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278 Cards in this Set

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Erikson's psychosocial stages of personality development
8 stages w/specific crises that need to be dealt with
Mood disorders
bipolar disorder
major depressive disporder
cyclothymia
dysthymicdisorder
Sadness vs. depression
sadness: transient, understandable in context, no significant impairment
Adjustment disorder
similar to a mild depressive episode
MDD and psychosis
10% of patients with MDD experience psychosis
Criteria for MDD
1 of following: blue mood for two weeks or anhedonia
4 of following:
fatigue
insomnia/hypersomnia
loss of appetite/increased appetite
psychomotor retardation/agitation
poor concentration
suicidal ideation
pathological guilt
Melacholia
classical presentation of severe recurrent depression
atypical depression
milder depression with reverse vegetative features
often chronic
strongly female predominant
Psychotic depression
most severe form of MDD
delusions and occasional hallucinations
Chronic depression
symptoms lasting at least 2 years
Depressions risks of chronicity and recurrence
30% chronic
75% recur
Gender differences in depression
2x as likely in women
except in old order amish
marriage is protective for men, but not women
rates identical when combined with substance abuse
depression physiology
chronic activation of HPA axis
too much cortisol
eventually less linked to stressful life events
Depression genetics
short 5-HT transporter promoter puts you at risk
Depression risk factors
low social support
history of maltreatment
short 5-HTT promoter
BDNF varient
Brain areas in MDD
somatosensory cortex
prefrontal cortex (exec)
hippocampus
cerebellum (?)
nucleus accumbens
anterior cingulate cortex - rational cognitive functions
amygdala
Anterior cingulate cortex (ACC) function
emotional and cognitive integration
pursue and consume rewards
reason out emotions
MDD brain atrophy
small hippocampi
increases with duration of untreated depression
can result in neuroendocrine dysregulation
exagerated stress response may lead to cell death
BDNF
neurotrophic factor expressed thoughout brain
may be downregulated in depression
antidepressants may normalize BDNF
Depression comorbidities
stroke, parkinson's, cancer, MI, rheumatoid arthritis
Bipolar types
Type 1: w/mania
Type 2: w/hypomania
NOS: neither of above
Schizoaffective disorder
similar to bipolar disorder, but with constant episodes of psychosis
Mania diagnosis
at least 1 week of abnormally elated or irritable mood
at least 3 of following:
grandiosity
decreased need for sleep
pressure speech
flight of ideas
distractability
increased goal-directed activity or agitation
poor judgmentor risky behaviors
Prevalence of psychosis in Mania
58% of pateints have at least 1 psychotic symptom
delusions more common than hallucinations
Mania vs. hypomania
maina: delusions or hallucinations, marked vocational or social impairment, requires hospitalization
Bipolar subforms
rapid cycling: 4+ episodes/year
mixed features: simultaneous mania and depression
Cyclothymia
mild form of bipolar disorder
Bipolar I comorbidities
anxiety
substance abuse
antisocial behavior
suicide risk and bipolar disorder
10-19% ultimately die of suicide, usually during depressive episode
15x greater risk
Mood stabilizer qualifications
effective in acute scenario, do not induce alternate mood symptoms, protect against relapse
Mood stabilizers
Lithium
Divalproex
carbamazapine
antipsychotics
ECT
Hypothalamic Pituitary Adrenal Axis
hypothal releases CRF, stimulates pituitary to release ACTH, stimulates adrenals to release glucocorticoids and catecholamines, glucocorticoids negatively feedback the hypothal
Effects of steroid hormones
metabolic mobilization
increased heart rate, blood pressure, and respiration
redistribution of blood flow
suppression of immune and digestive systems
Steroid receptors in brain
mineralocorticoid receptors have high affinity of glucocorticoids -> important in maintenance of basal HAP tone
glucocorticoid receptors have low affinity -> negative feedback
Cortisal daily peaks
biggest in the morning (arousal)
dinnertime, lunchtime
Acute effects of glucocorticoids
mobilize glucose
promote emotional and habitual memory
maintain fluid balance
inhibit immune cells
decrease bone mass
Addictive behaviors and HPA
behaviors relieve the HPA activity
