exam 2 psych Flashcards

Question

* ADHD- Predominantly hyperactive-Impulsive Presentation * ADHD- Predominantly Inattentive Presentation * ADHD-Combined Presentation

Answer 1

ADHD- Predominantly hyperactive-Impulsive Presentation * •6 or more symptoms of hyperactivity-impulsivity * •\< 6 symptoms of inattention ADHD- Predominantly Inattentive Presentation * •6 or more symptoms of inattention * •\< 6 of hyperactivity/impulsivity * •More often diagnosed in **girls** * •More often diagnosed **later** ADHD-Combined Presentation * •6 or more symptoms of inattention * •6 or more symptoms of hyperactivity-impulsivity

Answer 2

Social and interpersonal effects * •Demands on parents * •Classroom management * •Relationships with peers Course * •There is significant persistence of symptoms into adulthood in 15-20% of cases. * •In the majority, there is at least partial remission between 12 and 20 years of age. * •Hyperactivity is often first to diminish. * •Many adults continue to have learning problems and impulsivity. Management * •Consistency of contingencies and expectation * •Parental education, support, and skill development * •Behavioral therapy * •Cognitive Behavioral therapy * •Development of instructional support plan * •IEP * •Section 504

Answer 3

ADHD The pharmacological treatment approach in ADHD is to “retune” these brain areas by **increasing DA and NE signaling**. In essence “increasing signal to noise ratio”. * Methyphenidate based * Amphetamines * Other

Answer 4

Concerta: * ·Extended release tablet * ·Oral osmotic delivery system * ·12 hour duration of action * ·Pharmacokinetics not affected by food Metadate CD: * ·Provides efficacy “throughout the day” * ·Biphasic release (bead technology) * ·Pharmacokinetics affected by food Focalin: * ·d-isomer of methylphenidate * ·Prescribed at ½ of usual dose Daytrana (methylphenidate patch): * ·for children 6-12

Answer 5

**Side effects** (at normal Pharmacological doses, see drug abuse lecture for abuse side effects) * GI most common * ·Abdominal pain, nausea and weight loss, Restlessness, anxiety, insomnia, agitation, aggressiveness, High doses → Convulsions Cautions; * Avoid in patients with CV disease * Avoid in patients with Glaucoma. * High abuse potential (see drug abuse lecture) * Avoid MAOI * Not for previous drug users Other products * Adderall - also available as an extended release (mixed amphetamine salts) * Dextroamphetamine (Dexedrine; single amphetamine salt) * Lisdexamfetamine (prodrug of dextroamphetamine)

Answer 6

**Clonidine or Guanfacine** * Alpha2A adrenergic agonists

Answer 7

Oppositional Defiance Disorder and Conduct disorder

Answer 8

**ADHD Medications:** * •May need to use higher doses of stimulants compared to ADHD * •The Alpha2A-adrenergic agonists can be used alone or as an adjunct to methylphenidate. **Mood Stabilizers (see mood disorder lectures):** * •CD is thought to be a precursor for bipolar * •Lithium is effective at controlling aggression * •Can be combined with anti-psychotic. * •Valproate is an anticonvulsant that can be used as a mood stabilizer. **Atypicals (see psychosis lecture):** * •Antagonists at 5HT-2A and dopamine D2 receptors (and many others) * •Huge side effect profile

Answer 9

* •TS is likely due to disinhibition in cortico-striatal-thalamic- cortical loops, with an overly active caudate nucleus (similar to ADHD and OCD, both common comorbidities of TS). * •Dysfunction within these circuits results in an inability to suppress unwanted movements, behaviors, or impulses. Though many neurotransmitters may be involved TS patients have increased density of the presynaptic dopamine transporter and an increased density of postsynaptic D2 dopamine receptors, suggesting increased uptake and release of dopamine. * •Thus we typically target dopamine signaling for the tics

Answer 10

* •Pharmacologic * •Physical medicine – Physical therapy, spinal modulation * •Behavioral medicine - CBT * •Neuromodulation – TENS, Spinal cord stimulation, deep brain stimulation * •Interventional – Direct injection into pain area of substances such as glucocorticoids or locals * •Surgical \*\*Typically a therapeutic regimen will combine multiple approaches

Answer 11

**Non-opiod analgesics**

Answer 12

Drugs can be; * ·Agonist * ·Antagonist * ·Mixed agonist * ·Partial agonist – have limited agonist like effects

Answer 13

Use * ·Gold standard for comparison among opioids * **·Relief of moderate-to-severe acute and chronic pain; pulmonary edema; preanesthetic medication** **Source:** * ·From poppy plant, Papaver somniferum * ·Milky substance from seed capsule which is dried and powdered to make opium * ·Opium contains several alkaloids: * ·morphine, codeine, papaverine Structure: * ·Many semisynthetic compounds made by modification of morphine molecule Other effects: * ·Antitussive effects: prevent cough by action in medulla * **·Codeine/hydrocodone used for cough suppression** * o↓ sensitivity of CNS cough centers to peripheral stimuli * o↓ mucosal secretion * oaction occurs at doses less than that for analgesia * oantagonized by naloxone Pharmacokinetics: * ·Route of administration: s.c./i.m./ oral / suppository /pump * ·Low bioavailability of oral formulation (17-30%) due to 1st pass effect * ·Readily absorbed from GI tract, nasal mucosa, lung * ·Metabolism: glucuronide conjugation with urinary excretion * ·Active metabolites

Answer 14

Hydromorphone (Dilaudid)

Answer 15

Methadone (Dolophine) "Methadone maintenance" * •Used in Rx for opiate withdrawal * •1x/day at higher dose than for analgesia * •Tolerance develops * •Opioid craving is met without need for IV drug use * •If opiate such as heroin is taken while on methadone, effects are greatly reduced due to “cross tolerance”

Answer 16

Hydrocodone + acetaminophen (Lortab, Vicodin):

Answer 17

**Oxycodone** _·Oxycontin_ Delayed release formulation has large potential for abuse, can crush tablet and ingest all at once (drug abuse lecture) Combined formulations: * ·Oxycodone/ibuprofen: * ·Oxycodone/aspirin: * ·Oxycodone/acetaminophen:

Answer 18

* •Meperidine * •Fentanyl * •Sufentanyl * •Alfentanil * •Remifantanil

Answer 19

Meperidine (Demerol) * •µ- opioid agonist * •Excitement caused at toxic doses due to metabolite, normeperidine (CNS stimulant); not blocked by naloxone * •MAO inhibitors + Meperidine Possibly severe reaction: excitation, delirium, hyperpyrexia, convulsions, respiratory depression

Answer 20

**Fentanyl (Duragesic)** **\*Fentanyl derivatives** * Sufentanil (Sufenta) – m opioid agonist: * ·6000 x as potent as morphine * ·I.V. administration; anesthesia adjunct; post-op anesthesia * ·Less hemodynamic instability, respiratory depression, chest wall rigidity * ·Costly * Alfentanil-μ-opioid agonist: * Remifentanil- μ opioid agonist: * ·short acting * ·20x more potent than alfentanil * Carfentanyl - μ opioid agonist: * •Only human use is abuse

Answer 21

Propoxyphene (Darvon)

Answer 22

* •Pentazocine * •Buprenorphine * •Tramadol

Answer 23

Pentazocine (Talwin)

Answer 24

Buprenorphine (Buprenex)

Answer 25

Tramadol (Ultram)

Answer 26

* **•Dextromethorphan (Delsym, Tussin):** * •synthetic derivative of morphine * •suppresses response of cough center; elevates threshold * •no analgesia * •less constipation than codeine * •not antagonized by naloxone * •Robotripping, major agent in cough syrup abuse in teens

Answer 27

Topical * •Lidocaine – local anesthetic * •Capsaicin – chilli pepper alkaloid adjunctive * •TRPV1 antagonist * •Ion channel expressed on afferent nociceptors NMDA Antagonists: * •Ketamine – blocks NMDA and thus glutamate signaling * •See anesthetics lecture

Answer 28

•Centrally acting muscle relaxants are used primarily as antispasmodics or in the relief of lower back pain, all of these drugs can interact with other CNS depressants.

Answer 29

Clinical use: * •Muscle Spasms – IV or IM * •Muscle relaxant – oral as an adjunct therapy

Answer 30

Chlorzoxazone (Paraflex) \*

Answer 31

**Cyclobenzaprine (Flexeril) \*\*\***

Answer 32

Metaxalone (Skelaxin) \*\*\*

Answer 33

Methocarbamol (Robaxin) \*\*\*

Answer 34

Orphenadrine (Norflex) \*

Answer 35

Tizanadine (Zanaflex) \*\*\*

Answer 36

**_Opiods are not first line_** for pain treatment

Answer 37

*  Pain affects more Americans than diabetes, heart disease and cancer combined. *  Significant end of life issue as many hospitalized patients experience pain in the last days of their lives and despite therapies to alleviate most pain for those dying of cancer, 50-75% of patients die in moderate to severe pain. *  An estimated 1/5th of American adults report sleep disrupted by pain or physical discomfort. *  Most common types of pain, low back pain (27%), severe headache or migraine pain (15%), neck pain (15%) and facial ache or pain (4%). *  Back pain is the leading cause of disability in Americans under 45 years old.

Answer 38

Somatic: *  Arising from skin, bone, joint, muscle, connective tissue *  Typically throbbing and well localized Visceral: *  Arising from internal organs *  Can be referred or a more localized Four Stages: **Stimulation  transmission  perception  modulation** * Stimulation: *  Nociceptors found in somatic and visceral structures distinguish between noxious and innocuous stimuli. *  Activated by mechanical / thermal /chemical impulses. *  Mechanisms of stimuli include bradykinins, H+, K+, prostaglandins, histamine, cytokines etc. *  Receptor activation promotes action potentials that are transmitted along afferent nerves to the spinal cord. * Transmission: *  Occurs in Aδ and C-afferent nerve fibers. *  Fibers synapse in various laminae of the spinal cord’s dorsal horn resulting in release of various transmitters including glutamate, substance P and aspartate. *  Signal is transmitted through the spinothalamic tract (see figure). * Perception: *  Pain becomes a perceived conscious experience once the signal enters the cortical structures *  Behavioral and cognitive functions can modify pain perception. * o Decreased by – relaxation, exercise, distraction, meditation, guided mental imagery * o Increased by – change in neurobiochemical makeup such as depression, anxiety * Modulation: *  Body modulates pain via a number of endogenous systems * o Opioids * o Descending spinal tract

Answer 39

**Neuropathic pain** is pain that has become disengaged from the original stimuli; neuropathic pain is a result of nerve damage / plasticity changes while nociceptive pain is a function of normal nerve activity. Pain Classification: Acute / Chronic **Acute pain** is a normal physiological process warning us of disease states and potentially harmful situations. Acute pain is generally nociceptive in nature, common causes include: Surgery, acute illness, trauma, labor, medical procedures **Chronic Pain** While acute pain is a normal sensation triggered in the nervous system to alert you to possible injury and the need to take care of yourself, chronic pain is different. Chronic pain persists. Pain signals keep firing in the nervous system for weeks, months, even years. There may have been an initial mishap -- sprained back, serious infection, or there may be an ongoing cause of pain -- arthritis, cancer, ear infection, but some people suffer chronic pain in the absence of any past injury or evidence of body damage. Many chronic pain conditions affect older adults. Common chronic pain complaints include headache, low back pain, cancer pain, arthritis pain, neurogenic pain (e.g. diabetic neuropathy).

