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PR3136 > ANTI-PSYCHOTICS > Flashcards

ANTI-PSYCHOTICS Flashcards

1
Q

Typical anti-psychotic drugs (CFHT)

A
  1. Chlorpromazine (1st antipsychotic drug)
  2. Fluphenazine
  3. Haloperidol (one of the most commonly prescribed drug)
  4. Trifluoperazine
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2
Q

5 symptoms domains of schizophrenia

A
  1. Positive symptoms
  2. Negative symptoms
  3. Cognitive symptoms
  4. Anxiety/depression
  5. Aggressive symptoms
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3
Q

What is positive symptoms

A

Addition of abnormal behaviours

  • most disrupting to others
  • led to first referral to psychiatrist and diagnosis of schizophrenia

eg hallucinations, delusions, thought disorder, abnormal behaviours

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4
Q

What is negative symptoms

A

Subtraction of normal behaviours

  • becomes more dominant over time as disease progress
  • most disrupting to self
  • frequently associated with depression resulting in suicide in 10% of cases

eg withdrawal from social contacts, flattening of emotional responses

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5
Q

EPS

A

Extrapyrimidal symptoms

  1. Acute dystonia
  2. Tardive Dyskinesia
  3. Akathisia
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6
Q

What is cognitive dysfunction

A

Impairment of working memory
Impairment of selective attention

  • recently recognised to be a persistent core feature of the disease (not iatrogenic)
  • important to predict level of social and vocational functioning than positive symptoms
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7
Q

3 main theories to the etiology of schizophrenia

A
  1. Dopamine theory (Amphetamine)
    - dopamine agonist lead to schizophrenia
    F>H>T>C
  2. 5-HT theory (Lysergic acid diethylamide, LSD)
    - 5-HT agonist lead to schizophrenia
    - many atypicals have 5-HT antagonism (clozapine & olanzapine)
  3. Glutamate theory (Ketamine, PCP)
    - NMDA antagonist lead to schizophrenia
    - no current drugs as NMDA agonist

They are mainly theories of positive symptoms

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8
Q

4 dopamine pathways of the brain

A
  1. Nigrostriatum pathway (voluntary movement & EPS)
    - substantia nigra to dorsal striatum
  2. Mesolimbic pathway (rewards & emotions)
  3. Mesocortical pathway (cognitive & attention)
  4. Tuberoinfundibular pathway (lactation & gynaecomastia)
    - hypothalamus to anterior pituitary
    - cos dopamine is involved in the negative feedback of prolactin production
    - hence dopamine antagonist will allow prolactin production leading to lactation (even in non-pregnancy women) & gynaecomastia (males)
    - Amisulpride
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9
Q

Side effects of H1 receptor antagonist

A
  1. Sedation

2. Weight gain

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10
Q

Side effects of M1 muscarinic receptor antagonist

A
  1. Dry mouth
  2. Constipation
  3. Blurred vision
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11
Q

Side effects of alpha1-adrenergic receptor antagonist

A
  1. Postural hypotension
  2. Dizziness
  3. Reflex tachycardia
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12
Q

Potential benefits of HT-7 receptor antagonist

A

Pro-cognitive

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13
Q

All anti-psychotics MOA

A

D2 dopamine receptor antagonist

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14
Q

What is acute dystonia?

A
  • Parkinsonism-like syndrome
  • due to nigrostriatum pathway inhibition
  • reversible upon discontinuation of drug
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15
Q

What is tardive dyskinesia?

A
  • involuntary movement
  • develops over time
  • irreversible
  • most likely due to the upregulation of dopamine receptors in nigrostriatal pathway
  • occur in 20-40% of patients on typical anti-psychotic
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16
Q

What is akathisia?

A
  • compulsion to act associated with restlessness, anxiety & agitation
  • linked to the duration of drug use
  • irreversible
  • most likely due to the upregulation of dopamine receptors in nigrostriatal pathway
  • occur in 20-40% of patients on typical anti-psychotic
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17
Q

Haloperidol affinities to receptors (2)

A
  1. D2 dopamine receptor antagonist

2. alpha-1 adrenergic receptor antagonist

18
Q

Atypical anti-psychotics (COARA)

A
  1. Clozapine
  2. Olanzapine
  3. Amisulpride
  4. Risperidone
  5. Aripiprazole (partial D2 agonist)
19
Q

Why are atypicals anti-psychotics atypicals?