Corticotrophin Releasing Factor (CRF)
neuropeptide secreted in many places by brain
implicated in psychologic stress
elevated in depression
Serotonin distribution
95% in gut
5 % in CNS
CNS functions associated with serotonin
mood, sleep, eating, sexual function, nocioception, learning and memory, behavior
serotonin receptors important for depression
5HT1 (Gi) and 5HT2 (Gq) receptors
5HT3 receptor
the only serotonin receptor that's an ion channel
important for emesis
other serotonin receptors
5HT4, 5, 6, and 7
SERT
serotonin reuptake transporter
serotonin degrador
MAOa
aldehyde dehydrogenase
in pineal gland, melatonin is produced
Tricyclic antidepressants mechanism of action
inhibit NET and SERT
Cognitive Therapy theory
emotional disorders involve systematic biases, distortions, and/or deficits in thinking which cause people to have exaggerated reactions to manageable situations hampering good decision making
CBT grandfather
Aaron Beck, from Penn
Elements of a CBT session
Agenda
Mood check
Prioritization
Feedback
Homework
CBT prioritization
1. suicide
2. addictive behaviors
therapy interfering behaviors
CBT standard techniques
rational responding
self-monitoring
behavioral experiments
role-playing
metaphors
guided imagery (PTSD)
Rational response
a fair, objective way to view oneself with the goal of improving morale
Psychodynamic therapy
emphasis on uncovering painful affects and understanding past painful experiences, with goal to develop new perceptions anad habiors
Therapeutic alliance
1. agreement of goals
2. assignment of tasks
3. development of bonds
Core psychodynamic problems
depression
obsessionality
fear of abandonment
low self esteem
panic anxiety
trauma
Transference
unconscious redirecting of feelings by the patient from one person onto the therapist
Countertransference
the unconscious redirection of feelings by the therapist onto the patient
Psychodynamic strategies for change
emotional exploration
accurate perceptions
encouraging and supporting new behaviors
Suicide gender disparities
men 4x more likely to die
women 2-3x more likely to attempt
males age 75+ are highest risk
Successful suicide interventions
followup letters
followup phone calls/visits
Dialectal behavior therapy
safety plan
CBT (guided imagery)
Risk factors for suicide
previous suicide attempt
hopelessness
impulsivity/aggression
psychiatric diagnoses (MDD, bipolar, schizophrenia, substance use)
Heritability of suicide
30-50%
Diablectal Behavior Therapy
Type of CBT
weekly meetings
weekly therapist meetings
Suicide Safety Plan
Written list of coping strategies
1. recognize warning signs
2. internal coping strategies
3. socializing to distract
4. contact supports
5. contact mental health professionals
6. reduce potential for lethal acts
Suicide Prevention strategies
increase pleasurable activities
increase social supports
increase compliance with other services
Long term adaptation to stress
mobilization of remaining energy reserves
conservation of glucose
elevation of blood glucose concentration
conservation of salts and water
Exhaustion Phase
Collapse of vital systems after long-term stress response
Neurochemistry of anxiety
GABA
Serotonin
Norepinephrine
Dopamine (SAD, PTSD, OCD)
Behavioral Inhibition
timidity and withdrawal in novel situations
exaggerated HPA response
slow habituation
Cued vs. contextual fear conditioning
Cued: neutral CS paired w/ aversive US; amygdala

Contextual: background stimuli present w/ US - predicts where
hippocampal
Fear extinction
repeated presentation of CS without US
creates a competing memory

Ventromedial Pre-frontal cortex
Positive Reinforcer
strengthens a response by presenting a rewarding stimulus after a response
Negative reinforcer
strengthens a response by removing an aversive stimulus after a response
Maintains anxiety
Positive Punishment
weakens the likelihood of a response by presenting an aversive stimulus after the response
Negative Punishment
weakens the likelihood of a response by removing an appetitive stimulus after a response
Anxiety disorders
PTSD
OCD
Panic disorder
Specific Phobia
Social Phobia (SAD)
Generalized anxiety disorder
Specific Phobia treatment
One-session therapy
fear exposure
90% effective
Specific Phobia brain areas
Amygdala
Anterior Cingulate gyrus
Insula
Social Phobia
fear of being in social situations in which one will be embarressed or humiliated
