Psych Flashcards
(124 cards)
1
Q
Domains of disorder in Mental life
A
- Behavior:
- Substance abuse, eating disorders, pathological gambling, non-adherence, negative symptoms - Emotion:
- Major depression, bipolar, anxiety disorders - Thinking:
- Process (loose associations, tangentiality): ex: speaking fluently about real things but listener unable to follow train of thought
- Content (delusions, overvalued ideas, distortions) - Perception:
- Hallucinations (hearing/seeing something that’s not there), illusions, depersonalization
2
Q
Mental status exam
A
- Appearance and behavior
- hygiene, dress, alertness, level of cooperation, eye contact, psychomotor activity level, mannerisms, posture, gait - Speech:
- Rate, volume, clarity, stream, progression, prosidy, response latencies, pressured speech, language abnormalities - Mood: subjectively reported (direct quote/paraphrase)
- Affect: observed/objectively described
- Thought process
- Thought content
- Abnormal perceptions: hallucinations, visual, tactile, etc
- Abnormal ideas: delusions, suicidal/homicidal ideation - Cognitive capacities:
- Level of alertness
- Orientation
- Attention/concentration (tap to letters)
- General information/fund of knowledge (modify for educational level)
- Abstraction (proverb interpretation, similarities/contrasts)
- Judgement
- Insight
3
Q
Affect
A
Bizarre= phenomenon culture views as implausaible
Jealous= one’s partner unfaithful
Erotomanic= delusion that another person (usually famous) is in love with individual
Grandiose= delusions of inflated worth, power, knowledge, special relationship to deity/famous person
Passivity= delusion that feelings/thoughts/impulses/actions are under control of external force
Referential= delusion that events/objects, other people have personal significance
Persecutory= Central theme of being attacked, harassed, cheated, conspired against
Somatic= delusion focused on bodily health/function
Systematized= “delusional world”
4
Q
Hallucinations
A
Can present in any sensory modality:
- Auditory
- Gustatory
- Olfactory
- Tactile
- Visual
5
Q
Pentaxial system of DSM-IV
A
Axis 1= majory psychiatric diagnosis
- Schizo, bipolar
Axis II= personality disoders, mental retardation
Axis III= general medical conditions
Axis IV= Psychosocial/environmental factors (stress)
- Social support, medical illness
- Grade stress as mild, mod, severe
Axis V= Global assessment of functioning (GAF); current, past 12 months
- Rated on scale 0-100
- 100= superior functioning, sought out by others due to positive qualities
- 80= transient/expectable reactions to stressors with no more than slight impairment
- 60= moderate symptoms, moderate difficulty in social functioning
- 50= serious symptoms/impairment
- 10= persistent danger to self/others, inability to maintain personal health, serious suicidal act with expectation of death
6
Q
Prevalence of ADHD
A
3-7% in school-aged children
US/Worldwide prevalence is similar (5-12%)
Child psychiatric outpatient= 30-50%
Child inpatient= 40-70%
M:F in elementary children: 3-9:1 (Clinical)
2-3:1 in community
Girl:
- More likely to have inattentive type, comorbid anxiety, depression
- Less likely to have comorbid disruptive behaviors- less likely to receive treatment
Adults: 30-60% of cases persist
- 2-7% of all adults have residual ADHD
- M:F 1-2:1
- Males more likely to develop substance abuse, antisocial behavior
- Higher rates of MDD
- More frequent job, partner changes, money problems
- Girls/women- higher rates of unwed pregnancy
7
Q
Diagnostic criteria of ADHD: inattention criteria
A
6+ of following symptoms for 6+ months, maladaptive/inconsistent with developmental level:
- Makes careless mistakes in school/work/other activities
- Difficulty sustaining attention
- Does not seem to listen when directly spoken to
- Does not follow through on instructions, fails to finish schoolwork/chores, work
- Difficulty organizing tasks/activities
- Avoids, dislikes, reluctant to engage in tasks requiring sustained mental effort
- Often loses things necessary for tasks
- Easily distracted by surroundings
- Often forgetful in daily activities
8
Q
Diagnostic criteria of ADHD: hyperactivity/impulsivity
A
6+ of following symptoms for 6+ months, maladaptive/inconsistent with developmental level:
- Fidgets hands/feet
- Leaves seat when remaining seated is expected
- Runs/climbs excessively
- Difficulty in playing/engaging in leisure activity quietly
- Acts “on the go”, driven by motor
- Talks excessively
Impulsivity: - Blurts out answers before questions completed
- Difficulty awaiting turn
- Interrupts/intrudes on others
9
Q
Additional criteria for ADHD diagnosis
A
Hyperactive-impulsive or inattentive symptoms causing impairment before age 7
Some impairment present in 2+ settings
Clinically significant impairment in social, academic, occupational functioning
Do not occur during course of pervasive developmental disorder (autistic spectrum), schizophrenia, other psychotic disorder (not better accounted for by another disorder)
10
Q
Subtypes of ADHD
A
Three types:
- Combined= most common:
- Overactivity
- Impulsivity
- Distractibility - Predominently Hyperactive-impulsive type (v. young children)
- Predominantly inattentive type:
- Daydreamer/spacey
- comorbid anxiety, depression
- More likely to be overlooked (not overactive/impulsive)
11
Q
Situational factors and symptoms of ADHD
A
Worsened in:
- situations needing sustained attention/mental effort
- Unstructured, boring, minimally supervised
Improved/absent:
- Highly structured/novel setting
- Engaged in stimulating activity (computer game)
- Alone with interested adult (doctor’s office)
12
Q
ADHD symptoms in adults
A
- Difficulty organizing/prioritizing tasks
- Poor time management, procrastination
- Difficulty switching tasks
- Feeling overwhelmed by intense stimuli
- Starting too many projects at once
- Leaving projects unfinished
- Trouble listening to partners, friends, colleagues
- Irritability, rigidity, low frustration tolerance
- Appearing driven at work, keeping long work hours
- Road rage, multiple traffic violations
- Symptoms tend to decrease with age, may not be present in adolescents/adults
13
Q
Comorbidities of ADHD
A
54-84% meet criteria for Oppositional Defiant Disorder
1/3 of patients with ADHD have mood/anxiety disorder
¼-1/3 have learning/language problems
Tourettes/mental retardation
Adults:
- MDD
- Dysthymia
- Bipolar disorder
- Anxiety disorder
- Substance abuse
14
Q
Etiology of ADHD
A
Relative dysfunction of frontal cortex (heterogenous)
- Frontal cortex= planning, organization, focus, impulse control
- Genetic predominance
- Biological environmental insults
- School/home can influence severity, not presence
- Sugar/diet have not proved causes
15
Q
Biological etiologies of ADHD
A
Multiple neurotrans systems involved: NE, DA activity in frontal cortex decreased
Anatomic imaging: differences in brain areas associated with executive functioning
- Decreased frontal cortex activation
- Smaller frontal lobe volume
- Different symmetry of caudate, smaller cerebellar vermis
Imaging only used to rule in/out suspected focal brain finding
16
Q
Medical risk factors for ADHD
A
Prenatal: - Young mother, poor maternal health, cigarettes/alcohol, drugs Birth complications: - bleeding, hypoxia, toxemia, prolonged labor Perinatal: - Low birth weight, prematurity Infancy: - malnutrition, early deprivation Lead poisoning Brain injury Genetic disorders: - Fragile X, G6PD deficiency, TH resistance, phenylketonuria
17
Q
Clinical diagnosis for ADHD
