pahthophysiology and pharmacology of schizophrenia

Question 1

what are the positive symptoms of schizophrenia

Answer 1

1. disorders of thoughts and disorgaised behaviour
2. hallucinations
3. paranoia

Question 2

what are the negative symptoms of shizophrenia

Answer 2

1. social withdrawel
2. apathy/loss of energy
3. cognitive impairement
4. anhedonia

Question 3

what can influence the risk

Answer 3

stress 
poor social interactions 
poor maternal nutrition 
trauma at young age 
infectiosn at early age

Question 4

which neurotransmitters cause schizophrenia and how

Answer 4

dopamine being overactive in the brain

Question 5

3 main dopamine pathways in the brain

Answer 5

1. tuberoinfundibular pathway
2. nigrostriatal pathway
3. mesolimbic pathway

Question 6

explain the role of dopamine in tuberoinfundibular pathway

Answer 6

• released from the hypothalamus and works on the pituritary stalk ( more specifically the anterior pituitary gland)
• here it inhbiits the secretion of prolactin
• acts as a prolactin release inhibiting factor (PRIF)
• results in the tonic inhbiition of lactation

Question 7

explain the role of dopamine in the nigrostrial pathway

Answer 7

released from the substantia nigra and works on the dorsal striatum
here it affects the extra-pyrimidal motor systems and is involved in the initiation and control of movement

Question 8

explain the role of dopamine in the mesolimbic pathway

Answer 8

• released from the ventral tegmental area and works on the ventral striatum and amp; hippocampus and the frontal cortex
• at the cortex it regulates cognition mood and emotions
• at the ventral striatum and hippocampus regulates reward, addictio and sensory processing

Question 9

orignal theory of schizophrenia

Answer 9

• overactive dopamine systems in the brain cause schizophrenia (i.e. the mesolimbic pathway)

Question 10

mechanism of action of antipsychotics

Answer 10

• block the D2 receptors in the limbic/ cortical areas
• work as D2 receptor antagonists
• first ones were tricyclics

Question 11

what was the issue with tricyclics as dopamine antagonists

Answer 11

• they don’t have selectively for D2 receptors therefore cause side effectd e.g.
  1. H1 receptor activity causing sedation and weight gain
  2. M1 receptor activity causing dried mouth and blurred vision
  3. Alpha 1 receptor causing postural hypertension

Question 12

what are the side effects to using antipsychotics

Answer 12

• causes extrapyrimidal side effects
• can cause tremors
• rigid muscles
• loss of facial hair
• tardive dyskinesia (repetitive rhythmical involuntary movements)
• galactorrhoea
• gynaecomastia

Question 13

3 types of phenothiazines ( 1st gen antipsychotic)

Answer 13

1. chlorpromazine (group 1)
2. thioridazine (group 2)
3. fluphenazine (group 3)

Question 14

side effect profiles of group 1 phenothiazines

Answer 14

sedation

Question 15

side effect profiles of group 2 phenothiazines

Answer 15

anticholinergic side effects

Question 16

side effect profiles of froup 3 phenotiazines

Answer 16

extra-pyrimidal side effects

Question 17

2 other 1st gen anti-psychotic classifications besides phenothiazine

Answer 17

1. thioxanthenes e.g. flupenthixol- similar profile to phenothiazines
2. butyrophenones e.g. haloperidol- no anticholinergic effect but has EPS effect

Question 18

what are the second gen antipsychotics

Answer 18

clozapine 
olanzapine 
risperidone 
amisulpiride 
quetapine

Question 19

what is the advantage of 2nd over 1st gen antipsychotics

Answer 19

• have better EPS side effect profile

- better at treating negative symptoms

Question 20

what effect does risperidone and olanzapine have on a person

Answer 20

• increased weight gain and metabolic syndrome

- cause insulin resistance therefore diabetes

Question 21

what makes 2nd gen antipsychotics better at treating the negative symtpoms of schizophrenia

Answer 21

due to their low affinity for D2 receptors and high affinity for D3, D4 and 5-HT2A receptors

Question 22

why do we get a lot of adverse drug reactions with dopamine antagonists

Answer 22

due to importance of dopamine in brain

Question 23

2 main distinctions between typical and atypical antipsychotics

Answer 23

1. extrapyrimidal side effects more common in 1st gen

2. 2nd gen has a better efficacy against negative symptoms

Question 24

side effects of antipsychotics on D2 receptors

Answer 24

extrapyrimmidal e.g parkinsons

galactorrhoea

Question 25

side effects of antipsychotics on H1 receptors

Answer 25

sedation

Question 26

side effects of antipsychotics on M1 receptors

Answer 26

dry mouth
blurred visison
constipation

Question 27

side effects of antipsychotics on alpha 1 receptors

Answer 27

postural hypotension