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Pharmacology III > Schizophrenia > Flashcards

Schizophrenia Flashcards

1
Q

Is schizophrenia seen more in males or females?

A

Equal prevalence but onset tends to be earlier in males.

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2
Q

What are the comorbid conditions often associated with schizophrenia?

A 
HTN
DM
Cardiac
STDs
Substance abuse
Smoking
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3
Q

What is the etiology of schizophrenia

A 
Genetic susceptibility (multiple alleles)
Environmental exposure
Fetal disturbance (ie., infection, hypoxia) leads to abnormal neuron migration
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4
Q

What is the course of illness for schizophrenia?

A

Most deterioration in psychosocial functioning occurs within first 5 years
Early treatment predicts better long-term outcomes
Majority of patients experience at least 1 relapse

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5
Q

What are the positive sx of schizophrenia?

A 
Added to a normal patient's presentation
Hallucinations
Delusions
Bizarre behavior
paranoia or suspiciousness
disorganization
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6
Q

What are the negative sx of schizophrenia?

A 
Taken away from a normal patient's presentation
Avolition
Alogia
Affective flattening
Asociality
Anhedonia
Attentional impairment
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7
Q

What are the cognitive sx of schizophrenia?

A

Difficulties with concentration memory
executive functioning
Decision making

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8
Q

What types of hallucinations are there?

A 
Auditory
Visual
Tactile
Olfactory
Gustatory
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9
Q

What is a fixed, false belief held despite negative evidence, and not consistent with cultural norms

A

Delusion

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10
Q

What are the types of delusions?

A

Grandiose
Persecutory
Referential
Somatic

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11
Q

What are the types of disorganization with though disorder?

A 
Normal
Loose associations
Tangential
Circumstantial
Flight of ideas
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12
Q

How is schizophrenia diagnosed via the DSM-IV-TR

A

A.Two (or more) of the following, each present for a significant portion of time during a 1-month period: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms
B. For a significant portion of the time since onset of the disorder, 1 or more major areas of functioning such as work, interpersonal relations, or self-care are significantly below the level of prior to onset
C.Continuous signs of the disorder for at least 6 months. This must include at least 1 month fulfilling criterion A (unless successfully treated). This 6 months may include prodrome or residual symptoms
D.Exclusions
Schizoaffective or mood disorder has been excluded
Disorder is not due to a medical disorder or substance abuse
If history of pervasive developmental disorder is present, there must be symptoms of hallucinations or delusions present for at least 1 month

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13
Q

What are the subtypes of schizophrenia?

A 
Paranoid Type
Disorganized Type
Catatonic Type
Undifferentiated Type
Residual Type
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14
Q

What is the DSM-IV diagonistic criteria for schizoaffective disorder?

A

A.Period of illness where there is a Major Depressive, Manic, or Mixed episode concurrent with symptoms concurrent with symptoms that meet Criterion A for Schizophrenia
B.During the same of illness, there have been delusions or hallucinations for at least 2 weeks in the absence of prominent mood symptoms
C.Mood symptoms are present for a substantial portion of the total duration of the active and residual periods of the illness
D.Not due to the effects of a substance or general medical condition

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15
Q

What are the subtypes of schizoaffective disorder?

A

Bipolar Type
Manic or Mixed Episode +/- Major Depressive Episode
Depressive Type
If the mood disturbance only includes Major Depressive Episodes

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16
Q

What are the dopamine pathways?

A

Nigrostriatal
Mesolimbic
Mesocortical
Tubero-infundibular

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17
Q

What is the role of the nigrostriatal in the dopamine pathway?

A

Regulates motor movement

Blockade -> Extrapyramidal Movements (EPS)

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18
Q

What is the role of the mesolimbic in the dopamine pathway?

A

Hyperactivity -> Positive Symptoms (hallucinations, delusions)

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19
Q

What is the role of the mesocortical in the dopamine pathway?

A

Hypoactivity -> Negative Symptoms, Cognition Issues

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20
Q

What is the role of the tubero-infundibular in the dopamine pathway?