Nefazodone
Treatment for Social ANxiety Disorder
Panic Disorder
persistent, unexpected panic attacks, with or without agoraphobia
Interoceptive fears
fear of fears themselves
Neural correlates of Panic disorder
insula
anterior cingulate gyrus
periaqueductal gray matter (defensive behavior)
Panic disorder/agoraphobia treatnments
SSRIs
Tricyclic antidepressants
CBT
Generalized Anxiety Disorder
Excessive and uncontrollable worry for more than 6 months
sleep problems, muscle tension, trouble concentrating
Potential pathophysiology of Generalized Anxiety disorder
deficiency of GABA
patients use worry to dampen emotional experience
PTSD criteria
experienced actual or threatened death or serious injury
traumatic event is reexperienced
avoidance and numbing
increased arousal
longer than 1 month
Neurobiology of PTSD
hyperactive HPA
hyperactive amygdala and insula
failure to extinguish - vmPFC
weaker vmPFC-hippo coupling
reduced hippocampal size
Cortisol and PTSD
cortisol lowered in PTSD patients (usually when trauma occured at young age)
PTSD treatment
Prolonged exposure
imaginal exposure
Anterior Cingulate Cortex (ACC) and pain
perceives unpleasantness of pain
OCD obsessions criteria
unwanted thoughts, images that cause marked anxiety
attempts to ignore/suppress
not anxiety
recognized as the product of one's mind
OCD compulsions criteria
repetitive behaviors or mental acts performed in response to obsessions
aimed at reducing distress or preventing dreaded event
OCD clinical course
1. unremitting and chronic (most common)
2. phasic with periods of complete remission
3. episodic with incomplete remission
OCD comorbidities
mood disorders
anxiety
tics
OCD neurobiology
overactive Orbital cortex and caudate nucleus
Trichotillomania
compulsive hair pulling
OCD treatment
CBT
exposure in vivo
imaginal exposure
ritual prevention
cognitive interventions

SSRIs can mitigate OCD
Depression with medical illness
worse outcome, higher death rate esp. MI, AIDS, and stroke
Depression and cardiovascular disease
depression <-> CVD
increased inflammatory response
decreased heart rate variability
increased platelet activation and reactivity
behavior and lifestyle
increased HPA
Cytokines in depression
IL-1, IL-6, and TNF-alpha elevated
Cortisol effects on cardiovascular health
promotes atherosclerosis and hypertension
loss of supression of inflammatory cytokines
Hypercoagulability in depression
increased 5HT2A receptors on platelets
increased platelet activation
Depression and AIDS
higher mortality
Depression and Cancer
2-4x higher rates than in general population
Anticancer drugs associated with depression
Interferon (sudden onset)
corticosteroids
chemotherapeutics
Schizophrenia epidemiology
lifetime risk: 0.7
risk: immigrants, northern latitudes, urbanicity
higher incidence in men, equal gender prevalence
Prodromal psychosis
period of attenuated psychotic symptoms before onset of overt psychosis
Cognitive deficits
Schizophrenia diagnosis
characteristic symptoms for >1 month
-delusions, hallucinations
-disorganized speech/behavior
negative symptoms
Social/Occupational dysfunction
symptoms longer than 6 months
Ideas of Reference
symptom of psychosis
hidden messages
often inspires purpose in schizophrenia
Schizophrenia negative symptoms
alogia
flat affect
anhedonia
avolition
asociality
Alogia
reduced verbal communication
negative symptom of schizophrenia
Avolition
reduced motivation
negative symptom of schizophrenia
Asociality
reduced social drive and interaction
negative symptom of schizophrenia
Schizophrenia mood symptoms
25-33% experience significant depressive symptoms
Anxiety also common
Cognitive deficits in schizophrenia
Global deficit in cognition 1-2 standard deviations below population norm
es. verbal and visual learning/memory
detectable early, but dramatic decline btwn age 12-17, stable after symptom onset
Schizophrenia Illness course
premorbid (cog. deficit)
prodromal
psychotic
stable
Schizophrenia treatments
antipsychotics
supportive therapy
CBT
First vs. second generation antipsychotics
same positive symptom management
side effects:
1st - tardive dyskinesia, extrapyramidal symptoms
2nd - metabolic syndromes
Schizophrenia gross pathology
Enlarged ventricles
lost grey matter
Schizophrenia genes
DISC1
COMT (22q del)
dysbindin
neuregulin
Neurobiology of schizophrenia
dysbindin-1 = glu transporter
schizo = too much glutamine?
