CPTP 3.4 Neuropharmacology 2 (Antipsychotics) Flashcards Preview

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Flashcards in CPTP 3.4 Neuropharmacology 2 (Antipsychotics) Deck (38)
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1

When is the onset of schizophrenia?

Adolescence & young adulthood

2

There is a 'spectrum of symptoms' for schizophrenia. What does this divide the symptoms into?

• Positive symptoms

• Negative symptoms

3

What are the 'positive' symptoms of schizophrenia?

• Disorders of thought

• Hallucinations

• Paranoia

4

What are the 'negative' symptoms of schizophrenia?

Catatonic Behaviour

• Blunted emotions

• Social withdrawal

• Apathy

5

What is the importance of positive and negative symptoms?

They respond differently to different medications.

6

What brain differences are seen in those with schizophrenia?

• Developmental abnormalities in the limbic system

• Smaller temporal lobes

• Enlarged ventricles

7

Describe a theory of schizophrenia.

Dopamine theory of Schizophrenia: "Schizophrenia is caused by overactive MESOLIMBIC AND MESOCORTICAL dopamine systemS in the brain"

8

What are the three main dopamine systems in the brain?

• Nigrostriatal

• Mesolimbic/Mesocortical

• Tuberoinfundibular

9

Where does the tuberoinfundubular pathway run from and to? What does dopamine do at the destination?

Hypothalamus --> pituitary stalk Dopamine acts tonically as prolactin release inhibiting factor (PRIF)

10

Outline prolactin regulation

Stimulating:

• Suckling

• Hypothalamic nuclei release prolactin releasing factor (PRF)

• PRF Stimulates anterior pituitary to release prolacin

 

Inhibiting:

• Dopamine from tuberoinfundibular tract inhibits anterior pituitary prolactin release

11

What does prolactin do?

Stimulates milk production and differentiation of mammary tissue

12

Where is prolactin released from?

Anterior pituitary

13

What is released from the posterior pituitary?

Oxytocin

Vasopressin

14

Where does the nigrostriatal pathway run from and to? What does dopamine do at the destination?

substantia nigra --> dorsal striatum Involved in the initiation and control of movement (extrapyramidal pathway of movement)

15

What are the diseases of the nigrostriatal pathway?

• Parkinson's disease

• Huntington's chorea

16

What is the relevance of the nigrostriatal pathway with schizophrenia?

No direct relationship, but the drugs used to treat schizophrenia have side effects which affect this pathway

17

Where does the mesolimbic pathway run from and to? What does dopamine do at the destination?

Ventral tegmentum --> Ventral striatum & hippocampus Reward, addiction, sensory processing

18

Where does the mesocortical pathway run from and to? What does dopamine do at the destination?

Ventral tegmentum --> frontal cortex Cognition, mood

19

What causes dopamine imbalance in schizophrenia?

Increased synthesis of dopamine

20

How do antipsychotic drugs work?

They block D2 receptors in limbic and cortical areas

21

What were the first antipsychotic drug classes to be high-affinity D2 receptor antagonists? What are the side effects of this and why?

Phenothiazines and thioxanthenes Have tri-cyclic structures (like TCAs but arent) which means its not selective, and has affinity for many receptors:

H1:

• Weight gain

• Sedation

 

M1:

• Dry mouth

• Blurred vision

• Constipation

• Urinary retention

 

a1:

• Postural hypotension

 

D2 (nigrostriatal):

• Extrapyrimidal side effects

 

D2 (tuberoinfundibular)

• Galactorrhoea

• Gynaecomastea

 

NB: D2 for mesocortical and mesolimbic pathways is the therapeutic target

22

Antipsychotics which are specific to D2 receptors may still cause side effects. What are these? Why does this occur?

D2 (nigrostriatal):

• Extrapyrimidal side effects

 

D2 (tuberoinfundibular):

• Galactorrhoea

• Gynaecomastia

23

What does 'tardive' mean in tardive dyskinesia?

Tardive, because it begins 6 months after initiation of treatment

24

Is tardive dyskinesia permanent?

Yes

25

What are the extrapyramidal side effects?

• Parkinson's symptoms (rigidity, tremor, etc)

• Tardive dyskinesia (repetitive involuntary movement)

26

What are the side effect profiles of phenothiazines and thioxanthenes?

Group I: Sedation (H1)

Group II: Anticholinergic (M1)

Group III: Extrapyrimidal (D2)

27

What drug class ditched the tricyclic structure, and were more selective for just D2 receptors? Give an example.

Butyrophenones

• Haloperidol

28

What are the side effects of butyrophenones?

Extrapyramidal side effects remain

Prolactin side effect remain (galactorrhea and gynaecomastia)

29

Summarise the 1st generation antipsychotic classes and an example of each

Tricyclic compounds:

• Phenothiazines

• Thioxanthenes 

 

Selective:

• Butyrophenones 

30

What are 2nd generation antipsychotics also known as?

Atypical antipsychotics