A

Inhibits prolactin, thermoregulation

Blockade -> hyperprolactinemia

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21
Q

How does dopamine antagonism affect schizophrenia?

A

Improvement of positive symptoms
EPS
Hyperprolactinemia
Minimal improvement of negative symptoms

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22
Q

What are the treatment options for schizophrenia?

A

First Generation Antipsychotics (FGA)
Conventional agents, neuroleptics, or typical antipsychotics
Second Generation Antipsychotics (SGA)
Atypical antipsychotics

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23
Q

What are the phenothiazine first generation antipsychotics?

A 
Chlorpromazine (Thorazine®)
Thioridazine (Mellaril®)
Mesoridazine (Serentil®)
Perphenazine (Trilafon®)
Trifluoperazine (Stelazine®)
Fluphenazine (Prolixin®)
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24
Q

What are the non-phenothiazine antipsychotics?

A

Thiothixene (Navane®)
Haloperidol (Haldol®)
Loxapine (Loxitane®)
Molindone (Moban®)

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25
Q

What are the low potency first generation antipsychotics and what is important about them?

A

Less potent D2 antagonism
More Ach, alpha-antagonism, sedation
Chlorpromazine, thioridazine, mesoidazine

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26
Q

What are the medium potency first generation antipsychotics and what is important about them?

A

Moderate D2 antagonism as well as receptor selectivity

Perphenazine, loxapine, molindone

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27
Q

What are the high potency first generation antipsychotics and what is important about them?

A

More potent D2 antagonism
Less Ach, alpha-antagonism, sedation
Fluphenazine, haloperidol, thiothixene, trifluoperazine

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28
Q

What are the second generation antipsychotics (atypicals)?

A 
Aripiprazole (Abilify®)
Clozapine (Clozaril®) 
Olanzapine (Zyprexa®
Quetiapine (Seroquel®)
Risperidone (Risperdal®)
Ziprasidone (Geodon®)
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29
Q

Antipsychotics- MOA

A

Postsynaptic DA: 5 receptors
D1 and D5 activate adenylyl cyclase
D2 , D3 and D4 inhibit adenylyl cyclase
Every antipsycholic blocks D2 receptors

Typical Antipsychotics
Mesolimbic DA block: reduces Positive Symptoms
Not so good for Negative or Cognitive Symptoms

Atypicals: also block 5-HT>DA
Good for Positive Symptoms
Possibly better for Negative and Cognitive Symptoms
5-HT2 antagonists release dopamine from inhibition and decreases EPS

30
Q

What other receptors are antipsychotics known for blocking?

A

Also block adrenergic, cholinergic and histamine-binding receptors
Unknown what role these actions have in alleviating symptoms of psychosis
Undesirable side effects result of binding these receptors

31
Q

How well the drug acts at the D2 receptor is correlated with what?

A

How well the drug works

32
Q

What is D2 occupancy?

A

D2 occupancy is related to:
Clinical response (threshold 65%) (positive sx go away at 65%)
Prolactin elevation (threshold 72%)
EPS and akathisia (threshold 78%)

33
Q

Is the therapeutic window narrow or wide

A

Therapeutic window is narrow

In principle -> therapeutic response is possible (but not probable) without EPS, akathisia, or prolactin level

34
Q

What is Dx2 and 5-HT2 occupancy?

A

Depending on dose, drugs work at “typical” levels of D2 occupancy
However, when D2 occupancy is >80%, lose some of its “atypical” features

35
Q

What does olanzapine saturate?

A

Olanzapine saturates 5-HT2 receptors; therefore, at clinical doses, muscarinic M1 and histaminergic H1 also likely saturated

36
Q

Ziprasidone

A

5-HT2 occupancy exceeds D2 occupancy
Estimated steady-state 5-HT2 occupancy up to 90%
Estimated steady-state D2 occupancy up to 75%

37
Q

Clozapine

A

the “mother” of all atypical antipsychotics
Advantages over typical antipsychotics
Lack EPS, lack prolactin elevation, efficacy in refractory pts, greater efficacy on suicidality, efficacy against negative symptoms?
5-HT2 occupancy >80 occupancy
Inability to occupy >70% D2…works at levels of D2 occupancy that alone would not cause response

38
Q

What is the transient occupancy hypothesis with quetiapine?

