
43
Health risks in adolescence
risk taking: injury/accidents, sex, alcohol, dugs. Abuse, homelessness. Depression, suicide, truancy.
44
Neuroscience of adolescent risk-taking
dopamine remodling (increased sensitivity) without increase in self-regulation. Heightened attention to social stimuli (greater influence of peers).
45
Psychoanalytic view of personality
personality is primary pattern of ego defenses
46
Humanistic view of personality
personality influenced by conscious, subjective perception. Maslow's hierarchy
47
Social cognitive view of personality
conscious thought greatly influence action. reciprocal determinism of behavior, environment, person. Most critical belief is self-efficacy! (virtuous vs vicious cycles)
48
Trait theory of personality
focuses on individual differences (surface traits, source traits).
49
"Big Five" for trait theory
Extraversion, neuroticism (stable-unstable), conscientiousness (dependable, undependable), agreeableness, openness to experience
50
Biosocial theory of personality
NTs and environment mutually influence each other --> personality
51
General features of personality disorder
Enduring, cross-context, lead to impairment or distress. Lack of insight, ego syntonic, difficult to treat.
52
Personality disorder cluster A
"weird" odd/eccentric. Paranoid (Accusatory)--pervasive distrust, projection, anger; Schizoid (Aloof)--voluntary social withdrawal, few friends, no humor; Schizotypal (Awkward)--eccentric, odd beliefs, neologisms, not psychotic.
53
Personality disorder cluster B
"Wild" Dramatic, erratic. Antisocial--disregard for norms, persuasive, shallow, "slick" type, poorly-socialized type. Borderline--instability of relationships, self-image, frantic to avoid abandonment, extreme closeness/distance. Histrionic--excessive emotionality, attention seeking, flamboyant, flirtatious, seductive; Narcissistic -- Grandiosity, need for admiration, self centered, entitlement
54
Personality disorder cluster C
"Worried": Avoidant (Cowardly)--hypersensitive to rejection, inhibited, inadequate, desires relationships (vs shizoid)l OCPD (Compulsive)--orderliness, perfection, control, not emotionally expressive, distrusts emotion in others, ego-syntonic (vs OCD); Dependent (Clingy) -- submissive, need to be taken care of, sensitive to disapproval, low confidence.
55
Diagnostic criteria for ADHD
6+ maladaptive attention Sx; 6+ hyperactivity-impulsivity Sx; onset before age 7; impairment in >1 setting; not explained by another disorder
56
Systems of attention
Posterior: orient and engage (wake up and smell the coffee). NE
Anterior: Decreases responsively to novel stimuli (executive). DA from VTA --> PFC
57
Gene x Environment in ADHD
DRD4, DAT alleles confer risk. When combined with smoking, odds increase a LOT
58
Neuro deficits in ADHD
smaller, less developed PFC, Basal Ganglia, Cerebellum, ant cingulate. 3 year lag in development, but typically reached by 16. DA and NE dysregulation
59
assessment for ADHD
comprehensive, thorough, developmental approach
60
Treatment approach for ADHD
need moderate catecholamine levels (inverted U--fatigued-alert-stressed). 2 prongs: Executive function and Motivation (need constant reinforcement). Skills-based approach. Multi-modal.
61
Amphetamine (adderall) for ADHD
broad mechanism: prevents reuptake, increases vesicular release. NE, 5HT also respond.
62
Methylphenidate (Ritalin) for ADHD
Many formulations. Narrow mechanism: binds DAT and inhibits re-uptake. Slow!
63
Developmental Milestone themes
Gross motor: Head to Toe
Fine motor: flexor to extensor
Language: receptive to expressive
Social/emotional: me to you
64
6months milestones
crawling (hip, core, arms). Caregiver preference, consonant stringing.
65
1 yr milestones
walking, crawling, climbing, several single words
66
2 yr milestones
playing, drawing, 2/4 speech understandable. Parallel play
67
3 yr milestones
4-5 word phrases, 3/4 understandable. Transitioning to cooperative play. magical thinking
68
4 yr milestones
training wheels. 4/4 understandable. games, cooperative play. imaginary vs real.
69
Erikson's psychosocial stages
infancy: sense of self, toddler: sense of self-control. preschool: sense of self-confidence. School age: sense of achievement. Adolescent: sense of identity. Young adult: sense of connectedness, support. Middle adult: sense of completeness. Late Life: sense of fulfillment.
