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Therapeutics Neuro Gable
Exam 1 Schizo and Psychosis
79
Agriculture
2nd Grade
08/18/2010

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Term
DSM-IV-TR Axis System: Axis I
Definition

Clinical (psychiatric) Disorders

  • Disorders diagnosed at childhood (ADHD)
  • Dementia and delirium
  • Psychotic disorders (schizophrenia)
  • Affective disorders (major depression, bipolar disorders)
  • Anxiety disorders (OCD, panic disorders, etc)
  • Somatoform disorders (hypochondriasis)
  • Dissociative disorders (personality disorders, DID)
  • Substance use disorders (alcohol, cocaine)
  • Eating disorders
  • Sleep disorders
Term
DSM-IV-TR Axis System: Axis II
Definition

Personality Disorders, Mental Retardation

 

Term
DSM-IV-TR Axis System: Axis III
Definition

General Medical Conditions

Diabetes, HTN

 

Term
DSM-IV-TR Axis System: Axis IV
Definition

Psychosocial and Environmental Problems

Homeless, divorce, education problems, unemployed, abusive relationship

Term
DSM-IV-TR Axis System: Axis V
Definition
Global Assessment Functioning
Term

Mental Status Exam:

AMSIT

Definition

Appearance

Mood and Affect

Sensorium (orientation, memory, calculations)

Intelligence

Thought (form, content, abstract ability)

Term
D2 Blockade
Definition
  • involuntary movements (extrapyramidal system)
  • hyperprolactinemia
  • decrease in positive symptoms
Term
D2 Activation
Definition
  • psychosis
  • antiparkinsonian effect
  • psychomotor activation
  • enhanced motivation and cognition
Term
5HT-1a
Definition
Involved in anxiety
Term
5HT-2a
Definition
Decrease in negative symptoms
Term
5HT-1d
Definition
Blood flow (migraines)
Term
5HT-2c
Definition
Appetite (blockade = wt gain)
Term
5HT-3
Definition
Nausea/emesis
Term
GABA-A
Definition
  • Suppresses excess activity (seizures)
  • Alcohol, benzodiazepines, barbiturates act here
Term
GABA-B
Definition
  • Muscle relaxation
  • GHB, baclofen act here
Term
Dopamine Pathways in the Brain: Mesolimbic
Definition
Modulates arousal, memory, and behavior
Term
Dopamine Pathways in the Brain: Mesocortical
Definition
Responsible for higher-order thinking and executive functioning
Term
Dopamine Pathways in the Brain: Nigrostriatal
Definition
Modulates motor movements
Term
Dopamine Pathways in the Brain: Tuberoinfundibular
Definition
Prolactin regulation (DA inhibits prolactin secretion)
Term
Positive Symptoms of Schizophrenia
Definition
  • Hallucinations
  • Delusions
  • Disorganized thinking
  • Disorganized behavior
Term
Negative Symptoms of Schizophrenia
Definition
  • Flat affect
  • Alogia
  • Avolition
  • Asociality
  • Anhedonia
  • Ambivalence
  • Lack of insight/judgement
Term

DSM-IV-TR

Diagnosis of Schizophrenia

Definition

1. Active Psychotic Symptoms > 1 month

  • > 2 of the following: delusions, hallucinations, disorganized speech, disorganized behavior, negative symptoms
  • Only 1 criteria is necessary if delusions are bizarre or hallucinations are running commentary

2. Social/Occupational Dysfunction: Functioning below the highest expected level

 

3. Duration of Illness: > 6 months

 

4. Schizoaffective and Mood Disorder Exclusion

 

5. Substance/General Medical Condition Exclusion

 

Term
Phases of Schizophrenia: Prodromal
Definition
  • Early stages of schizophrenia
  • Social isolation or withdrawal
  • Impairment of functioning
  • Impaired personal hygeine
  • Blunted Affect
Term
Phases of Schizophrenia: Active
Definition
Bizarre delusions or hallucinations (usually when diagnosed)
Term
Phases of Schizophrenia: Residual
Definition
Continual negative symptoms
Term
Haloperidol: Initial Dosing and Max Dose
Definition

2 mg BID-TID

Max 20 mg/day

Term
High Potency 1st Gen Antipsychotics
Definition

Haloperidol

Fluphenazine

Thiothixene

Trifluoperazine

Term
High Potency 1st Gen Antipsychotics are Effective for:
Definition

Acute Psychotic Agitation

Aggression

Positive Symptoms

Term
Haloperidol: ADRs
Definition
EPS (dystonic rxn, akathisia, pseudoparkinsonism, increase prolactin)
Term
Haloperidol Decanoate: Dosages, Dosage Form, and Dosage Conversion
Definition