A

Transiently high D2 occupancy appears sufficient to obtain and maintain antipsychotic response
400mg Seroquel->57% D2 occupancy at 3 hrs->20% D2 occupancy at 9 hrs.

39
Q

What are the benfits of atypical (2nd generation) antipsychotics?

A

Efficacy for positive symptoms, clozapine effective for treatment resistant positive symptoms
Possible enhanced efficacy for negative and cognitive symptoms
Low incidence of tardive dyskinesia and EPS (look like PD patients)
Minimal or no effect on prolactin at usual doses (except risperidone)

40
Q

How should you dose antipsychotics?

A

Start with the lowest dose possible.
Divide doses to minimize SE
Prophylactic anticholinergics with high potency

41
Q

Antipsychotics- Side effects (neurological)

A

Neurological (Extrapyramidal) DA block
Occur with chronic use of typical neuroleptics
Low incidence with atypical neuroleptics

42
Q

Antipsychotics- Side effects (non-neurological)?

A

Non-Neurological (Low Potency medications)
Histaminergic: Sedation, Wt gain
Anticholinergic: Peripheral & Central
Alpha-Adrenergic: Orthostasis, EKG
Endocrine-Sexual: PRL, 5-HT
Hematologic: Agranulocytosis (clozapine black box warning)
Eye & Skin: retinopathy, photosensitivity
Seizure threshold: lowered
Liver: cholestatic jaundice

43
Q

Are neurological effects worse with typicals or atypicals?

A

Typicals

44
Q

Are non-neurologic side effects worse with typicals or atypicals?

A

Atypicals

45
Q

What are the extrapyramidal Sx (EPS) of anipsychotics?

A
  • Acute Dystonias
  • Parkinson-like symptoms (blocking of DA receptors in nigrostriatal pathway)
  • Akathisia (motor restlessness)
  • Tardive Dyskinesia (inappropriate postures of neck, trunk, and limbs)
  • Neuroleptic Malignant Syndrome
46
Q

What is a muscle spasm in the face, neck, trunk, eye, or larynx?

A

Acute dystonia

47
Q

What is the treatment for acute dystonia?

A

Treatment: Benadryl 50 mg IM (IV 25-50 for laryngospasm), Cogentin (benztropine (generic)) 1-4 mg IM
Prevention reduces incidence to 5%
Low dose
Benztropine 1 mg / every Haldol 5 mg

48
Q

What is antipsychotic-induced parkinsonism?

A 
Incidence 50-75% with high potency
Rigidity
Bradykinesia: mask face-gait problems
Resting Tremor
Flexed Posture
Dif Dx. with flat affect
49
Q

What is the tx for antipsychotic-induced parkinsonism?

A

Tx: Cogentin (benztropine), Artane 2 mg bid-tid

50
Q

What is a subjective feeling of reslessness and involved unable to sit still and pacing?

A

Akathisia

51
Q

What is used to tx akathisia?

A

Tx: Propranolol 30-90 mg/d (not in asthma or diabetes), Klonopin 1 mg bid

*Beta blocker

52
Q

What is slow choreo-athetotic movements and oro-facial movements?

A

Tardive dyskinesia

53
Q

What is used to tx tardive dyskinesia?

A

Tx?: Vit E 1600 U/d, Clozapine low risk

54
Q

What are the risk factors of tardive dyskinesias and when are they more seen?

A

Risk factors: elderly women, mood D/O, diabetes

More associated with typical (1st gen) antipsychotics

55
Q

What is neuroleptic malignant syndrome (NMS)?

