17: Antipsychotics Flashcards
What criteria must be met to be diagnosed with schizophrenia?
Must last 6+ months, including at least 1 month of delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behaviour, or negative sx.
Introduction of _____ in _____ reduced number of patients in psychiatric hospitals worldwide.
Chlorpromazine; 1955.
What percentage of the population suffers from schizophrenia? What percentage accounts for all healthcare costs?
1-1.5% of the population. Accounts for 2.5% of all healthcare costs.
What is the sex ratio of schizophrenia?
1.2:1, males affected slightly more often than females.
Describe the common social functioning of an individual with schizophrenia.
Very few friends/social contacts. 60-70% do not marry or have children.
What is the suicide risk for an individual with schizophrenia?
25-50% attempt suicide, 20x higher risk than general population.
What is a common stigma pertaining to schizophrenia?
70% of those questioned in a survey believed schizophrenics were dangerous and unpredictable.
What are the five symptom dimensions of schizophrenia?
Positive symptoms. Negative symptoms. Aggressive symptoms. Cognitive symptoms. Anxiety/depression.
What is the dopamine hypothesis pertaining to schizophrenia? List two pieces of evidence.
Schizophrenia due to excessive mesolimbic DA signaling.
Evidence: dopaminergic drugs induce psychotic-like sx; dopamine blockers alleviate sx, likely due to D2-like receptors.
Aside from dopamine, what two other neurotransmitter systems are targeted by antipsychotics?
Serotonin: 5-HT2A receptor.
Glutamate: 5-HT2 activation → enhance cortical glutamate neurons.
What are other terms for first-generation antipsychotics?
Neuroleptics, major tranquilizers, conventional or typical antipsychotics.
Second-generation antipsychotics (atypical) share what in common with first-generation? Why might atypicals be better?
Both groups block D2 and 5-HT2 receptors. Atypicals are more potent at the 5-HT receptors (better side effect profile).
What is the function of typical antipsychotics? What are the side effects?
Antagonize D2r eceptors, weaker antagonists at 5-HT2 receptors.
Side effects: motor (extrapyramidal).
What is the function of atypical antipsychotics? What are the side effects?
Antagonize 5-HT2 receptors, antagonize D3/4 receptors, weaker at D2 receptors. Treats negative sx.
Side effects: fewer motor than typical.
What are the three commonly used tests/models for testing antipsychotics?
Prepulse inhibition (PPI): loud noise preceded by warning noise. Schizophrenics do not show any PPI.
Early hippocampal lesions: reduces PPI in rodents.
Isolation rearing: shows behavioural and neurochemical similarities with human patients.
List five questionnaires/rating scales for schizophrenia. List one for measuring side effects of antipsychotics.
Schizophrenia:
Brief Psychiatric Rating Scale Positive and Negative Syndrome Scale Quality of Life Scale Clinical Global Impression Scale Global Outcome Assessment of Life in Schizophrenia (GOALS)
Side effects:
Extrapyramidal Symptom Rating Scale
PANNS studies measuring typical (haloperidol) vs. atypical (olanzapine) drugs found what? What was found in a PPI study?
Olanzapine resulted in significant effect on negative symptoms in week 12. No effect on positive symptoms. Significant effect for olanzapine from week 2.
PPI study: risperidone resulted in significant decrease from baseline, haloperidol greater effect than olanzapine.
Why do extrapyramidal sx occur? List three of the sx.
Due to effects on D2a ntagonism in nigrostriatal system.
Dyskinesias (movement disorders); Akathisia (extreme restlessness); Dystonias (muscle tension disorders).
Why do atypical antipsychotics have a lower risk of extrapyramidal sx? List two risks atypicals have.
Lower risk because D3/4affinity > D2, and 5-HT2A antagonism cancels out D2 effects.
Risk of agranulocytosis (bone marrow), potentially fatal.
Metabolic effects - more weight gain vs. typical antipsychotic.
What effect does olanzapine have on cocaine conditioned place preference?
Reduces cocaine CPP.
What poses a treatment problem for schizophrenia and why?
Anosognosia - lack of awareness of the nature of one’s illness. Factor in nonadherence to treatment regimens and increased risk of relapse.
What are the neurodevelopmental and neurogenerative hypotheses pertaining to schizophrenia?
Decline in four stages. Theorized apoptosis/necrosis occurs in Stage III.
What are three arguments for an autoimmune origin pertaining to schizophrenia?
Schizophrenia runs in families but an identical twin has only 50% chance to develop schizophrenia.
Rheumatoid arthritis/schizophrenia discordance.
3 immune response gene regions were associated with genes predisposing to schizophrenia.