Answer 40

**Six major approaches:** *  Pharmacologic * o Pharmacologically the choice of agent is based on pain type and patient characteristics, including the pathophysiology of the pain syndrome, other symptoms and comorbidities, other medications being taken, organ reserves, pharmacokinetics/pharmacodynamics, and the likelihood of adverse effects. *  Physical medicine – Physical therapy, spinal modulation *  Behavioral medicine - CBT *  Neuromodulation – TENS, Spinal cord stimulation, deep brain stimulation *  Interventional – Direct injection into pain area of substances such as glucocorticoids *  Surgical **Typically a therapeutic regimen will combine multiple approaches.** e.g Torn meniscus *  Ibuprofen as required *  Physical therapy followed by *  TENS (Transcutaneous electrical nerve stimulation) and Ice *  Potentially surgery if no improvement

Answer 41

**Specific Learning Disorder;** different areas of deficit may be ; * with impairment in reading * with impairment in mathematics * with impairment in writing * classified as mild, moderate, severe * Prevalence is thought to be between 2% and 10% of the population * 2-4x more common in boys * Tends to be familial **\*\*\*\*\*Patient with learning disorder will have average IQ, no sensory or motor deficits**

Answer 42

* •Not the result of a specific sensory, motor, or neurological disorder * •Intellectual deficit alone does not account for failures in academic development * •Not attributable to lack of educational opportunity and learning experiences * •Now also looking at failure to respond to efforts to remediate

Answer 43

* •Disorders involve skills that are multifactorial and integrative * •Various subtle dysfunctions can be part of the learning problem. * •Causes can be equally various * •Deficits in attention and concentration can be contributory **Associated features** * •Poor self-esteem * •Learned helplessness * •Social Difficulties * •School refusal/drop-out rate of up to 40% * •Co-occurring disorders including 10%-25% of individuals * •Mood disorders * •Behavior disorders * •ADHD **Management** * •Identification and evaluation * •Educational services * •Specialized instruction * •Test modifications/accommodations * •Additional services as needed (e.g., speech and language professionals * •Educating patient and family: understanding the problem

Answer 44

Developmental Coordination Disorder * •Difficulty with acquisition and execution of coordinated movement * •Not due to intellectual impairment, visual impairment, neurological condition Stereotypic Movement Disorder * •Repetitive, purposeless motor behavior * •Interferes with daily functioning

Answer 45

**Tic Disorders** * •Tourette’s Disorder * •Persistent (Chronic) Motor or Vocal Tic Disorder * •Provisional Tic Disorder •Estimates of \> 1:100 have some type of tic disorder xters of tics * •Behaviors may be as simple as coughs, jerks, or snorts, or more complex phenomena such as facial gestures, echolalia, grooming behaviors, or coprolalia. * •Tics may be voluntarily suppressed for a period of time, but the patient usually is overwhelmed eventually by the need to perform the behavior. * •Tics often change over time

Answer 46

* •ADHD (50-60%) * •OCD (30-70%) * •Common obsessions include: “Just right” Phenomenon, Violent images, sexual thoughts, symmetry * •Common compulsions: touching, blinking, repeating, hoarding * •**“Triad” Disorder** * **•ADHD** * **•OCD** * **•Tics**

Answer 47

**Persistent (Chronic) Motor/Vocal Tic Disorder**

Answer 48

Tourette’s disorder

Answer 49

* •Tenex * •Clonodine * •Atypicals * •Haldol * Suggestive of dopamine dysregulation * Motor component implicates nigrostriatal tract **Management** * •Education * •Define co-ocurring disorders * •Hierarchy of clinically impairing conditions * •Treat the impairing conditions * •Create balance of supportive/challenging environment

Answer 50

* •Language Disorder * •Persistent difficulties with acquisition and use across modalities * •Speech Sound Disorder * •Difficulty with speech sound production * •Childhood Onset Dysfluency Disorder (Stuttering) * •Difficulties with fluency and time patterning of speech * •Social (Pragmatic) Communication Disorder * •Difficulties with social use of verbal and nonverbal communication * May be the initial presentation of Learning Disorders * Require involvement of Speech/Language Pathologist * May present with secondary behavioral problems

Answer 51

Rumination Disorder

Answer 52

**•Conduct Disorder** **•Oppositional Defiant Disorder** •Also includes: * •Intermittent Explosive Disorder * •Pyromania * •Kleptomania * •Anti-social Personality Disorder

Answer 53

**•Primary feature of conduct disorder:** * •Persistent and repetitive pattern of behavior which violates the rights of others or age-appropriate social norms/rules **Characteristic behaviors** * •Aggression toward people or animals * •Can include sexual imposition or assault, or use of a weapon in more severe cases. * •Destruction of property * •Deceitfulness or theft * •Serious rules violations

Answer 54

**Asoociated personality features** * •Shallowness in relationships and attachments * •Inability to feel for others (lack of empathy) * •Impaired capacity for guilt or remorse **Incidence** * •6-16% among boys * •2-9% of girls •Two patterns of onset: * •Childhood onset-prior to age 10 * •Adolescent onset-no behaviors before age 10 * •Specify if: •With limited prosocial emotions * •Lack of remorse/guilt * •Callous-lack of empathy * •Unconcerned about performance * •Shallow or deficient affect * •Mild, Moderate, Severe **Family factors** * •Parental psychopathology (particularly antisocial personality and substance abuse) is thought to be causally important. * •Chaotic home environments, with inconsistent enforcement of rules and modeling of antisocial behavior by parents, are commonly observed.

Answer 55

Related problems * •Poor school performance * •Substance abuse * •Legal problems * •Learning disorders * •About 25-40% will meet criteria for antisocial personality disorder as adults. * •ADHD is a common comorbid disorder. Treatment * •Family therapy * •Psychotherapy - building capacity for relationships, response to social cues * •Consistent authoritative environment * •Social skills and assertiveness training

Answer 56

**Oppositional Defiant Disorder** _Characteristic behaviors_ * •Argumentative * •Difficulty managing limits/transitions * •Short-tempered and easily annoyed. * •Can be deliberately annoying * •Blame others for mistakes or misbehavior * •May be spiteful and vindictive * _Treatment_ * •Counseling or therapy for the child * •Evaluation of the family for dysfunctions that either contribute to the disorder or prevent the family from dealing with the child effectively * •Develop parental skills in behavior management. * •Rule out depression

Answer 57

•Some benefit for the use of ADHD medications with children with both Conduct Disorder and Oppositional Defiant Disorder * •Studies have only been conducted when there are both ADHD and symptoms of either CD or ODD * •Mood stabilizers are also helpful with CD * •Some thought that CD symptoms may be early signs of Bipolar Disorder

Answer 58

•Behavioral Therapy * •Bell & Pad * •Ultrasonic Bladder Alarm * •80% of typical enuretic volume •Medication * •DDAVP-desmopressin * •Synthetic vasopeptide * •Temporary suppression rather than cure

Answer 59

Encopresis

Answer 60

* •Behavioral Strategies * •Reinforcement of appropriate toileting behavior * •Use of bathroom after each meal * •Time (at least 15 minutes) * •Use of laxatives/enemas * •Education * •Biofeedback

Answer 61

* •Separation Anxiety * •Selective Mutism

Answer 62

* Definition * •Excessive anxiety in response to separation from major attachment figures or familiar surroundings. * •Unduly persistent and/or inconsistent with age. * Causal factors * •Fear provoking experiences * •Phobic anxiety modeled by parents * •Genetic factors * Characteristics * •Conforming and eager to please * •Prone to nightmares * •Physical complaints * •Secondary to anxiety * •Learned means for avoidance * •Morbid fears * •Restricted social lives * Management * •Gradually increase tolerance for separation from home and parents. * •Anxiety management * •Relaxation skills * •Cognitive strategies * •Supportive approach with positive incentives * •SSRI’s

Answer 63

* Definition * •Persistent failure to speak in specific social situations where speaking is expected, despite speaking in other situations * Management * •Variety of techniques have been tried including: * •Behavioral therapy * •Family therapy * •Speech therapy * •Pharmacological treatments * •Very difficult to treat

Answer 64

1. •Disinhibited Social Engagement Disorder 2. •Reactive Attachment Disorder Treatment * •Prognosis is poor * •Work to coordinate care * •Provide respite * •Educate caregivers

Answer 65

Personality disorders * Enduring patterns of inner experience and behavior that deviate markedly from expectations of an individual’s culture. * Pervasive, maladaptive, and cause significant impairment in social or occupational functioning * Lack insight, Sx may be ego-syntonic * Vulnerable to developing Sx of other disorders **5 criteria for all personality disorders** Enduring pattern of behavior/inner experience, manifested in two or more areas * Cognition * Affect * Interpersonal functioning * Impulse control Pattern * Pervasive and inflexible in a broad range of situations * Stable, onset no later than adolescence or early adulthood * Significant distress in functioning * Not accounted for by another mental/medical illness or by use of a substance International prevalence is about 6%, vary by gender, and many will meet criteria for more than one PD, classify for all they qualify for

Answer 66

Cluster A – schizoid, schizotypal, and paranoid * Eccentric, peculiar, and withdrawn * Familial association with psychotic disorders