A
Clinical evaluation
- Interviews
- Standardized parent/teacher behavior ranking scales
No imaging/lab studies
18
Q
Treatment response for ADHD
A
60-80% response rates
MTA study= psychostimulant medication
- 50% response in preschoolers
Treatment improvements:
- Motor control, social function with peers, attention, patience, task persistence, irritability, aggression, academic work quality, rule compliance, athletic performance
- Also linked to reduced adolescent substance abuse
19
Q
Psychopharmacology of ADHD
A
Medication= primary treatment
Specific predictor of response not IDed, though predictive based on relatives’ response to meds
Many require continued medication into adulthood
20
Q
Medications for ADHD
A
Psychostimulant meds= greatest effect size, first line = Methylphenidate (Ritalin, concerta) = Dexmethylphenidate (focalin) = Dextroamphetamine = Mixed amphetamine salts (Adderall)
Atomoxetine= NE reuptake inhibitor
- Second line, some evidence of efficacy
- Inhibits presynaptic NE importers
Alpha-2-adrenergic agonist meds (clonidine, Guanfacine): 3rd line
- Can also be used in comorbid tic disorder
- Good for overaroused children
Antidepressants= almost never used due to safety concerns in children/adolescents
- Bupropion= DA reuptake inhibitor
- Venlafazine= NE/Serotonin reuptake inhibitor
- Tricyclics= NE/Serotonin reuptake inhibitors (ONLY used in adults)
** All meds increase CNS dopaminergic, norepinephrine synapse levels
21
Q
Fear
A
A cognitive process that leads to the conclusion that there is a threatening stimulus; a clear and present danger in the outside environment
Involves a pathway for activation of the adrenal cortex BEFORE threat is even identified
- It is the appraisal of danger
22
Q
Anxiety
A
Feeling of arousal we experience when we perceive either concrete or abstract danger
This danger often exists in the form of a possible threat in the future
**remember: ALL fear activates anxiety, but not all anxiety comes from identifiable fear
23
Q
Pathologic anxiety
A
“The fear of fear itself”
- recurrent and unexpected
- Panic - Specific, but viewed as excessive/unreasonable
- Phobias - Chronic worry in all spheres
* * interferes significantly with the person’s normal routine, occupational (academic) functioning, or social activities relationships
- all anxiety disorders
24
Q
Theoretical/clinical orientations for Anxiety development
A
- Biological
- Born this way
- Baby who cries a lot, child who can’t have sleepovers
- “Anxious disposition” - Behavioral
- Developing fears after event (ex. having car accident makes one a nervous driver) - Cognitive
- Psychodynamic
- Relationship with parents, interactions with parents
25
Biologic theory of anxiety
Central noradrenergic system:
- Locus coeruleus is the major source of the brain’s adrenergic innervations
- Stimulation of the LC generates panic
Limbic system:
- GABA neurons mediate general anxiety, worry, and vigilance
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Serotonin systems (esp. raphe nuclei):
- important modulators of the two systems outlined above
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26
Cognitive behavioral model of anxiety
Behavioral: Anxiety is mistakenly paired
- Classical Conditioning: Neutral stimuli paired with noxious responses
- Stimulus Generalization
Cognitive: Anxiety is “disordered thought”
- catastrophic interpretations of events/symptoms
- hypersensitive alarm system
- impaired objectivity and “mislabeling”
- loss of voluntary control
- dichotomous thinking
- fortune telling without evidence
27
Anxiety disorders in DSM IV
9: PASS GO, PA
- Panic D/O with or without Agoraphobia
- Agoraphobia without Panic D/O
- Specific Phobia
- Social Phobia
- Generalized Anxiety Disorder
- Obsessive Compulsive Disorder
- Post Traumatic Stress Disorder
- Acute Stress Disorder
3 "other" diagnoses:
- Anxiety due to general medical condition
- Substance-induced anxiety disorder
- Anxiety disorder not otherwise specified
28
Panic disorder
“A discrete period in which there is the sudden onset of intense apprehension, fearfulness, or terror, often associated with feelings of impending doom. During these attacks, symptoms such as SOB, palpitations, CP, choking or smothering sensations, and fear of ‘going crazy’ or losing control are present.”
- Recurrent, UNEXPECTED attacks are required for diagnosis
- Agoraphobia may or may not be present
Onset: Most frequently in the third decade of life within 6 months of a major stressful life event.
Course: Within 2 months of first attack, symptoms intensify and become more frequent. Usually symptoms are chronic and unremitting
Prevalence: Studies vary, but lifetime prevalence likely 2% or more
- Often patients develop secondary depression (can't predict, disabling)
29
Agoraphobia
Essentially a fear of situations in which one might feel trapped
Most commonly develops in patients who are already experiencing panic attacks
Like panic disorder, usually chronic and unremitting
** Doesn't have to occur simultaneously with panic d/o
30
Social phobia
Marked and persistent fear of social or performance situations in which embarrassment may occur
Exposure to the situation almost invariably provokes an immediate anxiety response
Patient recognized fear is excessive or unreasonable
Most often, the situation is avoided, although it is sometimes endured with dread
- “Unlike agoraphobics, social phobics fear scrutiny rather than the crowd itself.”
Onset: Late childhood thru early adulthood
Course: Chronic; often with pervasively impaired functioning
Prevalence: unclear, perhaps as high a 5% lifetime prevalence, with female preponderance
31
Specific (simple) phobia
Persistent fear of specified stimulus other than panic, entrapment, or social criticism
Most common anxiety disorder
- 10% lifetime prevalence
32
Generalized anxiety disorder
Characterized by excessive anxiety and worry, occurring frequently and chronically, about numerous events or activities
The worry is difficult to control, and accompanied with some emotional or physical symptoms
The individual DOES NOT ALWAYS identify the worry as excessive, but DOES recognize subjective distress
33
Obsessive Compulsive Disorder
Obsessions are persistent ideas, thoughts, impulses, or images.
Obsessions are experienced as intrusive and inappropriate and cause marked anxiety or distress. Attempts to resist them fail.
Compulsions are repetitive behaviors or mental acts, with a goal of preventing or reducing anxiety or distress (no pleasure).
Compulsions are either clearly excessive or not connected in a realistic way to what they are designed to neutralize or prevent
34
Post-traumatic stress disorder
Characteristic symptoms develop following exposure to an extreme traumatic stressor
Response to stressor involves intense fear, helplessness or horror (passivity)
Symptoms include flashbacks, avoidance of associated stimuli, emotional numbing, and exaggerated startle response
Lifetime prevalence likely 10%
35
Anxiety disorder due to medical condition
A variety of medical conditions may cause anxiety symptoms
Usually endocrine, cardiovascular, respiratory, metabolic, or neurological
- ex: hyperthyroidism, pheochromocytoma
Some medical work up is indicated in the assessment of every patient with new-onset anxiety
36
Substance-induced anxiety disorder
Anxiety symptoms are judged to be due to the direct physiological effects of a substance (intoxication OR withdraw)
Not just alcohol and “street drugs” (think about medications, toxin exposures, caffeine, etc.)
