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278 Cards in this Set
- Front
- Back
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Erikson's psychosocial stages of personality development
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8 stages w/specific crises that need to be dealt with
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Mood disorders
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bipolar disorder
major depressive disporder cyclothymia dysthymicdisorder |
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Sadness vs. depression
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sadness: transient, understandable in context, no significant impairment
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Adjustment disorder
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similar to a mild depressive episode
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MDD and psychosis
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10% of patients with MDD experience psychosis
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Criteria for MDD
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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 |
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Melacholia
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classical presentation of severe recurrent depression
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atypical depression
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milder depression with reverse vegetative features
often chronic strongly female predominant |
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Psychotic depression
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most severe form of MDD
delusions and occasional hallucinations |
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Chronic depression
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symptoms lasting at least 2 years
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Depressions risks of chronicity and recurrence
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30% chronic
75% recur |
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Gender differences in depression
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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 |
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depression physiology
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chronic activation of HPA axis
too much cortisol eventually less linked to stressful life events |
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Depression genetics
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short 5-HT transporter promoter puts you at risk
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Depression risk factors
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low social support
history of maltreatment short 5-HTT promoter BDNF varient |
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Brain areas in MDD
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somatosensory cortex
prefrontal cortex (exec) hippocampus cerebellum (?) nucleus accumbens anterior cingulate cortex - rational cognitive functions amygdala |
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Anterior cingulate cortex (ACC) function
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emotional and cognitive integration
pursue and consume rewards reason out emotions |
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MDD brain atrophy
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small hippocampi
increases with duration of untreated depression can result in neuroendocrine dysregulation exagerated stress response may lead to cell death |
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BDNF
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neurotrophic factor expressed thoughout brain
may be downregulated in depression antidepressants may normalize BDNF |
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Depression comorbidities
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stroke, parkinson's, cancer, MI, rheumatoid arthritis
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Bipolar types
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Type 1: w/mania
Type 2: w/hypomania NOS: neither of above |
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Schizoaffective disorder
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similar to bipolar disorder, but with constant episodes of psychosis
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Mania diagnosis
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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 |
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Prevalence of psychosis in Mania
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58% of pateints have at least 1 psychotic symptom
delusions more common than hallucinations |
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Mania vs. hypomania
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maina: delusions or hallucinations, marked vocational or social impairment, requires hospitalization
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Bipolar subforms
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rapid cycling: 4+ episodes/year
mixed features: simultaneous mania and depression |
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Cyclothymia
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mild form of bipolar disorder
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Bipolar I comorbidities
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anxiety
substance abuse antisocial behavior |
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suicide risk and bipolar disorder
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10-19% ultimately die of suicide, usually during depressive episode
15x greater risk |
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Mood stabilizer qualifications
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effective in acute scenario, do not induce alternate mood symptoms, protect against relapse
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Mood stabilizers
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Lithium
Divalproex carbamazapine antipsychotics ECT |
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Hypothalamic Pituitary Adrenal Axis
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hypothal releases CRF, stimulates pituitary to release ACTH, stimulates adrenals to release glucocorticoids and catecholamines, glucocorticoids negatively feedback the hypothal
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Effects of steroid hormones
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metabolic mobilization
increased heart rate, blood pressure, and respiration redistribution of blood flow suppression of immune and digestive systems |
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Steroid receptors in brain
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mineralocorticoid receptors have high affinity of glucocorticoids -> important in maintenance of basal HAP tone
glucocorticoid receptors have low affinity -> negative feedback |
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Cortisal daily peaks
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biggest in the morning (arousal)
dinnertime, lunchtime |
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Acute effects of glucocorticoids
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mobilize glucose
promote emotional and habitual memory maintain fluid balance inhibit immune cells decrease bone mass |
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Addictive behaviors and HPA
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behaviors relieve the HPA activity
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Corticotrophin Releasing Factor (CRF)
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neuropeptide secreted in many places by brain
implicated in psychologic stress elevated in depression |
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Serotonin distribution