70
Non-prescription stimulant use in college
Common, associated with decline in performance
71
Mania
Distinct period >7 days of impulsivity, high energy, tangentiality, distractibility, decreased sleep, poor judgment
72
Bipolar vs schizoaffective
Bipolar has episodes of mood alone (+/- psychosis). Schizo has psychosis alone (if + mood = schizoaffective
73
BPD heritability, course, outcome
highly heritable, often mis-diagnosed for 10 yrs, very disabling, poor outcomes (suicide, relapse).
74
BPD Tx
Tx changes over time, several weeks needed to assess. need to optimize. Combination therapy is standards. Anti-depressants may worsen disease course!
75
5-HT function in brain
MODULATES responses: mood, homeostasis, sex, nociception, behavior
76
5-HT synthesis
Tryptophan is hydroxylated (RLS--Tph1 in periphery, Tph2 in brain), then decarboxylated (AADC)
77
important 5HTRs in brain
5HTR1 and 5HTR2. 5HTR3 promotes vomiting
78
Clinical strategies for modulating 5HT
Depression: SSRIs, MAOIs
Anxiety: 5HT1 agonist, SSRIs
Obesity: 5HT2 agonist
Vomiting: 5HT3 antagonist
79
Tricyclic antidepressants
inhibit both SERT and NET
80
Serotonin Syndrome
Overactivation of central serotonin receptors. Abdominal pain, diarrhea, sweating, fever, tachycardia, altered mental state. Occurs when switching among SSRIs or to other drug classes (MAOIs)
81
Catecholamine synthesis
```
Tyrosine --> Dopa by TH (RLS!)
Dopa --> Dopamine by LAAD
DA --> NE by Dopamine B Hydroxylase
NE --> E by PNMT
negative feedback!
```
82
Gs
Increased cAMP
83
Gi
decreased cAMP
84
Gq
increased Ca++
85
Types of adrenergic receptors
a1 (Gq)=stimulating
a2 (Gi) = inhibitory
b1, b2 (Gs) = stimulating
86
Termination of catecholamine signaling
Reuptake1 (SERT): high affinity, low capacity
Metabolic transformation (MAOs, others)
Reuptake 2: extra-synaptic: low affinity, high capacity
87
MAO isozymes
MAO-A: 5HT, NE, Tryptamine (depression)
| MAO-B: DA, tryptamine (Parkinson's?)
88
Carbidopa
Inhibits peripheral LAAD
89
reserpine
blocks VMAT DA uptake (HTN, snake bites, causes depression)
90
Bretylium, Guanethidine
inhibit NE release, anti-HTN and VFib
91
bromocriptine
selective D2 agonist (Parkinson's)
92
Cocaine and imipramine (tricyclic) MOA
NET inhibitors
93
Ultradian pulsality of GCs
Peak in morning. Prednisone/depression flattens!
94
U-shaped curve of GC activity
Adaptive: memory, immune cell trafficking, gluconeogenesis up. immune cell production, osteoblast activity down.
---> pathological: repro function, memory, growth down. Diabetes, muscle wasting, abdominal fat, osteoperosis, infection risk
95
addiction and HPA
addictive behaviors relieve HPA activity, withdrawal activates
96
HPA axis
hypothal---> CRF --> pituitary --> ACTH -->GCs, catechols -->neg feedback
97
CRF effects on brain
found throughout. increased arousal, fear, sympathetic response, decreased appetite, repro
98
Early life experiences and depression
High contact --> lower stress response, more GR in hippocampus (more sensitive to feedback?). Epigenetic phenomenon. Bad mothers have increased methylation of GR promoter
99
Common MOA of antipsychotics
Block D2 receptor. Works on positive Sx, not so great on neg Sx
100
Side-effects on antipsychotics
Parkinsonian mvmt disorders, acute dystonic reaction. Gynecomastia/galactorrhea. Lower seizure threshold, QTc prolongation
101
First generation antipsychotics
High potency: less antihistamine, antiadrenergic, anticholinergic effects
Low potency: more off-target side effects.
Antihistamine: SEDATION, weight gain
Anticholinergic: Delirium, blurry vision, constipation
Antiadrenergic: orthostasis, arrythmias
102
Second generation antipsychotics (properties, relative to 1st, side effects)
"Atypicals"
in addition to D2 blockate, block 5-HT2R. Good for bipolar disorder.