Answer 67

**Cluster A - _Paranoid PD_** * vEpidemiology * v2-4% prevalence, M\>W, increased incidence in family members of schizophrenics, may be misdiagnosed in minority groups, immigrants, and deaf individuals * vDifferential Diagnosis * vSchizophrenia * vSocial disenfranchisement and social isolation * vCourse and Prognosis * vChronic, causes lifelong marital and job-related problems * vTreatment * vPsychotherapy is the treatment of choice, avoid groups due to mistrust and misinterpretation of other’s statements * vAntipsychotics if experiencing transient psychosis

Answer 68

**Cluster A - _Schizoid_ PD** * vEpidemiology * v3-5% prevalence, M\>W, increased prevalence of schizoid PD in relatives of schizophrenics * vDifferential diagnosis * vSchizophrenia * vSchizotypal PD * vCourse * vChronic * vTreatment * vLack insight of individual psychotherapy, may find groups threatening, may benefit from day-programs or drop-in centers * vAntidepressants with comorbid depression

Answer 69

**Cluster A - _Schizotypal_ PD** * vEpidemiology * v4-5% prevalence * vDifferential diagnosis * vSchizophrenia * vSchizoid PD * vCourse * vChronic, small minority develop schizophrenia * vPremorbid personality type for patient with schizophrenia * vTreatment * vPsychotherapy is the treatment of choice à to help develop social skills * vShort course of antipsychotics at low doses if necessary, may help decrease social anxiety and suspicion in interpersonal relationships

Answer 70

* Antisocial PD * Borderline PD * Historic PD * Narcissitic PD

Answer 71

**Cluster B - _Antisocial_ PD** vEpidemiology * vPrevalence 3% in men and 1% in women * vHigher incidence in poor urban areas and in prisoners, no racial difference * vGenetic component: increased risk among first-degree relatives vDifferential diagnosis * vDrug abuse vCourse * vChronic with some improvement with age * vMany have multiple somatic complaints, coexisting substance abuse and depression are common * vIncrease morbidity from substance use, trauma, suicide, and homicide vTreatment * vPsychotherapy is generally ineffective, meds may be used to treat symptoms of anxiety and depression but use with caution due to addictive potential

Answer 72

**Borderline PD (cluster B)** vEpidemiology * vPrevalence up to 6%, W\>\>M, suicide rate 10% vDifferential Diagnosis * vSchizophrenia * vBipolar II disorder vCourse * vVariable, may develop stability in middle age * vHigh incidence of co-existing major depression and substance use disorders * vIncreased risk of suicide vTreatment * vPsychotherapy is the treatment of choiceà **DBT (dialectical behavior therapy)** as well as CBT, mindfulness skills, and groups * vMeds to treat psychotic or depressive symptoms may be needed

Answer 73

**Histrionic PD** (cluster B) vEpidemiology * v2% prevalence, W\>M vDifferential diagnosis * vBorderline PD vCourse * vChronic, some improvement in symptoms with age vTreatment * vPsychotherapy is the treatment of choice * vMeds for associated anxiety and depression as necessary

Answer 74

**_Narcissistic PD_** (cluster B) vEpidemiology * vPrevalence up to 6% vDifferential diagnosis * vAntisocial PD vCourse * vUsually chronic, higher incidence of depression and midlife crisis since there is such high value on youth and power vTreatment * vPsychotherapy is the treatment of choice * vAntidepressants may be used if a comorbid mood disorder is diagnosed

Answer 75

* Avoidant PD * Dependent PD * Obsessive - compulsive PD

Answer 76

Avoidant PD vEpidemiology * vPrevalence 2.4%, M=F vDifferential Diagnosis * vSchizoid PD * vSocial anxiety disorder * vDependent PD vCourse * vUsually chronic, may remit with age * vParticularly difficult during adolescence when attractiveness and socialization are important * vIncreased incidence of associated anxiety and depression * vIf support system fails, patient is left very susceptible to depression, anxiety, and anger vTreatment * vPsychotherapy most helpful à assertiveness and social skills training * vGroups may be beneficial * vSSRIs may be helpful for comorbid social anxiety disorder or major depression

Answer 77

**Dependent PD (cluster C)** vEpidemiology * vPrevalence approx. \<1%, W\>M vDifferential diagnosis * vAvoidant PD * vBorderline and histrionic PD vCourse * vChronic, prone to depression, particularly after loos of person on whom they were dependent * vDifficulties with employment since they cannot act independently or without close supervision vTreatment * vPsychotherapy – CBT, assertiveness and social skills training * vMeds for associated depression and anxiety symptoms

Answer 78

**Obsessive-compulsive pd (cluster C)** vEpidemiology * vPrevalence 1-2%, M\>W vDifferential diagnosis * OCD * vNarcissistic PD vCourse * vUnpredictable course * vSome can have comorbid OCD but most do not vTreatment * vPsychotherapy is the treatment of choice, usually CBT * vMeds used for associated symptoms as necessary

Answer 79

Personality change due to another medical condition * Examples: head trauma, stroke, epilepsy, CNS infection, neoplasm

Answer 80

Unspecified personality disorder

Answer 81

* vEarly referral to mental health providers * vPsychotherapy - considered first line * vMedication s - No medications approved by FDA . * vTreatment of comorbid psychiatric disorders Issues with treatment – countertransference reactions * Anger * Fear of physical and legal threat * Sympathy * Self doubt * Frustration and attraction Suggested actions * vBe aware of feelings * vLimit setting * vProper documentation * vPersonal safety * vRealistic expectations * vChaperone for exam * vDo not see patients afterhours or in social settings

Answer 82

**1.Avoidant PD** 2. Schizoid prefer to be alone, avoidant want relationship but are fearful of rejection 3. Assertiveness and social skills training

Answer 83

1. Antisocial PD 2. Conduct disorder 3. Drug abuse

Answer 84

1. Paranoid PD 2. Men 3. Groups due to mistrust and misinterpretation of others’ statements

Answer 85

1. Borderline PD 2. Women 3. Splitting 4. DBT

Answer 86

1. Dependent PD 2. Women 3. Depression

Answer 87

1. Histrionic PD 2. Women 3. Borderline patients are more likely to suffer from depression, brief psychosis, and to attempt suicide, HPD is generally more functional

Answer 88

1. Schizoid PD 2. Men 3. Day programs or drop-in centers

Answer 89

1. Narcissistic PD 2. Depression 3. Psychotherapy

Answer 90

1. OCPD 2. OCD is ego-dystonic, OCPD is ego-syntonic and OCPD do not have obsessions or compulsions 3. CBT

Answer 91

1. Schizotypal PD 2. Schizophrenia 3. These patients are not frankly psychotic, but they can become so transiently under stress, and they have no fixed delusions

Answer 92

* •Begins with abnormal instability or activation of certain cells which spread peripherally and stimulate the trigeminal system * – This can cause nearby stimulation of chemoreceptors (resulting in nausea and vomiting) and the autonomic nervous system (resulting in pallor, flushing, and congestion) * •Does not originate with constriction and subsequent dilation of cerebral blood vessels **2 types of migraines** * •Common; no aura * •Classic; has aura (reversible neurologic symptoms that precede the migraine in 20 minutes)

Answer 93

–At least 5 attacks fulfilling the following * •Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)- symptoms in children can be less duration * •Headache has at least two of the following characteristics: * –unilateral location * –pulsating quality * –moderate or severe pain intensity * –aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs) * •During headache at least one of the following: * –nausea and/or vomiting * –photophobia and phonophobia

Answer 94

•Same diagnostic criteria as common migraine except: * –Presence of an aura. * •Aura is the complex of neurological symptoms that occurs just before or at the onset of migraine headache * •Auras develop gradually over 5-20 minutes and last for less than 60 minutes * •Common auras are visual change, paresthesia, confusion

Answer 95

* •Pain is typically bilateral. Unilateral pain usually emerges in late adolescence or early adult life. * •Migraine headache is usually frontotemporal. * –Occipital headache in children is rare and calls for diagnostic caution. * •In young children, photophobia and phonophobia may be inferred from their behavior.

Answer 96

Migraine with brainstem aura

Answer 97

Retinal Migraine

Answer 98

•Abortive * –Disrupt the headache cycle once started •Preventative * –Decrease the frequency and severity of headache attacks * –Generally these medications are tried when: * •\>4-6 migrainous headaches days per month * •Multiple missed days of work or recurrent ED visits secondary to migrainous symptoms •Avoid triggers: * –Red Wine, certain foods (chocolate, some cheeses, MSG, heavy nitrite containing foods-i.e. highly processed meats), hunger from missing meals, sleep deprivation and irregular sleeping patterns, and stress

Answer 99

•NSAIDS * –Ibuprofen, Naprosyn, Ketorolac •5HT1 agonists (Triptans and Ergots)available in oral, inhaled and subcutaneous forms (examples below) * –Sumatriptan (short onset and duration) * –Zolmitriptan (intermediate onset and duration) * –Frovatriptan (long onset and duration) •Dopamine antagonists available in oral and subcutaneous forms * –Metoclopramide (Reglan) * –Prochlorperazine (Compazine)

Answer 100

•β-Adrenergic Blockers * –Propranolol * –Atenolol •Calcium Channel Blockers * –Verapamil •Tricyclic Antidepressants * –Amitriptyline * –Nortriptyline •Anticonvulsants (AED’s) * –Gabapentin (Neurontin) * –Valproic Acid (Depakote) * –Topiramate (Topamax) * –Others (zonesimide, keppra, etc…) •Serotonergic Drugs * –Cyproheptadine (Periactin)- particularly effective in children \*\*First line agents; **topiramate, amitriptyline, propanolol**

Answer 101

Cluster Headaches * one of the most painful headache conditions. They are defined as an episodic headache condition characterized by attacks of **_severe unilateral stabbing periorbital or temporal pain_**. They tend to occur in clusters for approximately 3-6 weeks. They are typically associated with at least one of the following associated * autonomic features

Answer 102

* •At least 5 attacks fulfilling criteria * •Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated * •Headache is accompanied by at least one of the following: * –ipsilateral conjunctival injection and/or lacrimation * –ipsilateral nasal congestion and/or rhinorrhoea * –ipsilateral eyelid oedema * –ipsilateral forehead and facial sweating * –ipsilateral miosis and/or ptosis * –a sense of restlessness or agitation * •Attacks have a frequency from one every other day to 8 per day

