Exam 2 Week 2

Question 1

Define

• •Patients exhibit gross disturbances in their comprehension of reality, as evidenced by
• False perceptions (hallucinations) and False beliefs (delusions).

**Explain biological basis

Answer 1

Psychoses

Dopamine hypothesis:

• •Abnormalities in DA neurotransmission in mesolimbic and mesocortical neuronal pathways

Supported by:

• •Drugs which block D2 receptors improve disorder
• •Affinity at D2 receptors correlated with clinical efficacy
• •Drugs which increase DA release (amphetamine) or block reuptake (cocaine) induce psychotic behavior.

Problems with hypothesis:

• •Receptors blocked immediately, psychosis disappears slowly

Question 2

Explain dopamine tracts and psychoses (5)

Answer 2

Question 3

Causes of acute psychosis (6)

Answer 3

•Drug abuse and withdrawal

• –Phencyclidine / hallucinogens
• –Amphetamines, cocaine
• –Alcohol withdrawal
• –Sedative-hypnotic withdrawal

•Toxic Agents

• –Heavy metals
• –Digitalis toxicity
• –L-Dopa

•Metabolic Causes

• –Hypoglycemia
• –Acute intermittent porphyria
• –Cushing’s syndrome
• –Hypo/hypercalcemia
• –Hypo/hyperthyroidism

•Nutritional causes

• –Thiamine deficiency

•Niacin deficiency

• –Vitamin B12 deficiency

•Neurological causes

• –Stroke
• –Brain tumor
• –Early Alzheimer’s or Pick’s disease
• –Hypoxic encephalopathy

Question 4

Schizoprenia

• Positive vs Negative symptoms

Answer 4

Positive symptoms:

• •Probably result from excessive neuronal activity in mesolimbic neuronal pathways; respond well to neuroleptics (antipsychotic drugs)

Negative symptoms:

• •Probably result from insufficient activity in mesocortical neuronal pathways
• •More difficult to treat
  
  • –Often persist after positive symptoms resolve and are associated with a poor prognosis
  • –Do not respond as well to neuroleptics; atypical antipsychotics may be more effective

Question 5

Antipsychotics MoA

• typical vs atypical
  
  • which block serotonin better?
  • whcih block dopamine better
  • which has more extrepyramidal side effects?
  • which treat negative symptoms
  • examples of each

Answer 5

•Mechanism of action:

• –Competitive blockade of DA and 5-HT receptors.
• Typical Antipsychotics: Affinity: D2 >5-HT2 receptors:
• Atypical Antipsychotics: Affinity for 5-HT2 > D2 receptors:
• ·Selectivity for mesolimbic over nigro-striatal regions in their effects on the DA system
• ·More likely to be effective in drug-refractory patients
• •Likely to improve positive & negative symptoms
• Less extrapyramidal symptoms with atypicals

Question 6

Adverse effects of antipsychotics are as a result of? (3)

Answer 6

–Adverse effects are attributed to blockade of the following receptors:

• •a1-adrenergic
• •Histamine H1
• •Muscarinic

Question 7

pharmacokinetics of antipsychotics

• absorption
• administration
• metabolism
• half life
• excretion

Answer 7

• •Absorbed erratically from GI tract
• •Parenteral administration of some antipsychotics available
• •Metabolized to active/inactive metabolites in liver
• •t1/2 = 20-40 hr
• •Renal excretion of glucuronide conjugates

Question 8

CNS actions of antipsychotics

Answer 8

• –Positive symptoms subside in 1-3 weeks
• –Spontaneous movement and complex behavior suppressed
• –Less agitation
• –Patient easily aroused, capable of answering direct questions
• –Intact intellectual function
• –Withdrawn patients become more responsive
• –Impulsive behavior decreases
• –Hallucinations, delusions and incoherent thoughts decrease

Question 9

• Actions of antipsychotics on dopamine receptors
• Dopaminergic neurptransmission
  
  • presynaptic vs postsynaptic effect

Answer 9

Actions at dopamine receptors

• •D2 receptors found pre/postsynaptically
• •D2 receptors coupled to Gi or Go
• •Blockade of D2 receptors results in (acute effects/presynaptic block)
  
  • –­DA synthesis and release
  • –­cAMP
  • –¯K+ currents

Dopaminergic Neurotransmission

•Presynaptic Effect

• –Short Term Treatment: Activated neurons
• –Long Term Treatment: Inactivated neurons

•Postsynaptic Effect

• –Short Term Treatment: Receptor Blockade
• –Long Term Treatment: Receptor Supersensitivity

Question 10

Describe time course of therapy response (antipsychotics)

• 1-3 days
• 1-2 weeks
• 3-6 weeks

Answer 10

Question 11

Antipsychotics specific drug info/use

• Haloperidol
  
  • use
• Chlorpromazine
  
  • contraindication
  • use
  • deposit where
• Thioridazine
  
  • deposit where
• what cant be an antiemetic (2)
• prochlorperazine (use)
• scopolamine (use)

Answer 11

•Haloperidol

• –treatment of Gilles de la Tourette’s syndrome/Huntington’s Disease

•Chlorpromazine

• –contraindicated in patients with seizures, lowers threshold
• –used for intractable hiccough, mechanism unknown
• –deposits in the lens and cornea common

•Thioridazine

• –deposits in retina at higher doses

•All except aripiprazole and thioridazine can be used as anti-emetics

• –block D2 receptors in CTZ

•Prochlorperazine

• –useful in treatment of “drug-induced” nausea (chemotherapy)

•Scopolamine

• –drug of choice for motion sickness

Question 12

Describe

Dopamine; extrapyramidal side effects

Answer 12

Question 13

Describe adverse effect

Answer 13

Dopamine; tardive dyskinesia

Question 14

Identify the adverse effect

Answer 14

Dopamine: Neuroleptic Malignant Syndrome

Question 15

Dopamine; prolactin

Answer 15

Question 16

adverse effect

Answer 16

Cholinergic (M1):

Question 17

adrenergic vs histamine adverse effect of antipsychotics

Answer 17

Question 18

Metabolic side effects of antipsychotics

• **Result in what?

Answer 18

Metabolic side effects - Weight gain

• •More common with atypical, though can occur with all
• •Substantial, often reversible
• •Sedation, lack of movement
• •Endocrinological changes

•Can result in

• –New Onset or Worsening of Type II Diabetes
• –Hypertension
• –Hyperlipidemia

Question 19

Other adverse effects of antpsychotics

• WBC values
• what tremor?
• cardiac effects

Answer 19

•Leukopenia, agranulocytosis:

• –Clozapine (1-2% of patients) rare with other antipsychotics
• –Potentially fatal
• –Occurs between 6-18 weeks of treatment
• •Regular monitoring of blood cell counts should be conducted.

•Perioral tremor – “rabbit syndrome”:

• –involuntary, fine, rhythmic motions of the mouth along a vertical plane, without involvement of the tongue.
• –Rare, tends to occur following prolonged antipsychotic use (years)
• –Can treat with anticholinergic antiparkinson drugs

•Cardiac Effects:

• –Thioridazine leads to minor T wave abnormalities in pharmacological doses
  
  • •Overdose associated with major ventricular arrhythmias
• –Ziprasidone QT prolongation

Question 20

Contraindication and drug interactions of antipsychosis

Answer 20

Pregnant and nursing mothers

•Drug Interactions

• –Central depressants and opioid analgesics
• –Amphetamines antagonize antipsychotic effects
• –Centrally acting anticholinergics may worsen tardive dyskinesia
• –SSRI’s may worsen extrapyramidal symptoms
• –Most antipsychotic agents can add to hypotensive effect of antihypertensives

Question 21

List DSM 5 psychtic disorders

Answer 21

DSM-5

• •Brief Psychotic Disorder
• •Schizophreniform Disorder
• •Schizophrenia
• •Schizoaffective Disorder
• •Delusional Disorder
• •*Schizotypal Personality Disorder
• Psychotic Disorder due to a General Medical Condition
• Psychotic Disorder due to a Substance

Question 22

Schizoprenia

• Important epidemiology fact

Answer 22

Schizophrenia has a lifetime prevalence of 1.1%

Question 23

Schizophrenia

• Etiology
• Developmental and psychological
• Genetic
  
  • risk of having it if twin has it
  • both parents
  • one parent or one siibling

Answer 23

• Etiology
  
  • Multiple causes
• Development and psychological - many therioes
  
  • •Babies born in late winter and early spring have a greater risk
    
    • •True for northern and southern hemispheres
    • •Prenatal exposure to a virus suspected
  • •Prenatal malnutrition and low birth weight
  • •Fetal hypoxia and preeclampsia
  • •Theories of the “schizophrenogenic mother” and double-bind communications (no win situations) have been disproven
  • •Families with high levels of “expressed emotions” are associated with relapse of symptoms but are not causal for the illness itself.
• Genetic; familial transmission
  
  • •Risk of disease in 1st degree relative ~10%
  • •Identical twins – 40-65% risk
  • •Both parents with schizophrenia
    
    • •Risk 40-50%
  • •One parent or one sibling
    
    • •Risk 5-20%

Question 24

Schizoprenia and genetics

• locus and chromosome number
• expression of?

Answer 24

• The most consistent genetic relationship at a population level is associated with the MHC locus on chromosome 6.
• In 2016, researchers at Harvard and Boston Children’s Hospital discovered that
• •Many structurally diverse alleles of complement component 4 (CD4) genes which promote widely varying expression of C4A and C4B
• •Expression of C4A in brain is directly correlated with risk for schizophrenia
• •In the brain, complement receptors are expressed primarily by microglia, the phagocytic immune cells of the central nervous system.
• •Possible that excessive or inappropriate synaptic pruning by microglia during adolescence and early adulthood could explain development of disease in some individuals

Question 25

Scizophrenia

• what deletion syndrome?

Answer 25

22q11 deletion syndrome – “DiGeorge Syndrome” or velo-cardio-facial syndrome

• •Only recurrent, clinically recognizable, genetic cause of schizophrenia with currently available laboratory testing
  
  • •~90% spontaneous mutation, 10% inherited
• •1% of patients with schizophrenia have this deletion
• •20-30% of 22q11 patients develop schizophrenia or schizoaffective disorder

Remember: CATCH 22

• ØCardiac abnormality (especially tetralogy of Fallot)
• ØAbnormal facies
• ØThymic aplasia
• ØCleft palate
• ØHypocalcemia/ Hypoparathyroidism

Symptoms of schizophrenia are indistinguishable though 22q11 patients are more likely to have intellectual impairment

Question 26

Schizophrenia

• what neurotransmitter system abnormalities

Answer 26

•Dopamine (DA)

• •Higher than normal number of D-2 receptors
• •PET scans show elevated activity of DA neurons in limbic system which correlate with positive symptoms
• •PET scans show diminished activity of DA neurons in frontal and prefrontal areas with correlate with negative symptoms

•Glutamate (Glu)

• •Decreased in schizophrenia
  
  • •Glu receptor antagonists (ie, PCP) cause schizophrenia-like psychotic symptoms
• •Linked to cognitive deficits in schizophrenia

Question 27

4 dopaminergic pathways targeted in schizophrenia

• origin

Answer 27

• •Nigrostriatal
  
  • •Originates in substantia nigra and projects to corpus striatum
    
    • •EPS and movement-related side-effects of antipsychotics
• •Mesolimbic
  
  • •Originates in VTA and projects to limbic areas
  • •Positive symptoms of schizophrenia
• •Mesocortical
  
  • •Originates in VTA and projects to prefrontal and frontal areas
  • •Negative symptoms of schizophrenia
• •Tuboinfundibular
  
  • •Originates in hypothalamus and projects to Pituitary
    
    • •DA secretion tonic inhibitory effect on prolactin release
  • •Hyperprolactinemia with antipsychotics

Question 28

Schizophrenia

• Structural/functional abnormalities

Answer 28

•MRI and PET

• •Over-activity in limbic areas – positive symptoms
• •Under-activity in frontal lobes – negative symptoms
• •Decreased number of synapses
• •Enlargement of the lateral ventricles
  
  • Loss of brain mass due to

Question 29

DSM 5 criteria of schizophrenia

Answer 29

•A. Two (or more) of the following, each present for a significant portion of time during a 1-month period. At least one of these must be (1), (2), or (3):

• •Delusions
• •Hallucinations
• •Disorganized speech
• •Grossly disorganized behavior or abnormal motor behavior to include catatonia
• •Negative symptoms
• B. For a significant portion of time level of functioning in one or more life areas is markedly below level prior to disease onset.
• C. Continuous signs of disturbance for 6 months or more.

