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Flashcards in Schizophrenia -Test 2 Deck (70):
1

What is the course of schizophrenia?

Most deterioration in psychosocial fxn occurs within the first 5 years

2

What are the positive symptoms of schizophrenia?

Added to normal patient’s presentation
Hallucinations, delusions, bizarre behavior, paranoia or suspiciousness, disorganization

3

What are negative symptoms of schizophrenia?

Taken away from a normal patient’s presentation
Avolition, alogia, affective flattening, asociality, anhedonia, attentional impairment

4

What are cognitive symptoms of schizo?

Difficulties with concentration, memory, executive functioning, decision-making

5

What types of hallucinations can ppl with schizo experience?

Auditory
Visual
Tactile
Olfactory
Gustatory

6

What are delusions? What types can ppl with schizo experience?

Fixed, false belief held despite negative evidence, and not consistent with cultural norms
Types
-Grandiose
-Persecutory
-Referential
-Somatic

7

What are the types of disorganization?

Normal
Loose associations
Tangential
Circumstantial
Flight of ideas

8

What is the diagnostic criteria for schizo?

Two (or more) of the following characteristic symptoms, each present for a significant portion of time during a 1-month period or less is successfully treated and 1 of the 2 must be *: Delusions *
Hallucinations *
Disorganized speech *
Grossly disorganized or catatonic behavior
Negative symptoms- affective flattening, alogia, or avolition

9

What is potentially happening to the brain in a pt with schizo?

Volume reductions: whole brain (3%), temporal lobe (6-9.5%); amygdala/hippocampus (5.5-6.5%)
Volume increase in lateral ventricles (36-44%)
Abnormal activation:Increased neuronal density and decreased synapse density in schizophrenia

10

What are the dopamine pathways?

Nigrostriatal, mesolimbic, mesocortical, tubero-infundibular

11

What does the nigrostriatal do?

Regulates motor movement
Blockade Extrapyramidal Movements (EPS)

12

What does the mesolimbic do?

Hyperactivity Positive Symptoms

13

What does the mesocortical do?

Hypoactivity Negative Symptoms, Cognition Issues

14

What does the tubero-infundibular do?

Inhibits prolactin, thermoregulation
Blockade hyperprolactinemia

15

What does dopamine antagonism do in pts with schizo?

Improvement of positive symptoms
Develop EPS
Develop Hyperprolactinemia
Minimal improvement of negative symptoms

16

What are the tx options for schizo?

Antipsychotics

17

What are the first generation (typical/conventional) antipsychotics?

Phenothiazines
Chlorpromazine (Thorazine®)
Thioridazine (Mellaril®)
Mesoridazine (Serentil®)
Perphenazine (Trilafon®)
Trifluoperazine (Stelazine®)
Fluphenazine (Prolixin®)

NON-Phenothiazines
Thiothixene (Navane®)
Haloperidol (Haldol®)
Loxapine (Loxitane®)
Molindone (Moban®

18

What are the low potency first gen?

Chlorpromazine, thioridazine, mesoidazine

19

What are characteristics of the low potency first gens?

Less potent D2 antagonism
More Ach antagonism, alpha-antagonism, sedation

20

What are the medium potency first gens?

Perphenazine, loxapine, molindone

21

What are characteristics of the medium potency first gens?

Moderate D2 antagonism as well as receptor selectivity

22

What are the high potency first gens?

Fluphenazine, haloperidol, thiothixene, trifluoperazine

23

What are characteristics of the high potency first gens?

More potent D2 antagonism
Less Ach, alpha-antagonism, sedation

24

What are the second gen (atypical) antipsychotics?

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

25

What is the MOA of antipsychotics?

Every antipsycholic blocks D2 receptors
1)Typical Antipsychotics
Mesolimbic DA block: reduces Positive Symptoms
Not so good for Negative or Cognitive Symptoms
2)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

26

What is D2 occupancy related to?

Clinical response (threshold 65%)
Prolactin elevation (threshold 72%)
EPS and akathisia (threshold 78%)

27

What is the deal of olanzapine and 5HT2 occupancy?

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

28

What are the advantages of clozapine 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

29

What is the transient occupancy hypothesis with quetiapine?

Transiently high D2 occupancy appears sufficient to obtain and maintain antipsychotic response

30

What are the benefits of second gen antipschotics?

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
Minimal or no effect on prolactin at usual doses (except risperidone)

31

How are antipsychotics initiated?

Start lowest dose possible
10-20 mg Haldol
300-500 mg Chlorpromazine equivalents

32

In acute agitation what can be combined with antipsychotics?

lorazepam 1-2 mg po/IM

33

What are the neurologic side effects of antipsychotics?