Answer 103

•Treating cluster headaches can be difficult given the short duration of the individual attack. The treatment should begin with immediate use of oxygen and if pain is still present at 20 minutes one should use intranasal or subcutaneous sumatriptan (preferred over oral due to improved onset time). * –Oxygen * •Administration of high concentration O2 (12L/min) for 15 minutes will decrease the headache duration-**_this is the most effective abortive agent_** * –Triptans- effective in about 75 percent of patients (pain-free at 20 minutes after administration) * •Should use a short onset, short duration drug (i.e. Sumatriptan) * –Intranasal administration of lidocaine drops is possibly helpful

Answer 104

* •High Dose Steroids * –Use of high dose prednisone during the patient’s cluster of events (typically dosed for 2-4 weeks) will dramatically lessen the frequency of attacks in the cluster. Is often combine with additional prophylactic agents (see below) * •Calcium Channel Blockers (i.e. Verapamil) –adjuvant agent of choice * •Others * **–Lithium**

Answer 105

Tension Headaches

Answer 106

•At least 10 episodes occurring on \<1 day per month on average (\<12 days per year) and fulfilling the following: * –Headache lasting from 30 minutes to 7 days * –Headache has at least two of the following characteristics: * •bilateral location * •pressing/tightening (non-pulsating) quality * •mild or moderate intensity * •not aggravated by routine physical activity such as walking or climbing stairs * –Both of the following: * •no nausea or vomiting (anorexia may occur) * •no more than one of photophobia or phonophobia

Answer 107

* Non pharmacology treatment * •Stress reduction * •Biofeedback * •Cognitive Behavioral Therapy * •Improved sleep hygiene * Abortive pharm * •Acetaminophen * •NSAIDS * •Aspirin * Prophylactic pharm * –Tricyclic Antidepressants * •Amitriptyline * •Nortriptyline * –Antiepileptic * •Gabapentin

Answer 108

**Idiopathic Intracranial Hypertension**

Answer 109

IIH **Epidemiology** * •IIH is a disorder of unknown etiology that predominantly affects obese women of childbearing age * •United States Incidence * –More than 90% of patients with IIH are women of childbearing age * •0.9 cases per 100,000 in general population (both sexes) * •19 cases per 100,000 population in women 20% over ideal body weight * •An 8:1 female-to-male ratio for a mean weight 38% over the ideal weight for height **Pathophysiology** * •Old School: * –Cerebral edema from the elevated ICP * •Early reports describing edema were later considered to represent fixation artifact (ie, from tissue preparation) rather than in vivo edema. * •New School * –Current hypotheses include the link between relatively obstructive segments in the distal transverse sinus and IIH and the presence of increased arterial inflow with an accompanying low-grade stenosis of the transverse sinus **Obesity contribution** * •Obesity increases intra-abdominal pressure and thereby raises cardiac filling pressures. * –These rises in pressure lead to impeded venous return from the brain (due to the valveless venous system that exists from the brain to the heart) with a subsequent elevation in intracranial venous pressure. * •If this process is not treated appropriately, chronic interruption of the axoplasmic flow of the optic nerves with ensuing papilledema as a consequence of this pressure may lead to irreversible optic neuropathy **Papilledema** * • Typically bilateral disc edema is noted secondary to the increased intracranial pressure * •Severity of disc edema does not help to distinguish underlying pathology * •Untreated increased intracranial pressure ultimately leads to optic atrophy and resultant loss of acuity

Answer 110

**Neuroimaging work-up** * •Disc edema necessitates neuroimaging with MRI (with and without) and MRV to rule our mass or dural venous sinus thrombosis * •IIH findings on MRI: * –normal or small slitlike ventricles * –enlarged optic nerve sheaths * –occasionally an empty sella Lumbar puncture * **_•Localize the landmarks_**: between spinous processes at L3-4 level. * –This level corresponds to the level of the posterior superior iliac crest. * –On obese patients, find the sacral promontory; the end of this structure marks the L5-S1 interspace. CSF data * •Normal opening pressures are typically 120-170mm H20 * •Diagnosis of IIH requires pressures of \>250mm H20 * •CSF can be drained to normal closing pressures

Answer 111

•Weight loss!! * –Diet * •As little as a 5-10% weight loss has been demonstrated to yield a reduction in ICP with accompanying resolution of papilledema. * –Bariatric Surgery: * •Review of case series/reports (62 total patients) * –52 (92%) experienced resolution of the presenting symptoms. * –Of the 35 patients who underwent postoperative funduscopy, 34 had resolution of papilledema. * –Of 12 patients who underwent pre- and postoperative visual field examinations, 11 showed resolution of visual field defects

Answer 112

* •Diuretics * –Acetazolamide (good data- see next slides) * –Furosemide (little data) * •Corticosteroid * –Can be used transiently in rapidly progressing visual deterioration * •Anticonvulsants * –Topiramate * •Weak carbonic anhydrase inhibitor * •side effect is weight loss (a necessary goal in most IIH cases), which can help put the disease in remission.

Answer 113

•Failed medical management resulting in: * –Continued elevations in ICP * –Progressive visual deterioration * –Worsening disc edema /early signs of optic atrophy •Fulminant IIH \*\*\*Shunts; ventriculoperitoneal and lumboperitoneal

Answer 114

**Giant cell arteritis (temporal arteritis)**

Answer 115

* •The reported incidence of GCA ranges from approximately 0.5 to 27 cases per 100,000 people aged 50 years or older * •Giant cell arteritis (GCA) is primarily a disease of cell-mediated immunity * “The primary inflammatory response involves the internal elastic lamina within the media of the arterial wall. The subsequent release of cytokines within the arterial vessel wall can attract macrophages and multinucleated giant cells. In turn, activated CD4+ T helper cells respond to an antigen presented by macrophages, which gives diseased vessels their characteristic histology. The inflammation tends to occur in a segmental or patchy manner, although long portions of arteries may be involved”

Answer 116

**Diagnosis** * •ESR and CRP are typically elevated * –ESR often exceeds 50mm/hr * •Can be normal in 10-20% * •Temporal artery biopsy **Treatment** * •Treatment is with **high doses steroids** which typically relieve the headache symptoms within three days. Given the chronic nature of this condition, most patients remain on a constant low dose steroid regimen for a couple of years. * •Long-term corticosteroid therapy has frequent and potentially serious consequences, including diabetes mellitus, vertebral compression fractures, steroid myopathy, steroid psychosis, and immunosuppression- related infections.

Answer 117

Seizure * –Not all seizures are clinically evident * –Clinical signs depend on localization of discharges * •Epilepsy is NOT a single seizure * •Epilepsy is defined as **_two unprovoked seizures at least 24 hours apart_**

Answer 118

Epidemiology * •Lifetime risk of single seizure is 9% * •Lifetime risk of being diagnosed with epilepsy is approximately 2% * –Prevalence o**f active epilepsy** is only about 0.8%. Etiology * •Children * –Genetic \> Infection \> Trauma \> Congenital \> Metabolic * •Adult * –Tumors \> Trauma \> Stroke \> Infection * •Elderly * –Stroke \> Tumor \> Trauma \> Metabolic \> Infection

Answer 119

* It is essential to classify seizure to help diagnose etiology and begin appropriate treatment. * International League Against Epilepsy Classification * –Determined by clinical expression combined with EEG findings * –They defined two subsets of seizure: * •Partial Onset * –Simple Partial Seizures * –Complex Partial Seizures * •Generalized Onset

Answer 120

**•Simple Partial Seizure** * –Focal ictal discharge that does not spread * –Patient remains completely aware of surroundings, no change in level of consciousness is noted * –May present as an aura only * •Epigastric rising, déjà vu, sensation of fear, olfactory hallucination * –May be isolated motor or sensory activity **•Complex Partial** * –Focal ictal discharge which may spread * –Level of consciousness is impaired * –Automatisms are often seen * •Lip smacking, repeat swallowing, perseveration of motor activity * –Often accompanied by post-ictal confusion

Answer 121

**Generalized seizures** •Multiple different types: * –Generalized Tonic Clonic (Grand Mal) * –Myoclonic * –Atonic * –Staring (Petit Mal or Absence) •Almost always associated with postictal confusion or lethargy –Exception to this rule is Absence Seizures (or Petit Mal)

Answer 122

Myoclonic seizure

Answer 123

**Atonic (Drop Attacks)**

Answer 124

Neonatal seizures

Answer 125

Infantile Spasms (West Syndrome)

Answer 126

**Childhood Absence Epilepsy**

Answer 127

Lennox-Gastaut Syndrome

Answer 128

**Febrile Seizure** •General Rules about Febrile Seizures * –1/3 will have more than one episode * •Highest rates of recurrence seen in those with onset before age 1 * –Risk of developing epilepsy is approximately 2% for simple febrile seizure-this is not much different than the general population * •Risk of epilepsy increases to ~10% if it’s a complicated febrile seizure * –These do not typically require imaging or treatment. Baseline EEG is occasionally obtained if history is compelling.

Answer 129

**Benign Focal Epilepsy of Childhood (Benign Rolandic Epilepsy)** •Seizures are variable depending on time of day * –Daytime seizures are usually focal with twitching of one side of the face, speech arrest, drooling from a corner of the mouth, and paresthesia of the tongue, lips, inner cheeks, and face * •Consciousness is preserved during these daytime seizures * –Nighttime seizure typically quickly generalizes to appear as global tonic clonic activity

Answer 130

Juvenile Myoclonic Epilepsy (JME)

Answer 131

**Temporal Lobe Epilepsy** * •Most often the epileptic zone is coming from the mesial temporal lobe, especially the hippocampus

Answer 132

**Frontal lobe Epilepsy**

Answer 133

**Non-epileptic Spells**

Answer 134

EEG * •The most helpful test in evaluation and diagnosis of epilepsy or evaluation of new onset seizures or seizure-like spell * •Helps distinguish between focal or generalized * •Epilepsy monitoring [Continuous Video EEG] can define and distinguish between epilepsy and non -epileptiform events.