poor migration of neurons
loss of synaptic integrity
Schizophrenia seasonality
highest rates for people born in March
lowest rates for people born in september
potential for in utero influenza
Schizophrenic sinuses
small posterior nasal cavities
Glutamate hypothesis
NMDA receptor blockade at the cortical interneuron can lead to glutamatergic hyperactivity in associated pyramidal cells -> positive and negative symptoms
too much glutamate -> neurotoxic
Mismatch negativity
After repetitive stimuli, an outlier stimulus provokes salience

not seen in schizophrenics
Anorexia nervosa criteria
Restricted caloric intake, body weight less than 85% of expected
Intense fear of gaining weight
Disturbance in self-appearance perception
*absence of 3 consecutive menstrual cycles
Anorexia subtypes
Restricting: no binging/purging
Binge-eating/purging
Anorexia signs and symptoms
Amenorrhea
Dry skin
Lanugo
excess energy
bradycardia (slow heart rate)
Anorexia onset
peak at age 14 and 18
onset frequently follows crisis w/family, school. or sexuality
dieting in effort to "take control"
Anorexia candidate genes
Serotonin 1D receptor
delta opioid receptor
Anorexia etiology
serotonin mismodulating impulse control
Anorexia treatment
Family therapy
possibly antipsychotics
hospitalization if acutely ill
Maudsley Family therapy
for adolescents with anorexia
phase 1: parents in control of food
phase 2: return to independent eating
phase 3: focus on general adolescent issues
Anorexia outcomes
30-50% make full recovery
5% per decade die of heart failure or suicide
Unfavorable prognostics of anorexia
vomiting
bulimia and purgative abuse
chronicity of illness
obsessive-compulsive personality
Bulimia nervosa criteria
Recurrent episodes of binge eating
Recurrent compensatory behavior in order to prevent weight gain
Binge/Purge at least 1/week for <3 months
Bulimic brains
poorer impulse control
inferolateral prefrontal cortex
Bulimia outcomes
75% respond to therapy
Bulimia complications
hypokalemia
erosion of dental enamel
parotid gland enlargement
Bulimia Treatment
CBT (faster)
interpersonal therapy (ultimately as effective)
antidepressants
Eating Disorder Not Otherwise Specified (EDNOS)
Binge eating disorder
binges w/out purges
Atypical Anorexia
anorexic eating habits and beliefs, but still over the weight criteria
M'Naghten Test
every defendant presumed to be sane unless:
laboring under such a defect of reason from a disease of the mind so as not to know the nature and quality of the act he was doing
OR that he did not know that what he was doing was wrong
Types of human aggression
Predatory: reward-based, intentional, and premeditated
Impulsive: aversively-stimulated, unplanned, and reactive
Agression definition
Overt behavior which has the potential (and often intention) to inflict pain or harm on another organism or self
Aggression differential diagnosis
Genetic syndromes
metabolic disorders
neurological disorders
psychiatric disorders
intoxication
drug withdrawal
Brain structures promoting aggression
Amygdala
Bed nucleus of the stria terminalis (BNST)
hypothalamus
periaqueductal gray
Brain structures suppressing aggression
septum
frontal cortex
raphe nucleii
Amygdala in aggression
selects appropriate aggressive (or submissive) behavior
Prefrontal cortex in aggression
vmPFC and orbitofrontal cortex inhibit aggressive and suicidal behaviors. inhibit amygdala
anterior cingulate cortex also suppresses aggression
Septum in aggression
inhibits aggression
Serotonin and aggression
serotonin has an inhibitory effect on aggressive behaviors and impulsivity
mediated through the 5HT1B receptor
Dopamine and aggression
dopamine may promote aggression
Brunner Syndrome
point mutation in MAO A. Results in increased serotonin, norepinephrine, and dopamine
increased aggressive behaviors
GABA and aggression
GABA usually decreases aggressive behaviors
at lower doses, it can disinhibit and cause aggression
Testosterone and aggression
stimulates amygdala, BNST, and inhibits septum