Considering substance-induced anxiety is necessary in the assessment of every patient with new-onset anxiety
37
Pharmacotherapy for anxiety disorders
SSRI= First line for:
- Generalized Anxiety D/O,
- Panic D/O with and without Agoraphobia,
- Social Anxiety D/O.
SSRI’s also used in PTSD and OCD (rarely effective as monotherapy)
- Citalopram
- Escitalopram
- Fluoxetine
- Sertraline
- Fluvoxamine
- Paroxetine
2. Mirtazapine
3. Buspirone
4. SNRIs (Duloxetine, Venlafaxine)
5. Benzodiazepines
- Used to treat symptoms in variety of anxiety disorders
- Bridge therapeutic efficacy in GAD, panic d/o, social phobia (SSRIs take weeks to build up effectiveness)
- Can be used as needed in phobia (ex: infrequent flier)
- Should be avoided in PTSD
OCD:
- SSRIs + behavioral therapy
PTSD:
- SSRIs + EMDR (eye movement control), CBT, psychotherapy, behavioral therapy
** May need to use other pscyhopharmacology for PTSD, OCD
38
Psychotherapy for anxiety disorder
Numerous psychotherapeutic approaches used to treat anxiety disorders.
Includes psychodynamic, interpersonal, supportive, cognitive-behavioral
** Psychotherapy alone can be used to treat most anxiety disorders (CBT has most data)
Psychotherapy + Pharmacotherapy
- Best for PTSD
- Best for most anxiety d/o
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Cognitive behavioral therapy
Best studied, manualized (not as idiosyncratic as pscyhotherapy)
40
Behavior therapy
NOT CBT
- Involves exposure to feared stimulus, desensitization
- Various forms useful in OCD, phobias, PTSD (exposed to detailed recall of traumatic events)
41
Psychosis
A state of mind in which a person loses the ability to distinguish what is real from what is not. There is a breakdown in processing what comes from within the brain, and what is derived from the senses. External events become invested with meaning derived from one’s inner life.
Syndrome:
- Delusions
- Hallucinations
- Disorganized speech/behavior
- Impaired reality testing
- NOT a specific disorder itself
42
Hallucinations
Perceptions in the absence of real stimulus.
| - In schizophrenia they are generally auditory (most common) or visual (25%).
43
Delusions
Fixed, false ideas or beliefs that society does not accept
- Often are paranoid or persecutory in nature.
- Can also be bizarre, somatic, grandiose or referential.
In schizophrenia a patient may have the delusion that their thoughts are being broadcasted or thoughts are inserted or withdrawn from their mind.
- In schizophrenia these can be paranoid and persecutory;
- generally bizarre and implausible (e.g. patient’s belief that aliens have implanted computer chips inside of their abdomen and can read their thoughts).
- Grandiose
- Erotomanic
** vs Delusional disorder where delusions are theoretically possible (e.g. patient’s belief that the government is tapping all of their phone calls).
44
Formal thought disorder
Disturbances in thinking that make ideas difficult to follow.
- This is a disturbance of process (vs. content) of thinking.
- Connections between the patients ideas may not be readily apparent.
- Examples include loosening of associations, clanging, neologisms, tangential, circumstantial and thought blocking
- NOT due to lesion (responds to antipsychotics, vs Wernicke's)
45
Positive symptoms
Symptoms seen in schizophrenia. They include hallucinations, delusions, agitation, anxiety and peculiar behaviors and rituals.
These are called positive symptoms as they are symptoms which have been “added” on to normal mental life
46
Negative symptoms
Symptoms seen in schizophrenia. These include social isolations, blunted affect (decreased emotional states), paucity of speech/thought, poor self-care and disorganization.
These are called negative symptoms as the patient has a decrease/removal of normal behavior; i.e., these are “lost” from mental life vs. positive symptoms that are “added” to mental life.
- Most detrimental aspect of Schizophrenia
Examples:
- Avolition (no desire to do anything)
- Anhedonia (derives no pleasure)
- Affective flattening
- Alogia (paucity of speech)
- Asociality
47
Epidemiology of Schizophrenia
1% of population (2.2 millionAmericans)
- 1/3-1/2 of all homeless
- 10% of inmates have Schizophrenia, bipolar, or depression (4x greater than in hospitals)
- 10-15% employed full-time
- 50% on disability ($1100 a month)
Men and women equally affected
- Onset earlier in men (15-25)
- Women "catch up" by age 35, tend to have better outcomes
Patients die young (25 years earlier)
- 10% die from suicide
- 18-55% attempt suicide
- Patients do not access care
48
Diagnosis of Schizophrenia
Onset= adolescence or early adulthood
- First break in Freshman/Sophomore year of college
Course of Illness:
1. Prodromal phase in 50%
- Outgoing person--> shy, reclusive, preoccupied with vague/odd concepts
- Poor peer relationships, academic problems
- Weeks to months of gradual deterioration, social withdrawal
2. Psychotic phase:
- Lose touch with reality
- 20% without further symptoms
- 30% have further episodes with baseline functioning
- 30% have decreased functioning but managed with meds
- 30% have multiple repeat psychosis, may live in group home, homeless
3. Residual phase:
- Phase between psychotic episodes
- In touch with reality, significantly impaired
- Predominantly negative symptoms
- Deterioration
49
Prognostic factors
1. Later onset= better prognosis
- Less exposure to changes in brain function in development
2. Acute better than Insidious
3. High premorbid function= better
4. Mood symptoms= better to see moods
- Respond better when they express moods (vs flat affect)
5. Predominantly positive symptoms better
6. Strong social supports
7. Women do better than men
8. Adherence to meds
50
DSM-IV Criteria for Schizophrenia Diagnosis
Criteria A: 2+ of following:
- Delusions
- Hallucinations
- Disorganized speech
- Grossly disorganized or catatonic behavior
- Negative symptoms
** If patient has specific other symptoms, only need 1 from Criteria A
Social/occupational dysfunction
Duration of at least 6 months
- 1 month meeting criterion A
- May include periods of prodromal/residual symptoms
* Keep standard DSM exclusions in mind (drugs, other health conditions)
51
First rank symptoms
Auditory Hallucinations:
- Hearing thoughts spoken aloud
- Hearing voices referring to him/herself, made in 3rd person
- Auditory hallucinations in form of commentary
Thought withdrawal, insertion (someone taking my thoughts, putting in new ones)
Thought broadcasting (everyone knows what I'm thinking)
Delusional/referential perceptions
- Ex: Light is red, martians are coming
Feelings or actions experienced as made or influenced by external agents
52
Schizophrenia subtypes
Paranoid Type:
- patient is preoccupied with one or more delusions or frequent auditory hallucinations.
