Pathophysiology and Pharmacology of schizophrenia

Question 1

what are the ‘positive’ symptoms of schizophrenia?

Answer 1

1. Disorders of thoughts and disorganised behaviour
2. Hallucinations (aural and visual)
3. Paranoia

Question 2

what are the ‘negative’ symptoms of schizophrenia?

Answer 2

1. social withdrawal
2. apathy/loss of energy
3. cognitive impairment
4. anhedonia

Question 3

Family studies suggest schizophrenia is genetic but in monozygotes, the likelihood of developing schizophrenia is 50%, this means genetics aren’t the only reason. What else could influence the risk?

Answer 3

1. stress
2. poor social interactions
3. poor maternal nutrition
4. trauma at early age
5. infections at early age

Question 4

which neurotransmitter causes schizophrenia and how?

Answer 4

dopamine and by being overactive in the brain

Question 5

what are the three main dopamine pathways in the brain?

Answer 5

1. The Tuberoinfundibular pathway
2. The Nigrostriatal pathway
3. The Mesolimbic/Mesocortical pathway

Question 6

Explain the role of dopamine in the tuberoinfundibular pathway?

Answer 6

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

Question 7

Explain the role of dopamine in the Nigrostriatal 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 & hippocampus and the frontal cortex
• at the cortex it regulates cognition mood and emotions
• at the ventral striatum and hippocampus regulates reward, addiction and sensory processing.

Question 9

what was the original dopamine theory of schizophrenia?

Answer 9

-an overactive dopamine system in the brain causes schizophrenia (i.e. the mesolimbic pathway)

Question 10

what is the mechanism of action of antipsychotics?

Answer 10

• they block the D2 receptors in the limbic/cortical areas
• they 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 selectivity for D2 receptors therefore cause side effects e.g
• H1 receptor activity causing sedation and weight gain
• M1 receptor activity causing dried mouth and blurred vision
• Aplha 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

what are the three types of phenothiazines (a first generation antipsychotic)?

Answer 13

1. Chlorpromazine (group 1)
2. Thioridazine (group 2)
3. Fluphenazine (group 3)

Question 14

what are the side effect profiles of group 1 phenothiazines?

Answer 14

sedation

Question 15

what are the side effect profiles of group 2 phenothiazines?

Answer 15

anticholinergic side effects (muscle and movement)

Question 16

what are the side effect profiles of group 3 phenothiazines?

Answer 16

extra-pyrimidal side effects (EPS)

Question 17

what are the two other 1st generation 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 efffect

Question 18

what are the second generation antipsychotics?

Answer 18

• Clozapine
• Olanzapine
• Risperidone
• Amisulpiride
• Quetiapine

Question 19

what is the advantage of 2nd over 1st generaton antipsychotics?

Answer 19

• have better EPS side effect profile

- better at treating negative symptoms

Question 20

what effect does risperidone and olanzapine have on an individual?

Answer 20

• cause increased weight gain and metabolic syndrome

- can also cause insulin resistance therefore diabetes

Question 21

what makes 2nd generation antipsychotics better at treating the negative symptoms 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 many adverse drug reactions with Dopamine antagonists?

Answer 22

due to the importance of dopamine in the brain

Question 23

what are the 2 main distinctions between typical and atypical antipsychotics?

Answer 23

1. extrapyrimidal side effects more common in 1st generation

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

Question 24

what is the side effects of antipsychotics on D2 receptors?

Answer 24

• extrapyrimidal e.g. parkinsons

- galactorrhoea (milk discharge from nipple)

Question 25

what is the side effects of antipsychotics on H1 receptors?

Answer 25

sedation

Question 26

what is the side effects of antipsychotics on M1 receptors?

Answer 26

• dry mouth
• blurred vision
• constipation

Question 27

what is the side effects of antipsychotics on alpha1 receptors?

Answer 27

-postural hypertension