Answer 135

* –Hemorrhage (Subdural, Intraparenchymal, and Subarachnoid) * –Stroke * –Infection (abscess and encephalitis) * –Tumors * –Vascular malformation * –Heterotopic tissue * –Mesial Temporal Sclerosis

Answer 136

•Cardiovascular * •Induces **vasoconstriction** and has positive inotropic and chronotropic effects on heart CNS effects * 5-HT neurons in raphe nuclei of brain stem and project throughout the brain and spinal cord. Regulate sensory perception and nociception Synthesis and inactivation of 5-HT * •Serotonin is preferentially inactivated by monoamine oxidase A (MAO-A) isoform, platelets only express the MAO-B isoform * **•5-Hydroxyindoleacetic acid (5-HIAA) is the urinary metabolite** of 5-HT 5-HT Receptors * •There are seven 5-HT receptor subtypes * •The role of 5-HT1B/1D receptors in migraine. * –\*5-HT1D induce vasoconstriction of cranial blood vessels. * –\*5-HT1B is an autoreceptor and its activation inhibits nociceptive trigeminal afferents, _which reduces migraine pain._ Role of Serotonin in Migraine * •Urinary and platelet 5-HT levels decrease during Migraine attacks * •\*Triptans are 5-HT1B/1D agonist used to treat migraine pain. Intravenous infusion of 5-HT aborts spontaneous headache

Answer 137

* •Migraine & Tension * –Most likely to encounter in clinical setting * •Cluster * –Prevalence much rarer (\<1 million/yr.) * –Many cases not easily recognized, especially in ER setting

Answer 138

Migraine headaches * Common; no aura * Classic; aura **Aura**; Sensory disturbance in brain prior to headache * **–Visual disturbance → scintillating scotoma** * **–Sensory disturbance → Focal paresthesia** * **–Motor disturbance** → Weakness or paralysis * **–Auditory Disturbance** → Excessively sensitive to noise or light

Answer 139

Migraine Stages * •Prodome (1 – 2 days prior to attack) GI effects Mood changes * •Aura (20- 60 min prior to attack) * •Attack 4hrs – 3 days * •Postdrome Characteristics of migraine attack * •POUND (**P**ulsating Headache lasting 4-72 h**O**urs that is **U**nilateral, **N**auseating and **D**ebilitating) Pathophysiology * •Genetically susceptible patients * •Triggers: stress, certain foods, odors, change in sleep habits * **•Neurovascular headache**: a disorder in which neural events results in further dilation of cranial blood vessels, which in turn, results in pain and further nerve activation * •Migraine is not caused by a primary vascular event * •Migraine is likely caused by brain-stem nuclei that normally mediate sensory input and exerts neural effects on cranial vessels

Answer 140

Migraine goals * 1.Abortive: disrupt headache cycle * 2.Preventative: Reduce the number of Migraine attacks with Migraine prophylactic drugs * 1.(\*if attacks are occurring frequently) * 2.4 - 6 migraine days per month Types of drugs * •Prophylactic drugs * •Reduce migraine frequency • Rescue/abortive drugs (Acute) * •Drugs used to treat Migraine attacks once they occur. * •These can be further divided into nonspecific pain-reducing drugs and migraine-specific drugs.

Answer 141

Prophylaction; beta blockers * **•Propranolol and Atenolol** taken orally (FDA approved) * •May take three weeks to be effective * •Relatively well tolerated and effective * •Side effects are reduced energy, tiredness * **•Contraindicated in patients with asthma**

Answer 142

**•Amitriptyline** and Nortriptyline are taken orally

Answer 143

Anticonvulsants * •Valproic acid, Topiramate, Gabapentin & Levetiracetam taken orally * • Effective in some patients. * *•Mechanisms of anti-migraine activity not clear. Increases in gamma-aminobutyric acid (GABA) signaling could play a role.* * **•_Valproic Acid_ is contraindicated in pregnancy because of teratogenicity.** * •Side effects include drowsiness, anorexia, nausea, ataxia, alopecia, tremor as well as liver toxicity. * • Used especially in migraine patients with epilepsy or anxiety disorders

Answer 144

Calcium Channel blockers * •Verapamil * –Also used for Cluster Headaches * *•Antihypertensive drug that reduces the incidence of migraine through mechanisms that are not clear* * •Side effects: * –negative inotropic cardiac effects and hypotension * –Constipation

Answer 145

**Prophylactic; BOTOX** * •Prophylaxis - Migraine (Chronic) * •Multiple injections given in head/neck muscle areas

Answer 146

**Migraine Abortive drugs** * •Nonspecific agents that treat pain and are used to abort a migraine attack include: NSAIDS, Ibuprofen, naproxen, acetaminophen, ketorolac * •Acetaminophen, Aspirin, ibuprofen, naproxen. Combinations of acetaminophen, aspirin and caffeine can also help * •Ketorolac (IV or oral) use for a max of 5 days * *because it can cause liver toxicity so you have to stop* * •Ibuprofen and acetaminophen can be used in pregnancy. * –\*All NSAIDs should be avoided in the last trimester due to increased bleeding and premature closure of the ductus arteriosus.

Answer 147

**Ergot Alkaloids** •Ergotamine and Dihydroergotamine * •The anti-migraine activity of ergot alkaloids are likely to be attributed their **_agonist effects at 5-HT1 receptors_** * •Also have partial agonist and antagonist activity at serotonergic, dopaminergic and adrenergic receptors Routes of administration: * •Ergotamine sublingual (extensive first pass effect). * •Dihydroergotamine: nasal spray, or injection (sc, im, or iv) Side effects * **_•Nausea and vomiting_** * •Problem given that nausea and vomiting are associated with migraine. * •Significant **_generalized vasoconstriction_** can also be a significant problem * •(Myocardial infarction, Peripheral ischemia, Vasoconstriction, Coronary, Vasospasm). * •Ergots cannot be used in pregnancy * **_•Pregnancy X drug_**, they may cause fetal stress and miscarriage.

Answer 148

* **_•Pregnancy X_** (vasoconstriction, fetal stress and miscarriage) * •Presence of peripheral vascular disease (tingling, peripheral vasoconstriction) * •Presence of Ischemic Heart Disease Can induce angina, coronary vasospasms * •Cannot be used in combination with Triptans (must have 24 hr delay)

Answer 149

**Triptans** * •There are several Triptans including Sumatriptan, Rizatriptan, Zolmitriptan, Naratriptan and Frovatriptan * •The Triptans are used to abort a migraine attack and they are not used for migraine prophylaxis **_•The Triptans cause significantly less nausea and generalized vasoconstriction as compared to the Ergot alkaloids_** •Mechanism: The Triptans have a more selective mechanism of action relative to the Ergots. They are selective 5-HT1 (specifically 5-HT1B/D) receptor agonists

Answer 150

Triptans; **Sumatriptan**

Answer 151

Triptans: Naratriptan and Zolmitriptan

Answer 152

Triptans; Frovatriptan

Answer 153

**Triptans; Rizatriptan**

Answer 154

**_•Adverse effects_** * –\*Headache recurrence * –Include tingling, paresthesia, dizziness, flushing, neck pain and drowsiness **_•Contraindications_** * –Use of ergot alkaloid within 24 hrs * –peripheral vascular disease * –ischemic heart disease **_•Drug interactions_** * –Should avoid concurrent use with Serotonin Selective Reuptake Inhibitors as it could induce serotonin syndrome that manifests as restlessness, hallucinations, loss of coordination, diarrhea

Answer 155

•Avoid Triggers * –See Dr. Ferguson’s Lecture (S17) •Live a boring life * –Extremely regimented everyday. Same sleep cycle/time, routine meal times, same amount/time for caffeine, etc.

Answer 156

**_Cluster headaches_** •Acute Treatments for cluster headache attack include: * –Oxygen (10 – 15 L/min, Dr. Ferguson listed 12 L/min) * –Triptans (rapid onset triptans; e.g., sumatriptan) * –Lidocaine (intranasal) •Prophylactic * –High dose prednisone * –Calcium channel Blockers (Verapamil) * •Mechanism not clear, see S26

Answer 157

Tension Headaches •Abortive medications * –Acetaminophen and NSAIDS •Prophylactic medications * •Tricyclic antidepressants (nortriptyline, amitriptyline) * –See S23 for potential mechanism * •Antiepileptic (gabapentin) * –See S24 for potential mechanism

Answer 158

**_Idiopathic Intracranial Hypertension (IIH)_** •Drug therapy includes the use of carbonic anhydrase inhibitors: * _**–\*Acetazolamide and Topiramate**_ •Mechanisms: * –reduce CSF production (see next two slides) •Side effects: * –Nausea and fatigue (similar to motion sickness), tingling in the hands and feet and altered taste, distal paresthesia, concentration difficulties and weight loss \*\*\*can also use diuretics and corticosteroids

Answer 159

1. Mood 2. Mood disorder \*\*Common medical causes; •Cerebrovascular disease, •Endocrinopathies, •Neurologic disorders •Viral illnesses •Carcinoid syndrome •Malignancy •Collagen vascular disease •Metabolic disorders •Neurological disorders •EtOH •Antihypertensives •Steroids •Levodopa •Sedative-hypnotics •Anticonvulsants •Antipsychotics •Diuretics •Sulfonamides •Withdrawal

Answer 160

Major Depressive Disorder

Answer 161

**Epidemiology** * • Lifetime prevalence of 17% * •Onset at any age, with average age of 40 * •Twice as prevalent in women during reproductive years, equal after menopause * •More common in rural areas vs. urban * •Increased mortality for patients with medical comorbidities * •Upwards of 15% will commit suicide **Age groups and variation** * •Child and adolescent population * •Somatic complaints, irritability, poor academic, truancy, substance abuse * •Geriatric population * •Depression more common in older persons than the general population (25-50%) * •Under-diagnosed and under-treated * •Correlation with low socioeconomic status, loss of a spouse, physical illness, and social isolation * •Important to rule out biological causes * •Higher risk of suicide!