A

They produce less severe EPS side effects

20
Q

1 severe side effect of Clozapine

A

Agranulocytosis, the loss of granulocyte leading to lower immune system

  • can be fatal
  • regular blood counts to be done
21
Q

Atypical of the atypicals anti-psychotic

A

Amisulpride

  • only have selected affinities to D2 and D3 receptors
  • reported to have affinity to HT-7 receptor antagonism (pro-cognitive)
  • do not have affinity to 5-HT2A receptors
22
Q

1 serious side effect of Amisulpride

A

Breast swelling, pain and lactation (even in non-pregnant women)
Gynaecomastia (in males)

  • increased prolactin secretion due to dopamine receptor antagonism in anterior pituitary gland
  • involve the hypothalamus and anterior pituitary gland
  • tuberoinfundibular pathway blocked
23
Q

D2 dopamine receptor partial agonist

A

Aripiprazole

  • requires dopamine (agonist to D2 receptor) in order for antagonism effect to work
  • without agonist, itself will be partial agonist
24
Q

Additional side effects of atypical anti-psychotics (2)

A
  1. Hyperglycemia & Diabetes (risperidone > clozapine & olanzapine)
    - irreversible (risperidone)
    - FDA required labelling on all atypical anti-psychotics to warn the risk of hyperglycemia/diabetes
  2. Weight gain
    - Olanzapine used experimentally for anorexia nervosa
25
Q

Why atypical anti-psychotics produce less EPS

A
  1. Potent 5-HT2A antagonism > D2 antagonism
    (clozapine & olanzapine)
  2. High D3 : D2 antagonism (favours nucleus accumbens over striatum)
    (amisulpride)
  3. High D4 : D2 antagonism (favours pre-frontal cortex over striatum)
    (clozapine)
  4. High D2 : D1 antagonism (reduces the impact of antagonism in striatum)
    (amisulpride & risperidone)
    - blockage of D1 leads to more severe impact on nigrostriatal pathway
26
Q

Explanation for reduced EPS for high D2 : D1 antagonism

A

D2 receptor at pre-synapse acts as a negative feedback to regulate dopamine secretion into synapse.
The antagonism of D2 receptor would inhibit the negative feedback regulation and allows dopamine release into synapse.
This results in less complete blockage of dopaminergic at post-synaptic membrane.

27
Q

Additional benefits of atypical anti-psychotics (3)

A 
1. Less EPS & more effective against negative symptoms
(clozapine, olanzapine & risperidone)
2. Ameliorate cognitive function
(clozapine & risperidone)
3. Better mood stabiliser
(clozapine, olanzapine & risperidone)

HOWEVER, the effectiveness against negative symptoms are weak. They are only more applicable for severe negative symptoms

28
Q

Causes of negative symptoms (5)

A
  1. Primary deficit of illness
  2. Secondary to EPS
  3. Secondary to depression
  4. Secondary to environment deprivation
  5. Secondary to positive symptoms
29
Q

Onset of Schizophrenia

A

Late adolescent, early adulthood due to neurodevelopment abnormalities involving the myelination of cortico-cortical pathways
- evidence of enlarged ventricles, abnormalities in laminar organisation of cortical cells (neurodevelopmental disorder)

30
Q

Causes of Schizophrenia (2)

A
  1. Genetics
    - 50% risk in monozygotic twin of affected individual
    - not all schizophrenia patients have the same mutation
  2. Environment
    - maternal viral infection during pregnancy
    - obstetric complications
31
Q

Most atypicals anti-psychotic receptor affinities

A
  1. 5-HT2A antagonist

2. D2 receptor antagonist

32
Q

Clozapine receptor affinities (6)

A
  1. H1 receptor antagonist
  2. alpha1-adrenoceptor antagonist
  3. M1 receptor antagonist
  4. D2 receptor antagonist
  5. 5-HT2A receptor antagonist
  6. 5-HT 7 receptor antagonist
33
Q

Olanzapine receptor affinities (5)

A
  1. H1 receptor antagonist
  2. alpha1-adrenoceptor antagonist
  3. M1 receptor antagonist
  4. D2 receptor antagonist
  5. 5-HT2A receptor antagonist
34
Q

Risperidone receptor affinities (5)

A
  1. alpha1-adrenoceptor antagonist
  2. alpha2-adrenoceptor antagonist
  3. D2 receptor antagonist
  4. 5-HT2A receptor antagonist
  5. 5-HT 7 receptor antagonist
35
Q

Aripiprazole receptor affinities (5)

A
  1. H1 receptor antagonist
  2. alpha1-adrenoceptor antagonist
  3. 5-HT2A receptor antagonist
  4. 5-HT 7 receptor antagonist
  5. D2 receptor antagonist
36
Q

Schizophrenia

A
  • chronic disease
  • late adolescent / early adulthood
  • highly disabling to social and vocational functioning
37
Q

Presentation of schizophrenia

A
  • periods of acute presentation with positive symptoms interspersed between negative symptoms predominate
  • negative symptoms generally become more dominate as disease progress
38
Q

Importance of analysing cognitive dysfunction (2)

A
  1. Important to predict the social and vocational functioning (btr than positive symptoms)
  2. Better treatment outcomes
39
Q

Atypical anti-psychotic and diabetes/hyperglycemia MOA

A
  1. 5-HT antagonism on beta-pancreatic cells

2. 5-HT antagonism on hypothalamus

40
Q

Experimental use for anorexia nervosa

A

Olanzapine

- typical anti-psychotic

PR3136 (19 decks)

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