Disorganized Type:
- the patient has disorganized speech and behavior as well as a flat or inappropriate affect.
Catatonic Type :
the patient has two or more of the following:
- motoric immobility,
- excessive motor activity which is purposeless and not influenced by external stimuli,
- extreme negativism as seen by an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved
- or mutism, echoalia or echopraxia
** Sensitive to ECT
Undifferentiated Type:
- Patient meets criterion (A) as above but they do not meet criteria for the paranoid, disorganized or catatonic types listed above.
Residual Type :
- There is an absence of prominent delusions, hallucinations, disorganized speech and grossly disorganized or catatonic behavior.
- Negative symptoms continue in an attenuated form (e.g. odd beliefs, unusual perceptual experiences)
53
Brain imaging in Schizophrenia
- Widening of lateral ventricles
- Atrophy of cerebellar vermis
- Decreased activity in Dorsolateral prefrontal cortex
* * NOT considered diagnostic- Imaging lines up with clinical diagnosis
54
Cognitive Isuues (executive function, attention and memory) deficits in Schizophrenia
Patients test as “brain damaged” on generalized neuropsychological batteries.
Not just an artifact of psychoses, lack of motivation or sedation from drugs.
Marked problems with conceptual tasks and shifting attention or cognitive “set.”
Wisconsin Card Sort Test – a test of abstract reasoning and problem-solving is especially sensitive to DLPFC (dorsolateral prefontal cortex) lesions, is impaired in schizophrenia.
Cognitive impairments in Schizophrenia:
- Representing/maintaining goals
- Focusing attention
- Sustaining attention
- Monitoring performance
- Prioritizing
- Modulating behavior based on social cues
- Verbal fluency
- Problem solving
55
Differential Diagnosis for Schizophrenia
* * Must rule out organic etiologies
- Drug intoxications (PCP, cocaine, amphetamines)
- Brain injury (temporal lobe)
- Alcoholic hallucinosis
- Huntington's disease
- L-dopa (Sinemet)
- Cushing's disease (hypercortisol)
- SLE
* * Epilepsy (Temporal Lobe) can be associated with delusions/psychosis. Can be distinguished from schizophrenia by following:
- Develops over years in TLE
- Lack premorbid changes
- Good capacity for relationships
- Do NOT deteriorate
- Lack family Hx of Schizophrenia
- Degree of psychosis has inverse relationship to seizure control (High control, few symptoms)
* * may also have affective disorder with psychotic features
- Ex: severe mania in Bipolar
* * Distinguish from Dementia:
- Patient has cognitive decline
- Onset later in life
* * Distinguish from Delirium:
- Disturbed conciousness (stupor)
- Pt NOT oriented to place, time
- Sudden onset
- Underlying illness causing change in mental status)
56
Etiology of Schizophrenia
Strong genetic predisposition
- 50-60% concordance in twins
- 40% with 2 parents affected
- Schizophrenia-spectrum disorders more common in 1st degree relatives
1) Schizoid= withdrawn, no interest in people
2) Schizotypal= interest in strange hobbies
- Polygenic model (no classic Mendelian pattern)
- Environmental factors
- Multiple chromosomes implicated
- Advanced paternal age= risk factor
- Anticipation may occur (HD, Friederich's ataxia)
- Likely to be exposed to maternal malnutrition, virus in utero
- Winterbirth
- Second trimester= time of greatest risk
- Perinatal factors (eclampsia/ preeclampsia, bleeding)
- Lower APGAR scores
Post-natal factors
- Lost one or both parents
- Urbanicity
- Stress (increase levels of bad neurotransmitters)
- Substance abuse (stimulant, hallucinogen) increases rates
57
Schizophrenia and the Dopamine Hypothesis
Dopamine agonists cause/exacerbate positive symptoms
- DA antagonists decrease positive symptoms
Post-mortem neurochemical data
Increased D2 receptors on PET scan with radio-labeled neuroepileptics
1. Increased DA in Mesolimbic system--> delusions (positive symptoms)
2. Less DA in Mesocortical pathway (VTA--> cortex)--> decreased cognitive functioning
Treatment: changes in brain:
3. Nigrostriatal pathway: excess DA anatagonists--> Parkinsonian symptoms
4. Tuberoinfundibular DA pathway: stop inhibition with DA antagonists--> lactation
58
Glutamate hypothesis
1. Theory states that schizophrenia is caused by dysregulation of the NMDA glutamate receptor.
2. The psychosis caused by PCP and ketamine is similar to the psychosis seen in schizophrenia.
Both positive and negative symptoms are mimicked.
3. Patients with schizophrenia who are given ketamine or PCP get much worse.
Glutamate= excitatory neurotransmitter of CNS
Brainstem neurotransmitter centers:
- Hypoactivity of (excitatory) NMDA receptors--> less negative inhibition--> increased release of monoamines (DA)
+ Decreased DA release in striatum, nucleus accumbens--> decreased cognitive function/ more negative symptoms
Cortico-striatal-thalamic loop:
- Glutamate--> GABA (thalamus)--> prevents too much information passing from thalamus to cortex
- Too little Glutamate--> less GABA stimulation in thalamus--> more information pass to cortex
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Schizophrenia Treatment
MEDS:
Antipsychotics for positive symptoms, especially exacerbations.
- Low dose antipsychotics for maintenance, increase for relapses using monitoring by therapist and family.
- Antipsychotic levels for non-responders (does too low, dose adequate but non-response, non-compliance)
- Can see refractory resistance to medications if patient stops meds
** Depot (long activing injection) antipsychotic medication for patients who are non-compliant with treatment and would prefer this route.
Clozapine, risperdone and olanzapine (atypical antipsychotics) evidence that improve negative symptoms
Change antipsychotic medication if failure to respond despite adequate blood levels for adequate time.
** Treat side effects adequately and promptly.
Pscyhosocial Tx:
- ECT
- Inpatient (for acute exacerbations)
- Day hospital (flare-ups, recovery)
- Day programs (Halfway house for structure, care)
- Family therapy (reduce external exacerbations, relapse monitoring)
- Pscyhotherapy (help patient live with illness, ADLs)
- CBT (focus on here and now)
60
Schizophreniform Disorder
Meets criteria for Schizophrenia but is less than 6 months of total illness duration
61
Schizoaffective disorder
Patient meets criteria for either major depression, bipolar mania or mixed episode in addition to meeting criteria for schizoaffective disorder.
The key is there is at least a two week period where they DO meet criteria for schizophrenia and DO NOT meet criteria for major depression, bipolar mania or mixed episode.
62
Brief Pscyhotic disorder
Patient has one or more of the following: delusions, hallucinations, disorganized speech, grossly disorganized behavior or catatonic behavior (none of which are culturally sanctioned). The episode lasts at least one day and less then one month in duration and the patient returns to baseline level of functioning.