Answer 162

•Physiologic * •CSF shows decreased 5HT and 5-HIAA in patients with clinical depression * •Thyroid dysfunction, hypercortisolism * •Sleep dysfunction * •Alteration in neurophysiology and neuroanatomy •Genetic * •First degree relatives of this with MDD have a 2-4 times increased risk as compared to the general population * •50-70% in monozygotic twins vs. 10-25% in dizygotic * Psychosocial factors * Immunologic disturbances

Answer 163

Major depressive disorder - SIGECAPS * •S - Sleep * •I - Decreased Interest * •G - Guilt * •E - Decreased Energy * •C - Decreased Concentration * •A - Change in Appetite * •P - Psychomotor retardation * •S - Suicidal ideation

Answer 164

* •50% of patients with a first-time episode will have had significant symptoms prior to diagnosis * •Episodes last 6-13 months untreated, 3 months treated * •Recurring episodes become more frequent and severe * •50-60% will respond to antidepressant medications * •Response significantly increased with inclusion of psychotherapy * •5-10% may suffer a manic episode 6-10yrs after diagnosis with MDD – typically occurs around early thirties after 2-4 MDEs * •Not a benign disorder – chronic disorder with frequent relapse! * •After first hospitalization * •50% recover in the first year * •25% relapse within the first 6 months * •30-50% in the first 2 years * •50-75% in 5 years * •Relapse significantly lower in those who continue pharmacologic prophylaxis

Answer 165

•Prognosis **_positively_** affected by: * •Mild severity of episodes * •Absence of psychotic symptoms * •Short hospital stay * •Stable social support and functioning * •Absence of personality disorder * •Advanced age of onset •Prognosis **_negatively_** affected by: * •Male gender * •Coexisting dysthymic disorder * •Substance abuse * •Comorbid anxiety disorders * •History of more than one previous MDE

Answer 166

•Pharmacotherapy * •Medications usually take **4-8 weeks** to work * •SSRIs, SNRIs, Alpha antagonists – safe and relatively well tolerated * •May have GI symptoms, headache, sexual symptoms (anorgasmia), rebound anxiety * •TCAs – lethal in overdose * •Sedation, weight gain, orthostatic hypotension, anticholinergic effects, QTc prolongation * •MAOIs – risk of hypertensive crisis when ingesting large quantities of tyramine * •Psychotherapy: CBT, DBT, supportive, psychodynamic, family psychotherapy * •ECT: induction of a seizure lasting ~1 min, use of general anesthesia, used in treatment recalcitrant patients * •64% to 87% of patients with severe MDD respond * •Up to 95% of patients with MDD with psychotic features * •TMS and rTMS: pulsed input of magnetic energy to stimulate nerve cells of the brain * •Used in treatment recalcitrant patients * •Non-convulsive, can be performed on a outpatient basis * •Daily for 4-6 weeks * •Vagal nerve stimulation * •Deep brain stimulation

Answer 167

**Dysthymic Disorder** Aka Persistent depressive disorder * •Affects 5-6% of all persons * •Onset before 25 years of age in 50% of patients * •30-50% of those in psychiatric clinics * •2-3x more common in females * •Frequently accompanies MDD, less likelihood of full remission between episodes. * •25% develop MDD, 20% develop a bipolar disorder, \>25% have life long symptoms. * •Patients can common experience “double depression” * •Treatment very similar to MDD – SSRIs, SNRIs, TCAs, MAOIs Psychotherapy

Answer 168

**Bipolar disorders** * •Prevalence equal in men and women for Bipolar I, but Bipolar II more common in women

Answer 169

* •Lifetime prevalence of 1-2% * •Men and woman affected equally * •No specific ethnic differences, however seen more frequently in high-income areas vs. low income * •Onset usually before the age of 30 with the mean age of 18 * •Can be diagnosed in children as young as 8 * •75% of women and ~70% of men who suffer from bipolar I disorder will begin disease course with a major depressive episode * •Most patients experience both depressive and manic episodes * •5-20% experience only manic episodes * •Manic episodes * •Rapid onset (hours to days to weeks) * •Untreated can last for roughly 3-6 months

Answer 170

* •A distinct period of abnormally and persistently elevated, expansive, goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day * •During that period, 3 or more of the following must be present (4 if the mood is only irritable) * •Inflated self-esteem or grandiosity * •Decreased need for sleep (eg. Feels rested after only 3 hours of sleep) * •More talkative or pressured speech * •Flight of ideas or subjective “racing thoughts” * •Distractibility * •Increase in Goal Directed activity (work or sexual) or psychomotor agitation (purposeless, non-goal directed activity) * •Increase in risk taking behavior (unrestrained spending, gambling, sexual indiscretion…) * •Mood disturbance severe enough to cause marked impairement in social or occupational functioning or to necessitate hospitalization * •The episode is not attributable to a substance or general medical condition

Answer 171

Mania * •D – Distractibility * •I – Irritability * •G – Grandiosity * •F – Flight of ideas * •A – Activity (increased) * •S – Sleep deficit * •T – Talkativeness

Answer 172

* Multifactorial: biological, environmental, psychosocial * Genetic factors * •1st degree relative of patients with bipolar disorder are 5-10x more likely to develop it * •40-70% Concordance rates in monozygotic twins; 5-25% in dizygotic * **•Highest** genetic link of all major psychiatric disorders * •GWAS have found several genetic variants * •One locus CACNA1C regulates Ca2+ channels * •Lithium down regulates Ca2+ channels **Neurobiology** * •Evidence from fMRI and diffusion tensor imaging studies * •Some patients may have disruptions in growth and pruning of white matter connections in areas of emotion regulation * •Decreased connections between prefrontal networks and limbic structures (esp. amygdala) * •Compared to healthy controls BP patients show reduced gray matter volume in hippocampus, lingual gyrus, amygdala, caudate, putamen, thalamus, insula, and dorsal prefrontal cortex

Answer 173

Course and Prognosis * •Untreated episodes can last for several months * •90% of those who suffer their first attack have a second within 5 years * •Course is usually chronic with relapses * •Episode interval stabilized to roughly 6-9 months after first 5 episodes * •May not necessarily include depression, pure mania in 5-20% * •5-15% are “rapid cyclers” * •60% will have at least one psychotic symptom during a mood episode in lifetime * •Psychosis can occur in manic, depressed, or mixed phases * •More common in manic episodes * •These **do not** occur in hypomanic episodes * •Hallucinations are typically auditory * •Delusions are most often grandiose, religious, and/or persecutory * •Prognosis worse than MDD Prognosis **negatively** affected * •Poor occupational status * •Alcohol dependence * •Psychotic features * •Depressive features * •Inter-episode depressive features * •Male gender Prognsis **positively** afffected by * •Short duration of manic episodes * •Advanced age of onset * •Few suicidal thoughts * •Few co-existing psychiatric or medical problems

Answer 174

* Monotherapy vs. combine therapy depends on severity on presentation and response to medications * Mood stabilizers: * •Lithium – first line agent, ~70% show partial reduction in mania, only medication used that reduces suicide risk * •Valproic Acid – first line agent, especially useful in rapid cyclers * •Carbamezapine, Oxcarbazepine * •Lamotrigine – first approved for bipolar depression •Atypical Antipsychotics: * •Risperidone, Olanzapine, Quetiapine, Aripiprazole, Ziprasidone * •Lurasidone – first approved for bipolar depression * ECT * Psychotherapy – focuses on recognition of symptoms in cycling, goal of improved function

Answer 175

* •Earlier age of onset than bipolar I * •Greater marital disruption than bipolar I * •Greater risk of attempting and completing suicide than bipolar I or major depressive disorder * •Up to 90% of life in a depressive episode DSM -5 criteria * •For diagnosis of bipolar II disorder – necessary to meet criteria for a hypomanic episode AND criteria for a past or current MDE * •Hypomanic episode * •A distinct period of abnormally and persistently elevated, expansive, goal-directed activity or energy, lasting **at least 4 consecutive days** and present most of the day, nearly every day * •Not severe enough to cause social or occupation impairment * •No history of manic episode or psychotic features!

Answer 176

Epidemiology * •Overall prevalence is unclear * •Some studies have shown bipolar II to be slightly more common in women * •Onset before 30 years of age like Bipolar I * •Frequently misdiagnosed as unipolar depression and thereby inadequately treated Prognosis and treatment * •Course tends to be chronic like Bipolar I * •Requires long-term treatment * •May have an overall better prognosis than bipolar I disorder * •Treatment - Largely the same as bipolar I, however, May require less periods of hospitalization

Answer 177

•Bipolar I * •2/3 depressed * •1/3 manic or mixed •Bipolar II * •90% depressed •NOTE: both types spend ~50% of their lives in mood episode

Answer 178

Cyclothymic disorder

Answer 179

Epidemiology * •3-5% of all psychiatric outpatients * •Lifetime prevalence of 1% * •Frequently co-exists with borderline personality disorder * •3:2 female to male ratio * •50-75% have an onset between 15 and 25 years of age * 30% have a family Course and prognosis * •Most have major depression as a primary feature * •Usually progresses to a chronic course * •1/3 of all sufferers will eventually develop bipolar I/II disorder * •Alcohol and other substance abuse common with cyclothymic disorder * •Present in 5-10% Treatment * •Mood stabilizers * •Lithium, carbamezapine, valproate * •Dosages similar to treatment of bipolar I * •Antidepressant therapy should be used with caution – patients susceptible to antidepressant-induced hypomanic or manic episodes * •Present in 40-50% of all patients with cyclothymic disorder * •Psychosocial therapy * •Best directed towards patient awareness of disorder * •Prevention of full-blown manic attacks

Answer 180

* TCA’s * Inhibition of presynaptic reuptake * SSRI * Specific serotonin reuptake inhibitors * SNRI * Combo reuptake inhibitors (of both 5-HT and NE) * *less side effects than TCA?* * MAOI * Monoamine oxidase inhibitors * *dont prescribe till nothing else is working* * Others

Answer 181

SSRI * **•First line drugs for depression and most anxiety disorders** * **•All SSRIs share some common characteristics.** * –Few autonomic side effects * –Increase alertness, usually taken in a.m. * –Seldom cause cardiac arrhythmias * –Low sedation * **Wide therapeutic window**

Answer 182

**SSRI** * **•Block the presynaptic serotonin reuptake pump** * –Increases the amount of serotonin available in the synapse * –Increases postsynaptic serotonin receptor occupancy * **•Inhibition is rapid after SSRI therapy is started, but antidepressant effects of SSRIs may not appear for three to six weeks after initiation of treatment** * –May be due to a gradual "down regulation" or decrease in some postsynaptic serotonin receptor types in response to the increased amount of synaptic serotonin available

Answer 183

SSRI Pharmacokinetics * •Well absorbed from gut * •Hepatic cytochrome P450 metabolism * •Protein binding ranges from 80-90% Adverse effects * •Relatively safe in overdose * •All side effects associated with excess 5-HT * •Cardiovascular effects are minimal * •All side effects less in Citalopram / Escitalopram

Answer 184

SSRI Black box warning * Antidepressants increase the risk of _suicidal thinking and behavior_ in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders;Fluoxetine is FDA approved for the treatment of OCD in children ≥7 years of age and MDD in children ≥8 years of age. * **•SSRI’s should not be used concurrently with monoamine oxidase inhibitors** * •Could lead to **“Serotonin Syndrome”** * ****–Agitation –Restlessness –Confusion –Insomnia –Seizures –Severe hypertension –GI symptoms –Diaphoresis –Rigidity –Hyperthermia –Tachycardia * Serotonin syndrome can be caused by a combination of drugs.e.g. **_Linezolid_ (oxazolidinone antibiotic) has some MAO-I activity** and can promote serotonin syndrome in patients on antidepressants * **Allow 1-3 months of washout after discontinuing a SSRI before starting an MAOI.**