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95% in gut
5 % in CNS |
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CNS functions associated with serotonin
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mood, sleep, eating, sexual function, nocioception, learning and memory, behavior
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serotonin receptors important for depression
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5HT1 (Gi) and 5HT2 (Gq) receptors
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5HT3 receptor
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the only serotonin receptor that's an ion channel
important for emesis |
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other serotonin receptors
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5HT4, 5, 6, and 7
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SERT
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serotonin reuptake transporter
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serotonin degrador
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MAOa
aldehyde dehydrogenase in pineal gland, melatonin is produced |
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Tricyclic antidepressants mechanism of action
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inhibit NET and SERT
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Cognitive Therapy theory
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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
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CBT grandfather
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Aaron Beck, from Penn
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Elements of a CBT session
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Agenda
Mood check Prioritization Feedback Homework |
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CBT prioritization
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1. suicide
2. addictive behaviors therapy interfering behaviors |
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CBT standard techniques
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rational responding
self-monitoring behavioral experiments role-playing metaphors guided imagery (PTSD) |
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Rational response
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a fair, objective way to view oneself with the goal of improving morale
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Psychodynamic therapy
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emphasis on uncovering painful affects and understanding past painful experiences, with goal to develop new perceptions anad habiors
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Therapeutic alliance
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1. agreement of goals
2. assignment of tasks 3. development of bonds |
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Core psychodynamic problems
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depression
obsessionality fear of abandonment low self esteem panic anxiety trauma |
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Transference
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unconscious redirecting of feelings by the patient from one person onto the therapist
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Countertransference
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the unconscious redirection of feelings by the therapist onto the patient
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Psychodynamic strategies for change
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emotional exploration
accurate perceptions encouraging and supporting new behaviors |
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Suicide gender disparities
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men 4x more likely to die
women 2-3x more likely to attempt males age 75+ are highest risk |
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Successful suicide interventions
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followup letters
followup phone calls/visits Dialectal behavior therapy safety plan CBT (guided imagery) |
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Risk factors for suicide
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previous suicide attempt
hopelessness impulsivity/aggression psychiatric diagnoses (MDD, bipolar, schizophrenia, substance use) |
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Heritability of suicide
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30-50%
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Diablectal Behavior Therapy
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Type of CBT
weekly meetings weekly therapist meetings |
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Suicide Safety Plan
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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 |
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Suicide Prevention strategies
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increase pleasurable activities
increase social supports increase compliance with other services |
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Long term adaptation to stress
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mobilization of remaining energy reserves
conservation of glucose elevation of blood glucose concentration conservation of salts and water |
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Exhaustion Phase
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Collapse of vital systems after long-term stress response
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Neurochemistry of anxiety
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GABA
Serotonin Norepinephrine Dopamine (SAD, PTSD, OCD) |
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Behavioral Inhibition
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timidity and withdrawal in novel situations
exaggerated HPA response slow habituation |
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Cued vs. contextual fear conditioning
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Cued: neutral CS paired w/ aversive US; amygdala
Contextual: background stimuli present w/ US - predicts where hippocampal |
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Fear extinction
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repeated presentation of CS without US
creates a competing memory Ventromedial Pre-frontal cortex |
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Positive Reinforcer
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strengthens a response by presenting a rewarding stimulus after a response
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Negative reinforcer
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strengthens a response by removing an aversive stimulus after a response
Maintains anxiety |
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Positive Punishment
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weakens the likelihood of a response by presenting an aversive stimulus after the response
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Negative Punishment
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weakens the likelihood of a response by removing an appetitive stimulus after a response
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Anxiety disorders
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PTSD
OCD Panic disorder Specific Phobia Social Phobia (SAD) Generalized anxiety disorder |
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Specific Phobia treatment
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One-session therapy
fear exposure 90% effective |
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Specific Phobia brain areas
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Amygdala
Anterior Cingulate gyrus Insula |
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Social Phobia
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fear of being in social situations in which one will be embarressed or humiliated