Dose: 50 mg/ml, 100 mg/ml

 

Intramuscular Injection

Sesame oil vehicle, slowly absorbed at IM site

 

Dose conversion: 10-15 x daily PO dose Haldol q month

Term
Adv/Disadv of 1st Gen Antipsychotics
Definition

Adv

  • Better for + symptoms of schizophrenia
  • Generic (cheaper)

Disadv

  • Possible worsening of - symptoms
  • Induces EPS

 

 

Term
Adv/Disadv of 2nd Gen Antipsychotics
Definition

Adv

  • More commonly used; 1st line therapy
  • + and - symptoms improve, but better for + symptoms of schizophrenia
  • May enhance cognitive functioning
  • Less risk for EPS

Disadv

  • More likely to see metabolic complications (diabetes, weight gain)

 

Term
High Potency FGAs have a high incidence of _____________ and low _________ side effects
Definition

EPS --> related to high D2 blockade

Anticholinergic

Term
Moderate Potency FGAs
Definition

Molindone

Loxapine

Perphenazine

Term
Compared to High Potency FGAs in terms of side effects, Moderate Potency FGAs have:
Definition
Lower incidence of EPS and anticholinergic side effects
Term
Molindone: Advantages of Use
Definition

Weight neutral

Possible weight loss with use

 

Term

Low Potency FGAs

 

Definition

Chlorpromazine

Thioridazine

Term
Compared to higher potency FGAs, Low Potency FGAs have:
Definition
  • More sedating side effects (H1 blockade)
  • Orthostatic hypotension (Alpha1 blockade)
  • High incidence of anticholinergic side effects (dry mouth, constipation, urinary retention, blurred vision, memory impairment)

NOT first-line agents

Term
Patients may be given a "cocktail" for rapid tranquilization during acute phases of illness
Definition
  • Haldol for psychosis and agitation
  • May also give Thorazine (chlorpromazine) or Prolixin (Fluphenazine)
  • Cogentin (benztropine) to avoid EPS (dystonic reaction)
  • Ativan for sedation and minimize agitation

 

Term

EPS: Acute Dystonia

What it is, Treatment

Definition
  • Sustained and painful muscle contractions involving the neck, back, eyes, larynx (laryngospasm can be fatal)
  • Occurs hours to days after initiation of medication
  • Risk factors: young, male, high doses of high potency FGAs

Treatment

  • IM benztropine (cogentin) 2 mg

OR

  • IM diphenhydramine (bendaryl) 25-50 mg
Term

EPS: Akathisia

What it is, Treatment

Definition
  • Restlessness, pacing, foot tapping, anxiety, agitation
  • Occurs days to weeks after initiation of medication
  • Often misdiagnosed as agitation or worsening psychosis

Treatment

  • Beta blockers (propranolol) 30-120 mg/day

OR

  • Benzodiazepines (lorazepam-Ativan)
Term

EPS: Pseudoparkinsonism

What it is, Treatment

Definition
  • Mask-like face, shuffled gait, stooped posture, drooling, resting tremor, rigidity, cogwheeling, pill-rolling
  • Occurs weeks to months after initiation of medication
  • Risk factors: elderly, female, high-dose antipsychotics

Treatment

  • Benztropine (Cogentin) 1-8 mg/day
  • Trihexyphenidyl (Artane) 2-15 mg/day (divided)
Term

EPS: Tardive Dyskinesia

What it is, Treatment

Definition
  • Smooth abnormal movements in mouth, face, eyes, hands, back or trunk
  • Occurs month to years after initiation of medication
  • Risk factors: long duration of treatment with typical antipsychotics, older age, female, high dose antipsychotic
  • Possibly irreversible
  • AIMS (Abnormal Involuntary Movement Scale) q 6 months

Treatment (prevention is best tx)

  • Use lowest effective dose
  • Switch to atypical agent or clozapine
  • Reevaluate need for antipsychotic
  • Vitamin E?? --> increases risk for cardiovascular complications
Term

Neuroleptic Malignant Syndrome (NMS)

What it is, Treatment

Definition
  • Symptoms: Muscle rigidity, hyperthermia, changes in mental status, autonomic dysfunction (changes in BP, tachycardia)
  • Labs: Increase CPK

Treatment

  • D/c antipsychotic, supportive care, dopamine agonist (bromocriptine), and/or smooth muscle relaxant (dantrolene)
  • Emergency medical treatment