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

34

What are the non-neuro ADRs?

Histaminergic: Sedation, Wt gain
Anticholinergic: Peripheral & Central
Alpha-Adrenergic: Orthostasis, EKG
Endocrine-Sexual: PRL, 5-HT
Hematologic: Agranulocytosis- most common with atypicals, clozipeme
Eye & Skin: retinopathy, photosensitivity
Seizure threshold: lowered
Liver: cholestatic jaundice

35

What are the EPS?

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
From blocking dopamine

36

What are acute dystonias?

Muscle spasm face, neck, trunk, eye, larynx

37

When are acute dystonias most commonly seen?

Early in tx and in young males

38

How are dystonias tx?

Benadryl 50 mg IM (IV 25-50 for laryngospasm), Cogentin 1-4 mg IM

39

How can dystonias be prevented?

Low dose (they are dose related)
Benztropine 1 mg / every Haldol 5 mg

40

What are s/s of antipsychotic induced parkinsonism?

Rigidity
Bradykinesia: mask face-gait problems
Resting Tremor
Flexed Posture

41

How is antipsychotic induced parkinsonism tx?

Cogentin, Artane 2 mg bid-tid

42

What is akathisia?

Subjective feeling of restlessness
Unable to sit still, pacing

43

What is the tx for akathisia?

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

44

What other drug group can cause akathisia?

SSRI

45

What is tardive dyskinesia?

Slow choreo-athetotic movements
Oro-facial muscles

46

What are risk factors for tardive dyskinesia?

elderly women, mood D/O, diabetes

47

What is the tx for TD?

Vit E 1600 U/d, Clozapine low risk

48

What are the s/s of neuroleptic malignant syndrome?

1. Fever >100.4F / 37.5C
2. Severe EPS: lead-pipe/cogwheel rigidity, sialorrhea, oculogyric crisis
3. Autonomic Dysfunction: BP fluctuations, tachycardia, tachypnea, diaphoresis

49

What other s/s are often present in NMS?

Alt. consciousness, delirium, leukocytosis (>15.000 WBC), CPK > 300, seizures, arrhythmias, mioglobinuria, ARF

50

What are risk factors for NMS?

multiple IM injections (halodol is IM), high dose, rapid increase of dose agitation, dehydration, heat, lithium use

51

What is the tx for NMS?

Stop ALL Antipsychotics
Dantrolene1-3 mg/kg/day NTE 10 mg/kg/d
Bromocriptine 5 mg tid-qid
Supportive Tx:IV fluids, antipyretics, cooling blankets, close cardiac & renal monitoring

52

what causes the antiemetic effects?

Block D2 receptor of chemoreceptor trigger zone of medulla

53

What doesn’t cause antiemetic effects?

Thioridazine

54

Which drugs cause antimuscarinic effects?

Thioridazine, chlopromazine, clozapine, olanzapine

55

What are the anticholinergic effects?

blurred vision, dry mouth, sedation, confusion, inhibit GI and urinary tract smooth muscle constipation and urinary retention

56

What is the PK profile of the typical antipsychotics?

lt1/2 approx 24 hrs (hs or bid)
Peak plasma level: 2-4 hrs (po) 30 min (IM)
Takes 5-7 days to steady-state
Mainly CYP2D6 metabolism
Tolerance but little dependence

57

What typicals are available in IM depot?

fluphenazine and haloperidol

58

What is the PK of clozapine?

Weak D1=D2 block, high 5-HT2 block

59

What is clozapine used to tx?

Schizophrenia, mood stabilizer
Effective in Negative and Positive Sx, low EPS, low TD

60

What is the major side effect of clozapine?

agranulocytosis

61

What should you do dependent on drug levels when your pt is taking clozapine?

If WBC

62

What are the other ADRs of clozapine?

Sedation
Dizziness, orthostatic hypotension
Hypersalivation
Weight Gain
Lower Seizure Threshold

63

What is risperidone used for?

Tx agitation in the elderly at low doses

64

What does risperidone elevate?

PRL

65

When is ziprasdone CI?

pts with cardiac arrhythmias

66

What is a benefit of ziprasidone?

Minimal weight gain

67

What does olanzapine do?

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

68

What are the ADRs of quetiapine?

low EPS, sedation, hypotension

69

what effect is commonly seen with atypical neurlopetics? With typical?

-weight gain
-parkinsonian effects

70

When should a pt receive maintenance therapy for at least 5 years minimum?

If they have had 2 or more episodes