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Nefazodone
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Treatment for Social ANxiety Disorder
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Panic Disorder
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persistent, unexpected panic attacks, with or without agoraphobia
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Interoceptive fears
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fear of fears themselves
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Neural correlates of Panic disorder
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insula
anterior cingulate gyrus periaqueductal gray matter (defensive behavior) |
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Panic disorder/agoraphobia treatnments
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SSRIs
Tricyclic antidepressants CBT |
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Generalized Anxiety Disorder
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Excessive and uncontrollable worry for more than 6 months
sleep problems, muscle tension, trouble concentrating |
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Potential pathophysiology of Generalized Anxiety disorder
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deficiency of GABA
patients use worry to dampen emotional experience |
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PTSD criteria
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experienced actual or threatened death or serious injury
traumatic event is reexperienced avoidance and numbing increased arousal longer than 1 month |
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Neurobiology of PTSD
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hyperactive HPA
hyperactive amygdala and insula failure to extinguish - vmPFC weaker vmPFC-hippo coupling reduced hippocampal size |
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Cortisol and PTSD
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cortisol lowered in PTSD patients (usually when trauma occured at young age)
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PTSD treatment
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Prolonged exposure
imaginal exposure |
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Anterior Cingulate Cortex (ACC) and pain
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perceives unpleasantness of pain
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OCD obsessions criteria
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unwanted thoughts, images that cause marked anxiety
attempts to ignore/suppress not anxiety recognized as the product of one's mind |
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OCD compulsions criteria
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repetitive behaviors or mental acts performed in response to obsessions
aimed at reducing distress or preventing dreaded event |
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OCD clinical course
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1. unremitting and chronic (most common)
2. phasic with periods of complete remission 3. episodic with incomplete remission |
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OCD comorbidities
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mood disorders
anxiety tics |
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OCD neurobiology
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overactive Orbital cortex and caudate nucleus
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Trichotillomania
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compulsive hair pulling
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OCD treatment
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CBT
exposure in vivo imaginal exposure ritual prevention cognitive interventions SSRIs can mitigate OCD |
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Depression with medical illness
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worse outcome, higher death rate esp. MI, AIDS, and stroke
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Depression and cardiovascular disease
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depression <-> CVD
increased inflammatory response decreased heart rate variability increased platelet activation and reactivity behavior and lifestyle increased HPA |
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Cytokines in depression
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IL-1, IL-6, and TNF-alpha elevated
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Cortisol effects on cardiovascular health
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promotes atherosclerosis and hypertension
loss of supression of inflammatory cytokines |
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Hypercoagulability in depression
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increased 5HT2A receptors on platelets
increased platelet activation |
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Depression and AIDS
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higher mortality
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Depression and Cancer
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2-4x higher rates than in general population
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Anticancer drugs associated with depression
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Interferon (sudden onset)
corticosteroids chemotherapeutics |
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Schizophrenia epidemiology
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lifetime risk: 0.7
risk: immigrants, northern latitudes, urbanicity higher incidence in men, equal gender prevalence |
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Prodromal psychosis
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period of attenuated psychotic symptoms before onset of overt psychosis
Cognitive deficits |
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Schizophrenia diagnosis
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characteristic symptoms for >1 month
-delusions, hallucinations -disorganized speech/behavior negative symptoms Social/Occupational dysfunction symptoms longer than 6 months |
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Ideas of Reference
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symptom of psychosis
hidden messages often inspires purpose in schizophrenia |
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Schizophrenia negative symptoms
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alogia
flat affect anhedonia avolition asociality |
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Alogia
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reduced verbal communication
negative symptom of schizophrenia |
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Avolition
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reduced motivation
negative symptom of schizophrenia |
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Asociality
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reduced social drive and interaction
negative symptom of schizophrenia |
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Schizophrenia mood symptoms
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25-33% experience significant depressive symptoms
Anxiety also common |
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Cognitive deficits in schizophrenia
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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 |
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Schizophrenia Illness course
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premorbid (cog. deficit)
prodromal psychotic stable |
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Schizophrenia treatments
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antipsychotics
supportive therapy CBT |
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First vs. second generation antipsychotics