Term
2nd Gen Antipsychotics
Definition
  • Clozapine
  • Risperidone
  • Olanzapine
  • Quetiapine
  • Ziprasidone
  • Aripiprazole
  • Paliperidone
  • Asenapine
  • Iloperidone
Term
2nd Gen Antipsychotics: Receptor Blockade
Definition

5HT-2 > D2

  • 5HT-2 blockade in mesocortical area may enhance DA transmission (relieving (-) symptoms)
  • Less risk of TD and EPS -- however EPS has been reported with most atypicals
Term
2nd Gen Antipsychotics: FDA class warning
Definition
  • Weight gain
  • Hyperglycemia
  • New onset of Diabetes Mellitus
Term
2nd Gen Antipsychs: Dissociation Ranking from D2 receptor
Definition

Quetiapine > Clozapine > Ziprasidone > Olanzapine > Aripiprazole > Risperidone

  • The faster the dissociation, the less likely EPS will develop
  • Risperidone binds tightly to D2 receptors, thus it is more likely to cause EPS
  • Fast dissociation usually = BID dosing
Term
5-HT2A antagonism results in:
Definition

Release of DA in nigrostriatal pathway and NOT in the mesolimbic pathway (minimal 5-HT2A receptors)

 

Term
Clozapine is not first line agent because:
Definition
it can cause agranulocytosis
Term
Clozapine Benefits:
Definition
  • Decreases violence and aggression
  • Treats refractory psychosis
  • Reduces suicidal ideation
  • Improves tardive dyskinesias
  • Least likely to cause EPS
Term
Clozapine: Adverse Effects
Definition
  • Life-Threatening Agranulocytosis
  • Seizure-risk (higher doses)
  • Sedation (H1 and M1)
  • Weight gain (H1 and 5-HT2C antagonism)
  • Hyperlipidemia/Hyperglycemia
  • Sialorrhea
  • Anticholinergic effects (dry mouth, constipation)
  • Tachycardia/Myocarditis
  • Orthostasis/Hypotension (alpha1 antagonism)
  • Respiratory depression

 

Term
Agranulocytosis: Lab Values
Definition

CBC with differential:

  • ANC < 500/mm3

In order to start Clozapine:

  • WBC must be > 3500/mm3
  • ANC must be > 2000/mm3
Term
Agranulocytosis: Clinical Signs and Symptoms
Definition
  • Flu-Like Symptoms
  • Fever
  • Sore Throat
  • Easy Bruising
  • Mouth Ulcers

 

Term
Clozapine CI
Definition
  • History of drug-induced dyscrasia
  • Uncontrolled seizure disorder
  • WBC < 3500 cells/mm3
  • History of a myeloproliferative disorder
  • Current pregnancy (relative)
  • < 16 yo (relative)
  • Paralytic ileus
Term
Pre-Clozapine Work-Up
Definition
  • Brief Psychiatric Rating Scale
  • CBC with differential  (within 7 days of initiation)
  • Physical examination
  • Blood pressure (supine and standing)
  • Oral temp
  • Pulse (tachycardia not uncommon)
  • Pregnancy test
  • Recommended tests: ECG, liver function tests (AST, ALT, Alk phos), creatinine, and BUN
Term
Clozapine: Hematologic Monitoring
Definition

CBC with Differential

  • Weekly x 6 months
  • Biweekly x 6 months
  • Monthly (every 28 days)

Eosinophils

  • Eosinophilia => 4000/mm3 (hold clozapine)
  • Prolonged elevations --> possible hypersensitivity rxn (fever, rash, myalgias, arthralgias) --> release of vasoactive compounds
Term
Clozapine Dosing Guidelines
Definition

Initial Dosing:

12.5 mg BID or 25 mg/day

  • Increase by 50 mg/day in 1st 2 weeks
  • Subsequent increase no more than once or twice weekly and not to exceed 100 mg/day

Max dose = 900 mg/day

 

NO PRN DOSING

Term
Drug Interactions with Clozapine
Definition
  • Phenytoin --> decreases clozapine levels
  • Carbamazepine --> agranulocytosis
  • Ciprofloxacin --> increase Cloz levels
  • Benzodiazepines (lorazepam, clonazepam) --> respiratory depression
  • Benztropine or Diphenhydramine --> increased anticholinergic side effects
  • Epinephrine (CI) --> hypotension
  • Cigarette smoking --> decreased clozapine levels
Term
Risperidone: Dose, Dosage Form
Definition

