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61 Cards in this Set
- Front
- Back
Describe the dopamine hypothesis of schizophrenia. |
Overactivity of one of the three dopamine transmitter systems in brain – antipsychotics work by inhibiting dopamine neurotransmission – over simplistic. |
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Describe recent modifications to the dopamine hypothesis of schizophrenia.
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Positive symptoms are due to increased activity in the mesolimbic dopamine pathway. |
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Describe the negative symptoms that support the dopamine hypothesis of schizophrenia (3). |
Patients with schizophrenia show impairments consistent with impairment in reward system function; 1. anhedonia 2. decreased motivation 3. failure to use feedback to enhance goal directed behaviour |
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Describe the hypothesised role of glutamate in schizophrenia.
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Glutamate may be involved in both negative and positive symptoms and cognitive impairments.
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In schizophrenia, changes in which neurotransmitters are consdered important in cognitive changes seen?
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Cholinergic and GABA-ergic changes are considered important in the cognitive changes. |
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What are the five key dopamine pathways in the brain?
Exam tip - must know these! |
Mesolimbic Dopamine Pathway |
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Mesolimbic Dopamine Pathway: - Dopamine levels in untreated schizophrenia? |
VTA - nucleus accumbens High Positive symptoms, reward, pleasure (? agg) |
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What are the accepted criteria that a biomarker must fulfil to be called an endophenotype?
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- Associated with illness in the population |
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Define pathonomic. How is it relevant to schizophrenia?
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Pathonomic = occurs in one disease only |
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Describe three key negative symptoms that can be identified solely on observation.
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1. Reduced speech – restricted speech quantity, uses few words and nonverbal responses; impoverished content of speech – words convey little meaning. |
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Describe three key negative symptoms that can be identified with some questioning.
Exam tip:know how to differentiate the different positive and negative symptom pathways. |
1. Reduced emotional responsiveness |
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Anti-psychotic drugs: 1st Generation: Typical Antipsychotics: |
All anti-psychotics are dopamine D2 receptor antagonists |
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When anti-psychotic drugs/neuroleptics are used to treat acute schizophrenia... |
25% patients go into remission without medication |
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When using anti-psychotic drugs / neuroleptics for maintenance tx of schizophrenia, what is the annual relapse rate:
1. On treatment? 2. Off treatment? |
Annual relapse rates On tx = 10-20% Off tx = 60%+ |
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How long should anti-psychotics be taken in treatment of first episode of psychosis?
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Length of tx for first episode – 9 months
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How long should anti-psychotics be taken for after 2+ episodes of psychosis?
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Continue tx to prevent further relapse for minimum of 5 years without further episodes (unless episodes brief, minimal functional impact and interspersed with lengthy periods when the person is well). |
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Apart from maintenance tx of schizophrenia, what else can anti-psychotic drugs/neuroleptics be indicated for?
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1. Other acute psychoses – e.g. mania, psychotic depression (esp with delusions and/or agitation), puerperal psychosis |
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Why do anti-psychotic medications have side effects that are additional to those associated with lowered dopamine?
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Most anti-psychotics also affect other neurotransmitter systems – e.g. histamine, acetylcholine, adrenaline and serotonin |
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Why were atypical antipsychotics developed?
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Atypical antipsychotics have been developed because of their more selective action on the dopamine system and/or action on other neurotransmitter systems (most notably serotonin) |
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What are three main types of side-effects caused by anti-psychotic medication?
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1. Dopaminergic effects on the striatum (EPSE) |
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Apart from dopamine, what else do new gen antipsychotics affect?
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New generation (atypical) antipsychotics affect serotonin as well (SDAs) |
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What can help with negative symptoms? |
Glutamate antagonists can help with negative symptoms |
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Why does schizophrenia consist of a wide range of symptoms?
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Schizophrenia likely effects a host of symptoms perhaps by disturbing a fundamental balance among neurotransmitters |
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What are the three “generations” of drugs which are used to treat schizophrenia and related psychotic disorders (anti-psychotics)
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1st gen: neuroleptics or typical antipsychotics |
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How do each of the generations of anti-psychotics differ (3)? |
1. Different neurotransmitter systems |
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Which receptors do atypical anti-psychotics affect?
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Atypical anti-psychotics are both D2 receptor and serotonin 2A (5HT2A) antagonisis
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Is the affinity of an atypical anti-psychotic greater for 5-HT2A or D2 receptors?
