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Pharm3- fixed > Schizophrenia -Test 2 > Flashcards

Schizophrenia -Test 2 Flashcards

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1
Q

What is the course of schizophrenia?

A

Most deterioration in psychosocial fxn occurs within the first 5 years

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2
Q

What are the positive symptoms of schizophrenia?

A

Added to normal patient’s presentation

Hallucinations, delusions, bizarre behavior, paranoia or suspiciousness, disorganization

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3
Q

What are negative symptoms of schizophrenia?

A

Taken away from a normal patient’s presentation

Avolition, alogia, affective flattening, asociality, anhedonia, attentional impairment

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4
Q

What are cognitive symptoms of schizo?

A

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

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5
Q

What types of hallucinations can ppl with schizo experience?

A 
Auditory
Visual
Tactile
Olfactory
Gustatory
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6
Q

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

A 
Fixed, false belief held despite negative evidence, and not consistent with cultural norms
Types
-Grandiose
-Persecutory
-Referential
-Somatic
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7
Q

What are the types of disorganization?

A 
Normal
Loose associations
Tangential
Circumstantial
Flight of ideas
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8
Q

What is the diagnostic criteria for schizo?

A

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

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9
Q

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

A

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

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10
Q

What are the dopamine pathways?

A

Nigrostriatal, mesolimbic, mesocortical, tubero-infundibular

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11
Q

What does the nigrostriatal do?

A

Regulates motor movement

Blockade Extrapyramidal Movements (EPS)

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12
Q

What does the mesolimbic do?

A

Hyperactivity Positive Symptoms

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13
Q

What does the mesocortical do?

A

Hypoactivity Negative Symptoms, Cognition Issues

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14
Q

What does the tubero-infundibular do?

A

Inhibits prolactin, thermoregulation

Blockade hyperprolactinemia

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15
Q

What does dopamine antagonism do in pts with schizo?

A

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

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16
Q

What are the tx options for schizo?

A

Antipsychotics

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17
Q

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

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

NON-Phenothiazines
Thiothixene (Navane®)
Haloperidol (Haldol®)
Loxapine (Loxitane®)
Molindone (Moban®
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18
Q

What are the low potency first gen?

A

Chlorpromazine, thioridazine, mesoidazine

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19
Q

What are characteristics of the low potency first gens?

A

Less potent D2 antagonism

More Ach antagonism, alpha-antagonism, sedation

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20
Q

What are the medium potency first gens?

A

Perphenazine, loxapine, molindone

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21
Q

What are characteristics of the medium potency first gens?

A

Moderate D2 antagonism as well as receptor selectivity

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22
Q

What are the high potency first gens?

A

Fluphenazine, haloperidol, thiothixene, trifluoperazine

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23
Q

What are characteristics of the high potency first gens?

A

More potent D2 antagonism

Less Ach, alpha-antagonism, sedation

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24
Q

What are the second gen (atypical) antipsychotics?

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

Pharm3- fixed (12 decks)

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