Question 30

Define the following symptom of schizophrenia and types (6)

• Fixed, false beliefs

Answer 30

Delusions; Abnormality of Thought Content

• Delusions are“fixed, false beliefs”; cannot be changed by logical reasoning and are inconsistent with beliefs typical for the patient’s cultural group (though they may have cultural content); may be pervasive to patient’s life or may be circumscribed and difficult to locate on typical interview

Types of delusions

• •Persecution (very common) – others are trying to harm, spy on, interfere with affairs of patient
• •Delusions of reference – random events have special meaning to patient
• •Delusions of influence – belief patient’s thoughts are controlled by outside sources
• •Thought broadcasting – patient’s thoughts are being sent directly to an outside source
• •Grandiose – patients belief they are elevated in importance; more common in psychotic mania
• •Somatic – belief the body has been manipulated in some way; device inserted, body controlled by others, etc.

Question 31

Define symptom of schizophrenia

• Perceptual disturbance; sensory experiences that occur without corresponding environmental stimuli

Answer 31

Hallucinations

Hallucinatory experiences are common

• •National Comorbidity Survey conducted early 1990s found 28.4% of individuals endorsed one or more
• •Large scale study in Europe in 2000 found 38.7% endorsed

Subtypes:

• •Auditory hallucinations – range from indistinct/muffled sounds to complex and multiple voices
  
  • •Command hallucinations – voice(s) tell patient to perform an action; may be so persistent that they are difficult to resist
• •Visual hallucinations – occur in schizophrenia but are more common in “organic” (non-psychiatric) disorders such as delirium
• •Other hallucinations – tactile, gustatory, olfactory; more common in non-psychiatric illnesses but in schizophrenia often connected to delusional system

Question 32

Schizophrenia Spectrum Disorders

• How does disorganized speech manifest?

Answer 32

Disorganized speech can manifest as:

• •Loosening of associations – connections among ideas become absent or obscure
• •Neologisms – creation of words
• •Verbigerations – persistent repetition of words/phrases
• •Echolalia – repetition of word or phrase of examiner
• •Mutism – functional inhibition of speech
• •Word salad – unintelligible mixture of random words
• •Thought blocking – sudden interruption in speech (and presumably flow of thought)

Question 33

Identify negative symptoms of schizophrenia (5)

Answer 33

• •Affect – flattened, blunted, inappropriate; confounded by Parkinsonian effect of drugs
• •Sense of self – lost perception of separateness from others/community
• •Avolition – difficulty initiating and maintaining goal-directed activities
• •Poverty of thought
• •Poverty of speech

Question 34

Cognitive symptoms of schizophrenia

• largest contributor to what?

Answer 34

•Cognitive symptoms – over time largest contributor to day-to-day dysfunction

• •Impaired executive functioning – planning, decision-making, mental flexibility
• •Impaired attention and memory
  
  • •Working memory
• •Impaired learning
  
  • •Loss of educational and occupational progress

Question 35

Schizophrenia

• Clinical Course
• Onset - bimodal
  *

Answer 35

Clinical course - highly variable

• •Prodromal phase vs not
• •Remission (residual phase) vs none
• •Deteriorating course vs Full remission/recovery (rare)

Onset - bimodal

• •Late teens to early 20s
  
  • •Earlier in men than women
  • •Multiple stresses including separation from parents, transition from education to work settings, marriage, children, etc.
  • •Stage of neurodevelopment
• •Second smaller peak in late 40s particularly for women

Question 36

Schizophrenia

• precipitain events?
• initial presentation
  
  • prognostic significance

Answer 36

• Like many illnesses, schizophrenia may have precipitating event (e.g., social or economic stress, trauma, drug use, etc.)
• Initial presentation – variable and has prognostic significance
• •Abrupt onset – develops over 1-2 days in response to stressor
  
  • •GOOD prognosis as most resolve quickly
• •Insidious prodromal phase – onset over months with social withdrawal, peculiar behavior, neglect of hygiene, blunted affect, odd beliefs, apathy
  
  • •POOR prognosis

Question 37

Schizophrenia - prognostic variables

• Poor vs good

Answer 37

• •POOR – predominance of negative symptoms, insidious onset, poor cognitive performance on testing, abnormalities on CT, lack of mood symptoms, childhood onset
• •GOOD – predominance of positive symptoms, acute onset, female, good premorbid functioning, presence of mood symptoms, family history of mood disorders

Question 38

Schizoaffective disorder - DSM 5 criteria (4)

Answer 38

• •A. An uninterrupted period of illness during which there is a major mood episode (major depressive or manic) concurrent with Criterion A of schizophrenia
• •B. Delusions or hallucinations for 2 or more weeks in the absence of a major mood episode (depressive or manic) during the lifetime of the illness
• •C. Symptoms that meet criteria for a mood episode are present for a majority of the total duration of the active and residual portions of the illness.
• •D. The disturbance is not attributable to the effects of a substance or another medical condition.

Specify type: 
Bipolar Type: if the disturbance includes a Manic or a Mixed Episode (or a Manic or a Mixed Episode and Major Depressive Episodes) 
Depressive Type: if the disturbance only includes Major Depressive Episodes

Question 39

Differential diagnoses of schizoaffective disorders

• bipolar I vs major depressive disorder
• schizoaffective vs mood disorder

Answer 39

Bipolar I Disorder with psychotic features

• •Manic episodes – Many individuals with severe mania experience psychotic symptoms including AVHs, delusions, bizarre behaviors, etc. Psychotic features are typically mood congruent. Careful history will reveal additional mood symptoms. Behavioral observations and MSE will also likely reveal differentiating factors.
• •Major depressive episodes – Psychotic features are typically mood congruent. Depressive features (flat affect, anhedonia, psychomotor retardation, etc.) may resemble negative symptoms of schizophrenia.
• Major Depressive Disorder with psychotic features

•Major depressive episodes – Psychotic features are typically mood congruent. Depressive features (flat affect, anhedonia, psychomotor retardation, etc.) may resemble negative symptoms of schizophrenia.

Schizoaffective Disorder vs Mood Disorder with psychotic features

• •Schizoaffective disorder requires full 2 weeks or more during course of lifetime of the illness with psychotic symptoms and absence of major mood symptoms
  
  • •Sets Schizoaffective apart from Mood Disorder with psychotic features
• •Schizoaffective requires criteria for a mood episode are present for a majority of the total duration of the active and residual portions of the illness
  • •Sets Schizoaffective apart from Schizophrenia

Question 40

Schizophrenia

group vs individual therapy

community treatment (4)

Answer 40

Group vs individual therapy

• •Group Therapy – a mainstay of treatment in both inpatient and outpatient settings; used in conjunction with medications
  
  • •Communication
  • •Symptom alleviation
  • •Social skills
• •Individual Therapy – focus on supportive therapy; attempts to build close therapeutic relationships and/or nondirective techniques cause anxiety (particularly in paranoid patients)
  
  • •Education, problem solving, reasonable expectations, crisis intervention, limit setting, illness self-management

Community treatment (4)

• •Case management
  
  • •Help patient access community resources
  • •Treatment planning and monitoring
• •Intensive case management (ACT, MHICM, etc.)
  
  • •Have fewer clients and see patient multiple times per week
  • •Oversee med administration including transporting to medical appointments
  • •Assist with finances – bill paying, insurance, housing issues, etc.
• •Advocacy - NAMI
• •Vocational training/rehabilitation

Question 41

Other schizophrenia spectrum disorders (3)

Answer 41

• •Brief psychotic disorder – only requires 1 symptom (hallucinations, delusions, etc.) and duration is between 1 day and 1 month.
  
  • •Return to premorbid functioning is required (given provisional specifier while symptomatic)
• •Schizophreniform disorder – all same criteria as schizophrenia but duration is 1 month to 6 months.
• •Delusional Disorder – 1 or more delusions in setting of otherwise retained functional behavior
  
  • •Erotomanic, grandiose, jealous, persecutory, somatic, mixed, unspecified

Question 42

identify delusional disorder

• •Delusional belief that 1 or more individuals (or pets) in patient’s life has been replaced by identical-looking imposters
• •Can be isolated to delusion only or occur as part of schizophrenia
• •Can develop following brain injury or as part of neurodegenerative process
• •May develop in some as “mirror-image” of prosopagnosia (inability to recognize faces)
  
  • •Visual ability to recognize faces in intact but unconscious feeling of familiarity is impaired

Answer 42

•Capgras Syndrome

Question 43

Identify delusional disorder

• •Delusional belief that patient is infested with parasites
• •Sometimes accompanied by “matchbox sign”
  
  • •Collection of fibers, hair, etc. that patient believes is/was under their skin

Answer 43

•Delusional parasitosis (aka, Ekbom’s Disease or Morgellon’s Disease)

• •Morgellon’s may be subtype in which patient beliefs that “thread-like fibers” under the skin

Question 44

Treatment of schizophrenia spectrum disorders

*

Answer 44

• Treatment takes recovery-oriented approach – goal is to achieve optimum functioning in community with as much autonomy as possible
• Approximately 90% of individuals may live outside of hospital setting the majority of the time
• •Require antipsychotic medications
• •1st generation versus 2nd generation
• •Long acting depot

•Hospitalization – utilized for risk of SI/HI, command hallucinations of threatening nature with belief patient may act on them, extreme paranoia, significant confusion with deterioration in functioning

Question 45

Classification of somatic symptom and related disorders

Answer 45

1. Somatic Symptom Disorder
2. Illness Anxiety Disorder
3. Conversion Disorder (Functional neurological symptom disorder)
4. Psychological Factors affecting other medical conditions
5. Factitious Disorder (self vs by proxy)
6. Malingering (not in DSM5 but part of the differential at times)
7. Other specified somatic symptoms and related disorder (doesn’t meet full critieria)
8. Unspecified Somatic Symptom and Related Disorder (doesn’t fit another disorder)

Question 46

Identify disorder

• Previously known as ‘hypochondriasis’
• One or more somatic symptoms that are distressing or significantly disrupt ones life
• Excessive thoughts/feelings or behaviors related to one of the following:
  
  • 1. Persistent thoughts about the seriousness of the symptoms
  • 2. High levels of anxiety re health or symptoms
  • 3. Excessive time and energy devoted to these symptoms/health concerns
• Lasts more than 6 months
• May focus on pain, symptoms may change over time but still with a focus on health concerns

Answer 46

Somatic Symptom Disorder

• In general, patients with somatic symptom disorder believe they have a serious illness that has not yet been detected and it is difficult to persuade them otherwise despite lab tests, imaging etc. And yet their beliefs do not meet criteria for delusional beliefs/psychosis.
• Estimates vary, but believed to be 4-15% of general medical clinic populations. (Believed to occur in 3% of medical students in the first 2 years of medical school)
• Men and women equally affected, no differences in educational or socioeconomic backgrounds. Usually has onset before age 30
• These can be the “difficult” patients with low tolerance for pain/bodily sensations.
• Some cases could be understood as needing to be in the sick role that may allow an escape from difficult problems
• Usually associated with depression and anxiety symptoms
• Some of these patients may just be having a somatic presentation of a major depression, thus depression should be aggressively treated in such patients
• Panic disorder can present with multiple bodily symptoms which are episodic (heart racing, chest tightness, SOB, numbness and tingling of limbs etc) so need to r/o
• Different than Illness Anxiety Disorder which is a fear they may have a disease rather than a focus on many symptoms and convinced they have a disease

Question 47

Identify condition

• A somatic disorder for those preoccupied with being sick or developing a sickness but without many or any somatic symptoms, (unlike somatic symptom disorder where the patient has multiple symptoms)
• Prevalence of 4-15% of general medical clinic population
• No known differences in races, gender, socioeconomic status, education level or marital status
• Fear of illness may be viewed as a request to be in the sick role, similar to somatic symptom disorder

