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5BBM0218 Physiology and Pharmacology of CNS > L12: Sz > Flashcards

L12: Sz Flashcards

1
Q

What is the incidence of schizophrenia in the general population?

A
  • 1%
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2
Q

What is the incidence of schizophrenia if there is a family history of the disorder?

A
  • around 6-17% if there is a family history of the disorder
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3
Q

What are some environmental risk factors associated with schizophrenia?

A
  • maternal infections and malnutrition during pregnancy, cannabis exposure, urban living, and stress during adolescence
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4
Q

What is the neurodevelopmental nature of schizophrenia?

A
  • Sz considered neurodevelopmental disorder - meaning it arises from impairments in the development of the brain during gestation.
  • It involves impairment of timing in the tuning & synapse stabilization processes during brain development
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5
Q

What is the pathology of Sz in terms of brain structure?

A
  • Sz associated with reduced cortical grey matter & support neurodegeneration within the cortex
  • Post-mortem studies have shown that cortical pyramidal cells in the schizophrenia brain have reduced dendritic length and spine density.
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6
Q

What are the positive symptoms of schizophrenia?

A
  • Delusions: False beliefs not based in reality
  • Auditory hallucinations: Hearing voices/sounds that are not present
  • Illusions: Misinterpretation of sensory stimuli.
  • Thought disorder: Disorganized & incoherent thinking.
  • Abnormal behaviour: Displaying unusual/bizarre actions.
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7
Q

What are the negative symptoms of schizophrenia?

A
  • Avoiding social interactions and isolating oneself.
  • Flattened emotions: Reduced emotional expressiveness and responsiveness.
  • Lack of drive: Decreased motivation and initiative.
  • Disorganized speech: Difficulty organizing thoughts and expressing ideas clearly.
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8
Q

What are the cognitive symptoms of schizophrenia?

A
  • Attention deficits: Difficulty focusing and sustaining attention.
  • Learning and memory problems: Impairments in acquiring and retaining new information.
  • Executive function problems: Challenges in planning, decision-making, and problem-solving
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9
Q

What is the dopamine hypothesis of schizophrenia?

A
  • The dopamine hypothesis suggests that hyperactivity of dopamine pathways in the brain results in the positive symptoms of schizophrenia
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10
Q

What evidence supports the dopamine hypothesis?

A
  1. Amphetamine-induced symptoms: Administration of amphetamine, which causes the release of dopamine, leads to paranoia, hallucinations, and repetitive movements, even in animals.
  2. L-DOPA in Parkinson’s patients: L-DOPA, a precursor to dopamine, can induce psychosis in some patients with Parkinson’s disease (PD)
  3. Genetic association: Genetic impairments in the dopaminergic system, such as D2/3 receptors, BDNF, and COMT, have been linked to schizophrenia.
  4. Post-mortem findings: The brains of individuals with schizophrenia show an increased number of D2 dopamine receptors, which may be related to chronic use of antipsychotic drugs.
  5. Antipsychotic drugs’ action: Effective antipsychotic drugs work by blocking dopamine D2 receptors, leading to upregulation of these receptors to compensate for the blockage
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11
Q

What are the two main classes of anti-psychotic drugs?

A
  1. Typical antipsychotics (first generation) - used before the 1980s.
  2. Atypical antipsychotics (second generation) - used after the 1980s.
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12
Q

How do anti-psychotic drugs work?

A
  • anti-psychotic drugs target receptors associated with dopamine hyperactivity, based on the dopamine hypothesis of sz
  • they also have additional effects on serotonin (5-HT) receptors.
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13
Q

What is the typical plasma half-life of anti-psychotic drugs?

A
  • 15-30 hours, which allows for once-daily dosing
  • Intramuscular depot injections can also be given, lasting 2-4 weeks
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14
Q

What are typical antipsychotics and what receptors do they target?

A
  • Typical antipsychotics (like chlorpromazine and haloperidol) = class of antipsychotic drugs used to treat Sz & other psychotic disorders
  • primarily target dopamine receptors, particularly the D2 subtype (but also interact with other receptors)
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15
Q

What is the order of affinity for typical antipsychotics at different receptors?