63
Delusional disorder
Patient with Schizophrenia has a delusion that could be possible for at least 1 month
Types:
- Erotomanic
- Grandiose
- Jealous
- Persecutory
- Somatic
- Mixed
64
Prevalence of Mood disorders
(12-month/Lifetime)
Major Depressive Disorder: 5/15%
Dysthymia: 1/2%
Bipolar I and II: 2/4%
* Depression= 3rd most important cause of loss of work days
- 15% suicide risk
Epidemiology
- Increased incidence in Whites, womens
- Increased in those separated/divorced
- Same rates in income levels
- Increased with medically ill pts
65
Symptoms of clinical depression
#1= Depressed mood, Loss of interest
SIG E CAPS
Sleep (increased or decreased)
Interest (decreased)
Guilt
Energy (decreased)
Concentration (decreased)
Appetite/weight (increased or decreased)
Psychomotor agitation/retardation
Suicidal ideation
Diagnosis of depression= 2+ weeks of depressed mood, loss of energy, sleep, appetite disturbances, possible suicidal thinking. Can be single episode or recurrent
Atypical depression: weight gain, increased appetite, hypersomnia, heavy feelings in body
66
Diagnostic strategy for mood disorders
1) What is the polarity (Mania?)
2) If no mania, hypomania, consider other issues:
- Apparent Etiology
- Characteristics of depression (syndrome)
Symptoms must meet some characteristics:
1) must be present for 2+ weeks, "most of the time", "nearly every day"
2) symptoms should not be due to other specific reasons: substance abuse, medical condition, bereavement, bipolar disorder, schizophrenia
67
Depressive disorder and related symptoms: blood pressure changes
Normal depression= Normal BP
Dysthymia= essential HTN
MDD= essential HTN (accelerated)
Substance-induced mood disorder= Secondary HTN
Mood disorder d/t medical condition= secondary HTN
68
Dysthymic disorder
Depressed mood MOST of the days
Rule of 2s:
- At least 2 symptoms of depression
- Lasts at least 2 years
- Not symptom-free for 2+ months
69
Adjustment disorder with depressed mood
1. Depression related to a specific problem
2. Not depressed almost all the time
- Depressed thoughts are related to that specific problem
3. Depression is causing impairment in functioning
4. Not a person with strong preexisting vulnerability
* think of it as MALadjustment disorder
* If symptoms, severity meet criteria for MDD, don't call it adjustment disorder
70
Etiologies of MDD
1. Genetics (large role)
2. Adverse Life experiences:
- Early life (predispose): loss of parent in early childhood, abuse
- Later life (precipitate): loss, anger, learned helplessness
71
Pathophysiology of MDD
1. Neurotransmitters:
Monoamine hypothesis: NE, serotonin, DA
- Broadly distributed in CNS, interactive
- Involved in mood regulation
- Affect arousal, sleep, motivation, aggression, pain perception, autonomic regulation
- Short serotonin transporter alleles= greatest risk (vs long)
2. Hypercortisolism
- Increased cortisol, not suppressed by dexamethasone
3. Changes in sleep architecture
- Normal= REM increases as sleep progresses
- Depression= more REM early in sleep (starts dreaming quickly), less deep sleep (stage 3-4, delta/slow wave)
4. Neurotrophic processes (Brain derived neurotrophic factor= BDNF)
72
Antidepressants
MOA: increased monoamine activity (serotonin, NE, DA)
First generation:
- Tricyclics
- Monoamine oxidase (MAO) inhibitors
Second generations:
- SSRIs: fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine
- Serotonin-norepinephrine reuptake inhibitors (SNRIs): venlafaxine, desvenlafaxine, duloxetine, milnacipran
- Other antidepressants: buproprion, mirtazapine, vilazodone
73
Duration of treatment for depression
Acute phase: 6-12 months
Continuation phase: 4-12 months
Maintenance phase: several years to lifelong
Risk of recurrence:
- 1 episode= 50%
- 2 episodes= 80%
- 3 episodes= 90% (should keep on long-term antidepressant therapy)
74
Electroconvulsive therapy
Useful when:
1. Quick response essential
2. Failed to respond to antidepressant medication
```
Effective and safe
Use is infrequent because:
- Stigma/patient preference
- Short-term memory impairment
- Almost always need to find effective medicaiton to be used after ECT stopped
```
75
Psychotherapy
As effective as antidepressants except in severe major depressive disorder
No side effects!
May produce benefits in aspects of life other than depression
May not only relieve depression but positively impact life
Classification:
1. Individual therapy
2. Group therapy
Types:
1. Supportive therapy
2. Psychodynamic therapy
3. Cognitive therapy (most tested, proven type of therapy)
76
Features of Mania
1. Elevated mood – abnormal, persistent (1 week or more) OR Irritable mood
2. Elevated self-esteem/ grandiosity
3. Increased goal-directed activity or agitation
```
DSM-IV:
Elevated/irritable mood + DIGFAST (3+):
- Distractability
- Insomnia
- Grandiosity
```
- Flight of ideas
- Activity
- Speech
- Thoughtlessness
77
Clinical features of bipolar disorders
Equal frequency in males and females
- Mean onset at 30 years
- ~10% only have manic episodes
- Usually spend more time in depressed/hypomanic phases than manic phase
78
Features of hypomania
Need to distinguish from normally good mood:
1. Clear change from usual non-depressed mood
2. Clear change in functioning uncharacteristic of person
3. Disturbance in mood & change in functioning are observable by others
Same as Mania except less severe:
1. No marked impairment in functioning
2. No need for hospitalization
3. No psychotic features
79
Bipolar I disorder
At least ONE manic episode
80
Bipolar II disorder
At least one hypomanic episode and one major depressive episode
- NO manic episode EVER
81
Etiology of bipolar disorder
- 50% have family history of Bipolar disorder
- Risk in child or sibling of a patient with bipolar disorder ~ 10%
Twin studies: 80% concordance in monozygotics, 20% in dizygotics
** Genetic markers on chrom 18 + 22
82
Mood stabilizers for Bipolar Disorder
Lithium
Divalproex (from valproic acid)
Carbamazepine/ Oxcarbazepine
Lamotrigine
Second-generation “antipsychotics” (“atypical antipsychotics”):
- Aripiprazole (Abilify)
- Risperidone (Risperdal)
- Quetiapine (Seroquel)
- Clozapine (Clozaril)
- Ziprasidone (Geodon)
- Olanzapine (Zyprexa)
* * DON'T use antidepressants in depressed phase of bipolar disorder:
- Don't work well
- May cause switch to mania
- May increase cycling of illness
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Insomnia
Insomnia Symptoms: difficulty falling asleep, frequent (or lengthy) awakenings, poor quality of sleep in a person who has adequate time available for sleep.
Sleep deprivation: inadequate opportunity for sleep; sleep is relatively normal.
Insomnia Disorder: insomnia complaint + distress or significant daytime impairment (daytime sleepiness, impaired cognitive function, mood disturbances).
