Exam 2 Week 2 Flashcards

Question

Scizophrenia * what deletion syndrome?

Answer 1

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

Answer 2

•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**

Answer 3

* •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

Answer 4

•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

Answer 5

•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.

Answer 6

**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.

Answer 7

**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

Answer 8

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)

Answer 9

* •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

Answer 10

•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

Answer 11

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

Answer 12

* 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**

Answer 13

* •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

Answer 14

* •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

Answer 15

**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

Answer 16

**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

Answer 17

* **•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

Answer 18

**•Capgras Syndrome**

Answer 19

•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

Answer 20

* 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

Answer 21

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)

Answer 22

**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

Answer 23

**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

Answer 24

**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

Answer 25

* 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*

Answer 26

* 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)

Answer 27

**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

Answer 28

* 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)

Answer 29

* 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

Answer 30

* “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

Answer 31

* **•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.

Answer 32

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

Answer 33

**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

Answer 34

* •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

Answer 35

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

Answer 36

**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

Answer 37

**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

Answer 38

**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

Answer 39

**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

Answer 40

* •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.

Answer 41

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

Answer 42

* Play therapy * Couples therapy * Family therapy * Group therapy

Answer 43

**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

Answer 44

* •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

Answer 45

**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.

Answer 46

**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

Answer 47

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

Answer 48

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

Answer 49

**Acute Insomnia**

Answer 50

Inadequate sleep hygiene

Answer 51

**•Psychophysiological insomnia**

Answer 52

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

Answer 53

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

Answer 54

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

Answer 55

**•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)

Answer 56

**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

Answer 57

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

Answer 58

* •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

Answer 59

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

Answer 60

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

Answer 61

•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

Answer 62

**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

Answer 63

**•Periodic limb movement of sleep**

Answer 64

**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

Answer 65

Circadian rhythm sleep disorders - **Shift work disorder**

Answer 66

**Jet Lag**

Answer 67

* 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 ## Footnote **_Hypnotics should not be used for more than one month._**

Answer 68

**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.

Answer 69

Zolpidem (Ambien)

Answer 70

**Zaleplon (Sonata)** * *used in people who wake up in middle of night and can't fall back to sleep*

Answer 71

Eszopicione (Lunesta)

Answer 72

Barbiturates (BARBs) * **_Depress CNS activity at low concentrations._** * **_Depress activity of nerve, skeletal muscle and smooth and cardiac muscle at high concentrations!!!_**

Answer 73

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

Answer 74

•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

Answer 75

Diphenhydramine (Benadryl), Doxylamine (Unisom)

Answer 76

Ramelton (Rozerem)

Answer 77

Alcohol (ETOH)

Answer 78

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_**

Answer 79

Disulfiram (Antabuse) * Treat alcoholism

Answer 80

1. Naltrexone 2. Acamprosate

Answer 81

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

Answer 82

**_Modafinil (Provigil)_**

Answer 83

Gamma hydroxybutyrate (Xyrem)

Answer 84

* 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

Answer 85

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

Answer 86

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

Answer 87

* •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

Answer 88

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

Answer 89

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

Answer 90

Sedatives * Benzodiazepams * Barbiturates * Propofol * Alcohol

Answer 91

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

Answer 92

**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)

Answer 93

**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

Answer 94

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

Answer 95

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**

Answer 96

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)

Answer 97

**_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

Answer 98

**_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

Answer 99

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

Answer 100

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.

Answer 101

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

Answer 102

* 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

Answer 103

1. Tolerance 2. **_Positive and negative reinforcement_** 3. Enabling 4. Kindling

Answer 104

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!

Answer 105

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

Answer 106

* **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)

Answer 107

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!**

Answer 108

**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.**

Answer 109

Pneumonic **ABCDE** * **Inability to consistently **_A_**bstain;** * **Impairment in **_B_**ehavioral control;** * ****_C_**raving;** or increased “hunger” for drugs or rewarding experiences; * ****_D_**iminished recognition of significant problems** with one’s behaviors and interpersonal relationships; and * **A dysfunctional _E_motional response**

Answer 110

* 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?!?!

Answer 111

* 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

Answer 112

**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

Answer 113

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

Answer 114

**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**

Answer 115

* Early universal screening, brief intervention and referral * Medication assisted therapy(MAT) is needed for pregnancy and opiate use disorder (OUD) * Infants born to mothers with OUD should be monitored for neonatal abstinence syndrome (NAS) * Breastfeeding is encouraged for women receiving MAT * Postpartum therapy is essential * Contraception, contraception, contraception

Answer 116

**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

Answer 117

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

Answer 118

**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**) * **_Methadone 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** * Improve perinatal outcome, decreases IUGR * Avoidance of IV drug use * Decreased risk of HIV, hepatitis, subacute bacterial endocarditis, weird sepsis, abcess * Minimization of “drug-seeking” behaviors * ›Prostitution, STDs, * Scheduled administration * ›Circumvents recurrent withdrawal * ›Decreased fluctuations in opioid level * **Bubrenorphine**; also used. help you go into immediate withdrawal

Answer 119

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) * May be prescribed from physicians office * Significantly lower rates of illicit opioid consumption * Fewer withdrawal symptoms * Lower potential for respiratory depression * Methadone more effective for polypharmacy and those still seeking the high In pregnant OUD (opiod use disorder) patient * Shorter length of hospitalization for buprenorphine-exposed (p=.021) * Suggest buprenorphine possibly superior to methadone

Answer 120

**Buprenorphine (Subutex)**

Answer 121

Maternal Addiction and Recovery Center (MARC) * Open enrollment * Weekly group therapy by addictions counselor * Individual therapy monthly or more often if needed * Weekly NA or AA meetings * Nursing staff empathy * Combined OB and addiction treatment * Patients integrated into clinic population * In hospital addiction assessment * ›Long standing benzodiazapine addiction a contraindication * Monitored withdrawal prior to initializing buprenorphine * Dosage optimization prior to discharge * **192 patients converted to buprenorphine** * 36% failed to make initial counseling appointment * ›No common theme * Of patients making at least one appointment, 20% have been discharged * ›Non-compliance * ›Relapses (after stabilization) * 52 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

Answer 122

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

Answer 123

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

Answer 124

\*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

Answer 125

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

Answer 126

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

Answer 127

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

Answer 128

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

Answer 129

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

Answer 130

Magnetic Seizure therapy (MST)

Answer 131

**Light Therapy**

Answer 132

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

Exam 2 Week 2 Flashcards

(162 cards)