Not more effective, but better tolerated than 1st gen.
Side effects: Weight gain, metabolic syndrome. Clozapine: agranulocytosis
103
aripiprazole (abilify)
atypical-atypical: partial DA agonist in parts of the brain. Can make psychosis worse in some people
104
Clozapine
Atypical antipsychosic. Risk for
105
Common mechanism of all antidepressants
increase monoamines: NE, 5-HT, DA.
| Can also be used to treat anxiety!
106
MAOIs side-effects
reduced metabolism of tyramine from food --> hypertensive crisis.
Also may unmask suicidality in short-term
107
TCA adverse effect
overdose: torsade de pointe
108
SSRIs side-effects
safest of the anti-depressants. libido, insomnia. May unmask suicidality in the short-term
109
Potential MOAs of lithium/mood stabilizers
stabilize membrane potential? Enhance monamine function?
110
Sedating effects of benzos
GABA-A increase. NB: treating Sx, not disorder
111
Benzos with lesser hepatic burden
lorazepam, oxazepam, temazepam
112
addiction potential of benzos
Fast onset, short duration (e.g. Xanex) has highest addiction potential
113
Two strategies for medicating dementia
ACE inhibition, NMDA blockade
114
Absorption of alcohol
Rapid, small intestine. Accelerated by CO2, concentration, habituality. Rate predicts BAL
115
Distribution of alcohol
Vdist ~ total body water (.5-.7L/kg). Vdiff predicts BAL
116
Metabolism of alcohol (enzymes, kinetics)
10% excreted, 90% metabolized. ADH, MEOS (when ADH saturated, byproducts are toxins). ALDH: inhibited by disulfuram. ADH: first order (t1/2~1hr). MEOS: zero-order (8g/hr)
117
unit of alcohol
12g
118
alcohol effect on drug metabolism
chronic: tolerance. CYP inc, met dec. Occasional: competitive inhibition, met dec.
119
adverse alcohol effects
cardiomyopathy, triglycerides, liver failure, reduction and poor function of hematopoiesis and immune system,
lower sleep quality, malignancy, sexual dysfunction, fetal alcohol syndrome. All impacts are dose-dependent
120
Alcohol Abuse Criteria
Maladaptive patter of alcohol use leading to significant impairment or distress
121
Alcohol Dependence criteria
3+ Sx including tolerance, withdrawal, using more than intended, impairment, use despite consequences, unsuccessfully cutting down. When tolerance or abuse, is dependence with physiological dependence
122
Stages of treatment
Identification, detox, rehab, aftercare
123
Alcohol withdrawal (Sx, Tx)
Tremor, insomnia, anxiety, sweating, seizures, DTs
| Tx: benzos, beta-blockers, anticonvulsants
124
Alcohol relapse prevention Rx
Naltrexone (opiod antag), acamprosate (GABA antag), topiramate (anticonvulsant) OK
125
methadone
full opiod agonist used for detox. Potential for abuse. Oral, long-acting, cheap. No injection risk. Stable levels (unlike highs/troughs of heroin)
126
Buprenorphine
partial opiod agonist used for detox. Difficult to overdose on. Lower level of physical dependence.
127
Naloxone
Opiod antagonist. used for relapse prevention. Few side effects. Depot injection
128
Fatal Withdrawals
alcohol, benzos, NOT opiates
129
opiate withdrawal
not fatal, just sucks
| BUT relapse can kill you--> decreased tolerance!
130
General types of alleles predisposing to addiction
1) increase euphoria/reward (GABA-A risk allele)
| 2) decrease experience of adverse effects (alpha-5 Neuronal AChR)
131
Opiod neuroanatomy, action
```
mu-spinal and supra-spinal
Delta: Spinal (Dorsal horn)
euphoria: VTA DA neurons
Respiratory depression: brainstem
Anti-tussive: brainstem (d-isomers eg dextromethorphan lack euphoria!)
```
132
Suboxone
buprenorphine-naloxone prevents injection
133
A118G opiod allele
increases euphoria experienced. Effectively blocked by naltrexone.
134
Depression and medical illness
Mortality (not just suicide)
increased prevalence of depression among medically ill (depression associated with getting disease and worse outcomes)
Bidirectional relationship between depression and medical illness
135
Depression and cardiovascular mortality mechanisms
Behavioral and lifestyle
Platelet activation
decreases heart rate variability
increased inflammatory response
