Pathophysiology and Pharmacology of schizophrenia Flashcards
what are the ‘positive’ symptoms of schizophrenia?
- Disorders of thoughts and disorganised behaviour
- Hallucinations (aural and visual)
- Paranoia
what are the ‘negative’ symptoms of schizophrenia?
- social withdrawal
- apathy/loss of energy
- cognitive impairment
- anhedonia
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?
- stress
- poor social interactions
- poor maternal nutrition
- trauma at early age
- infections at early age
which neurotransmitter causes schizophrenia and how?
dopamine and by being overactive in the brain
what are the three main dopamine pathways in the brain?
- The Tuberoinfundibular pathway
- The Nigrostriatal pathway
- The Mesolimbic/Mesocortical pathway
Explain the role of dopamine in the tuberoinfundibular pathway?
- 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
Explain the role of dopamine in the Nigrostriatal pathway?
- 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
Explain the role of dopamine in the Mesolimbic pathway?
- 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.
what was the original dopamine theory of schizophrenia?
-an overactive dopamine system in the brain causes schizophrenia (i.e. the mesolimbic pathway)
what is the mechanism of action of antipsychotics?
- they block the D2 receptors in the limbic/cortical areas
- they work as D2 receptor antagonists
- first ones were tricyclics.
what was the issue with tricyclics as dopamine antagonists?
- 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
what are the side effects to using antipsychotics?
- causes extrapyrimidal side effects
- can cause tremors
- rigid muscles
- loss of facial hair
- tardive dyskinesia (Repetitive rhythmical involuntary movements)
- galactorrhoea
- gynaecomastia
what are the three types of phenothiazines (a first generation antipsychotic)?
- Chlorpromazine (group 1)
- Thioridazine (group 2)
- Fluphenazine (group 3)
what are the side effect profiles of group 1 phenothiazines?
sedation
what are the side effect profiles of group 2 phenothiazines?
anticholinergic side effects (muscle and movement)
what are the side effect profiles of group 3 phenothiazines?
extra-pyrimidal side effects (EPS)
what are the two other 1st generation anti-psychotic classifications besides phenothiazine?
- thioxanthenes e.g. flupenthixol - similar profile to phenothiazines
- butyrophenones e.g. haloperidol - no anticholinergic effect but has EPS efffect
what are the second generation antipsychotics?
- Clozapine
- Olanzapine
- Risperidone
- Amisulpiride
- Quetiapine
what is the advantage of 2nd over 1st generaton antipsychotics?
- have better EPS side effect profile
- better at treating negative symptoms
what effect does risperidone and olanzapine have on an individual?
- cause increased weight gain and metabolic syndrome
- can also cause insulin resistance therefore diabetes
what makes 2nd generation antipsychotics better at treating the negative symptoms of schizophrenia
due to their low affinity for D2 receptors and high affinity for D3, D4 and 5-HT2A receptors.
why do we get many adverse drug reactions with Dopamine antagonists?
due to the importance of dopamine in the brain
what are the 2 main distinctions between typical and atypical antipsychotics?
- extrapyrimidal side effects more common in 1st generation
2. 2nd generation has a better efficacy against negative symptoms
what is the side effects of antipsychotics on D2 receptors?
- extrapyrimidal e.g. parkinsons
- galactorrhoea (milk discharge from nipple)
what is the side effects of antipsychotics on H1 receptors?
sedation
what is the side effects of antipsychotics on M1 receptors?
- dry mouth
- blurred vision
- constipation
what is the side effects of antipsychotics on alpha1 receptors?
-postural hypertension