Dosage: 4-6 mg/day

Maximum: 16 mg/day

 

Start dosing low and BID for best tolerability

Doses > 6 mg increases risk for EPS

 

Dosage Forms: tablet, solution, ODT (M-tab), long-acting injection

Term
Risperidone: ADRs
Definition
  • Orthostasis (dizziness)
  • Weight gain
  • EPS
  • Increase Prolactin (decreased libido, amenorrhea -- osteoporosis, galactorrhea, gynecomastia)
Term
Risperdal Consta: Dosage, Dosage Form
Definition

IM injection given every 2 weeks

 

Recommended starting dose:

2-4 mg PO --> 25 mg q 2weeks

4-6 mg PO --> 37.5 mg q 2 weeks

6-8 mg PO --> 50 mg q 2 weeks

 

Water based injection, less painful

 

Continue PO x 3 weeks

Term
Olanzapine: Dosage, Dosage Forms
Definition

Dosage:

10-20 mg/day

Smokers may require 30-40 mg/day

Max 30 mg/day

 

Dosage Forms:

tablets, ODT, short acting injection (IM), long acting injection (Relprevv) --> IM admin. with benzodiazepines = severe hypotension

 

Term
Olanzapine: ADRs
Definition
  • Sedation
  • Dry mouth
  • Constipation
  • Weight gain
  • Hyperlipidemia
  • Hyperglycemia/Diabetes
Term
Zyprexa Relprevv: Dosing
Definition

Long-Acting Olanzapine IM Injection

 

10 mg PO = 210 mg q 2 weeks or 405 q 4 weeks (1st 8 weeks)

Maintenance = 150 mg q 2 weeks or 300 mg q 4 weeks

20 mg PO = 300 mg 2 weeks

Term
Quetiapine: Dosage, Dosage Forms
Definition

Dosage:

300-800 mg/day

Max 800 mg/day

 

Dosage Forms:

Tablets, ER

Term
Quetiapine: ADRs
Definition
  • Orthostasis
  • Headache
  • Sedation
  • Weight gain
  • Hypertriglyceridemia
Term
Ziprasidone: Dosage, Dosage Forms
Definition

Dosage:

80-160 mg/day (given BID)

Bioavailability increases 2x when given with food

Max: 160 mg/day

 

Dosage Forms:

Capsules, short-acting injection (IM)

Geodon (IM) -- max 2 x 20 mg doses in 24 hr

IM administration with benzodiazepines = severe hypotension

Term
Ziprasidone: ADRs
Definition
  • Insomnia
  • Nausea
  • Headache
  • QTc prolongation longest among atypicals -- ECG required before initiation at some facilities
Term
Aripiprazole: MOA
Definition

D2 partial agonist/antagonist

5-HT1A partial agonist

5-HT2A antagonist

Term
Aripiprazole: Dosage, Dosage Form
Definition

Dosage:

10-30 mg/day

Max 30 mg/day

 

Dosage Form:

tablets, solution, ODT, short-acting IM -- CAN administer benzodiazepines concomitantly with IM

 

Term
Aripiprazole: ADRs
Definition
  • Insomnia
  • Anxiety
  • Akathisia
  • Headache
  • Nausea
Term
Paliperidone: Dosage, Dosage Forms
Definition

Dosage:

6 mg/day (titrate weekly)

Max 12 mg/day

Taken with food increases bioavailability by 60%

 

Dosage Forms:

OROS capsules, long-acting injection - paliperidone pamitate

Term
Paliperidone: ADRs
Definition
  • Tachycardia
  • Nausea
  • Weight gain
  • Dizziness
  • Anxiety EPS
Term
Invega Sustenna: Dosage, Dosage Forms
Definition

IM paliperidone

 

Dosage:

Q monthly

Initial dose -- 234 mg IM deltoid

1 week later: 156 mg IM deltoid

 

Maintenance dose: IM deltoid or gluteal

39 mg IM = 3 mg PO

117 mg IM = 6 mg PO

234 mg IM = 12 mg PO

Term
Asenapine: Dosage, Dosage Form
Definition

Dosage:

5 mg BID

 

Dosage Form:

sublingual tablet

 

Term
Asenapine: ADRs
Definition
  • Oral hypoesthesia
Term
Iloperidone: Dosage
Definition

1 mg BID

Increase to target 12-24 mg/day

Term
Iloperidone: ADRs
Definition
  • Orthostasis (alpha blocker)
  • Dizziness
  • Sedation
  • HA
  • Weight gain
  • Nausea
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