- Upset about lack of sleep
Common:
- 30% of adults report occasional insomnia
- 10% of adults report chronic insomnia
- Prevalence: higher in women than in men
- Prevalence increases with age
- Patients rarely report sleep problems to physicians
Classification:
- Primary: insomnia is primary symptom
- Due to other conditions: insomnia secondary to medical, psychiatric, substance use disorders
- Insomnia due to other sleep disorder (Restless leg syndrome, obstructive sleep apnea)
Treatment:
- Behavioral therapy:
1. Sleep restriction therapy (limit time in bed, no more than 4 hours/ prohibit naps, keep sleep log---> increase time in bed as sleep efficiency increases)
2. Relaxation training: cognitive (imaginary training/meditation, somatic/autogenic training)
3. Stimulus control therapy
- Patient gets out of bed when awake (worrying about sleep creates vicious cycle of promoting sleeplessness though secondary conditioning)
- Associate bed/bedroom only with sleeping
- Go to bed only when sleepy
- Use bed only for sleeping (i.e., no reading, eating, watching TV or family activities in the bed or bedroom)
- If you find yourself unable to sleep, get up and go into another room until you think you will be able to sleep
84
Sleep hygiene rules
```
Reduce time in bed
AVOID:
- Trying to sleep/daytime naps
- Clock watching
- Late night exercise
- Tobacco/alcohol, caffeine
```
85
Insomnia
Difficulty falling or staying asleep, early morning awakening
- Disturbed sleep despite adequate opportunity for sleep
Definition: 1+ of following:
- Difficulty initiating sle ep
- Difficult maintaining sleep
- Waking up too early
- Nonrestorative or poor-quality sleep
Daytime impairment
Types:
1. Acute (< 1 month)
2. Sub-actue (1-3 months)
3. Persistent (> 3 months)
86
Insomnia: associated impairments and risk factors
Associated impairments:
1. Increased:
- Pain
- Risk of depression
- Absenteeism
- Accidents
- Healthcare utilization
- Daytime fatigue
2. Decreased:
- Cognitive function
- Quality of life
- Job performance
Risk factors:
- Women 1.5 times more likely than men
- Advancing age: 65% of adults > 65 years
- Occupation (untraditional schedule)
- Co-morbidities (medical, psychiatric)
- Substance abuse
- Family history
87
Insomnia: etiology
Hyperarousal-->
- HPA axis activation
- Sympathetic activation
- Functional neuroanatomic changes
- Increased metabolic rate
- Cognitive arousal
- EEG arousal
- -> insomnia, daytime impairments
88
Comorbid insomnias
```
Inadequate sleep hygiene
Sleep apnea
Restless legs
Circadian rhythm disorders
Psychiatric conditions (major depression- REM sooner, less deep sleep)
Drugs and medications
GERD--> arousals/awakenings
COPD--> desaturation in REM sleep
```
89
Treatment strategies for depressives with insomnia
Monotherapy:
- Sedating antidepressant only for insomnia and MDD: trazodone, mirtazepine (have anticholingergic effects, weight gain)
Polytherapy:
- Antidepressant for MDD plus sedating agent (low dose sedating antidepressant, hypnotic)
Can use non-pharmacologic therapies for insomnia (therapy, behavioral therapy):
- Stimulus control therapy
- Relaxation therapies (biofeedback)
- Restrict time in bed (increase as sleep efficiency improves)
- Cognitive therapy (dispel unrealistic/exaggerated notions about sleep)
- Paradoxic intention (try to stay awake)
- Sleep hygiene education (promote habits helping sleep)
- Cognitive-behavioral therapy (combines sleep restriction, stimulus control, sleep hygiene education with cognitive tx)
90
Excessive daytime somnolence (EDS)
Sleepiness, weariness, fatigue, tendency to fall asleep at inappreopriate times
- Inadequate sleep hygiene
- Sleep deprivation
- Narcolepsy
- Obstructive sleep apnea syndrome
- Meds, neuro conditions
- Drugs
- Circadian rhythm disorders
Types of Sleep deprivations:
- Total= complete lack of sleep
- Partial= Reducation in length of sleep
- Acute= few nights (2 hours sleep reduction)
- Chronic= days, weeks, months, years (brain too tired to realize pathologically sleepiness)
Narcolepsy=
- Excessive daytime somnolence
- Cataplexy (weakness)
- Hypnagogic hallucinations
- Sleep paralysis (REM sleep invades wakefulness)
- Autonomic behavior
- Disrupted nocturnal sleep
Pharmacotherapy:
- Modafinil
- Methylphenidate (Ritalin)
- Dextramphetamine/methamphetamine
91
Parasomnias
Undesirable activity during sleep (walking, talking, eating)
- Sleepwalking
- Sleep talking
- Sleep terror
- Nightmares
- REM sleep behavior disorder
- Sleep bruxism (grinding teeth)
Wakefulness and REM sleep
- Can move in sleep
Wakefulness and Non-REM sleep
- Woken up (half awake, half asleep), can't appreciate what they're doing
92
Restless leg syndrome
Four diagnostic criteria:
- Urge to move legs (arms, body parts) with/without uncomfortable/unpleasant sensations
- Begins or worsens during periods of rest/inactivity
- Partially/totally relieved by movement
- Worse in evening/night
Ancillary features:
- Family history (1st degree relative= 3-5 time higher prevalence)
- Responds to dopaminergic tx (Pramipexole, Ropinorole)
- Periodic limb movements in sleep/wakefulness
- Variable clinical course
- Sleep disturbance
- Med eval/PE reveal no abnormalities
Pathophys:
- Dopamine dysfunction
- Iron deficiency (needed for dopamine synthesis)- supplement if serum ferritin below 50 mcg/L
93
Sleep apnea
Snoring, EDS, interrupted sleep
- Observed breathing pauses during sleep
- Choking/gasping during sleep
Symptoms: STOP
- Snoring
- Tiredness
- Observed stop in breathing
- increased blood Pressure
Risk factors: BANG
- BMI > 35
- Age > 50
- Neck circumference > 40 cm
- Gender= male
Consequences of OSA:
- Carotid atherosclerosis
- Cardiac arrhythmias
- Systemic HTN
- Pulmonary HTN
- MI
- Stroke
- Increased mortality
- Depression
- Impaired memory, cognitive function
Treatment:
- CPAP, bi-level positive airway pressure
- Oral appliances
- Meds
- Oxygen
- Surgical interventions
- Tracheotomy
94
Circadian rhythm sleep disorders
Desynchronization between timing of instrinsic clock and extrinsic light-day and social/activity cycles
- Leads to complaints of excessive sleepiness and insomnia
95
Delayed sleep phase syndrome
Evening insomnia, morning sleepiness
- Normal to go to sleep at late hour, can't go to bed earlier
Onset in adolescence or young adulthood
- Prevalence= 7-16%
- SDC patients = 5=10%
Etiology unclear, related to:
- Behavioral factors, Delayed awakening times
- Genetic vulnerability (FH in 40%)
- Dim light exposure in evening
Treatment: Phototherapy in morning to wake up
96
Advanced sleep phase syndrome
Complaints of evening sleepiness, morning insomnia
- Normal sleep at early (advanced) hour
- Persistant, stable
- Onset late adulthood
- Prevalence= 1% middle-aged adults
- Exaggeration of normal phase advance noted with aging
- Genetics= mutation in circadian clock
Treatment: phototherapy in evening to delay sleepiness
97
Etiology of addiction
5 levels of drug use:
1. Abstinence= no use or accidental use
2. Experimentation= no pattern of use, limited negative consequences
3. Recreational/social= drug-seeking to experience known effect, no pattern of use
4. Habituation= definite pattern of use indicating craving with no negative impact on life
5. Abuse= Continued use with negative impact on life
6. Addiction=
- Drug-seeking behavior
- Pattern of use with cravings
- Negative consequences
- Compulsion with loss of control over drug use
98
Dependence
“Physical dependence”
Defined by withdrawal symptoms
Not a direct correlate to drug abuse
Can be caused by a withdrawal of a number of nonpsychoactive drugs:
- Sympathetic vasoconstrictors or bronchodilators
- Organic nitrate vasodilators
99
Addiction
```
"Psychological dependence”
Behavioral pattern of compulsive drug abuse:
- Overwhelming involvement with the drug
- Securing its supply
- Harm to user and society
```
All addictive drugs induce strong feelings of euphoria and reward.