Answer 47

Ilness Anxiety Disorder

• Preoccupation with having or acquiring a serious illness
• None or only few mild somatic symptoms. If there is a family history of an illness, the preoccupation is clearly excessive or disproportionate
• High levels of anxiety re health and easily alarmed re health status
• Frequently checks body for signs of illness
• Preoccupied re health for at least 6 months
• The illness related concerns are not better explained by another mental disorder such as somatic symptoms disorder, panic disorder, body dysmorphic disorder, OCD, delusional disorder somatic type, depression or other anxiety disorder
• Differentiated into care seeking type vs care avoiding type
• May be dismissed as chronic complainers and may not receive medical work up
• In other cases, invasive diagnostic and therapeutic procedures may be performed without indication, putting patients at risk
• Pharmacotherapy may be indicated for anxiety as well as therapy to help support the patient with their concerns, and perhaps focus on other areas in the patient’s life that may be causing anxiety

Question 48

Identify condition

• An unconscious process (pt not able to control)
• Neurologic symptoms - motor or sensory (most common are seizure like symptoms, paralysis, blindness and mutism, but can also numbness, weakness, deafness etc ) without “organic” cause
• Example: pt with thrashing seizure like movements but with normal brain EEG during the movements
• Typically related to underlying psychiatric disorder, trauma or conflict
• Patients are not “faking”. They cannot control their symptoms.
• Referred to historically as “hysteria”
• Gain is primarily psychological rather than secondary gain (not trying to get out of something)

Answer 48

Conversion Disorder or Functional Neurological Symptom Disorder

• Freud’s described a the famous case of “Anna O” , which was a case of conversion disorder
• She had episodes of blindness, inability to speak, abnormalities of speech
• He hypothesized that the conversion symptoms reflected unconscious conflicts and hypnosis and “talking therapy” were noted to improve the symptoms
• This one case led to many of Freud’s theories of how the mind works, “uncovering unconscious conflicts”
• Now recognized that conversion disorder is not a valid model for most psychiatric disorders, either their causes or treatments

Question 49

Management of Conversion disorder

Answer 49

• Best approach is to let the patient know they have conversion disorder, that it will get better and begin to treat the psychiatric disorders (aggressively treat depression, anxiety, insomnia, therapy for trauma/conflict
• Family/friends should ignore movements, leave patient if they occur to reduce frequency. Attention may increase conversion symptoms
• The longer the symptoms occur, the more difficult they may be to treat (Why?) - NOT TRUE. The symptoms could be as a result of depression or traumatic experience

Question 50

Identify psychological factors affecting other medical conditions

**effects of stress on the body (image)

Answer 50

• Physical disorders that are adversely affected by emotional or psychological factors
• A medical condition must always be present for the diagnosis to be made
• Stress Theory: Stress – a circumstance that disturbs normal physiologic or psychological functioning. Exampe: “Fight or flight response” – HTN/tachycardia/increased cardiac output may adversely affect civlized humans
• Early studies revealed negative effects of stress of cardiac, GI sxs
• Can also include stress that affects patients compliance with treatment (example: diabetes)

Question 51

Identify condition

• Patients do not have medical illness but knowingly fake, pretend, simulate, induce or aggravate illness to be in the sick role.
• Motivation is primary gain to be in the sick role

Answer 51

Factitious Disorder

• Persons with factitious disorder have comorbid psychiatric disorder ssuch as mood disorders, personality disorders and substance use disorders
• Factitious disorder by proxy – knowingly induces/simulates illness in others (typically a mother to a child but may be to elderly or disabled person,pet). This is considered a form of abuse. Some anecdotal (but not all) cases associated with illness or trauma as a child requiring prolonged hospitalization
• Can be predominantly psychological or physical symptoms
• To induce symptoms patients may inject feces, take substances, give incorrect histories

Question 52

Identify clues to trigger suspicion of factitious disorder (10)

Answer 52

• Unusual, dramatic presentation of symptoms that defy medical understanding
• Symptoms do not respond to to usual treatments
• Emergency of new unusual symptoms when other symptoms resolve or ability to predict emergence/progression of symptoms
• Eagerness to undergo procedures or testing
• Reluctance to give access to collateral sources of information (refuse to sign releases of information or contact family/friends)
• Extensive history of multiple surgeries
• Multiple drug allergies
• Medical profession (esp. nursing)
• Few visitors
• Not allowing patient to be alone (if by proxy)

Question 53

Describe factitious disorder vs Malingering vs conversion disorder

Answer 53

• Different from Malingering: In malingering someone knowingly “fakes” a disorder for secondary gain (to get out of the army, to prevent going to jail/trial etc, to postpone a test) while in Factitious disorder someone knowingly fakes a disorder for primary gain (to be in the sick role)
• Different from Conversion Disorder as conversion disorder patients do not knowingly produce physical symptoms (unconscious process). They have no awareness their symptoms are not real whereas both Factitious disorder and Malingering are well are they are faking their symptoms

Question 54

Other somatic disorders per DSM5

Answer 54

• “Other specified somatic symptoms and related disorder” – similar to discussed disorders noted but generally don’t meet the time requirements (lasting at least 6 months etc)
• Unspecified Somatic Symptom and Related Disorder - disorders involving somatic symptoms but do not meet the criteria for the disorders discussed

Question 55

Definition of psychotherapy

Answer 55

• •Psychotherapy is a formal process of interaction between two parties for the purpose of amelioration of distress in one of the two parties relative to any or all of the following areas of disability or malfunction: cognitive functions, affective functions or behavioral functions, with the therapist having some theory of personality’s origins, development, maintenance and change along with some method of treatment logically related to the theory and professional and legal approval to act as a therapist.

Question 56

Identify Major Models of Psychotherapy (4)

Answer 56

• •Psychoanalytic
• •Humanistic
• •Behavior
• •Cognitive

Question 57

descrive psychoanalytic psychotherapy

Answer 57

Psychoanalytic

• •Major focus is conflicts
• •Some are conscious and others unconscious
• •Change occurs through critical self-examination
• •Looking to achieve balance between inherent drives (Id) and defenses (ego/super ego)
• •Neurosis may develop when:
  
  • •Individual is unable to cope with increased burden of normal development
  • •Loss, disappointment etc. leads one to seek comfort/gratification in fantasy world rather than deal with reality
  • •Circumstances mimic earlier developmental period, individual responds as they did in an earlier stage

Question 58

psychoanalytic psychotherapy

• Therapeutic process

Answer 58

• •Patient lies on the couch looking away from the analyst
• •Free association
• •Therapist listens in non-critical, non-judgmental way, benign interest
• •Therapist’s values and judgments are excluded
• •Highly controlled
  
  • •Fixed schedule of appointments, fees
  • •Any attempt by patient to change this is examined in terms of their issues/process
  • •May include as many as 4 sessions/week possibly for several years
  • •Therapist makes note of every aspect of interaction with the patient

Question 59

1. •Define
   
   • •Inappropriate repetition in the present of a relationship that was appropriate in the patient’s childhood
   • •Redirection of feelings and desires and especially those unconsciously retained from childhood towards a new object
2. Define
   
   • •Therapist may also develop emotional response to their patients based on their own life experiences

Answer 59

1. Transference
   
   • •Analysis of transference leads to resolution of conflict and change
2. Countertransference

Question 60

Identify model of psychotherapy

• •Formulated by Carl Rogers
• •Trust that person can set their own goals and monitor their progress towards those goals
• •Actualizing tendency-movement of individual towards reaching their full potential

**Describe the therapeutic process

**Goals

Answer 60

Humanistic-Person Centered Therapy

Therapeutic process

• •Person seeking treatment assumes major role for choosing their therapist, determining the frequency of sessions and length of treatment and how they want to use the time within each session
• •Therapist works to create an environment where they convey genuineness, unconditional positive regard and empathy
• •These are the conditions necessary and sufficient for therapeutic effectiveness

Client work towards;

• • Improving self-concept, developing self-regard
• •Having a locus of evaluation that is internal, not based on what others think of them
• •Living their life in a way that they are open and flexible to experiencing the world, not responding in predetermined, rigid ways

Question 61

Identify model of psychotherapy

• •Based on modern learning theory as put forth by Pavlov and B.F. Skinner
• •Most different from psychoanalytic theory/therapy
• •Commitment to scientific approach

***describe basic concepts

Answer 61

Behavioral therapy

• •Abnormal behaviors are not necessarily pathological, just “problems of living”
• •Abnormal behaviors are reinforced in the same way as normal behaviors
• •Behavior should be analyzed in the here and now, is best understood within the framework of a particular situation
• •Insight is not essential to produce change

Question 62

Behavioral therapy

• Therapeutic process; applied behavior analysis
• Techniques/methods

Answer 62

Therapeutic process

• •Applied Behavior Analysis (it is an evidence based treatment)
  
  • •Assume behavior is a function of consequences
  • •Identify reinforcers that serve to maintain abnormal behaviors
  • •Work to restructure the reinforcement schedule/type
  • •Behavior will change
• •Thoughts are considered an internal process and not necessarily relevant to producing behavioral change

Techniques/Methods

• •Reinforcement
• •Punishment
• •Extinction
• •Stimulus Control
• •Shaping

Question 63

Identify model of psychotherapy

• Pioneered by Aaron Beck and Albert Ellis
• Focus on the importance of information processing

*** basic concepts

• •Systematic errors in reasoning become apparent during times of stress
• •These cognitive distortions arise from our individual learning histories that are impacted by our biological makeup, psychological development and social relationships
• •Dysfunctional thoughts serve to create and maintain negative mood states

***example

Answer 63

Cognitive Therapy

Example; Depression

• •Beck identified a negative cognitive triad that relates to depression:
• •Negative view of self
• •Negative view of the world
• •Negative view of the future
• •Each disorder has a specific set of distortions that is typical

Question 64

Therapeutic Process of Cognitive therapy

Answer 64

• •Relationship is collaborative between the patient and the therapist
• •Clearly defined goals
• •Still rely on genuiness, warmth and empathy
• •Initial session includes history taking and the development of a problem list
• •Often an agenda is set at the beginning of each session
• •Use of Socratic dialogue
  
  • •Clarify and define the problem
  • •Assist in identification of thoughts, images & assumptions
  • •Examine the meanings of events
  • •Assess consequences of maintaining dysfunctional thoughts
• • Guided discovery
• •Homework is a major tool
• •Can work to change automatic thoughts
• •Core beliefs or schema work is done at a deeper level and typically takes longer
• •Treatments can be manualized so that it is possible to determine about how many sessions it will take to resolve the problem

•Examples of dysfunctional thoughts

• •I’m either sick or 100 percent cured
• •Everyone has to like me in order for me to be a good person
• •If I can’t do something right the first time, I’m not going to do it at all
• •I got a B on the last Psychopathology test and now I know that I don’t have what it takes to be a doctor.

Question 65

Cognitive therapy - therapeutic process

**Identify techiques

Answer 65

• •Reattribution
• •Redefining
• •Decentering
• •Decatastrophizing
• •Hypothesis testing
• •Exposure therapy
• •Behavioral rehearsal
• •Diversion techniques
• •Activity scheduling
• •Graded task assignment

Question 66

List other modalities of psychotherapy (4)

Answer 66

• Play therapy
• Couples therapy
• Family therapy
• Group therapy

Question 68

Describe psychotherapy modality

• •Typically non-directive
• •Therapist follows the child’s lead
• •Dynamic in nature
• •Relationship is critical

Answer 68

Play therapy

• •Play room becomes the canvas that child can play out their concerns
• •Typical materials include dolls, blocks, puppets, sand box, art materials etc.
• •Therapist works to reflect feelings of child, provide their inner voice
• •Rules of the playroom include times to start and stop, how materials and people are to be treated, collaborative clean up

Question 69

Psychotherapy modality

• Couples therapy
  
  • communication styles

Answer 69

• •Typically occurs when couples are in conflict regarding some aspect of their marriage
  
  • •Could be currently together or not such as in the case of conflict regarding custody in a divorced couple

Therapeutic process

• •May involve two therapists, each of whom is working with one member of the couple
• •Identification of individual goals and goals for the couple can be a focus
• •Identification and modification of negative communication patterns is a major focus

Communication Styles

• •Prepare rebuttal during disagreement
  
  • •Stop hearing content / feeling.
• •Assumptions unchecked
  
  • •“I know what she’s thinking.”
• •Blaming
  
  • •Generating defensiveness.
• •Verbal assaults
  
  • •Name-calling, minimizing, belittling. Emotional scarring.
• •Silence
  
  • •“Cold shoulder”, rejection, distancing

Question 70

Psychotherapy modality

• •Practice began in the 1950’s
• •Came out of movements in Social Psych, Child Guidance Movement, Social Work and research on family dynamics, schizophrenia and marital counseling
• •Focus on content vs. process

Answer 70

Family Therapy

Therapeutic process

• •Techniques come out of theoretical orientation
• •Problem is identified as the family’s problem, not one member of the family
• •Communication and problem-solving skills are a focus
• •Boundaries may also be a focus
• •Minuchin-Structural
  
  • •Manipulate the family system by varying structure, changing seating, isolating parts of the system etc.