Answer 185

**Fluoxetine** is prototype

Answer 186

MoA * NE and 5-HT reuptake inhibited (SNRI) * ·Similar effect on neurotransmitters as TCAs * ·considerably less side effects due to less antagonist effects Use * Duloxetine (Cymbalta) Acute and maintenance treatment of major depressive disorder, treatment of generalized anxiety disorder; management of pain associated with diabetic neuropathy, management of fibromyalgia * Venlafaxine (Effexor); Major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder * Desvenlafaxine (Pristiq); Major depressive disorder, active metabolite of Venlafaxine (thus similar side effects) rarely used except as controlled release formulation

Answer 187

**Bupropion (Wellbutrin, Zyban)**

Answer 188

Hypericum (St. John’s Wort) * •Source: Hypericum perforatum * •Inhibitor of MAO * •Inhibitor of 5-HT reuptake * •Improve mood, sleep; * •decrease anxiety * •If taken with SSRI: * –hypertensive crises * •Studies in US do not support its use in treatment of major depression

Answer 189

Trazodone (Desyrel)

Answer 190

Mirtazapine (Remeron)

Answer 191

**•Lithium** – “Mood Stabilizer” * –Reduces both manic and depressive symptoms * –Greater activity against manic symptoms

Answer 192

**Anticonvulsants** * •Carbamazepine (Tegretol); **block Na+ channels** * Fewer adverse effects as compared to lithium * Monitor serum Na+ and CBC’s, hepatic function * •Valproate (Depakote); **Block Na+ channels, increase GABA** * Very effective in “rapidly cycling” patients * Contraindicated in hepatic disease * Monitor platelets/hepatic function * •Lamotrigine (Lamictal); **block Na+ channels, inhibit glutamate release** * Titrate slowly due to risk of Steven-Johnson’s syndrome

Answer 193

Anxiety * •Anxiety is essentially a universal experience * •Anxiety is not intrinsically abnormal or pathological * •Anxiety has adaptive value and serves useful functions * •Anxiety is a complex mixture of physiological and psychological processes * •Expressed in individually variable ways * •Differences expressed in language Anxiety Disorders * •Anxiety, like any human function or process, can be disordered * •Excessive or disproportionate * •Produced by otherwise innocuous stimuli * •Arising spontaneously and inappropriately * •Can be a primary disorder, or can arise secondary to many medical conditions * •As well as other psychiatric conditions Fear and anxiety * •Fear is thought of as a response to a known, identifiable, external threat * •Anxiety is a response to a vague, internal, non-present threat * •More anticipatory in nature * •The difference is not as important as it once was, when psychodynamic theories of neurosis dominated conceptions of anxiety

Answer 194

* •**Endogeneous anxiety** occurs spontaneously, without identifiable precipitant * •Assumed to reflect internal, primarily biological states * **•Exogeneous anxiety** is associated with environmental stress or threat Manifestations of anxiety * •Varies greatly in its manifestations from one person to another. * •May or may not be obvious to others * •Can present with various combinations of physical or psychological symptoms * •Often presented in primary care in terms of physical and somatic complaints

Answer 195

Psychological symptoms * •Feelings of fear, worry * •Apprehensiveness * •Sense of impending doom * •Difficulty concentrating * •Hypervigilance * •Irritability * •Avoidance * •Derealization Somatic complaints * •Insomnia and fatigue * •Headache * •Dizziness and lightheadedness * •Shortness of breath * •Palpitations and chest pain * •Upset stomach and diarrhea * •Lump in the throat * •Motor tension, restlessness * •Paresthesias * •Dry mouth * •Frequent urination Physical Signs * •Diaphoresis * •Cool, clammy skin * •Tachycardia * •Flushing and pallor * •Hyperreflexia * •Trembling, easy startling

Answer 196

Anxiety disorders * •Panic disorder * •Agoraphobia * •Obsessive-compulsive disorder * •Generalized anxiety disorder * •Post traumatic stress disorder (PTSD) * •Acute stress disorder * •Social and simple phobia * •Anxiety due to a general medical condition * •Substance induced anxiety disorder

Answer 197

Panic disorder •Essential feature is **panic attacks** * •Discrete, intense, and unanticipated episodes of marked physical and emotional symptoms * •Typically last 20-30 minutes •Common symptoms of panic attacks * •Trembling * •Shortness of breath * •Feeling of impending doom; *fear reoccurence of future attack* * •Chest pain * •Sweating * •Nausea

Answer 198

Panic disorder * •About 3 in 4 patients describe initial attack as entirely spontaneous * •Not surprisingly, _often presents in ER as possible heart attack_ * •Often involves fear that one is going to die, something terrible is going to happen, or that one will go crazy or lose control in some fashion. * •Commonly associated with agoraphobia. * •Nine of ten patients have at least one comorbid disorder * •Most frequent: depression (40-80%), substance abuse, other anxiety disorders * •Age of onset typically between late teens and early 30s; unusual after age 40 * •Onset often occurs within 6 months of a significant stressful life event * •4-8x higher risk of panic disorder among first degree relatives of panic disorder patients; 2-3x more common in women

Answer 199

**Agoraphobia**

Answer 200

* **•Obsessions** are recurrent and intrusive ideas, thoughts, images, or impulses,experienced as senseless or repugnant * •Compulsions are actions the person feels compelled to take, and usually feels unable to resist * **•Compulsions** are repetitive stereotyped actions associated in an unrealistic way with an obsessional idea * •Example: obsessions about contamination and compulsive hand-washing * •The action in some way discharges tension * •Patients can resist compulsive acts for a time, usually experiencing escalating tension and anxiety * •Both obsessions and compulsions are experienced as unwanted and irresistible * •The obsessions and compulsions interfere with functioning, by virtue of the distress they cause, the time they take, interference with other activities, etc. * •Two of three patients are depressed * •Onset is typically in the **late teens or early twenties** * •Mean age of onset is 20 * •Fewer than 15% have onset after age 35 * •Commonly treated with **medication (antidepressants) and behavioral therapies**

Answer 201

**Generalized anxiety Disorder**

Answer 202

•Associated with traumatic events outside the range of normal experience * •Confrontation with threat of death, serious injury, or other threat to physical integrity * •Experience of intense fear, helplessness, horror * Onset may be delayed for long periods after the precipitating event * Symptoms tend to fluctuate over time * •Only about 30% recover completely * •Vulnerability to subsequent stressors

Answer 203

**Major symptoms of PTSD** * •Persistent re-experiencing of the stressor through nightmares or flashbacks * •Avoidance of related stimuli * •intense response to stimuli that are reminders of the precipitating event * •Blunted response to the present environment * •Diminished interest in activities * •Feelings of detachment or estrangement * •Emotional constriction **Typical features of PTSD** * •Persistent symptoms of increased arousal * •exaggerated startle response * •insomnia * •hypervigilance * •irritability * •poor concentration * •Survivor guilt

Answer 204

Acute Stress disorder

Answer 205

**Phobias** **Social Phobia** * •Specifically involves fear of being humiliated or embarrassed in public situations. * •Common situations include speaking or eating in public, meeting strangers or attending parties * •Fears of looking foolish or being laughed at or criticized * •fearfulness can engender a kind of self-fulfilling prophecy * •Common comorbid depression, isolation Simple phobias * •More focal and circumscribed * •Types * •Animals * •Natural Environment * •Situations * •Blood-injection-injury * •Blood-injection-injury * •Runs in families * •Bradycardia and hypotension follow initial tachycardia

Answer 206

**Integrated approach to treatment** * •Education * •Support * •Correction of maladaptive thinking * •Skill development * •Behavioral techniques for modification of arousal * •Medication

Answer 207

**SSRIs (Fluoxetine / Sertraline)** SSRI– commonly used in depression (will cover mechanism in more depth in mood disorder lecture) * •Amygdala, prefrontal cortex, striatum and thalamus are regulated by serotonergic projections from raphe nuclei. * •Increased serotonin is believed to lead to a downstream adaptive change in receptors rather than acute actions. These changes normalize activation of amygdala and CSTC loop

Answer 208

SNRIs (Venflaxine) Use and side effects similar to SSRI

Answer 209

**Imipramine**

Answer 210

**Benzodiazepines (BDZs)**

Answer 211

Respiratory Effects * Anxiolytic dose; None * Hypnotic dose; None * Anesthetic dose; Slight decrease Cardiovascular Effects * None, except at really high doses

Answer 212

* •Important in choice of BDZ. * –Rate of onset, duration of action, & accumulation with continued dosing vary considerably among different agents. * •Highly lipid soluble * –lipophilicity varies 50 fold among BDZ’s * •Completely absorbed from GI tract. * **_–Antacids prevent BDZ absorption._** * •Cross placenta and are secreted into breast milk.

Answer 213

* Hepatic metabolism * BDZ’s do not induce or inhibit cytochrome P450 isozymes. * t1/2 of active metabolite may be \>\> parent * Long t1/2’s can cause cumulative effects with multiple dosing * Phase I: Initial oxidative step, results in N-desalkylated active metabolites. Quickest reaction, inhibited by cimetidine. * Phase II: Hydroxylation at R3 to yield another active metabolite. Slowest reaction * Phase III: Glucuronidation followed by urinary excretion

Answer 214

* **•Drowsiness and confusion are the most common** * •Motor incoordination at higher doses * •Cognitive impairment * **•Anterograde amnesia (forget experiences 1-3 hr after dose) (useful for anesthesia)** * • Visual disturbances (blurred vision) * •Digestive disturbances (nausea, vomiting, constipation) * •Dry mouth, Bitter taste * •Vertigo * **•Rebound …dose tapering required for short half-life drugs (very common)** * **•Interaction with alcohol and other depressants can lead to respiratory depression and death**

Answer 215

* •Elderly: doses should be 1/3 to ½ of those typically prescribed * –BDZ’s with shorter t1/2 more appropriate (Lorazepam, Oxazepam) * •Liver Disease: BDZ effects potentiated because of ¯ in metabolism * –BDZ’s with no active metabolites are more appropriate * •COPD: Effects of Midazolam on respiration are exaggerated in patients with asthma, chronic bronchitis and emphysema * •Obstructive Sleep Apnea: Hypnotic doses of BDZ’s may aggravate sleep related breathing disorders. * –Probably related to the muscle relaxant effects of BDZs. * **_•Alcohol or other Sedative-Hypnotics:_** Effects of BDZs are additive with these and can cause overdose with severe respiratory depression * •Pregnancy and Nursing: * –BDZ’s cross placenta and enter into breast milk * _–Chlordiazepoxide and diazepam_ have been reported to increase the chance of birth defects when used during the first 3 months of pregnancy.