Consists of compulsive, relapsing drug use despite negative consequences.
Triggered by cravings in response to contextual cues.
* * Addiction to drugs and alcohol is a disease!, no a matter of willpower
- Disease model= organ (brain) has defect (neurobiological changes) that produce signs and symptoms (craving) of a disease
100
Causes of addiction
1. Hereditary
2. Stress (corticotrophin-releasing factor (CRF)
3. Reward system (DA)
4. Memory system (Glutamate)
101
Anatomy of addiction
ALL addictive drugs activate mesolimbic DA system:
- Originates in the VTA and projects to the nucleus accumbens, amygdala, hippocampus and prefrontal cortex
Physiology of addictive drug target:
1. Class I-GPCRs: Gi/o coupled GPCRs
- include: Opioids, Cannabinoids, GHB, LSD
2. Class II-Ionotropic receptors or ion channels:
- Include: Nicotine, Alcohol, Benzodiazepines, Phencyclidine, ketamine
3. Class III-Dopamine Transporters:
- include: Cocaine, Amphetamine, Ecstasy
102
Tolerance
Escalation in dose necessary to maintain comparable effect.
- May be caused by a shorter duration of action in target system (Pharmacokinetic Tolerance)
- May be caused by a decrease in receptor number or function (Pharmacodynamic Tolerance)
- GPCR desensitization through β-arrestin leads to an increase in dependence
Causes:
1. PK changes (enzyme induction= barbituates)
2. Pharmacodynamic changes (receptor # changes= morphine)
3. Immunological changes (Antibody formation= insulin)
4. Behavioral changes (compensation- alcohol)
5. Combination of any/all of the above
Behavioral tolerance: compensate for drug's effects
Functional tolerance= due to compensatory changes in receptors, effector enzymes, membrane actions
Withdrawal= adaptive changes become apparent once drug exposure terminated
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Physical dependence
Occurence of withdrawal syndrome= physical dependence
Withdrawal syndrome:
- Altered physiological state caused by repeated administration of drug or substance which demands continual use to prevent physical dependence
Degree of physical dependence determined by:
1. Structure of the drug:
- Alcohol, barbiturates = severe
- Narcotic analgesics = moderate
- Stimulants = mild
2. Dose
3. Time
Cross-dependence is based on similar pharmacological effects
- Intensity of withdrawal is a reflection of the degree of physical dependence
- Typically, patient requires 1-3 weeks of drug reduction following long-term, high dose therapy to observe little or no withdrawal symptoms
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Opioid Abuse
Mu most commonly abused= morphine, heroin, codeine, oxycodone
- Withdrawal symptoms may include (severe) intense dysphoria, nausea, muscle aches, lacrimation, sweating, diarrhea, yawning, and fever.
Addiction is rare as an analgesic, but VERY ADDICTIVE as a recreational drug.
Treatment: Naloxone—reverses effects of morphine or heroin within minutes (promotes an acute withdrawal syndrome).
Treatment of long-term opioid addiction: long-lasting opioid (methadone, buprenorphine) is often substituted for a shorter acting opioid (heroin)
- All inhibit adenylyl cyclase (inhibitory pathway)
- Differing effects based on local distribution, dimerization and/or neuronal specificity
105
Effects of Mu Opioids
Activates K+ channels--> inhibits GABA neurons (inhibitory neurons)
GABA:
- GABAergic inhibition
THC:
- Gi/o GPCR
- Inhibit activation
GHB
- Gi/o GPCR
- Targets GABA receptors
106
Opioid addiction
Physical effects:
- Depressed mental status
- Depressed respiratory rate
- Miosis
Withdrawal:
- Withdrawal symptoms typically begin 8-10 hrs after last dose
- Non-life threatening (except in neonates which are prone to seizures)
Signs and symptoms
- Anxiety, lacrimation, rhinorrhea, yawning sweating, insomnia, weakness, chills, nausea, vomiting, hyperthermia (mild), hypertension (mild), piloerection, mydriasis (enlarged pupils)
Treatment:
- Supportive
- Referral to a drug detox center (methadone, clonidine)
107
Sedative-Hypnotic Toxicity Addiction
Sedative-Hypnotic toxicity:
- ETOH
- Benzodiazepines
- Barbituates
- GHB (liquid ecstasy, liquid X, scoop, easy lay)
- Chloral hydrate (pediatric use); alcohol potentiates effects
MOA:
- Enhance GABA activity--> enhances Cl- influx into post-synaptic cell--> stops depolarization (depresses neuron activity)
Toxicity:
- Depressed mental status, depressed respiratory rate, lethargy, coma, hypothermia
* * GHB: May also initially cause agitation, combativeness, seizure
- Can cause bradycardia, rapid reawakening, amnesia
* * Chloral hydrate can also cause dysrhythmias
Withdrawal:
- Benzodiazepines: Anxiety, tremors, nausea, vomiting, insomnia, seizures (day 8 or 9)
- Alcohol: Motor agitation, anxiety, insomnia, seizures (Rum fit)
* * Under sever conditions: hallucinations, disorientation, tachycardia, hypertension, hyperthermia
Treatment:
- Supportive (prevent seizures, delirium, replace electrolytes & thiamine)
- Urine alkalinization enhances the elimination of Phenobarbital
- Consider beta-blockers to reverse chloral hydrate induced dysrhythmias
- Consider flumazenil (Romazicon) for the treatment of acute benzodiazepine toxicity (iatrogenic)
- Severe withdrawal: Hospital admission, Drug substitution and taper
108
Receptor-mediated drugs
Cannabinoids
Gamma-hydroxybutyric Acid (GHB)
LSD
109
Drugs affecting ionotropic receptors
Nicotine
Benzodiazepines
Alcohol
** Treatment of ethanol withdrawal relies on Benzodiazepines
110
Drugs binding transporters: Cocaine
Inhibit voltage-gated sodium channels (peripheral nervous system)
- Block Dopamine transporters (Central nervous system)
- Block reuptake of DA, NE, serotonin (cocaine, ecstasy, methamphetamine)
Can be snorted, smoked, injected
- Speedball= cocaine + heroin
Effects:
- Loss of appetite, hyperactive, sleep little
- Leads to acute increase in MAP, tachycardia, and often ventricular arrhythmias
- Increases risk of intracranial hemorrhage, ischemic stroke, MI, and seizures.
