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Neuropharmacology > Drugs for Psychosis and Mania > Flashcards

Drugs for Psychosis and Mania Flashcards

1
Q

What is psychosis?

A

a mental state in which there is a loss of contact with reality

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2
Q

What is mania?

A

madness or frenzy accompanied by an elevated or irritable mood, increased energy, reduced need to sleep, exaggerated self-importance, reckless behaviour and thought disturbances

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3
Q

What is schizophrenia?

A

a chronic disease with the onset in late adolescence/early adulthood and it is highly disabling to social and vocational functioning

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4
Q

What are the 5 domains of schizophrenia symptoms?

A
  • positive symptoms
  • negative symptoms
  • aggressive symptoms
  • cognitive symptoms
  • anxiety/depression
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5
Q

What are positive symptoms of schizophrenia?

A

addition of abnormal behaviours interspersed between periods where negative symptoms dominate

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6
Q

Give examples of positive symptoms of schizophrenia

A
  • delusions (often paranoid)
  • hallucinations e.g. exhortatory voices
  • thought disorder including feeling that thoughts are controlled by an outside agency
  • abnormal behaviours e.g. stereotypical or aggressive behaviours
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7
Q

What are positive symptoms of schizophrenia generally the result of?

A

increased subcortical release of dopamine, which augments D2 receptor activation and a disturbed cortical pathway through the nucleus accumbens

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8
Q

Give examples of negative symptoms of schizophrenia

A
  • withdrawal from social contacts
  • flattening of emotional responses
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9
Q

What are negative symptoms of schizophrenia?

A

the subtraction of normal behaviours that become more dominant as the disease progresses

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10
Q

What are negative symptoms of schizophrenia generally the result of?

A

reduced D1 receptor activation in the prefrontal cortex and decreased activity of the nucleus caudatus

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11
Q

What is cognitive dysfunction?

A

the impairment of selective attention and working memory

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12
Q

Why are cognitive dysfunction symptoms important in schizophrenia?

A

they predict the level of social and vocational functioning, and hence treatment outcome, better than positive symptoms

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13
Q

What are environmental factors of schizophrenia?

A
  • neurodevelopmental abnormalities
  • maternal viral infections during pregnancy
  • obstetric complications
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14
Q

What is the onset of schizophrenia in late adolescence consist with?

A

neurodevelopmental abnormality involving myelination of cortico-cortical pathways

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15
Q

What are the 3 proposed neurochemical theories of schizophrenia?

A
  • dopamine theory
  • 5-HT theory
  • glutamate theory
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16
Q

What is the dopamine theory?

A

dysregulation of dopamine activity in the brain plays a central role in the development of symptoms

17
Q

What is the 5-HT theory?

A

dysregulation of 5-HT system, particularly involving the 5-HT2A receptor, contributes to the development of symptoms

18
Q

What is the glutamate theory?

A

dysregulation of the glutamate neurotransmitter system, particularly involving NMDA receptors, plays a central role in the development of symptoms

19
Q

What are the 2 key typical antipsychotics?

A

chlorpromazine and haloperidol

20
Q

What are the 4 key atypical antipsychotics?

A

amisulpride, clozapine, olanzapine, risperidone

21
Q

What do typical antipsychotics do?

A

control positive symptoms and produce EPS by blocking D2 receptors

22
Q

What do atypical antipsychotics do?

A

control positive and negative symptoms and produce less EPS

23
Q

What EPS does blocking of D2 receptors cause?

A
  • dry mouth, constipation, blurred vision via M1 receptors
  • sedation, weight gain via H1 receptors
  • postural hypotension, dizziness via alpha-adrenergic receptors
24
Q

What is chlorpromazine derived from?

A

antihistamine drugs

25
Q

What is the most widely used antipyschotic drug and why?

A

haloperidol since its single selective mechanisms reduce the side effects

26
Q

What are motor EPS?

A

dystonias and tardive dyskinesia

27
Q

What is the cause of motor EPS?

A

actions on the extrapyramidal motor pathways

28
Q

What does the extrapyramidal motor pathway involve?

A

the basal ganglia, including the striatum and substantia nigra

29
Q

What are the pyramidal motor pathways?

A

the output from the primary motor cortex via the pyramids of the medulla oblongata to the spinal cord

30
Q

What is acute dystonia?

A

a tremor at rest due to D2 antagonism in the nigrostriatal pathway that occurs within the first few weeks of treatment and is reversible when the drug is stopped

31
Q

What is tardive dyskinesia?

A

is involuntary movements of the face due to upregulation or super-sensitivity of dopamine receptors

32
Q

What do many atypical antipsychotics have?

A
  • greater affinity at 5-HT2 receptors
  • greater affinity at D4 receptors
  • mixed antagonism at α-adrenoceptors, H1 histamine receptors, muscarinic acetylcholine receptors, and 5-HT2 receptors
33
Q

What is the core MOA of most atypical antipsychotics?

A

serotonin-dopamine antagonism

34
Q

How do atypical antipsychotics reduce the incidence of tardive dyskinesia?

A

they dissociate more rapidly and so are more readily displaced by competition from endogenous dopamine

35
Q

What are benefits of atypical antipsychotics?

A
  • more effective against negative symptoms e.g. clozapine, olanzapine, risperidone
  • ameliorate cognitive dysfunction better than typical antipsychotics e.g. clozapine, risperidone
  • better at mood stabilization e.g. clozapine, olanzapine, risperidone
  • antagonism at presynaptic 5-HT2 heteroreceptors on dopaminergic terminals may regulate dopamine levels in the PFC
36
Q

What does combination of atypical antipyschotics with antidepressants do?

A

stabilise mood but also increase range of adverse effects

37
Q

What are adverse effects of atypical antipsychotics?

A
  • same EPS as typical antipsychotics
  • clozapine-induced agranulocytosis
  • hyperglaecemia
  • diabetes
  • increased prolactin secretion

Neuropharmacology (12 decks)

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