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same positive symptom management
side effects: 1st - tardive dyskinesia, extrapyramidal symptoms 2nd - metabolic syndromes |
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Schizophrenia gross pathology
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Enlarged ventricles
lost grey matter |
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Schizophrenia genes
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DISC1
COMT (22q del) dysbindin neuregulin |
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Neurobiology of schizophrenia
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dysbindin-1 = glu transporter
schizo = too much glutamine? poor migration of neurons loss of synaptic integrity |
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Schizophrenia seasonality
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highest rates for people born in March
lowest rates for people born in september potential for in utero influenza |
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Schizophrenic sinuses
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small posterior nasal cavities
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Glutamate hypothesis
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NMDA receptor blockade at the cortical interneuron can lead to glutamatergic hyperactivity in associated pyramidal cells -> positive and negative symptoms
too much glutamate -> neurotoxic |
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Mismatch negativity
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After repetitive stimuli, an outlier stimulus provokes salience
not seen in schizophrenics |
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Anorexia nervosa criteria
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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 |
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Anorexia subtypes
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Restricting: no binging/purging
Binge-eating/purging |
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Anorexia signs and symptoms
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Amenorrhea
Dry skin Lanugo excess energy bradycardia (slow heart rate) |
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Anorexia onset
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peak at age 14 and 18
onset frequently follows crisis w/family, school. or sexuality dieting in effort to "take control" |
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Anorexia candidate genes
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Serotonin 1D receptor
delta opioid receptor |
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Anorexia etiology
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serotonin mismodulating impulse control
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Anorexia treatment
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Family therapy
possibly antipsychotics hospitalization if acutely ill |
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Maudsley Family therapy
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for adolescents with anorexia
phase 1: parents in control of food phase 2: return to independent eating phase 3: focus on general adolescent issues |
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Anorexia outcomes
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30-50% make full recovery
5% per decade die of heart failure or suicide |
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Unfavorable prognostics of anorexia
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vomiting
bulimia and purgative abuse chronicity of illness obsessive-compulsive personality |
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Bulimia nervosa criteria
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Recurrent episodes of binge eating
Recurrent compensatory behavior in order to prevent weight gain Binge/Purge at least 1/week for <3 months |
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Bulimic brains
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poorer impulse control
inferolateral prefrontal cortex |
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Bulimia outcomes
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75% respond to therapy
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Bulimia complications
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hypokalemia
erosion of dental enamel parotid gland enlargement |
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Bulimia Treatment
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CBT (faster)
interpersonal therapy (ultimately as effective) antidepressants |
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Eating Disorder Not Otherwise Specified (EDNOS)
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Binge eating disorder
binges w/out purges |
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Atypical Anorexia
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anorexic eating habits and beliefs, but still over the weight criteria
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M'Naghten Test
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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 |
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Types of human aggression
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Predatory: reward-based, intentional, and premeditated
Impulsive: aversively-stimulated, unplanned, and reactive |
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Agression definition
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Overt behavior which has the potential (and often intention) to inflict pain or harm on another organism or self
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Aggression differential diagnosis
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Genetic syndromes
metabolic disorders neurological disorders psychiatric disorders intoxication drug withdrawal |
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Brain structures promoting aggression
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Amygdala
Bed nucleus of the stria terminalis (BNST) hypothalamus periaqueductal gray |
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Brain structures suppressing aggression
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septum
frontal cortex raphe nucleii |
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Amygdala in aggression
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selects appropriate aggressive (or submissive) behavior
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Prefrontal cortex in aggression
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vmPFC and orbitofrontal cortex inhibit aggressive and suicidal behaviors. inhibit amygdala
anterior cingulate cortex also suppresses aggression |
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Septum in aggression
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inhibits aggression
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Serotonin and aggression
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serotonin has an inhibitory effect on aggressive behaviors and impulsivity
mediated through the 5HT1B receptor |
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Dopamine and aggression
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dopamine may promote aggression
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Brunner Syndrome
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point mutation in MAO A. Results in increased serotonin, norepinephrine, and dopamine
increased aggressive behaviors |
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GABA and aggression
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GABA usually decreases aggressive behaviors
at lower doses, it can disinhibit and cause aggression |
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Testosterone and aggression
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stimulates amygdala, BNST, and inhibits septum
more aggression |