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The affinity of an atypical anti-psychotic is greater for 5-HT2A receptors than for D2 receptors |
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What are the advantages of atypical antipsychotics over typical anti-psychotics?
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Less risk of Parkinsoniam and tardive dyskinesia
Effective at treating both positive and negative symptoms |
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What is one negative of atypical anti-psychotics and one common side effect?
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They don't have any effect on cognitive dysfunction |
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What was the first atypical anti-psychotic to become commonly used?
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Clozapine (no new movement disorders from clozapine onwards) |
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What is the potential risk arising from clozapine use, and what must be done about it?
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Causes agranular cytosis – need blood monitoring (of white blood cell count) |
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If tx failure with any anti-psychotic, what is the second tx of choice?
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Clozapine
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Atypical anti-psychotics: what are the results of clinical trials?
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Cloazpine less likely to cause EPSE such as parkinsonism and akathesia |
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In an emergency situation of acute psychosis, what medications would be used?
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In an emergency situation of psychosis, would commence D2 antagonist (which will take 2-4 weeks before effect) and also immediately benzodiazepine (fast acting, causes significant sedation, makes patient more comfortable until hall/del settles down) |
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What is a partial agonist?
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Partial agonists – have affinity for a receptor but only partial efficacy (partially activate the receptor; modulator) |
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What is the third generation anti-psychotic?
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Aripiprazole (abilify) is considered an atypical anti-psychotic, but is a partial agonist at D2 receptors Partial agonists: have affinity for a receptor but only partial efficacy |
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What are SDAs? Give the two types and examples.
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SDAs = Serotonin 2A/D2 antagonists |
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What are DPAs? Give the two types and examples.
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DPA = D2 receptor partial agonists |
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What are the 5 stages of treatment for positive symptoms? (E, 1, 2, 3, N) |
Stages of treatment for positive symptoms: |
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What are the three stages of treatment for aggressive symptoms? (E, 1, 2) |
Stages of treatment for aggressive symptoms:
Emergency - SDA, BZ, D2 First line tx – SDA, DPA Second line tx – D2, clozapine, BZ, mood stabiliser |
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What are the 2 stages of treatment for negative symptoms? |
Stages of treatment for negative symptoms:
1st line tx: SDA, DPA 2nd line tx: ADM, NRI, modafinil, amisulpride, clozapine. |
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What are the 2 stages of tx for cognitive symptoms? |
Stages of treatment for cognitive symptoms:
1st line tx: SDA, DPA 2nd line tx: alpha 2 agonist, 5HT1A, NRI, modafinil, AChEl, ACh decreasing med. |
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What are the main adverse effects of clozapine (7)? no need to know this? |
1. Agranulocytosis |
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What is the effectiveness of clozapine in treating positive symptoms? |
The only 2nd gen antipsychotic effective for refractory positive symptoms – clinical improvement in 30-60%. |
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What are the main adverse effects of Risperidone (3)? |
1. Insomnia, agitation |
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What are two advantages of risperidone?
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1. Enhanced relapse prevention |
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What are the main adverse effects of olanzepine (6)? |
1. Headache |
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What are two advantages of olanzepine (SDA)? |
Few EPS |
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What are the main adverse effects of quetiapine (5)? |
1. Sedation |
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What is an advantage of quetiapine (SDA)? |
Few or no EPS |
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What are the main adverse effects of Amisulpride (DPA)? |
Prolactin elevation |
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Which receptor sites is the action of Amisulpride (DPA) specific to? |
D2 and D3 specific |
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What are the main adverse effects of Ziprasidone (SDA) (2)? |
1. Insomnia |
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What are two advantages of ziprasidone? |
1. Weight neutral |
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What is 1 adverse effect of Aripiprazole? |
Mild dose-related EPS |
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What are advantages of aripiprazole?
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1. Partial D2 agonist |
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Which SDA is weight neutral? |
ziprasidone |
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Which atypical antipsychotic can cause agranulocytosis? |
Clozapine |
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Which atypical antipsychotics cause few or no EPS (3)? |
Olanzepine and Quetiapine - few or no EPS Aripiprazole - mild dose-related EPS |
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Which atypical antipsychotic has a cholinergic action, causing anticholinergic SEs? |
Quetiapine - sedation - postural hypotension - dizziness - constipation |
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Which atypical antipsychotic can cause insomnia? |
Risperidone, Ziprasidone |