Question 71

Psychotherapy modality

• •Can be used with a variety of issues
• •Peer support/positive peer pressure can be especially powerful
• •Validation that the patient is not the only one with a particular problem
• •Can be done in any orientation, CBT, Dynamic, Behavioral

***Why does it work?

Answer 71

Group Therapy

Therapeutic process

• •Process becomes important
• •People are likely to play the same roles in a group that they play in their outside life
• •If they can learn new ways of managing things within the group then they may be able to apply them outside the group
• •Therapist as facilitator

Why does it work?

• •Some believe that it is particular strategies/techniques
• •Dismantling studies
• •Others believe it is the relationship
• •Common factors research

Question 72

Categories of sleep disorders (8)

Answer 72

1. 1.Insomnia
2. 2.Sleep-related breathing disorders
3. 3.Hypersomnia of central origin
4. 4.Circadian rhythm sleep disorders
5. 5.Parasomnias
6. 6.Sleep-related movement disorders
7. 7.Isolated symptoms and normal variants
8. 8.Other sleep disorders

Question 73

Insomnia

• must meet what 3 criteria

Answer 73

1. 1.Difficulty initiating and/or maintaining sleep, waking too early, chronically nonrestorative sleep or poor quality sleep
2. 2.Sleep difficulty persists even with adequate opportunity and circumstances for sleep
3. 3.There are related daytime complaints

Question 74

Identify type of insomnia (1 of 6)

• •Less than three months duration
• •Related to identifiable stressor
  
  • •Stressful life event
  • •Consumption or withdrawal from caffeine, nicotine, EtOH
  • •Acute or chronic injury or illness
  • •Medications
  • •Change in environment

Answer 74

Acute Insomnia

Question 75

Identify type of insomnia (2 of 6)

• •Irregular sleep schedule
• •Use of sleep disturbing substance before bedtime
• •Mentally or physically stimulating activities before bedtime
• •Frequent use of bed or bedroom for activities unrelated to sleep
• •Uncomfortable sleep environment

Answer 75

Inadequate sleep hygiene

Question 76

Identify type of insomnia

•Learned sleep-preventing behaviors

• •Difficulty relaxing
• •Racing thoughts
• •Worry / anxiety about inability to fall asleep – vicious cycle

Answer 76

•Psychophysiological insomnia

Question 77

Types of insomnia

1. •<1% of population

• Lifelong difficulty in initiating or maintaining sleep
• Begins in infancy or early childhood

May be associated with neurologic disorders such as ADHD
2. •Complain of insomnia even when sleep studies reveal normal EEG sleep stages

• Overestimate time to fall asleep
• Underestimate total sleep time

3. •Pulmonary disease, pain, heart failure

• Depression, anxiety
• Neurologic disease (Parkinson [30%], Alzheimer [25%])
• Medications – caffeine, theophylline, appetite suppressants, Ca++ channel blockers, antidepressants, beta blockers, glucocorticoids

Answer 77

1. Idiopathic insomnia
2. Paradoxical insomnia
3. Associated with a medical condition

Question 78

Insomnia

• Epidemiology
• Clinical Features
• Differential diagnosis
• situations that are not insomnia

Answer 78

Insomnia Epidemiology

• •One of the most common medical problems
• •Prevalence increases with age
• •Women more than men
• •More insomnia in persons with life stressors

Clinical features

• •Complain of difficulty falling asleep (>30 min) or staying asleep (<6 hours of sleep / night) on three or more nights per week
• •Or complaints that should suggest possible insomnia to the clinician
• •Fatigue or malaise – Increased accidents
• •Poor attention, concentration
• •Mood disturbance – Reduced energy
• •Daytime sleepiness

Differential Diagnosis

• •If associated with another condition then classified as Insomnia associated with ____
• •Otherwise classified as an independent or primary disorder

Situations that are not insomnia

• •Short duration sleep (no daytime complaints)
• •Sleep deprivation
  
  • •Volitional
  • •Daytime complaints
  • •Will sleep if given opportunity

Question 79

Identify sleep disorder

• •A sleep disorder that involves cessation or significant decrease in airflow in the presence of breathing effort.
• •The most common type of sleep-disordered breathing
• •Characterized by recurrent episodes of upper airway collapse during sleep which are associated with recurrent oxyhemoglobin desaturations and arousals from sleep.
• •Most common in men, 18-60 years old

Answer 79

Sleep-related breathing disorders - Obstructive sleep apnea

Clinical features

• •Daytime sleepiness
• •Snoring – ask bed partner
• •Other complaints
  
  • •Sensation of choking, gasping, smothering on awakening
  • •Awakening with a dry mouth
  • •Moodiness, irritability
  • •Lack of concentration, memory impairment

Question 80

Sleep-related breathing disorders - Obstructive sleep apnea

• Physical exam findings
• Diagnosis
• Treatment

Answer 80

•Physical exam findings

• •Narrow airway
• •Large neck and / or waist circumference (neck > 17 in. for men, > 16 in. for women)
• •Elevated blood pressure
• •Signs of pulmonary htn (peripheral edema, jvd)

•Diagnosis

• •Polysomnography – expensive, screen pts first
• •Diagnostic criteria
  
  • •Asymptomatic pt: > 15 apneas, hypopneas or respiratory effort-related arousals per hour of sleep
  • •Symptomatic pt: > 5 apneas, hypopneas or respiratory effort-related arousals per hour of sleep
  • •> 75% of apneas, hypopneas must be obstructive
  • •Mild, moderate and severe disease

•Treatment: positive airway pressure therapy (CPAP machines)

Question 81

Identify diagnostic method

**Used to diagnose what sleep condition?

•Parameters monitored

• •Electroencephalography (EEG) to monitor sleep stages
• Electrooculography (EOG) monitor horizontal and vertical eye movements to document onset of REM and note the presence of slow-rolling eye movements seen at sleep onset
• •Electromyography (EMG) to monitor atonia during REM (mentalis or submentalis), bruxism (masseter), periodic limb movements (anterior tibialis) and effort during respiratory events (intercostal)

Answer 81

Polysomnography; used to dx obstructive sleep apnea

• •Two channels monitor airflow
• •Other parameters that can be monitored:
  
  • •ECG
  • •Pulse oximetry
  • •Respiratory effort
  • •End tidal or transcutaneous CO2
  • •Sound recordings to measure snoring
  • •Continuous video monitoring

Question 82

Identify sleep disorder

• •Repetitive cessation or decrease of both airflow and ventilatory effort during sleep; primary and secondary
• •Risk factors
  
  • •Age > 65 years
  • •Gender: > 10x more common in men than women
  • •Heart failure
  • •Stroke
  • •Long-acting opioid use

***Clinical findings

Answer 82

Sleep-related breathing disorders; Central sleep apnea

Clinical Findings

• •Daytime sleepiness
• •Poor subjective sleep quality
• •Insomnia
• •Poor concentration
• •Paroxysmal nocturnal dyspnea
• •Morning HAs
• •PE findings of associated conditions such as heart failure, stroke

Question 83

Central sleep apnea

• Diagnosis
• diagnostic criteria
• treatment

Answer 83

• •Diagnosis
  
  • •Polysomnography
• •Diagnostic criteria – specific for primary CSA and for CSA associated with other conditions
• •Treatment
  
  • •If asymptomatic, may just observe
  • •Treat underlying disorder if present
  • •Positive airway pressure

Question 84

Identify sleep disorder

• •Disorder of sleep-wake control; elements of sleep intrude into wakefulness and elements of wakefulness intrude into sleep
• •Clinical features
  
  • •Daytime sleepiness
  • •Cataplexy
  • •Sleep paralysis
  • •Hypnagogic hallucinations

**Identify etiology (loss of what? genetic factors?)

Answer 84

Hypersomnia of central origin - Narcolepsy

• •Etiology - Loss of orexin signaling
  
  • •Loss of orexin-A and orexin-B from lateral hypothalamus
    
    • •90% reduction in orexin-producing neurons in hypothalamus (autoimmune process?)
    • •No detectable orexin-A in CSF
  • •Orexin-A and -B are excitatory, stabilize wakefulness, prevent inappropriate transitions to REM or NREM sleep
  • •Loss of orexins results in REM sleep-related phenomena while awake (cataplexy, hypnagogic hallucinations, sleep paralysis)
• •Etiology - Genetic factors
  
  • •Usually occurs sporadically
  • •DQB1*0602 haplotype present in 95% of pts with cataplexy & 96% of pts with orexin deficiency

Question 85

Describe in detail the clinical features of narcolepsy (4)

Answer 85

1. Daytime sleepiness
   
   • •Chronic sleepiness without more than normal amount of sleep in 24 h
   • •Fall asleep throughout day with little warning
   • •Awake refreshed in morning, sleepiness improved with brief nap
2. •Cataplexy (highly suggestive of narcolepsy)

• Emotionally-triggered transient muscle weakness, often partial affecting face, neck, knees
• Trigger: strong, positive emotions (laughter, joking, excitement)
• Lasts less than 2 min
• Develops later than daytime sleepiness, usually within 3 to 5 years

3. •Sleep paralysis

• Complete paralysis for 1-2 minutes after waking
• May also occur with falling asleep

4. •Hypnagogic hallucinations

• Occur while falling asleep
• Visual, tactile or auditory
• Vivid, frightening
• Maybe a mixture of dreaming and wakefulness experienced during REM

Question 86

Hypersomnia of central origin - Narcolepsy

• Diagnosis
• Diagnostic criteria

Answer 86

•Diagnosis

• •Careful history
• •Polysomnography
  
  • •Rules out or identifies coexisting sleep disorders
  • •Pts with narcolepsy enter REM sleep within 20 minutes of sleep onset vs. healthy individuals who enter REM sleep 80 – 100 min after sleep onset
• •Multiple Sleep Latency Test (MSLT)
  
  • •Subjects are monitored while trying to fall asleep
  • •Sessions are repeated four to five times
  • •Sleep latency (time to sleep onset) is measured
  • •Sleep latency in narcoleptics < 8 min
  • •Sleep latency in healthy subjects ~10 – 15 min
  • •Narcoleptics experience sleep onset REM (SOREM) periods
• •Diagnostic criteria
  
  • •MSLT with sleep latency < 8 min and at least two SOREMs
  • •Exclusion of other causes of chronic daytime sleepiness

Question 87

Identify sleep realted movement disorder

• •Spontaneous, continuous leg movements associated with unpleasant paresthesias; worse at rest and at night, relieved by movement
• Clinical features
  
  • •Discomfort in legs that occurs at rest and is relieved by movement
  • •Symptoms worsen as day progresses, maximal at night
  • •Difficulty falling asleep
  • •Frequent night awakenings

**Primary vs secondary associations (etiology)

Answer 87

Restless Leg Syndrome

•Primary RLS

• •Etiology unknown
• •Evidence for a genetic component and for a central nervous system cause

•Secondary RLS associations

• •Iron deficiency
• •End-stage renal disease, hemodialysis
• •DM – Pregnancy
• •MS – Drugs
• •Parkinson – Venous insufficiency

Question 88

Identify sleep movement disorder

• •Sudden jerking leg movements
• •Last 0.5 – 5 sec, repeated every 20 to 40 sec
• •Often accompanies RLS
• •May cause partial or total arousal from sleep
• •Insomnia and daytime sleepiness

Answer 88

•Periodic limb movement of sleep

Question 89

Diagnosis of RLS (primary and secondary) vs Periodic limb movement disorder

Answer 89

RLS (Restless leg Syndrome)

• •Primary – Clinical diagnosis based on typical symptoms and normal neurologic exam
• •Secondary – typical symptoms; neurologic exam may be abnormal in presence of neurologic disorders (Parkinson, MS)
• •Polysomnography is not necessary
• •Labs – check for Fe deficiency

•Periodic limb movement disorder

• •Polysomnography reveals repetitive movements with typical timing
• •Movements cannot be explained by another disorder

Question 90

Identify sleep disorder

• •Primarily in individuals working the night shift
• •Sleepy at work and while driving home
• •BUT have difficulty sleeping past noon
• •Treatment
  
  • •Change to day or evening shift OR
  • •Maintain a daily sleep routine consistent over seven days a week

Answer 90

Circadian rhythm sleep disorders - Shift work disorder

Question 91

Identify sleep disorder

• •Caused by travel across time zones
• •Traveler’s sleep-wake cycle becomes out of sync with the time of day
• •Traveling east to west is easier especially for individuals with sleep-wake cycle longer than 24 hours
• •Traveling west to east is easier for individuals with sleep-wake cycle shorter than 24 hours
• •Maximum rate of adjustment is 2-3 hrs per day

Answer 91

Jet Lag

Question 92

Insomnia (Egleton)

• timeline of insomnia (4)

Answer 92

• Insomnia
  
  • The inability to fall asleep or stay asleep; results in drowsiness, fatigue and lack of alertness during the day
• Transient Insomnia
  
  • •Few days; follows acute stressor
• Short-term insomnia
  
  • •Usually situational; may last several weeks
    
    • –If hypnotic is warranted, intermittent use is recommended
• Long-term insomnia
  
  • •Lasts > 3 weeks; may be due to underlying disorder
    
    • –May require special evaluation to determine underlying cause

Hypnotics should not be used for more than one month.