- Blocks coronary arteries (vasospasm, platelet aggregation)
- Euphoria, agitation, combativeness, seizures
- Strokes
- Rhabdomyolysis, renal failure
- Hyperthermia, dehydration
- Diaphoresis
111
Treatment of opioid overdose
ABCs, Supportive care
Antidote= naloxone (Narcan)
- Warning= may induce opioid withdrawal
- t1/2 is 30-45 minutes which is shorter than t1/2 of most opioids
Treatment:
- Supportive care (Narcan, methadone, rehab)
- Refer to specialist care
112
Ecstasy
Block reuptake of DA, NE, serotonin
- Produces vasoconstriction and local anesthetic effects
- Structurally similar to amphetamines, mescaline
- Ingested as tablets
- Commonly abused at Rave parties
Causes:
- Euphoria, hallucinations, jaw tension, bruxism, hyponatremia
113
Methamphetamine
Long-acting cocaine
| - Easy to make
114
Treatment for Stimulant overdose
Supportive:
- Hyperthermia: ice water over body, fans, pharmacologic sedation
- Hypertension: sodium nitroprusside, phentolamine
- Seizures: benzos, phenobarbital
- Hyponatremia from ecstasy: hypertonic saline if seizures, coma, neurologic defects
115
Hallucinogens
LSD:
- Euphoria, panic attacks, paranoia, psychotic reactions
Phencyclidine (PCP, angel dust)- structurally related to ketamine
- Clinical effects similar to stimulants
Marijuana (smoked or ingested):
- Drowsiness, euphoria, paranoia, distortion of time and space
Treatment: supportive
116
Inhalants
Hydrocarbons (spray paint, hairspray, paint thinner)
- Euphoria, dysrhythmias
- Chronic abuse of toluene: metabolic acidosis, hypokalemia, hypochloremia, severe weakness
Nitrous oxide (whip-its)
- Transient euphoria and CNS depression
- Chronic abuse: polyneuropathy, weakness, megaloblastic anemia
Treatment:
- Supportive
- Consider the use of beta-blockers when treating hydrocarbon induced dysrhythmias
117
PK of EtOH
Lipophilic
Rapidly absorbed by stomach and SI
- Quicker from empty stomach than full stomach
Metabolized via dehydrogenase system: ALDH (buildup of acetaldehyde)
```
Elimination:
- Nondrinkers: 15-20 mg/dL/hr
- Chronic drinkers: 25-30 mg/dL/hr
Tissue levels parallel blood levels
ETOH bloods levels: measured in mg/dL
- 80 mg/dL (0.08%) legal driving limit in many states
```
118
Pharmacodynamics of EtOH
1. ETOH dissolves into lipid membranes of CNS
- Disturbs nerve function (sedative hypnotic)
2. Binds to the subunit of GABA complex
- Augments GABA activity
3. Decreased activity of glutamate on excitatory glutamate receptors
Production of NADH favors lipid metabolism
Physiologic effects:
- Dilates blood vessels
- Causes acid secretion in the stomach at low concentrations
- Irritates gastric mucosa at high concentrations
- Reduces ADH secretion (urination increases)
- Has antiseptic action
119
CNS effects of EtOH
Low concentrations of ETOH (.02%):
- Impaired sensory function and muscle coordination
- Reduced memory and concentration
- Faulty judgment
- Euphoria, relaxation, disinhibition
- Increased perceptions of own activities with decreased performance
Marked mental impairment (driving a car) occurs at .05% - .1%
Death occurs at levels > 400 mg/dL
Chronic abuse:
1. Tolerance develops
2. Thiamine deficiency:
- Wernicke’s encephalopathy: depressed mental status, ataxia, intranuclear ophthalmoplegia/nystagmus
- Korsakoff’s psychosis/syndrome: depressed mental status, short-term memory loss (confabulation)
3. Physical dependence
- ETOH withdrawal syndrome
4. Cerebral atrophy
- Subdural hematoma
120
Other systemic effects of chronic EtOH use
Liver:
1. Cirrhosis
2. Drug metabolizing enzymes (p450)
- At first are induced
- Later on, liver damage reduces drug metabolizing capacity
Stomach:
1. Acid secretion stimulated by low ETOH concentrations
2. Mucosal damage with bleeding with chronic ETOH use and high ETOH concentrations
Cardiovascular system:
1. Dilates blood vessels
2. Small amounts (1-2 glasses of wine/day) reduces risk of cardiovascular complications
3. Chronic use of high doses leads to myocardial damage
Kidney:
- Diuresis due to reduced ADH secretion
Pregnancy:
- ETOH consumed in moderate to large amounts during pregnancy can cause fetal alcohol syndrome
- CNS impairment, facial abnormalities
- Retarted growth of the newborn
Pancreatitis
Sexual performance: dose dependent:
- Low dose remove inhibitions
- Higher doses increases the desire but decreases performance for both men and women
121
EtOH and drug interactions
ETOH can interact with drugs in different ways:
1. Increases the actions of some drugs
- Compete for same enzyme
- Reduces metabolism of the drug due to liver damage
2. Can irritate the stomach
- Be cautious when giving NSAIDS and ASA to chronic ETOH abusers
3. ETOH and Tylenol (APAP) can cause liver damage
- Toxic metabolite
122
Therapeutic uses of EtOH
Used on the skin as an anti-infective agent
Dehydrated ETOH can be injected close to pain conducting nerves, which are killed
- Trigeminal neuralgia
Therapy for ethylene glycol and methanol poisoning (toxic alcohols)
- poisoning= resembles EtOH intoxication, but no EtOH in blood tests
- metabolism--> severe metabolic acidosis
- Ethylene glycol--> renal failure
- Methanol--> blindness
* * Must block metabolism (which causes buildup of acidic byproducts)
- Give alcohol infusion to block metabolism and buildup of toxic metabolites
- Now give med to block Alcohol Dehydrogenase
123
Management of Acute EtOH intoxication
Supportive
Correct hypoglycemia & ketosis - glucose
Give thiamine (100 mg IV, IM, or PO), K+, Mg+2, folate, multivitamins
Rule out trauma, especially head trauma
124
Management of EtOH withdrawal
Signs/symptoms:
- Agitation, anxiety, insomnia, seizures
- Supportive, drug substitution
Drug substitution: open Cl- channels (like EtOH)
- Benzos
- Barbituates
* * Do not stop abruptly (withdrawal)
- Supply thiamine
- Drug substitution and taper
Treatment for alcoholism: Disulfiram (Antabuse)
- Blocks aldehyde dehydrogenase
- Acetaldehyde accumulates causing: Flush, anxiety, headache, palpitations, tachycardia