more aggression
HPA axis and aggression
chronic HPA decreases aggression
acute spikes may increase aggression
Vasopressin
aka antidiuretic hormone
produced in hypthal, amygdala, and BNST
increases aggressive behavior
inhibited by serotonin
activated by testosterone
Treatment of Aggressive behaviors
Emergency: benzodiazepines, antipsychotics
Long term:
atypical antipsychotics, mood stabilizers, anitdepressants
Haloperidol
D2 antagonist used in long-term aggression management
high dose may cause akathisia
Akathisia
uncomfortable need to move
Bipolar, unipolar depression, and schizophrenia
may share common risk factors
DISC1
mutation linked to schizophrenia in scottish pedigree
others developed bipolar, or had no symptoms
everyone had slowed mismatch sensitivity
Neuregulin1 (NRG1)
tyrosine kinase ligand
associated with schizophrenia
large gene (1.5 Mb)
also see slowed mismatch sensitivity
ErbB4
tyrosine kinase
linked to schizophrenia, thought through the same pathway as NRG1
CHRNA7
nicotinic receptor
microdeletions implicated in schizophrenia
~lots of schizophrenics are chain smokers~
22q deletion
facial abnormalities
abnormal aortas
psychosis
Bipolar genetic risk
ANK3
CACNA1C - L type Ca channel
ANK3
chaperone protein for ion channels
implicated in bipolar and schizophrenia
CACNA1C
voltage-gated L-type calcium channel
implicated in bipolar and autism
Drug with highest risk of addiction
nicotine
Reward system
nucleus accumbens - cocaine, heroin, nicotine
ventral tegmental area - heroin
globus pallidus - alcohol
Effects of addictive drugs on dopamine levels
big spike
Innate tolerance
higher risk of becoming dependent
Pharmacokinetic tolerance
rapid metabolism of drug
Pharmacodynamic tolerance
down-regulation of drug receptors
Behavioral tolerance
learning to compensate for drug effects
Conditioned tolerance
learning to reliably predict drug arrival so body systems can adapt quickly
Sensitization
Reverse of tolerance
may occur under repeated, spaced dosing of stimulants
Addiction neurobiology
suppressed D2 receptors in nucleus accumbens
High baseline D2 receptors
more likely to induce unpleasant effects of drug -> less likely to become dependent
Brain areas in cue-induced cravings
Anterior Cingulate gyrus
Amygdala
Tolerance
a decreased response to a drug with repeated administration
Sensitization
increased response to drug with repeated administration
stimulants
Compulsion
irresistible impulse to act, regardless of the rationality of the motivation
Craving brain regions
amygdala
anterior cingulate gyrus
Smoking cessation statistics
46% try to quit each year
20% are current smokers
leading preventable cause of death
Heritability of nicotine
50%
Nicotine biochemistry
nicotinic cholinergic receptor agonist
T1/2 = 90 minutes
metabolized via CYP2A6
Nicotine and Dopamine
activation of nicotinic receptors promote release of dopamine from presynaptic neurons during phasic firing. Meanwhile, they inhibit background dopamine release. The larger dopamine differential causes addiction
Test of Nicotine Dependence
Smokes first cigarette w/in 30 min of awakening
Smokes when ill
Smokes a pack a day or more
Current Nicotine Treatments
Cold turkey
Cessation counseling
nicotine replacement therapy
bupropion
varenicline
combo
Cold Turkey nicotine approach
5% long-term abstinence
brief interventions by doctors can increase success rates
Brief nicotine intervention
set quit date 2 weeks ahead
emphasize abstinence as goal
prescribe pharmacotherapy
Intensive nicotine counseling
prescribed after 2+ failed attempts
CBT
Nicotine Cessation Pharmacotherapy eligibility
Everyone except:
those smoking fewer than 10/day
pregnant/breastfeeding
adolescent smokers
Nicotine Replacement
patch, gum, nasal spray, inhaler, lozenge
nasal spray most closely mimics pharmacodynamics
doubles likelihood of quitting
Bupropion
Antidepressant; smoking cessation
Effective in combo with nicotine replacement too
Varenicline
Partial alpha4beta2 nicotinic acetylcholine receptor agonist