Question 93

Treatment options of sleep disorders (summary table)

Answer 93

Question 94

Benzodiazepams used in sleep disorders (3)

Answer 94

Flurazepam

• •Significantly reduces both sleep-induction time and the number of awakenings,
• •increases the duration of sleep.
• •long-acting effect
• •little rebound insomnia.
• •Effective for up to 4 weeks
• •Half-life of approximately 85 hours, which may result in daytime sedation and accumulation of the drug.

Temazepam

• •Useful in patients who experience frequent wakening (reduce ability to react to external stimuli)
• •Peak sedative effect occurs 1 to 3 hours after an oral dose
• •should be given 1 to 2 hours before the desired bedtime.

Triazolam

• •short duration of action and, therefore, is used to induce sleep in patients with recurring insomnia
• •Effective in treating individuals who have difficulty in going to sleep.
• •Tolerance frequently develops within a few days, and withdrawal of the drug often results in rebound insomnia, leading the patient to demand another prescription or higher dose.
• •Best used intermittently rather than daily.

Question 95

• •Non-BDZ drug used for treatment of insomnia
  
  • –Acts at BDZ receptors
  • –quick onset (1-2 hr); t1/2 of 2.5 hr
• •Selective hypnotic effect; minimal anxiolytic, anticonvulsant, muscle relaxant effects; minimal rebound insomnia
• •Side effects:
  
  • –dizziness, headache
  • –confusion, sleepiness
• •Can interact with alcohol
• •Preserves sleep structure

Answer 95

Zolpidem (Ambien)

Question 96

Sleep medication

• •Binds BDZ receptor
• •Rapid onset, short duration; t1/2 of 1 hour can be dosed in middle of night for broken sleep
• •Causes rebound insomnia after 1st night of withdrawal, but soon resolves
• •Comparable abuse potential to BDZ’s

Answer 96

Zaleplon (Sonata)

• used in people who wake up in middle of night and can’t fall back to sleep

Question 97

Sleep medication

• •Longer half life than Zolpidem, Zaleplon
• •BDZ like drug
• •Not restricted for short term use (unlike zolpidem or zaleplon)

Answer 97

Eszopicione (Lunesta)

Question 98

Sleep medication

Uses:

• •Sedative hypnotic; use has declined
• •Sedation of children during illnesses
• •Antagonize effects of CNS stimulants.
  
  • –Superior to BDZ’s in this use
• •Anticonvulsants
• •“Truth serum”
• •Induction of anesthesia: Thiopental
• •Use minimized due to
  
  • –drug tolerance, ↑CYP activity physical dependence; severe withdrawal symptoms
• •Coma at toxic doses
• •No antidote

Answer 98

Barbiturates (BARBs)

• Depress CNS activity at low concentrations.
• Depress activity of nerve, skeletal muscle and smooth and cardiac muscle at high concentrations!!!

Question 99

BARBS

• effects on sleep
• resp and cardio effects
• Hepatic
• other

Answer 99

Effect on sleep

• •↓sleep latency
• •↓ awakenings
• •↓ time spent in stages 3 & 4
• •↓number of REM cycles and time spent in REM
• •Tolerance develops to these effects

Respiration and Cardiovascular Effects:

• •Depress neurogenic drive of respiration
• •Minimal cardiovascular effects at hypnotic doses

Hepatic:

• •Induction of hepatic enzymes (Cytochrome P450’s)
• •Activates d-aminolevulinic acid synthetase and may exacerbate porphyria
  
  • –Absolutely contraindicated for acute or intermittent porphyria

Other:

• •BARB’s cross placenta and appear in breast milk
• •Tolerance to the hypnotic effects of BARBs does occur
• •Cross tolerance to other CNS depressants
• •Withdrawal reactions will occur

Question 100

BARBS

***Acute toxicity and treatment

***Explain abstinenece syndrome

Answer 100

•Symptoms

• –Stupor/coma
• –Respiratory depression
• –Circulatory collapse

•Treatment

• –Removal of unabsorbed drug by lavage
• –Artificial ventilation
• –Hemodialysis
• –Charcoal

Abstinence syndrome

• •Chronic use downregulates GABA receptors, increases cholinergic activity and elevates glutamate receptors
• •Potentially life threatening
• •Upon withdrawal, intense cholinergic activity, little GABA activity
• •NET EFFECT = EXCITEMENT
• •Treatment: Hospitalization and stabilization with lowest dose that prevents syndrome

Question 101

Sleep medication

• •Histamine H1 antagonists
• •Used in treatment of mild insomnia
• •Less effective than BDZ’s

Answer 101

Diphenhydramine (Benadryl), Doxylamine (Unisom)

Question 102

Sleep medication

• Synthesized in pineal gland from tryptophan
• Secreted as hormone according to a diurnal rhythmn
• Increases in late evening, peaks in the middle of the
• night and decreases toward morning
• Dietary supplement; Not reviewed by FDA for effectiveness, safety, purity
• May decrease insomnia

Answer 102

Melatonin

Question 103

sleep medication

Answer 103

Ramelton (Rozerem)

Question 104

Identify CNS depressant

Mechanism:

•not totally clear

• –May act on cell membranes
• –+ve allosteric modulator of GABA receptor
• –Decreases Na+ and Ca2+ influx

Effects:

• •Low doses may result in stimulation
• •Additive effects with other CNS depressants
• •Relaxation → Ataxia → Coma → Death
• •Peripheral vasodilation
• •Increased salivary/gastric secretions
• •Diuretic
• •Accumulation of lipid in liver (Fatty liver)
• •Increases HDL in plasma; Good effect controversial
• •Chronic, excessive use causes cardiomyopathy

Answer 104

Alcohol (ETOH)

Question 105

Ethanol

• uses
  
  • topical application
  • methanol poisoning tx (side effects)
• **what med treats alcoholism

Answer 105

Topical application:

• Reduction of fever
• Prevention of decubitus ulcers
• Disinfectant
• Removing toxicodendrol

Methanol poisoning can be treated with Fomepizole (competitive inhibitor) or ethanol (competitive substrate).

Fomepizole – rare side effects; headache, nausea

Less therapeutic uses:

• Absorbed completely from GI tract
• Food slows absorption

Disulfiram: Flushing, tachycardia, hyperventilation, nausea. Disulfiram used in treatment of alcoholism

Question 106

•Inhibition of aldehyde dehydrogenase

• –resulting in accumulation of acetaldehyde in blood causing flushing, tachycardia, hyperventilation, nausea.

Answer 106

Disulfiram (Antabuse)

• Treat alcoholism

Question 107

Treatment of alcohol withdrawal/relaspse

1)

• –Opioid receptor antagonist
• –Reduces craving/blunts pleasurable effects
• –May decrease DA release in nucleus accumbens
• –Nausea is major side effect

2)

• –Structural analog of GABA
• –Decreases glutamate neurotransmission during alcohol withdrawal
• –Relapse prevention
• –Diarrhea is major side effect

Answer 107

1. Naltrexone
2. Acamprosate

Question 108

Narcolepsy medications

Answer 108

Most medications that improve sleepiness do so by enhancing dopamine signaling and most cataplexy-suppressing medications increase norepinephrine and/or serotonin signaling

Question 109

Narcolepsy medication

_********_

Answer 109

Modafinil (Provigil)

Question 110

Narcolepsy med

Answer 110

Gamma hydroxybutyrate (Xyrem)

Question 111

What causes delirium in the elderly (Holyrod case)

• condition
• medications (3)

Answer 111

• UTI
• Meds;
  
  • •Diphenhydramine (Benadryl) is anticholinergic – causes urinary retention. *Tylenol PM has benadryl
  • •Alprazolam (xanax) is a benzo – sedative and it is addictive. It can also cause delirium
  • •Percocet (chronic opiod – oxy and acetamunphen); not good for chronic pain. Can cause confusion/delirium and it is addictive

Question 112

List commonly abused drugs (to know from exam) - 6

Answer 112

• •Opioids
• •Amphetamines (stimulant)
• •Cocaine (stimulant)
• •Benzodiazepines (sedative)
• •Alcohol (sedative)
• •Nicotine

Question 113

Why are certain drugs addictive

Answer 113

• •Its all about mesolimbic dopamine.
• •Promotes pleasure sensations

Question 114

Describe the general circuitry of addiction

Answer 114

Question 115

Opiods as drug abuse

• prescription
• street
• MoA
• effects
• Overdose

Answer 115

• •Prescription use as pain killers
  
  • –Morphine, hydocodone, oxycodone, methadone tramadol, fentanyl, carfentanil , loperamide
  • –As a class, most diverted and abused prescription medications in USA.
• •Street drugs
  
  • –Heroine, opium, krokodil

Overdose

• ·Depressed mental status, decreased respiratory rate, decreased tidal volume, decreased bowel sounds, constricted pupils (though neither meperidine nor propoxyphene constrict pupils).
• ·Can be complicated by hypothermia, coma, seizure, head trauma, aspiration pneumonia and rhabdomyolysis.
• Loperamide:
  
  • Poor man’s methadone 100 x therapeutic dose
  • OD gives dysrhythmia and prolonged QT, death from cardiac rather than respiratory
• Also check for needle tracks and skin popping

Question 116

Opiod OD tx

• Emergent tx
• Maintenance
• withdrawal
  
  • pt complains of? (3)

Answer 116

Emergent; Goal is to improve ventilation not mental status

• ·Ventilation
• ·IV or IM naloxone
• ·If respiratory depression remains give more naloxone as bolus

Maintenance

• Methadone maintenance gold standard
  
  • ·t1/2 24 to 36 hours
  • ·Relieves opioid craving and withdrawal symptoms and when given in sufficient doses, blocks the euphoric effects of opioids.
  • ·Detoxification involves the use of tapering doses to achieve a smooth transition from opioid use to a drug-free state.
• IS AN OPIOID and can also be abused
• Buprenorphine
  
  • ·Partial Mu agonist Kappa antagonist
  • ·can induce withdrawal abstinence for at least 24hr required prior to buprenorphine
  • ·Oral with our without naloxone (Nal doesn’t cross gut – reduces abuse)
  • ·Gradual taper to “wean “
• Naltrexone:
  
  • ·Antagonist
  • ·Used for prevention of relapse

Question 117

Opiod OD drug examples

1)

• Oxycodone (OxyContin) delayed release formulation
• Acts for 12 h (longest acting pain reliever on the market)
• Crushing pills and then swallowing, snorting or injecting leads to heroin high
• Cheap
• can be combined with non opiod like acetaminophen

2)

• •Diacetylmorphine metabolized to 6-monoacetylmorphine then morphine
• •Both Diacetylmorphine and 6-monoacetylmorphine have higher BBB penetration than morphine
• •Effect due to both 6-monoacetylmorphine and morphine
• •6-monoacetylmorphine specific heroin metabolite detectable in urine tests
• •Very rarely supplied pure, often cut with other stuff

3)

• Which is more common in WV and is a major issue in pregnant women

Answer 117

1. Oxycodone (Dazidox, Oxycontin) - “Hillbilly Heroin”
2. Heroin
   
   • Cheese heroin; Nut job, Muck, Frown, Slab
3. Opiods plus gabapentin
   
   • •Very common in WV
   • •Gabapentin potentiates opioid action (unknown mechanism)
   • •Means more bang for your buck
   • Major issue in pregnant women, we have 50 ish confirmed NAS cases of opioid + gabapentin

Question 118

What class of drugs Typically work by increasing GABA signaling or via promoting endogenous opioid signaling

Answer 118

Sedatives

• Benzodiazepams
• Barbiturates
• Propofol
• Alcohol

Question 119

Benzodiazepine OD

• when does it become a problem? (hint when taken with what other sedative?)
• What is the antidote
• Abrupt withdrawal cal lead to?
• treated with?