Answer 216

Tolerance and Dependence _Tolerance:_ * Hypnotic * Muscle relaxant * Anticonvulsant No tolerance to anxiolytic effects **Physical Dependence** can occur with extended therapy _Withdrawal_ * •Symptoms are similar to those for which BDZ was originally prescribed * •Severity depends on the drug, dose and t1/2 * •Drugs with shorter t1/2 have more severe symptoms * •Symptoms (rebound insomnia and anxiety) occur more frequently with short acting BDZ’s

Answer 217

Typical withdrawal regimen * •Patient was taking 40 mg/day diazepam for muscle relaxant effects following shoulder dislocation * Gradual withdrawal is indicated for people on BDZs for prolonged periods *(reduce little every week) ??*

Answer 218

Flumazenil (Romazicon)

Answer 219

**Buspirone (Buspar): Non-BDZ**

Answer 220

**Pregabalin (Lyrica)**

Answer 221

**Meprobamate (Miltown)**

Answer 222

**Propanolol (Inderal)**

Answer 223

1. Hydroxyzine (Atarax): 2. Mirtazapine (Remeron)

Answer 224

**Epilepsy** •Idiopathic Epilepsy: * –No specific anatomic cause for seizure * –May be inherited •Symptomatic Epilepsy: * –Drug use * –Hypoglycemia * –Brain Injury * –Tumors

Answer 225

•Generalized * –Convulsive * –Absence * –Myoclonic * –Atonic * –Febrile * –Status epilepticus • •Partial * –Simple * –Complex

Answer 226

* •Generalized tonic-clonic seizures so frequent that another seizure occurs before the patient returns to normal consciousness from the postictal state * **•Medical emergency with a high mortality rate** * **_HYPOXIA lead to BRAIN DAMAGE_**

Answer 227

* I.V. BDZ (lorazepam / diazepam /midazolam) * Followed by I.V. Phenytoin / Fosphenytoin * •This is given even if seizure has stopped indication is to prevent seizure from reoccurring * If refractory * •More phenytoin and more BDZ * Then if still refractory * •Phenobarbital / Pentobarbital / Midazolam / Propofol * –No consensus on best option * •May need to supply respiratory support

Answer 228

**•AURA:** * –Warning: sensation/mood may help to identify location of seizure * –Present in: * **_•Convulsive / Partial_** * –Absent in: * **_•Absence, Myoclonic_** **•ICTUS:** * –The seizure itself **•POSTICTUS:** * –The period after the seizure * **_•Absent in absence_**

Answer 229

* •It is estimated that 85% of patients with uncomplicated tonic-clonic seizures can achieve complete seizure control. •Therapeutic Goals: * –Cessation of all seizures * –No alteration in *(important because may be on therapy for the res of their life)* * •Intellect or alertness * •Physical abilities * •Reproductive ability due to therapy

Answer 230

* •Treat underlying causes of the seizures: * –Work at the source to prevent the pathological firing of the neurons of the seizure foci. * –Prevent the spread of excitation from the source to surrounding normal tissue. * •Proper drug selection for the individual patient: * –Factors influencing anticonvulsant selection: *(important issues for compliance)* * •Drug’s potential effectiveness * •Drug’s potential for causing problems * •Convenience * •Cost * •Avoid unnecessary drug combinations

Answer 231

•Utilize serum levels of anticonvulsants * –They can help the physician avoid producing unpleasant and unexpected consequences of drug toxicity. * –They can help insure adequate dosages in patients with persisting seizures * –They can help increase patient compliance

Answer 232

**Phenytoin (Dilantin)\*\***

Answer 233

Pharmacokinetics/chemistry * •Oral administration (I.V. for Status Epilepticus) * •Highly protein bound in plasma (~90%) * •Phenytoin metabolism is rate limited and the enzyme system involved is saturable within the therapeutic range of plasma concentrations Side effects * Gingivial Hyperplasia; Would not be popular side effects for teen age girls. Would hurt compliance * Common in children ~20% * Note can also occur with:• Cyclosporine • Nifedepine, diltazem, verapamil * Hirsuitism Drug interactions * •Metabolism of phenytoin can be enhanced (Carbamazepine)/decreased via microsomal enzymes. * •Phenytoin induces CYP3A4 * –May reduce levels of Digoxin, steroids, vitamin K. * –Patients should be treated with vitamin K supplements to prevent hypoprothrombinemia and bleeding.

Answer 234

Fosphenytoin (Cerebryx)

Answer 235

**Carbamazepine (Tegretol)\*\*** •Almost completely metabolized to the 10,11-epoxide, which is pharmacologically active **_•Autoinduction of metabolism_** * –CYP 1A2 / 2C / 3A * –**Rate of metabolism increases in first 4-6 weeks** * **•Naïve patient t 1/2 = 30 hr** * **•After a few weeks t½ = 10-20 hr** •Process stabilizes after about a month Side effects * •G.I. upset * •Vertigo, diplopia, blurred vision, ataxia * •Hematological disorders – aplastic anemia (rare), thrombocytopenia, hyponatremia, agranulocytosis, leucopenia * •Hepatotoxicity * –Routine liver panels

Answer 236

Phenobarbital (Luminol)\*

Answer 237

**Valproic acid / Divalproex (Depakote)\*\*** Uses: * •Absence seizures refractory to ethosuximide * –Often used as first choice * •Myoclonic seizures * •Reflex epilepsies (especially photosensitive) * •Generalized tonic clonic seizures-used as combination therapy * •Complex partial seizures-used as combination therapy * •Bipolar disorder

Answer 238

features * •Low molecular weight fatty acid * •Well absorbed from gut and is metabolized to active metabolites and inactive conjugates before excretion * •Multiple formulations including oral, extended release, “sprinkles” Side effects: * •**_Alopecia (5%)_** * •Transient GI effects (16%); nausea and vomiting * •CNS-mild behavioral effects, ataxia, tremor, not a CNS depressant * •Hepatic failure (rare); elevated liver enzymes (dose dependent) * **–Patients under 2 years of age are at the greatest risk of liver failure.** * **•Possible decrease in platelet and clotting function** * **–avoid in patients with bleeding disorders**

Answer 239

Ethosuximide (Zarontin)\* * •Blocks t-type Ca2+ channels of thalamic interneurons that appears to interrupt the neuronal hypersynchrony of thalmocortical pathways seen in absence seizures

Answer 240

Lorazepam (Ativan)\*\* * Prototype of the benzodiazepines * •Other benzodiazepine drugs commonly used: * Clonazepam (Klonopin)\* * •Inhibits Spread: Myoclonic, Atonic * Clorazepate (Tranxene) * •Metabolized to Diazepam; adjunctive treatment * Clonazepam and diazepam * **_•IV agent status epilepticus_**

Answer 241

**Gabapentin (Neurontin)** Mechanisms of Action * •Blocks voltage dependent Ca2+ channels that have α2σ1 subunits * • Chemically related to GABA, but does not work through the GABA receptor * •Increases release of GABA from central neurons * •No direct effect on GABA receptors Uses * •Partial seizures – adjunctive to other anticonvulsants * •Adjunctive therapy for partial seizures-Pediatric patients (3-12 y.o.) * •Postherpetic neuralgia * **•Diabetic Neuropathy** * •Migraine Side effects * •CNS: ataxia, dizziness, drowsiness, nystagmus, tremor * •Weight gain * •Dyspepsia, constipation Drug interactions * •Does not alter serum concentration of other anticonvulsants * •Bioavailability is reduced with concurrent use of antacids

Answer 242

Lamotrigine (Lamictal)\*\*

Answer 243

Topiramate (Topamax)\* Mechanisms of action * •Inhibits voltage-dependent sodium channels of presynaptic membrane * •Potentiates the action of GABA by binding to a novel modulatory site on the GABAA receptor * •Blocks excitatory amino acid receptors (kainate/AMPA) Uses * •Adjunctive therapy in partial seizures * •Adjunctive therapy in primary generalized seizures * •Lennox-Gastaut syndrome in patients \> 2 years of age * •Good monotherapy in patients with refractory Partial and Tonic / Clonic generalized * •Migraine

Answer 244

**Levetiracetam (Keppra)\*\***

Answer 245

Pregabalin (Lyrica)

Answer 246

Oral Contraceptives * •The effective levels of contraceptives are altered by anticonvulsants * –Hepatic metabolism * –Plasma protein binding * •Consequences * –Unplanned pregnancy * –Increased birth defects Pragnancy Planned pregnancy * •increase folic acid prior to conception * •Switch from barbiturates and phenytoin and stabilize on new drug * •Possible Teratogenic Effect of Phenytoin Administration: * –“Fetal Hydantoin Syndrome”: Characteristics: cleft lip, cleft palate, congenital heart disease, slowed growth, mental deficiency * •25-30% of women with epilepsy will have increased seizures during pregnancy DESPITE continued use of medication. * –Changes in metabolism: increased drug clearance, increased maternal volume

Answer 247

* •More frequent lab values * •Optimal therapy: Monotherapy at lowest possible dose to control seizures * •Do not completely remove anticonvulsant * •Do not switch anticonvulsant if pregnancy was unplanned * •Lack of Anticonvulsant Therapy During Pregnancy in Epileptic Patients: * –Frequency of Seizures Increase * –Anoxic conditions can increase the incidence of birth defects (7% compared to 2-3% in general population) * •Malformations increase with combination therapy * •Lower doses may be beneficial in 1st trimester * •Therapeutic drug monitoring: * –To detect alterations in metabolism—especially important during last trimester when increased drug clearance may require dosage adjustment

Answer 248

* Vagal Nerve Stimulation * Implant of pulse generator * •Mechanism unknown * Uses * •Partial onset seizures * •Refractory patients for multiple drugs * •Depression * •Very expensive * Surgery * •Removal of epileptic foci * •Only as a last resort

exam 2 psych Flashcards

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