A

highest to lowest:
1. Dopamine D2 receptors
2. Alpha adrenoceptors
3. Dopamine D1 receptors
4. 5-HT2 receptors (serotonin receptors)
5. Muscarinic acetylcholine receptors (mACh receptors)
6. Histamine H1 receptors

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16
Q

How do typical antipsychotics act at the dopamine D2 receptors?

A
  • act as antagonists at dopamine D2 receptors.
  • bind to receptors without activating them - effectively blocking the receptor’s response to dopamine.
17
Q

What are the effects of typical antipsychotics on different receptor systems?

A
  • Dopamine D2 receptor blockade in the mesolimbic pathway treats positive symptoms of schizophrenia.
  • Alpha adrenoceptor blockade can lead to sedation and hypotension.
  • Dopamine D1 receptor blockade may contribute to some side effects.
  • 5-HT2 receptor blockade may contribute to some efficacy against negative symptoms.
  • Muscarinic acetylcholine receptor blockade can cause anticholinergic side effects like constipation and dry mouth.
  • Histamine H1 receptor blockade can cause sedation
18
Q

What are some common side effects of typical antipsychotics?

A
  • sedation (due to blocking H1 receptors),
  • hypotension (due to blocking a1 receptors)
  • anti-cholinergic effects (e.g., constipation, dry mouth, and blurred vision)
  • gynecomastia (due to D2 blockade in the tuberoinfundibular pathway)
  • mood disturbances (due to blocking D2 receptors in the mesolimbic pathway)
19
Q

What are some movement impairments associated with anti-psychotic drugs?

A
  • movement impairments caused by anti-psychotic drugs known as extrapyramidal side effects
  • involve the nigrostriatal pathway, which includes D1, D2, and D3 receptors.
20
Q

What is pseudoparkinsonism, and what causes it?

A
  • a movement impairment characterized by symptoms similar to PD, such as tremors, rigidity, and bradykinesia (slowness of movement)
  • mainly caused by the blockade of D2 receptors
21
Q

What are acute dystonias and akathisia, and how are they related to anti-psychotic drugs?

A
  • acute dystonias = involuntary muscle contractions that lead to facial grimacing and muscle spasms of the neck and face
  • Akathisia = feeling of inner restlessness, and patients may rock their feet back and forth.
  • Both side effects can occur in about 20% of patients and are reversible.
22
Q

What is tardive dyskinesia, and what causes it?

A
  • movement disorder characterized by involuntary & repetitive movements e.g. protruding tongue, lip smacking, facial dyskinesia, and involuntary movements of the limbs
  • caused by upregulation of D2 receptors due to chronic use of anti-psychotic drugs
  • If not treated, tardive dyskinesia may become irreversible
23
Q

What are some examples of atypical anti-psychotic drugs?

A

clozapine, olanzapine, and risperidone
(remember these!)

24
Q

What receptors do atypical anti-psychotic drugs mainly target and in what order of affinity?

A

highest to lowest (as antagonists for):
- 5-HT2 receptors
- D4 dopamine receptors
- D2 dopamine receptors.
- their affinity for D1 receptors, alpha receptors, mACh receptors, and histamine H1 receptors is similar.

25
Q

How do atypical anti-psychotic drugs treat positive symptoms of schizophrenia?

A
  • block D2 and D4 receptors in the mesolimbic pathway, leading to the treatment of positive symptoms
26
Q

Why do atypical anti-psychotic drugs have fewer extrapyramidal side effects?

A
  • do not affect D4 receptors in the nigrostriatal pathway, which is responsible for extrapyramidal side effects
27
Q

What are some side effects of atypical anti-psychotic drugs, and which drug is associated with leucopenia?

A
  • Side effects of atypical anti-psychotic drugs include weight gain and impaired glycemic control (T2D).
  • Leucopenia, a loss of neutrophils, basophils, and eosinophils, is only seen with clozapine.
28
Q

What side effect is unique to clozapine among the atypical antipsychotics?

A

Leucopenia, a loss of neutrophils, basophils, and eosinophils

5BBM0218 Physiology and Pharmacology of CNS (17 decks)

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