*****Identify a drug used in the hangover movie and it is date rape drug added to drinks

Answer 119

Benzodiazepine

• •Generally safe in overdose unless coupled to other depressants (Alcohol etc) typical symptoms include CNS depression with normal vital signs. Respiratory depression only seen in conjunction with other depressants
• •Antidote Flumazenil used only in cases of severe overdose, otherwise only supportive care given
• •Abrupt withdrawal can lead to:
  
  • –tremors, anxiety, perceptual disturbances, dysphoria, psychosis, and seizures
• •Treated with IV diazepam

Flunitrazepam (Rohypnol):

• •“Roofie” drug used in The Hangover
• •“Date rape” drug which is added to drinks

Question 120

Identify sedative OD and the treatment

• •Has an effect on both GABA and opioid transmission, stimulating both.
• •Naltrexone can be used to prevent the opioid stimulation

Answer 120

Alcohol

• •Disulfiram (Antabuse)

DUI Facts:

• •Highest BAC for DUI reported in US 0.72! The women was found passed out in car. Was unconscious for 12 hours, but recovered.
• •Highest BAC internationally reported in Poland 1.374 (also survived)

Question 121

Identify stimulant OD

• •Directly increase the levels of dopamine in the nucleus accumbens
• •All work in the same way, Metamphetamine is the most effective, due to increased BBB crossing.
• •All have same effects just METH is better at it

***effects

Answer 121

Amphetamines

MoA;

• Increase neurotransmission in central NE, DA and 5-HT systems by:
• Dose related release of NE, DA, 5-HT
  
  • Low dose: preferential action on NE release
  • Moderate dose: NE and DA release
  • High dose: NE, DA, 5-HT release
• Blockade of reuptake of NE, DA, 5-HT
• Inhibition of MAO

Meth

• •Abused orally, nasally, IV
• •Rapid onset, prolonged symptoms

Question 122

Amphetamines

• Adverse effects
  
  • acute vs chronic
  • CV effects
  • GI
• Other adverse effects

Answer 122

Acute

• Restlessness, anxiety, insomnia
• Agitation, Aggressiveness
• High doses → Convulsions

Chronic

• Paranoid schizophrenia-like state
• Delusions
• Hallucinations

***Acute and chronic effects above ; Looks like Schizophrenia, meth can be an organic reason for drug induced schizophrenia

CV; Palpitations, Arrhythmias, Hypertension, Anginal Pain, Circulatory collapse

GI; Anorexia, Nausea, Vomiting, Abdominal cramps, Diarrhea

Question 123

Amphetamines

• Tolerance
• Overdose
• Withdrawal

Answer 123

Tolerance

• •Less tolerance to toxic CNS effects (i.e. convulsions)
• •Tolerance to euphoria and anorectic effects with chronic use
• •Withdrawal symptoms of mental depression, fatigue and hunger
• •Addiction and physical dependency possible

Overdose; Symapthomimetic toxidrome:

• ·CNS stimulation (agitation, delirium acute psychosis) – if severe sedate with benzodiazepine and then with antipsychotic if required (Chlorpromazine, Haloperidol, Droperidol, Ziprasidone)
• ·Tachycardia
• ·Hypertension – avoid beta blockers
• ·Dilated pupils
• ·Diaphoresis
• ·Hyperthermia – evaporative cooling
• ·Stabilization of airways, breathing and CV function
• ·Activated charcoal prevents further absorption if oral
• ·Modification of urine pH, promotes renal

WIthdrawal

• •Mental depression
• •fatigue
• •ravenous hunger

Question 124

Identify drug

• ·Designer drug “Ecstasy”; “Adam”; “XTC”, “E”
• ·Amphetamine derivative
• ·Popular club / rave drug especially in Europe
• ·Has had some clinical trials for PTSD

Mechanism of action:

• ·Indirect serotonergic agonist
  
  • o↑ release of 5-HT; Blocks reuptake of 5-HT

•Actions:

• ·Can have prolonged effect up to 1 week
• ·Sympathomimetic and psychotomimetic
• ·Increased euphoria, emphathy
• ·Enhances pleasure, Heightens sexuality, Expands consciousness, positive change in self-image

Answer 124

MDMA (3,4-methylenedioxymethamphetamine)

Toxicity

• ·Narrow margin of safety
• ·Cardiac arrhythmias
• ·Hyperthermia
• ·Convulsions
• ·Rhabdomyolysis
• ·Renal failure
• ·Fatalities may occur
• ·Chronic use may cause hepatic damage

Psychiatric effects:

• ·Psychosis
• ·Depression (after long term use)

Question 125

identify drug abused

• •Delirium, violent behavior
• •Pulse may be weak, irregular rapid
• •Tonic-clonic seizures can be induced
• •Malignant encephalopathy
• •Cardiac failure: rapid elevation of blood pressure which can lead to stroke, irregular heartbeat, cardiac arrest
• ****25 year old male with CHEST PAINS

****Identify metabolites that only works with alcohol

**Identify treatment

**Prolonged use

Answer 125

Cocaine Tox (OD)

CNS stimulation

• Prolongation of DA effects in limbic system → Euphoria
• Chronic cocaine intake → DA depletion → Triggers craving for cocaine

Metabolites

• benzoylecgonine - spontaneous hydrolysis ~50%
• Ecgonine - plasma / liver pseudocholinesterase 40-50%
• Norcocaine - Liver P450 induced n-demythylation ~5%
• Cocaethylene
  
  • Formed only in presence of alcohol via a transesterification ~17%
  • Crosses BBB
  • Active metabolite, blocking reuptake
  • As potent as cocaine

Treatment

• Agitation
  
  • •Benzodiazepine (diazepam / lorazepam)
• Hypertension
  
  • •Benzodiazepine (sedation)
  • •Phentolamine
  • •NO BETA BLOCKERS
• MI
  
  • •Aspirin
  • •Nitroglycerin
  • •Phentolamine
  • •NO BETA BLOCKERS
• •Bromocriptine used during withdrawal to reduce craving of drug
  
  • –DA receptor agonist; effectiveness not firm

Prolonged use

• •Addiction and Physical dependency common
• •Continued use may result in adverse conditions:
  
  • –Malnutrition
  • –Weight loss
  • –Sexual problems
  • –Mental confusion
  • –Anxiety

Question 126

Identify substances based of toxicity symptoms

• Toxicity
  
  • •Central respiratory paralysis
  • •Severe hypotension caused by medullary paralysis
• Withdrawal
  
  • •Peak 1-2 days after quitting and then decreases over a period of weeks
    
    • –Irritability
    • –Anxiety
    • –Restlessness, frustration
    • –Difficulty concentrating
    • –Headache
    • –Insomnia

***Identify; origin, MoA, uses, effects, adverse effects

Answer 126

Nicotine

Origin

• •Principal alkaloid of plants of genus Nicotiana
• •Lipid, soluble tertiary amine
  • –Rapidly absorbed, distributed
  • –Metabolite: cotinine
  • –Tars in cigarette smoke accelerates metabolism of nicotine and other drugs
• Cigarettes accelerate metabolism of certain drugs

Uses; Smooking cessation therapy

MoA and effects

• •Activates cholinergic nicotinic receptors (CNS, PNS)
• •Nicotine initially stimulates, then blocks the receptor
• •Inhibits MAO → Activate DA neurotransmission →dependence?
• •Stimulates release of NE and DA
• •This promotes
  
  • –Mild euphoria
  • –↑ arousal, concentration
  • –Improved memory
• •Appetite suppression

Adverse effects

• •Irritability
• •Tremors
• •Intestinal cramps/diarrhea
• •Increased heart rate
• •Increased blood pressure

Question 127

How does one develop alcohol abuse behavior

Answer 127

Alcohol abuse behavior is multifactorial

§Distal Antecedents (Social) – when individual is young experiences with

• §Peer groups
• §Family interactions
• §Parental drug use

§Distal Antecedents (Individual)

• §Early learning
• §Drug exposure
• §Genetic predisposition
• §Development events – including epigenetics

§Immediate Antecedents (Social/Cultural)

• §Licensing laws
• §Social pressures
• §availability

§Immediate Antecedents (Individual)

• §Mood states
• §Expectations

§Avoidance Learning

§Approach Learning

Question 128

Terminology

• At risk drinking
• Heavy drinking **********
  
  • max amount of drinks per day
  • max per week
• AUD
  *

Answer 128

1. At risk drinking – heavy drinking in the absence of criteria for alcohol use d/o (AUD)
2. Heavy drinking – both at risk drinking and symptomatic drinking. No current symptoms, but higher risk alcohol related problems (mental, liver, etc.)

• Maximum recommended drinks (per NIAAA)
• —Per day
  
  • —Men <65years – 4
  • —Men >65 or Women – 3
• —Per week
  
  • —Men <65 years – 14
  • —Men >65 or Women – 7

3. AUD: (remember the C’s: loss of Control, Craving, unable to Cut down, Continued use despite Consequences) – Next pg.

Question 129

Define

• a)Slowed thinking
• b)Decrease reaction time
• c)Slurred speech
• d)Incoordination
• e)Unsteady Gait
• f)Nystagmus
• g)Impaired memory
• h)Coma +/- respiratory
• suppression (more than
• 0.6% often fatal)

Answer 129

Alcohol Intoxication

Blood Alcohol Levels

• •0.05% – thought, judgment, and inhibitions loosened
• •0.1% voluntary motor actions affected
• •0.2% - entire motor area of brain depressed, emotional behavior affected
• •0.3% - confusion, stupor
• •0.4-0.8% - coma, respiratory drive compromised

Question 130

List 4 symptoms of alcohol withdrawal******

Answer 130

• a)Tremulousness is classic but can expand to include psychotic and perceptual disturbances, seizures, confusion (Delirium tremens)
  
  • a)Shakes begin 6-8 hours after last drink
  • b)Psychosis 8-12 hours
  • c)Seizures 12-24 hours
  • d)DTs 72 hours (be alert for first week)
• b)Irritability, anxiety, sweating, flushing, autonomic instability (hypertension, tachycardia)
• c)Autonomic hyperactivity
  
  • a)Worsened by fatigue, malnutrition, physical illness, depression
• d)Seizures
  
  • a)Stereotyped, tonic-clonic, generalized

Question 131

Other terminology to know

1. decreased response to the same dose of substance or the need for increasing doses of the substance to elicit the same response (down regulation of receptors/lowered response)
2. *******Reward acts as initial drive for repeated use (pos. reinforcement). Neg. reinforcement: by taking something away - becomes the drive. With continued use, the negative reinforcement becomes the main drive – the anti-reward system. See under pathophysiology.
3. The friend who lends money to the alcoholic, “so he won’t be forced to steal” is enabling that addiction. Helping, but not helping.
4. Each withdrawal leads to more severe withdrawal symptoms than the previous withdrawal syndrome or past seizure, next w/d increased risk for seizure.

Answer 131

1. Tolerance
2. Positive and negative reinforcement
3. Enabling
4. Kindling

Question 132

Medical consequences of alcohol abuse

• Neurological and psychiatirc
  
  • **2 conditions as result of thiamine deficiency

Answer 132

1.Alcohol-induced Persisting Amnestic Disorder (aka Wernicke-Korsakoff Syndrome)

• I.Thiamine deficiency
• I.Wernicke’s encephalopathy (set of acute symptoms)
  
  • I.Ataxia
  • II.Confusion
  • III.Opthalmoplegia
  • IV.Often remits after treatment with thiamine for 1-2 weeks

II.Korsakoff’s syndrome (chronic condition)

• I.Amnesia
• II.Confabulation
• III.Treat with thiamine 3-12 months
  
  • I.Prognosis poor - 20% recovery rate

Note: Glucose depletes thiamine stores – always give thiamine first!

