Schizophrenia -Test 2 Flashcards
What is the course of schizophrenia?
Most deterioration in psychosocial fxn occurs within the first 5 years
What are the positive symptoms of schizophrenia?
Added to normal patient’s presentation
Hallucinations, delusions, bizarre behavior, paranoia or suspiciousness, disorganization
What are negative symptoms of schizophrenia?
Taken away from a normal patient’s presentation
Avolition, alogia, affective flattening, asociality, anhedonia, attentional impairment
What are cognitive symptoms of schizo?
Difficulties with concentration, memory, executive functioning, decision-making
What types of hallucinations can ppl with schizo experience?
Auditory Visual Tactile Olfactory Gustatory
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
What are the types of disorganization?
Normal Loose associations Tangential Circumstantial Flight of ideas
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
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
What are the dopamine pathways?
Nigrostriatal, mesolimbic, mesocortical, tubero-infundibular
What does the nigrostriatal do?
Regulates motor movement
Blockade Extrapyramidal Movements (EPS)
What does the mesolimbic do?
Hyperactivity Positive Symptoms
What does the mesocortical do?
Hypoactivity Negative Symptoms, Cognition Issues
What does the tubero-infundibular do?
Inhibits prolactin, thermoregulation
Blockade hyperprolactinemia
What does dopamine antagonism do in pts with schizo?
Improvement of positive symptoms
Develop EPS
Develop Hyperprolactinemia
Minimal improvement of negative symptoms
What are the tx options for schizo?
Antipsychotics
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®
What are the low potency first gen?
Chlorpromazine, thioridazine, mesoidazine
What are characteristics of the low potency first gens?
Less potent D2 antagonism
More Ach antagonism, alpha-antagonism, sedation
What are the medium potency first gens?
Perphenazine, loxapine, molindone
What are characteristics of the medium potency first gens?
Moderate D2 antagonism as well as receptor selectivity
What are the high potency first gens?
Fluphenazine, haloperidol, thiothixene, trifluoperazine
What are characteristics of the high potency first gens?
More potent D2 antagonism
Less Ach, alpha-antagonism, sedation
What are the second gen (atypical) antipsychotics?
Aripiprazole (Abilify®) Clozapine (Clozaril®) Olanzapine (Zyprexa® Quetiapine (Seroquel®) Risperidone (Risperdal®) Ziprasidone (Geodon®)
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
What is D2 occupancy related to?
Clinical response (threshold 65%) Prolactin elevation (threshold 72%) EPS and akathisia (threshold 78%)
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
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
What is the transient occupancy hypothesis with quetiapine?
Transiently high D2 occupancy appears sufficient to obtain and maintain antipsychotic response
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)
How are antipsychotics initiated?
Start lowest dose possible
10-20 mg Haldol
300-500 mg Chlorpromazine equivalents
In acute agitation what can be combined with antipsychotics?
lorazepam 1-2 mg po/IM
What are the neurologic side effects of antipsychotics?
Extrapyramidal) DA block
Occur with chronic use of typical neuroleptics
Low incidence with atypical neuroleptics
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
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
What are acute dystonias?
Muscle spasm face, neck, trunk, eye, larynx
When are acute dystonias most commonly seen?
Early in tx and in young males
How are dystonias tx?
Benadryl 50 mg IM (IV 25-50 for laryngospasm), Cogentin 1-4 mg IM
How can dystonias be prevented?
Low dose (they are dose related) Benztropine 1 mg / every Haldol 5 mg
What are s/s of antipsychotic induced parkinsonism?
Rigidity
Bradykinesia: mask face-gait problems
Resting Tremor
Flexed Posture
How is antipsychotic induced parkinsonism tx?
Cogentin, Artane 2 mg bid-tid
What is akathisia?
Subjective feeling of restlessness
Unable to sit still, pacing
What is the tx for akathisia?
Propranolol 30-90 mg/d (not in asthma or diabetes), Klonopin(clozapine) 1 mg bid
What other drug group can cause akathisia?
SSRI
What is tardive dyskinesia?
Slow choreo-athetotic movements
Oro-facial muscles
What are risk factors for tardive dyskinesia?
elderly women, mood D/O, diabetes
What is the tx for TD?
Vit E 1600 U/d, Clozapine low risk
What are the s/s of neuroleptic malignant syndrome?
- Fever >100.4F / 37.5C
- Severe EPS: lead-pipe/cogwheel rigidity, sialorrhea, oculogyric crisis
- Autonomic Dysfunction: BP fluctuations, tachycardia, tachypnea, diaphoresis
What other s/s are often present in NMS?
Alt. consciousness, delirium, leukocytosis (>15.000 WBC), CPK > 300, seizures, arrhythmias, mioglobinuria, ARF
What are risk factors for NMS?
multiple IM injections (halodol is IM), high dose, rapid increase of dose agitation, dehydration, heat, lithium use
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
what causes the antiemetic effects?
Block D2 receptor of chemoreceptor trigger zone of medulla
What doesn’t cause antiemetic effects?
Thioridazine
Which drugs cause antimuscarinic effects?
Thioridazine, chlopromazine, clozapine, olanzapine
What are the anticholinergic effects?
blurred vision, dry mouth, sedation, confusion, inhibit GI and urinary tract smooth muscle constipation and urinary retention
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
What typicals are available in IM depot?
fluphenazine and haloperidol
What is the PK of clozapine?
Weak D1=D2 block, high 5-HT2 block
What is clozapine used to tx?
Schizophrenia, mood stabilizer
Effective in Negative and Positive Sx, low EPS, low TD
What is the major side effect of clozapine?
agranulocytosis
What should you do dependent on drug levels when your pt is taking clozapine?
If WBC
What are the other ADRs of clozapine?
Sedation Dizziness, orthostatic hypotension Hypersalivation Weight Gain Lower Seizure Threshold
What is risperidone used for?
Tx agitation in the elderly at low doses
What does risperidone elevate?
PRL
When is ziprasdone CI?
pts with cardiac arrhythmias
What is a benefit of ziprasidone?
Minimal weight gain
What does olanzapine do?
positive and negative Sx, low EPS, sedation, wt gain, mood stabilizer
What are the ADRs of quetiapine?
low EPS, sedation, hypotension
what effect is commonly seen with atypical neurlopetics? With typical?
- weight gain
- parkinsonian effects
When should a pt receive maintenance therapy for at least 5 years minimum?
If they have had 2 or more episodes