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HPA axis and aggression
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chronic HPA decreases aggression
acute spikes may increase aggression |
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Vasopressin
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aka antidiuretic hormone
produced in hypthal, amygdala, and BNST increases aggressive behavior inhibited by serotonin activated by testosterone |
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Treatment of Aggressive behaviors
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Emergency: benzodiazepines, antipsychotics
Long term: atypical antipsychotics, mood stabilizers, anitdepressants |
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Haloperidol
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D2 antagonist used in long-term aggression management
high dose may cause akathisia |
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Akathisia
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uncomfortable need to move
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Bipolar, unipolar depression, and schizophrenia
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may share common risk factors
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DISC1
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mutation linked to schizophrenia in scottish pedigree
others developed bipolar, or had no symptoms everyone had slowed mismatch sensitivity |
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Neuregulin1 (NRG1)
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tyrosine kinase ligand
associated with schizophrenia large gene (1.5 Mb) also see slowed mismatch sensitivity |
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ErbB4
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tyrosine kinase
linked to schizophrenia, thought through the same pathway as NRG1 |
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CHRNA7
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nicotinic receptor
microdeletions implicated in schizophrenia ~lots of schizophrenics are chain smokers~ |
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22q deletion
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facial abnormalities
abnormal aortas psychosis |
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Bipolar genetic risk
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ANK3
CACNA1C - L type Ca channel |
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ANK3
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chaperone protein for ion channels
implicated in bipolar and schizophrenia |
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CACNA1C
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voltage-gated L-type calcium channel
implicated in bipolar and autism |
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Drug with highest risk of addiction
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nicotine
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Reward system
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nucleus accumbens - cocaine, heroin, nicotine
ventral tegmental area - heroin globus pallidus - alcohol |
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Effects of addictive drugs on dopamine levels
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big spike
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Innate tolerance
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higher risk of becoming dependent
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Pharmacokinetic tolerance
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rapid metabolism of drug
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Pharmacodynamic tolerance
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down-regulation of drug receptors
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Behavioral tolerance
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learning to compensate for drug effects
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Conditioned tolerance
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learning to reliably predict drug arrival so body systems can adapt quickly
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Sensitization
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Reverse of tolerance
may occur under repeated, spaced dosing of stimulants |
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Addiction neurobiology
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suppressed D2 receptors in nucleus accumbens
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High baseline D2 receptors
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more likely to induce unpleasant effects of drug -> less likely to become dependent
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Brain areas in cue-induced cravings
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Anterior Cingulate gyrus
Amygdala |
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Tolerance
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a decreased response to a drug with repeated administration
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Sensitization
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increased response to drug with repeated administration
stimulants |
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Compulsion
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irresistible impulse to act, regardless of the rationality of the motivation
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Craving brain regions
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amygdala
anterior cingulate gyrus |
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Smoking cessation statistics
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46% try to quit each year
20% are current smokers leading preventable cause of death |
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Heritability of nicotine
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50%
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Nicotine biochemistry
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nicotinic cholinergic receptor agonist
T1/2 = 90 minutes metabolized via CYP2A6 |
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Nicotine and Dopamine
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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
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Test of Nicotine Dependence
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Smokes first cigarette w/in 30 min of awakening
Smokes when ill Smokes a pack a day or more |
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Current Nicotine Treatments
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Cold turkey
Cessation counseling nicotine replacement therapy bupropion varenicline combo |
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Cold Turkey nicotine approach
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5% long-term abstinence
brief interventions by doctors can increase success rates |
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Brief nicotine intervention
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set quit date 2 weeks ahead
emphasize abstinence as goal prescribe pharmacotherapy |
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Intensive nicotine counseling
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prescribed after 2+ failed attempts
CBT |
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Nicotine Cessation Pharmacotherapy eligibility
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Everyone except:
those smoking fewer than 10/day pregnant/breastfeeding adolescent smokers |
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Nicotine Replacement
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patch, gum, nasal spray, inhaler, lozenge
nasal spray most closely mimics pharmacodynamics doubles likelihood of quitting |
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Bupropion
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Antidepressant; smoking cessation