Question 133

Condition from alcohol abuse

1)

• –Lesions are symmetrical and paraventricular involving mammillary bodies, thalamus, hypothalamus, midbrain, pons, medulla, fornix, and cerebellum

2.

• –Accounts for ~4% of dementia cases in US
• –confabulation

Answer 133

1. Wernicke-Korsakoff Syndrome
2. Alcohol-induced persisting dementia

Question 134

Some neurlogical consequence from alcohol abuse (6)

Answer 134

• Subdural hematoma (shrinkage of brain, increased risk for latter, can be confused with intoxication- careful)
• 4. Ischemic and hemorrhagic stroke
• 5. Seizure (ETOH lowers seizure threshold in people with epileptics)
• 6. Peripheral neuropathy (Vit. deficiency/direct toxicity/pressure on nerve – “Sat. night palsy”. Sensory def. in stocking-glove distribution)
• 7.In baby of mother who drinks — Fetal Alcohol Syndrome —Leading cause of mental retardation.
• 8.Multiple psychiatric d/o’s: alcohol induced -MDD (30%), -bipolar d/o, -anxiety d/o, -psychotic d/o, -sleep d/o, -sexual dysfunction d/o, -neurocognitive d/o (see previous slide)

Question 135

Treatment (alcohol abuse)

A. Meds

• reduse ETOH conseumption (lower craving)
• block enzyme aldehyde dehydrogenase
• increase GABA

B. Treat underlying psych conditions

C. Withdrawal

D. what to do after detox????

Answer 135

A. Medications:

• I.Med to reduce ETOH consumption by lower craving and lower mood elevating effect when drinking ETOH (Naltrexone – opioid antagonist).
• II.Med to block the enzyme aldehyde dehydrogenase with “flu-like symptoms” if drinking alcohol (Disulfiram).
• III.Med that increases GABA and complex effect on excitatory NMDA (Acamprosate)

B. Treat the underlying psychiatric disorder or the effect of the alcohol use. (Antidepressants still useful despite e.g. continued alcohol use, although less so, if not abstinent).

• Patients with MDD and anxiety nearly 2x more ETOH, Bipolar 40% more, 50% of pts with schizophrenia abuse substances.
• Substance induced mood/anxiety or psychotic disorder present in 25-50% of cases admitted to IP.

C. Withdrawal (including DT): Benzodiazepines mainstay of treatment (GABAa)

D. Rehabilitation after detox: Most patients relapse within days of a detox! Regular AA = mainstay of recovery long term (attachment improved, lowered impulsivity and lower depression. Similar recovery for atheists as AA approach, belief there is a higher power outside of oneself, stronger than alcohol addiction).

• Also Family therapy, Aversion therapy, Motivational Interviewing, CBT and other behavioral therapies.
• BRIEF SCREEN and intervention by PCPs 30% of patients change or lower their drinking behavior!

Question 136

Identify definition

Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors.

Answer 136

Addiction

Addiction is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. Without treatment or engagement in recovery activities, addiction is progressive and can result in disability or premature death.

Question 137

_Characteristics of Addiction. ****KNOW_

Answer 137

Pneumonic ABCDE

• Inability to consistently Abstain;
• Impairment in Behavioral control;
• Craving; or increased “hunger” for drugs or rewarding experiences;
• Diminished recognition of significant problems with one’s behaviors and interpersonal relationships; and
• A dysfunctional _E_motional response

Question 138

Comparison of other chronic diseases to drug addiction

Answer 138

Question 139

Take home points of addiction in WV

• what 2 is getting better
• what 4 is getting worse
• what was rapidly abused in place of opiods and is now slowly declining?
• what gender is dying more

Answer 139

• Rx opioids and benzo’s – getting better
• Illicit heroin, fentanyl, cocaine, meth – getting worse
  
  • ​We have a fentanyl problem in WV
  • Meth is also a new problem. It is starting to be worse than heroin
• WV overdose rates / mortality are growing faster than US
• People dying – not young and dumb, more mature addicts
• More men than women – overall and in treatment
• Gabapentin – abuse took off in a hurry, slow decline
  
  • It was down for a very long time but when opiods were prescribed, providers switched to prescribe gabapentin and then people abused gabapentin rapidly. There is a slow decline now.
• Soap box
  
  • How can we treat chronic pain?!?!

Question 140

Predictors of effective treatment of addiction

Answer 140

• No single treatment is appropriate for all individuals
• Needs to be readily available
• Needs to be affordable (insurance coverage)
• Attends to multiple needs of the individual
• Plan must be modified to meet changing needs
• Remain in treatment for adequate period of time
• Provide assessment of co-occurring medical illness
• Counseling (group and/or individual) to address critical psychological issues
• Treatment of co-occurring mental illness (30-70% of individuals)
• Medical detox is on the first stage, does little to change long term use
• Monitor any mood altering substances during or after treatment
• Long term process and may require multiple episodes of intervention/treatment

Question 141

How does medication assisted treatment of addiction work?

• benefits ?

Answer 141

Medication Assisted Treatment

• Must work through the same receptors
• Short term prevention of withdrawal
• Long term control of cravings
• Allow an addict to regain control of their lives

Benefits of MAT

• Increased retention in treatment
• Reduced drug use
• Increased rate of abstinence from illicit drugs
• Decreased criminal activity
• Decreased infectious disease transmission
• Decreased overdose rates
• NAS – easier to treat
• Restore familial relationship
• Return as productive members of society

Question 142

Examples of MAT (medical tx of addiction)

1)

• uA slow acting, opioid agonist
• uTaken orally, long half life, dampening the high
• uUsed since 1960’s to treat heroin addiction
• uRegulated by law to OTP’s (outpatient treatment programs)
• uTypically dispensed daily
• uSchedule 2 drug

2)

• uA partial opioid agonist, strong receptor affinity
• uMinimal dopamine release, minimal euphoria
• uReduces cravings, ceiling effect
• uFirst approved in 2002 through DATA
• uCertification required but dispenses outside OTP, in physician office
• uSchedule 3
• uSubutex, Suboxone, Bunavail, Zubsolv, Sublocade

3)

• uOpioid antagonist
• uNo dopamine release, i.e., no euphoria
• uNot addictive, no dependency, no sedation
• uOral, IM, implant formulations
• uUsed for alcoholism as well
• uMust be drug free prior to starting
• uEffective in judicial system

***Identify phases of treatremnet

Answer 142

1. Methadone
2. Buprenorphine
3. Naltrexone

Phases of Treatment

• Phase One: Induction – finding the right dose
• Phase Two: Maintenance – providing stability
• Phase Three: Detoxification – weaning patient to lower dose/off

Question 143

• Short comings of MAT (Methadone, naltrexone, bubrenorphine)
• Why do we need MAT

Answer 143

Short-comings of MAT

• Low to medium intensity
• Primarily treats opioid dependence
• Difficulty controlling chronic pain
• Difficult to wean patients off with excessive street market for buprenorphine
• 2 years to change 20+ years of addiction
• Difficulty controlling co-morbid anxiety d/o
• Limited ability to provide inpt or outpt detox for naltrexone therapy

Why do we need MAT?

• 42/1000 West Virginians with illicit drug abuse/dependence in the past year 4% or 1/25
• 38/1000 West Virginians needing but not receiving treatment for illicit drug abuse/dependence
• 4/1000 West Virginians receiving treatment for illicit drug abuse/ dependence 90% don’t get treatment

Question 144

Summary of tx of substance abuse in pregnancy

Answer 144

• žEarly universal screening, brief intervention and referral
• žMedication assisted therapy(MAT) is needed for pregnancy and opiate use disorder (OUD)
• žInfants born to mothers with OUD should be monitored for neonatal abstinence syndrome (NAS)
• žBreastfeeding is encouraged for women receiving MAT
• žPostpartum therapy is essential
• žContraception, contraception, contraception

Question 145

6 screening questions for substance abuse

**Pneumonic

***DSM 5 criteria

Answer 145

CRAFT

DSM 5 criteria for substance use disorder

• 1.Use in larger amounts or for longer periods of time than intended
• 2.Unsuccessful efforts to cut down or quit.
• 3.Excessive time spent taking the drug
• 4.Failure to fulfill major obligations
• 5.Continued use despite knowledge of problems
• 6.Important activities given up
• 7.Recurrent use in physically hazardous situations
• 8.Continued use despite social or interpersonal problems
• 9.Tolerance
• 10.Withdrawal
• 11.Craving

Severity is designated according to the number of symptoms endorsed:

0 - 1: No diagnosis

2 - 3: mild SUD

4 - 5 : moderate SUD

6 or more: Severe SUD

Question 146

Effects of opiods in pregnancy - prenatal counseling regarding risks

Answer 146

• žBirth defects: absolute risk is low—some evidence for increased risk in studies with small sample sizes and potential confounding
  
  • Opiods DO NOT cause birthdefects
• žFetal growth restriction: increased risk of association based on strong evidence
• žPreterm birth: increased risk of association based on strong evidence

Question 147

• What is the main goal of treatment in addiction during pregancy
• what is the current treatment of choice

Answer 147

Medication assisted treatment (MAT) for addiction during pregnancy

• The main goal of treatment is to PREVENT RELAPSE
  
  • Ongoing therapy is what prevents the relapse (e.g IOP - intensive outpatient programs)
• žMethadone maintenance is current treatment of choice for opiate addicted pregnant women. Also preferred for long standing polysubstance abuse .Better for people who still crave the high
  
  • žImprove perinatal outcome, decreases IUGR
  • žAvoidance of IV drug use
    
    • Decreased risk of HIV, hepatitis, subacute bacterial endocarditis, weird sepsis, abcess
  • žMinimization of “drug-seeking” behaviors
    • ›Prostitution, STDs,
  • žScheduled administration
    
    • ›Circumvents recurrent withdrawal
    • ›Decreased fluctuations in opioid level
• Bubrenorphine; also used. help you go into immediate withdrawal

Question 148

MAT in pregnancy

• Use of buprenorphine vs methadone

Answer 148

Methadone vs bubrenorphine

• Buprenorphine
  
  • No evidence of the long term effects of bubrenrphone in NAS tx
  • You can’t overdose on it
• Methadone -
  
  • preferred for long standing polysubstace abuse.
  • Less convenient.
  • Higher risk of overdose mortality
  • longer tx duration of NAS

Bubrenorphine (compared to methadone)

• žMay be prescribed from physicians office
• žSignificantly lower rates of illicit opioid consumption
• žFewer withdrawal symptoms
• žLower potential for respiratory depression
• žMethadone more effective for polypharmacy and those still seeking the high

In pregnant OUD (opiod use disorder) patient

• žShorter length of hospitalization for buprenorphine-exposed (p=.021)
• žSuggest buprenorphine possibly superior to methadone

Question 149

Identify medication (prenancy addiction)

1)

• žPartial opioid agonist
• žSublingually
• žDosage 4 – 24mg
• žWith naloxone (Suboxone)
  
  • ›Poor oral absorption
  • ›May precipitate withdrawal when given parenterally

Answer 149

Buprenorphine (Subutex)

Question 150

Describe MARC for pregancy addiction

Answer 150

Maternal Addiction and Recovery Center (MARC)

• žOpen enrollment
• žWeekly group therapy by addictions counselor
• žIndividual therapy monthly or more often if needed
• žWeekly NA or AA meetings
• žNursing staff empathy
• žCombined OB and addiction treatment
• žPatients integrated into clinic population
• žIn hospital addiction assessment
  
  • ›Long standing benzodiazapine addiction a contraindication
• žMonitored withdrawal prior to initializing buprenorphine
• žDosage optimization prior to discharge
• ž192 patients converted to buprenorphine
• ž36% failed to make initial counseling appointment
  
  • ›No common theme
• žOf patients making at least one appointment, 20% have been discharged
  
  • ›Non-compliance
  • ›Relapses (after stabilization)
• ž52 Women have delivered
  • Good news; ›55 babies….3 sets of twins
  • Disturbing news;
    • –30% of these mothers infected with hepatitis C
      
      • –90% today due to heroin vs pain pills
    • –Median hospital stay 22 (range 7 to 48) days for infants requiring treatment
    • –NO dosage threshold

Question 151

Describe symptoms of opiod withdrawal in pregnancy

• early vs severe vs fetal

Answer 151

Question 152

Describe NAS

• ****What is the hallmark of neonatal withdrawal?