Relieves craving and w/drawal
Blocks satisfaction and rewarding effects of nicotine
Adverse effects of varenicline
Suicidal thoughts
small cardiovascular risk
DSM drug dependence criteria
use for >12 months
3 of the 7:
tolerance
withdrawal
more use than intended
unsuccessful efforts to quit
significant time spent in procurement
functional impairment
continued use in the face of adverse medical or psychiatric complications
Routes of administration
Least rapid
oral
intranasal
intravenous
intrapulmonary
Most rapid
IV complications
HIV, Hep C
Endocarditis, sepsis, pneumonia
Candida, aspergillus
Abscess, vessel damage
Emboli
Nicotine Medical complications
Cancer (incl pancreas, kidney, cervix)
coronary artery disease
stroke
emphysema
More nicotine medical complications
low bone density
vascular cell injury
thrombi
adverse lipid profile
peptic ulcers
low birth weights
Alcohol and the Liver
acetaldehyde and oxygen radicals cause liver inflammation
scarring
blood backs up, causing esophageal varices, which can rupture
Alcohol neurologic complications
Dementia
Cerebellar degeneration
peripheral neuropathy
Wernicke-Korsakoff
Wernicke-Korsakoff Syndrome
Acute: thiamine deficiency. disorientation, ocular muscle dysfunction, gait disurbance
Chronic: mamillary body degeneration, memory loss, and confabulation
Alcohol Withdrawal Syndrome
Autonomic arousal: tachycardia, hypertension, hyperreflexia, high temp, tremor, insomnia, anxiety
Nausea, vomiting and diarrhea
Lasts 3-5 days
GABA deficient state
Delirium Tremens
severe alcohol withdrawal
hallucinations, delirium, psychosis seizures, and death
Alcohol withdrawal treatment
Benzodiazepines
Opiates
Heroin, morphene, codeine, oxycodone, methadone, buprenorphine
Opiate withdrawal
Not medically dangerous, but very unpleasant
Detox with methadone
Opiate overdose
Little tissue toxicity
May lead to lethal respiratory depression
Reversible with naloxone
Stimulants
cocaine amphetamine, methamphetamine, methylphenidate
Adverse stimulant effects
vasospasms -> MI, stroke, renal failure, spontaneous abortion, bowel infarction
Hypertension
electrophysiological abnormalities
Hyperthermia
Rhabdomyolysis
Rhabdomyolysis
breakdown of muscle fibers
myoglobin causes renal failure
Cocaethylene
toxic metabolite formed with simultaneous alcohol and cocaine use. cardiac death increased 24x
Stimulant brain damage
targets the frontal cortex
Hallucinogens
LSD, mescaline, PCP, ketamine, MDMA, GHB, marijuana
Ecstasy effects
hyperthermia, seizures, rhabdomyolysis, electrolyte imbalance, hepatic injury
Marijuana medical complications
Respiratory disease, decreased libido, immunosuppresion, arrhythmias, cognitive disturbances, traffic accidents
GHB effects
"date rape" druge
fulminant hepatic failure
PCP and Ketamine effects
NMDA receptor antagonists
increased cardiac output
acute psychosis, violent behavior
Barbiturate effects
GABA A agonists
acute respiratory depression
nystagmus, slurred speech, ataxia
Barbiturate withdrawal
seizures can be lethal
looks like alcohol withdrawal
Benzodiazepine effects
GABA A agonists
unlikely to overdose unless combined with alcohol
Benzodiazepine withdrawal
looks like alcohol withdrawal
Inhalant complications
hepatoxicity, sudden death, cognitive dysfunction
Addiction and psychiatric disorder
substance-induced psych disorder
self-medication (underlying psych)
co-occurring
Opiate withdrawal
panic/anxiety, insomnia, agitation, increased autonomic symptoms
Stimulant intoxication
pressured speech, sexual arousal, paranoia
easily confused w/mania/psychosis
Stimulant Withdrawal
Looks like major depression
Naturally occurring opioids
Codeine
Morphine
Naltrexone
orally-active opioid antagonist
Naloxone
opioid antagonist
inactive via oral administration
Somatic vs. visceral pain
somatic: sharp, intense, A-delta fibers
visceral: diffuse, C fibers
Both types of pain alleviated by opioids
Opioid mechanism of action
inhibition of pain perception in cortical and subcortical brain
"hurts, but who cares?"