A

Medical Emergergency, mortality 20% (now 4%)
1. FEVER>100.4F / 37.5C
2. SEVERE EPS: lead-pipe/cogwheel rigidity, sialorrhea, oculogyric crisis
3. AUTONOMIC, DYSFUNCTION: BP fluctuations, tachycardia, tachypnea, diaphoresis
Also: Alt. consciousness, delirium, leukocytosis (>15.000 WBC), CPK > 300, seizures, arrhythmias, mioglobinuria, ARF

56
Q

What are the risk factors associated with NMS?

A

Risk factors: multiple IM injections, high dose, rapid increase of dose agitation, dehydration, heat, lithium use

57
Q

What is the treatment for NMS?

A

Stop ALL Antipsychotics
Dif. Dx: fever & delirium
Dantrolene (muscle relax) 1-3 mg/kg/day NTE 10 mg/kg/d
Bromocriptine (DA Agonist) 5 mg tid-qid
Supportive Tx:
IV fluids, antipyretics, cooling blankets, close cardiac & renal monitoring

58
Q

What are the antiemetic effects?

A

Block D2 receptor of chemoreceptor trigger zone of medulla

Exception is thioridazine

59
Q

What are the antimuscarinic effects?

A

Thioridazine, chlopromazine, clozapine, olanzapine
Anticholinergic effects include blurred vision, dry mouth, sedation, confusion, inhibit GI and urinary tract smooth muscle constipation and urinary retention

60
Q

What are the other effects that are seen with low potency and atypicals?

A

Alpha-adrenergic blockade causes orthostic hypotension, light-headedness
Poikilothermia (body temp varies with environment)
D2 blockade in pituitary->increased prolactin release
More common with high potency and typicals
Chlorpromazine and clozapine antagonize H1 receptor->sedation

61
Q

Typical antipsychotics- Pharmacokinetics

A 
t1/2 approx 24 hrs (hs or bid)
SE limit the amount given in one dose
Peak plasma level: 2-4 hrs (po) 30 min (IM)
Takes 5-7 days to steady-state
Mainly CYP2D6 metabolism
Tolerance but little dependence
IM depot (slowly over time release) available in fluphenazine and haloperidol form outpt tx or noncompliance
Slow release over 3 weeks
30% develop extrapyramidal symptoms
62
Q

Clozepine (Clozaril)

A 
Atypical antipsychotic
Weak D1=D2 block, high 5-HT2 block
(5-HT2/D2 = 20/1)
alpha1, alpha2, H1, M1
Tx Res. Schizophrenia, mood stabilizer
Effective in Negative and Positive Sx, low EPS, low TD
63
Q

What is the biggest side effect of clozapine?

A

AGRANULOCYTOSIS (1%), 80% in 1st 4 mo. (BLACK BOX WARNING FOR AGRANULOCYTOSIS)
Potentially fatal in 1-2%
If WBC<1,000 stop & do not re-start
Do not use with Carbamazepine or other bone marrow suppressors

64
Q

Clozapine- Side effects

A 
Agranulocytosis
Sedation
Dizziness, orthostatic hypotension
Hypersalivation
Weight Gain
Lower Seizure Threshold
65
Q

Risperidone

A

Atypical antipsychotic

low EPS at doses <6 mg/d; Treat agitation in the elderly; Elevates PRL; minimal sedation

66
Q

Ziprasidone

A

Atypical antipsychotic
need bid, tid
t1/2 5 hrs; low EPS; contraindicated in pts with cardiac arrhythmias; minimal weight gain

67
Q

Olanzapine (Zyprexa®)

A

Atypical antipsychotic

positive and negative Sx, low EPS, sedation, wt gain, mood stabilizer

68
Q

Quetiapine (Seroquel®)

A

Atypical antipsychotic

need bid, low EPS, sedation, hypotension

69
Q

Aripiprazole (Abilify®)

A

Atypical antipsychotic

Low EPS

70
Q

What commonly occurs with atypical neuroleptics?

A

Weight gain

71
Q

What commonly occurs with typical neuroleptics?

A

Parkisonian effects

72
Q

What is the maintenence of medications for patients with schizophrenia?

A

2+ episodes should receive maintenance therapy for at least 5 years
High dose maintenance therapy preferred in preventing relapse

Pharmacology III (19 decks)

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