Effective in combo with nicotine replacement too |
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Varenicline
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Partial alpha4beta2 nicotinic acetylcholine receptor agonist
Relieves craving and w/drawal Blocks satisfaction and rewarding effects of nicotine |
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Adverse effects of varenicline
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Suicidal thoughts
small cardiovascular risk |
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DSM drug dependence criteria
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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 |
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Routes of administration
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Least rapid
oral intranasal intravenous intrapulmonary Most rapid |
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IV complications
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HIV, Hep C
Endocarditis, sepsis, pneumonia Candida, aspergillus Abscess, vessel damage Emboli |
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Nicotine Medical complications
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Cancer (incl pancreas, kidney, cervix)
coronary artery disease stroke emphysema |
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More nicotine medical complications
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low bone density
vascular cell injury thrombi adverse lipid profile peptic ulcers low birth weights |
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Alcohol and the Liver
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acetaldehyde and oxygen radicals cause liver inflammation
scarring blood backs up, causing esophageal varices, which can rupture |
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Alcohol neurologic complications
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Dementia
Cerebellar degeneration peripheral neuropathy Wernicke-Korsakoff |
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Wernicke-Korsakoff Syndrome
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Acute: thiamine deficiency. disorientation, ocular muscle dysfunction, gait disurbance
Chronic: mamillary body degeneration, memory loss, and confabulation |
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Alcohol Withdrawal Syndrome
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Autonomic arousal: tachycardia, hypertension, hyperreflexia, high temp, tremor, insomnia, anxiety
Nausea, vomiting and diarrhea Lasts 3-5 days GABA deficient state |
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Delirium Tremens
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severe alcohol withdrawal
hallucinations, delirium, psychosis seizures, and death |
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Alcohol withdrawal treatment
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Benzodiazepines
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Opiates
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Heroin, morphene, codeine, oxycodone, methadone, buprenorphine
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Opiate withdrawal
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Not medically dangerous, but very unpleasant
Detox with methadone |
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Opiate overdose
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Little tissue toxicity
May lead to lethal respiratory depression Reversible with naloxone |
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Stimulants
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cocaine amphetamine, methamphetamine, methylphenidate
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Adverse stimulant effects
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vasospasms -> MI, stroke, renal failure, spontaneous abortion, bowel infarction
Hypertension electrophysiological abnormalities Hyperthermia Rhabdomyolysis |
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Rhabdomyolysis
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breakdown of muscle fibers
myoglobin causes renal failure |
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Cocaethylene
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toxic metabolite formed with simultaneous alcohol and cocaine use. cardiac death increased 24x
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Stimulant brain damage
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targets the frontal cortex
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Hallucinogens
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LSD, mescaline, PCP, ketamine, MDMA, GHB, marijuana
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Ecstasy effects
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hyperthermia, seizures, rhabdomyolysis, electrolyte imbalance, hepatic injury
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Marijuana medical complications
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Respiratory disease, decreased libido, immunosuppresion, arrhythmias, cognitive disturbances, traffic accidents
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GHB effects
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"date rape" druge
fulminant hepatic failure |
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PCP and Ketamine effects
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NMDA receptor antagonists
increased cardiac output acute psychosis, violent behavior |
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Barbiturate effects
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GABA A agonists
acute respiratory depression nystagmus, slurred speech, ataxia |
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Barbiturate withdrawal
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seizures can be lethal
looks like alcohol withdrawal |
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Benzodiazepine effects
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GABA A agonists
unlikely to overdose unless combined with alcohol |
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Benzodiazepine withdrawal
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looks like alcohol withdrawal
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Inhalant complications
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hepatoxicity, sudden death, cognitive dysfunction
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Addiction and psychiatric disorder
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substance-induced psych disorder
self-medication (underlying psych) co-occurring |
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Opiate withdrawal
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panic/anxiety, insomnia, agitation, increased autonomic symptoms
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Stimulant intoxication
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pressured speech, sexual arousal, paranoia
easily confused w/mania/psychosis |
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Stimulant Withdrawal
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Looks like major depression
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Naturally occurring opioids
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Codeine
Morphine |
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Naltrexone
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orally-active opioid antagonist
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Naloxone
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opioid antagonist
inactive via oral administration |
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Somatic vs. visceral pain
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somatic: sharp, intense, A-delta fibers
visceral: diffuse, C fibers Both types of pain alleviated by opioids |
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Opioid mechanism of action
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inhibition of pain perception in cortical and subcortical brain