Opioid CNS actions
analgesia
euphoria (in some people, dysphoria)
respiratory depression
Prolactin release
Nausea
anti-tussive
Opioid cardiovascular effects
peripheral vasodilation
Opioid eye effects
pupillary constriction
Opioid Lung effects
respiratory depression
Opioid GI effects
decrease propulsive contractions in colon -> constipation
Opioid pharmacokinetics
Morphine duration: 3-4 hrs
higher dose required orally than IV
metabolism: liver, glucuronide conjugation
renal excretion
Opioid receptors
Mu - spinal and supraspinal (periaqueductal grey) analgesia
Delta - spinal analgesia for visceral pain
Kappa - dysphoric effects
Opioid euphoria
inhibited GABA-ergic neurons in VTA -> more dopamine release ->stimulates nucleus accumbens and prefrontal cortex
Opioid nausea
Area Postrema
Respiratory depression
Brainstem, decreasing neuronal sensitivity to CO2
Opioid anti-tussive effects
Brainstem
produced by both d and l isomers(d isomers lack all other effects)
Opioid GI effects
produced at the level of the local gut ganglia
Opioid pupillary effects
produced at level of the oculomotor nucleus
Opioid cardiovascular effects
produced at the vagal nucleus
Endogenous opioid receptor ligands
Endorphin - Mu and delta
Enkephalin - Mu and delta
Dysnorphin - Kappa

Gi pathway -> reduced firing
Opioid antagonists
Naloxone: IV only, rapid onset
Naltrexone: orally active, lasts 48 hrs, alcohol addiction
Mechanism of opioid dependence
pharmacodynamic tolerance -
Mu phosphorylation -> more cAMP (switch to Gs mechanism)
Mu internalization
loss of dendritic arborization
inhibition of neurogenesis in hippocampus
Chronic opioid use
results in decreased cognitive function: smaller hippocampi and fewer dendrites
Opioid withdrawal
Anxiety, Agitation, Diarrhea, pupillary dilation
Methadone maintenance
Lowers rates of HIV and hepatitis
Lowers rate of re-arrest
increases employment rates
Opioid anti-tussive effects
Brainstem
produced by both d and l isomers(d isomers lack all other effects)
Opioid GI effects
produced at the level of the local gut ganglia
Opioid pupillary effects
produced at level of the oculomotor nucleus
Opioid cardiovascular effects
produced at the vagal nucleus
Endogenous opioid receptor ligands
Endorphin - Mu and delta
Enkephalin - Mu and delta
Dysnorphin - Kappa

Gi pathway -> reduced firing
Opioid antagonists
Naloxone: IV only, rapid onset
Naltrexone: orally active, lasts 48 hrs, alcohol addiction
Mechanism of opioid dependence
pharmacodynamic tolerance -
Mu phosphorylation -> more cAMP (switch to Gs mechanism)
Mu internalization
loss of dendritic arborization
inhibition of neurogenesis in hippocampus
Chronic opioid use
results in decreased cognitive function: smaller hippocampi and fewer dendrites
Opioid withdrawal
Anxiety, Agitation, Diarrhea, pupillary dilation
Methadone maintenance
Lowers rates of HIV and hepatitis
Lowers rate of re-arrest
increases employment rates
Buprenorphine
orally-active partial mu agonist
relieves withdrawal without causing euphoria
available by prescription
A118G SNP for opioids
causes decreased transcription of Mu receptor
Hyporesponsive to opioids
hyperresponvie to opioid antagonists
attain greater euphoria with alcohol ->blocked by naltrexone
Naltrexone alcohol cessation therapy
mu opioid receptor antagonist
reduces alcohol euphoria
reduces risk of relapse
Benzodiazepine uses
promote sleep
treat anxiety
relieve alcohol withdrawal
treat seizures
perioperative amnesia
High potency benzos
most likely to be abused
alprazolam
lorazepam
triazolam
clonazepam (longer t1/2)
Low potency benzos
low risk of abuse
oxazepam
librium and dizaepam used for alcohol withdrawal
Withdrawal and half life
drugs with longer half-lives tend to have milder withdrawals
Opioid pseudo-addiction
Focus on obtaining opioids for pain relief
looks like addiction, but disappears with adequate medications
Opioid abuse prevention
educate public
alter prescribing practices
make opioids less abusable