Answer 152

NAS - Neonatal Abstinence Syndrome

• *Passive exposure of the newborn occurs when a mother uses a neuroactive drug during her pregnancy
• *When the infant is deprived of these substances through the birthing process, a withdrawal syndrome may develop
• *Classic NAS consists of a wide variety of CNS signs of irritability, GI problems, autonomic signs of dysfunction, and respiratory symptoms
• The hallmark of neonatal withdrawal is a striking disorder of movement, most aptly termed “jitteriness”
• *Autonomic over-reactivity is typically exhibited by yawning, sneezing, mottling and fever
• Cerebral irritation results in an irritable and hypertonic infant

Question 153

Describe pathogenesis of NAS

• chart/progression
• Disuse hypersensitivity
• alternate pathways

Answer 153

NAS pathogenesis

• *Endogenous opiates (endorphins, enkephalins and dynorphins)
• *Complex interactions between endogenous opiates and their receptors are important in the developing brain
• *Locus coeruleus is a nucleus in the brain stem (pons) where norepinephrine is synthesized and involved with physiological response to stress and panic
• *When the opiate is withdrawn, the inhibiting effect gone
• *This results in a supranormal increase in norepinephrine levels, which are the likely cause of the signs and symptoms of NAS

Disuse Hypersensitivity

• *A drug may depress certain neural systems
• *Render the targets hypersensitive to their usual stimuli
• *Removal of the depressing drug results in a rebound hypersensitivity of the affected targets
• May be caused in part by an increase in synthesis of certain receptors

Alternate Pathways

• *Drug may depress a primary neural pathway
• *An alternate pathway, usually of minor activity, may become more prominent in attempt to compensate
• When the drug is removed, both pathways may operate in an additive fashion

Question 154

Identify treatment of NAS (neonatal abstinence syndrome)

• opiod agents (3)
• Adjunct agents (5)

Answer 154

*Opioid agents used

• *Morphine
  
  • *Full mu opiate receptor agonist
  • *Half life 8-9 hours (seen numbers as low as 4 hrs)
  • *Metabolized in the liver then renally excreted
  • *Common preparation OMS 0.4mg/ml
  • *Dose range 0.03- 0.1 mg/kg/dose given every 3-4 hours
    
    • *Most start with 0.04 or 0.05mg/kg/dose
  • *Can titrate up or down for symptom control
• *Methadone
  
  • *Full mu opiate agonist (synthetic)
  • *Half life ranges 16-32 hrs (most report around 26 hours)
  • *Metabolized extensively by hepatic N-demethylation
  • *Common oral solution is 1mg/ml
  • *Dosing range 0.05- 0.1 mg/kg/dose every 6-12 hours
• *Buprenorphine
  
  • *Partial mu opioid receptor agonist
    
    • *Exhibits ceiling effect
  • *Half life around 31-36 hours
  • *Metabolized by both N-dealkylation to norbuprenorphine and glucuronidation

*Adjunct agents

• *Phenobarbital
  
  • *GABA receptor agonist
  • *Half life in neonates 67-115 hours
  • *Preferred adjunct when polysubstance abuse with benzodiazepines
  • *Dosing scheme of oral loading dose of 20 mg/kg or 10 mg/kg every 12 hours for 2 or 3 doses followed by 5-10 mg/kg/day
  • *Some infants discharged home and outgrow dose
• *Clonidine
  
  • *α2-adrenergic receptor agonist
  • *Half life about 12-33 hrs
  • *AAP dosing recommends of 0.5-1 mcg/kg/dose given every 3-6 hours
    
    • *Some clinical trials used 1mcg/kg/dose
    • *One PK paper suggested 1.5 mcg/kg/dose administered every 4 hours starting in the second week of life to accommodate increased clearance over the first month of life.
• *Ativan
• *Gabapentin
• *Keppra

Question 155

Adolescent substance Use - warning signs

• social/behavioral
• Medical
• stats

Answer 155

Warning signs

_*Social/Behavioral:_

• *School performance/delinquency
• *Sexual practices
• *Neurodevelopment/Cognition

_*Medical:_

• *Abscesses/Skin infections
• *Hep C/HIV
• *Mental health concerns

Stats;

• *Ages 12-17 yrs: 6.2% use Rx opiates for non-medical purposes
• *Adolescents have a much quicker interval from Rx misuse to IV drug use
• *Youth Drug Overdose:
  
  • *WV had almost 2x the national numbers
  • *Males 2.5x more likely to die

Question 156

Explain Marijuana/Cannabis

• what is cannabis
• what do our bodies make ? function
• properties
• How THC works

Answer 156

What is cannabis

• *Plants are categorized based on the amount of THC or the THC/CBD ratio
• *Hemp-producing strains are specifically bred to produce low THC levels
• *Hash oil, hashish (resin), marijuana (dried leaves/flowers)

Pharmacology

• *Our body makes endocannabinoids
  
  • *Regulation of movement, memory, appetite, body temperature, pain, and immunity
  • *Anandamide structure similar to THC
• *5 cannabinoid receptors have been identified
  
  • *CB1- predominantly in CNS
    
    • *Neuronal proliferation
    • *Migration
    • *Synaptogenesis
  • *CB2- immune cells, retina, spleen

Pharmacology

• *Psychoactive substance
• *Lipophilic
  
  • Lots of the cannabis is lipophilic so stays in fat (breast) so even if they quit before breastfeeding, the cannabis still stays in the breast and can be transferred to patients
• *Small molecular size
• *Easily crosses cellular barriers
• *Rapidly absorbed in the bloodstream

Pharmacology

• *THC acts to decrease inhibitory GABA release
• *This allows for less refractory period between neuronal depolarization
• *Allows neurons to fire quickly
• *Also induces apoptosis

Question 157

List neuromodulation therapies

Answer 157

Neuromodulation

• ECT (electroconclusive therapy)
• rTMS (repetitive transcranial magnetic stimulation)
• Magnetic seizure therapy
  
  • ECT vs TMS
• Light therapy
• DBS (deep brain stimulation)
• Other
  
  • focus ultrasound

Question 158

ECT

• how does it work
• Main uses (2)
• No beneficial for what tx?
• Contraindicatons?
  
  • absolute vs relative
• adverse effects
  
  • major one
• Results of ECT

Answer 158

Electroconvulsive therapy

• In modern practice, ECT is delivered as a series of brief treatments (typically 8-14) 2-3 times per week under general anesthesia
• Electrical stimulation induces a brief, controlled seizure lasting ~30-90 sec
• Electrode placement (unilateral or bilateral)
  
  • • Bitemporal (BT)
  • • Right unilateral (RUL) – offers near-equivalent efficacy with reduced cognitive side-effects
• Administering brief or ultra-brief pulses results in greater charge efficiency and fewer cognitive side-effects. Limits “spread” of stimulus and allows for more concentrated application of stimulus in brain areas that regulate mood.
• Primary Indications for Use
  
  • ¡Major depressive disorder – 64% to 87% of patients with severe MDD respond; up to 95% of patients with MDD with psychotic features
    
    • §Concomitant medical or mental illness or individuals highly refractory to multiple other forms of treatment are less likely to respond
  • ¡Bipolar disorder – response rate of ~80%; used most frequently in medication non-responders, delirious mania, and rapid cycling
• ¡ECT is not beneficial for
  
  • §Anxiety Disorders
  • §Personality Disorders
  • §Substance-use Disorders
  • §Autism Spectrum Disorders
  • §Persistent Depressive Disorder
• ¡Treatment plan needs to be comprehensive and address co-morbidities
• CONTRAINDICATIONS
  There are no absolute contraindications.
• Relative contraindications:
  1. recent intracranial hemorrhage
  2. recent thromboembolic stroke
  3. intracranial lesion causing mass effect
  4. recent MI, particularly if sequelae are present
  5. unstable angina or decompensating heart failure
  6. Unstable vertebral fracture
• Adverse effects
  
  • 1.Postictal disorientation – lasts few minutes to a few hours following seizure with avg 30min.
  • 2.Inter-ictal confusion – treatment induced delirium that persists during course of treatment; uncommon and if present a need for workup of other potential causes of delirium
  • 3.Memory impairment - anterograde and retrograde amnesia; usually completely resolved by 6 months post treatment.
    
    • a.anterograde resolves more quickly (days to weeks)
    • b.retrograde can last longer (months) and is more specific for events near time of ECT treatments
• Results of ECT
  
  • 1.Stimulates release of large amount of monoamine neurotransmitters, particularly dopamine and serotonin
  • 2.Decreased metabolic activity in frontal and cingulate cortex after ECT
  • 3.fMRI shows a reduction in global connectivity within the left dorsal lateral prefrontal cortex following ECT (see pic)
  • 4.Increases brain derived neurotrophic factor (BDNF)
  • 5.Induces neurogenesis and mossy fiber sprouting from granule cells in rat hippocampus

Question 159

Identify neuromodulation therapy

• ¡developed as effort to reproduce benefit of electrical stimulation seen with ECT but with less invasive and more focal technique.
• ¡method to noninvasively study corticospinal tract function
  • §Application of pulse generates compound motor action in corresponding contralateral muscle group via corticospinal tract

***Identify MoA, contraindications (2) and alternative methods

Answer 159

Repetitive Transcranial Magnetic Stimulation (rTMS)

• MoA; through repeated stimulation of targeted neural circuits
  
  • •TMS induces neuroplasticity
  • •Strengthens connections in targeted pathways
  • •Takes advantage of known relationships between pathways to up- or down-regulate target circuits
• Contraindications
  
  • ¡Small increased risk for seizures
  • ¡Implanted metallic hardware (e.g., aneurysm clips or bullet fragments)
  • ¡Cochlear implants
  • ¡Implanted electrical devices (e.g., pacemakers, intra-cardiac lines, and medication pumps)
  • ¡Caution advised with unstable non-psychiatric medical illnesses
• Alternatve treatment methods
  
  • ¡Accelerated Repetitive
  • ¡High dose Repetitive
  • ¡Theta Burst Repetitive
    
    • §2014 used for depression
    • §3 bursts at 50Htz Q200ms
    • §Treatment time = 6min
  • ¡Deep rTMS
    
    • §Wider, broader stimulation area
    • §20 min sessions
  • ¡Bilateral Repetitive

Question 160

Identify neuromodulation therapy

• Developed as effort to combine the benefits of both ECT and rTMS without the drawbacks of either.
• Compared to ECT, it has;
  
  • •More focal electrical field
  • •Weaker and more focal seizure activity
  • •Superior cognitive outcomes
  • •Preserved antidepressant efficacy

Answer 160

Magnetic Seizure therapy (MST)

Question 161

Identify neuromodulation therapy

• ¡Treats Seasonal Major Depressive Disorder
  
  • §Mild to moderate severity
• ¡Use 10,000 lux
• ¡Position 12-24in away
• ¡Typical schedule is 1 session for 30-min daily
• ¡Keep eyes open (but don’t stare at light)
• ¡Some respond immediately, others take days or several weeks

Answer 161

Light Therapy

Question 162

Identify neuromodultaton therapy

• Invasive/surgical
• ¡Investigational treatment for treatment resistant depression
  
  • §2015 – Level III trials
• ¡One or more electrodes implanted in targeted brain regions
• ¡Electrode placement done under local anesthesia while patient awake
• ¡Second procedure done under general anesthesia runs wires under skin of neck to attach to pulse generator in chest

Answer 162

Deep Brain Stimulation (DBS)

• ¡Stimulation is continuous (not pulsatile)
  
  • §Bilateral vs Unilateral
• ¡Parameters adjusted using hand held device
  
  • §Can modify voltage, pulse width, frequency, etc.
• ¡Various brain regions being investigated including
  
  • §Subcallosal cingulate gyrus
  • §Ventral anterior internal capsule and ventral striatum
  • §Nucleus accumbens
  • §Medial forebrain bundle
  • §Inferior thalamic peduncle
  • §Habenula