"hurts, but who cares?" |
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Opioid CNS actions
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analgesia
euphoria (in some people, dysphoria) respiratory depression Prolactin release Nausea anti-tussive |
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Opioid cardiovascular effects
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peripheral vasodilation
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Opioid eye effects
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pupillary constriction
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Opioid Lung effects
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respiratory depression
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Opioid GI effects
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decrease propulsive contractions in colon -> constipation
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Opioid pharmacokinetics
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Morphine duration: 3-4 hrs
higher dose required orally than IV metabolism: liver, glucuronide conjugation renal excretion |
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Opioid receptors
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Mu - spinal and supraspinal (periaqueductal grey) analgesia
Delta - spinal analgesia for visceral pain Kappa - dysphoric effects |
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Opioid euphoria
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inhibited GABA-ergic neurons in VTA -> more dopamine release ->stimulates nucleus accumbens and prefrontal cortex
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Opioid nausea
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Area Postrema
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Respiratory depression
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Brainstem, decreasing neuronal sensitivity to CO2
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Opioid anti-tussive effects
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Brainstem
produced by both d and l isomers(d isomers lack all other effects) |
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Opioid GI effects
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produced at the level of the local gut ganglia
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Opioid pupillary effects
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produced at level of the oculomotor nucleus
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Opioid cardiovascular effects
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produced at the vagal nucleus
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Endogenous opioid receptor ligands
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Endorphin - Mu and delta
Enkephalin - Mu and delta Dysnorphin - Kappa Gi pathway -> reduced firing |
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Opioid antagonists
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Naloxone: IV only, rapid onset
Naltrexone: orally active, lasts 48 hrs, alcohol addiction |
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Mechanism of opioid dependence
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pharmacodynamic tolerance -
Mu phosphorylation -> more cAMP (switch to Gs mechanism) Mu internalization loss of dendritic arborization inhibition of neurogenesis in hippocampus |
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Chronic opioid use
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results in decreased cognitive function: smaller hippocampi and fewer dendrites
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Opioid withdrawal
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Anxiety, Agitation, Diarrhea, pupillary dilation
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Methadone maintenance
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Lowers rates of HIV and hepatitis
Lowers rate of re-arrest increases employment rates |
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Opioid anti-tussive effects
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Brainstem
produced by both d and l isomers(d isomers lack all other effects) |
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Opioid GI effects
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produced at the level of the local gut ganglia
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Opioid pupillary effects
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produced at level of the oculomotor nucleus
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Opioid cardiovascular effects
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produced at the vagal nucleus
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Endogenous opioid receptor ligands
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Endorphin - Mu and delta
Enkephalin - Mu and delta Dysnorphin - Kappa Gi pathway -> reduced firing |
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Opioid antagonists
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Naloxone: IV only, rapid onset
Naltrexone: orally active, lasts 48 hrs, alcohol addiction |
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Mechanism of opioid dependence
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pharmacodynamic tolerance -
Mu phosphorylation -> more cAMP (switch to Gs mechanism) Mu internalization loss of dendritic arborization inhibition of neurogenesis in hippocampus |
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Chronic opioid use
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results in decreased cognitive function: smaller hippocampi and fewer dendrites
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Opioid withdrawal
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Anxiety, Agitation, Diarrhea, pupillary dilation
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Methadone maintenance
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Lowers rates of HIV and hepatitis
Lowers rate of re-arrest increases employment rates |
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Buprenorphine
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orally-active partial mu agonist
relieves withdrawal without causing euphoria available by prescription |
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A118G SNP for opioids
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causes decreased transcription of Mu receptor
Hyporesponsive to opioids hyperresponvie to opioid antagonists attain greater euphoria with alcohol ->blocked by naltrexone |
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Naltrexone alcohol cessation therapy
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mu opioid receptor antagonist
reduces alcohol euphoria reduces risk of relapse |
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Benzodiazepine uses
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promote sleep
treat anxiety relieve alcohol withdrawal treat seizures perioperative amnesia |
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High potency benzos
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most likely to be abused
alprazolam lorazepam triazolam clonazepam (longer t1/2) |
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Low potency benzos
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low risk of abuse
oxazepam librium and dizaepam used for alcohol withdrawal |
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Withdrawal and half life
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drugs with longer half-lives tend to have milder withdrawals
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Opioid pseudo-addiction
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Focus on obtaining opioids for pain relief
looks like addiction, but disappears with adequate medications |
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Opioid abuse prevention
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educate public
alter prescribing practices make opioids less abusable |
