pahthophysiology and pharmacology of schizophrenia Flashcards
what are the positive symptoms of schizophrenia
- disorders of thoughts and disorgaised behaviour
- hallucinations
- paranoia
what are the negative symptoms of shizophrenia
- social withdrawel
- apathy/loss of energy
- cognitive impairement
- anhedonia
what can influence the risk
stress poor social interactions poor maternal nutrition trauma at young age infectiosn at early age
which neurotransmitters cause schizophrenia and how
dopamine being overactive in the brain
3 main dopamine pathways in the brain
- tuberoinfundibular pathway
- nigrostriatal pathway
- mesolimbic pathway
explain the role of dopamine in tuberoinfundibular pathway
- 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
explain the role of dopamine in the nigrostrial 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 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
orignal theory of schizophrenia
- overactive dopamine systems in the brain cause schizophrenia (i.e. the mesolimbic pathway)
mechanism of action of antipsychotics
- block the D2 receptors in the limbic/ cortical areas
- work as D2 receptor antagonists
- first ones were tricyclics
what was the issue with tricyclics as dopamine antagonists
- 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
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
3 types of phenothiazines ( 1st gen antipsychotic)
- chlorpromazine (group 1)
- thioridazine (group 2)
- fluphenazine (group 3)
side effect profiles of group 1 phenothiazines
sedation
side effect profiles of group 2 phenothiazines
anticholinergic side effects
side effect profiles of froup 3 phenotiazines
extra-pyrimidal side effects
2 other 1st gen anti-psychotic classifications besides phenothiazine
- thioxanthenes e.g. flupenthixol- similar profile to phenothiazines
- butyrophenones e.g. haloperidol- no anticholinergic effect but has EPS effect
what are the second gen antipsychotics
clozapine olanzapine risperidone amisulpiride quetapine
what is the advantage of 2nd over 1st gen antipsychotics
- have better EPS side effect profile
- better at treating negative symptoms
what effect does risperidone and olanzapine have on a person
- increased weight gain and metabolic syndrome
- cause insulin resistance therefore diabetes
what makes 2nd gen antipsychotics better at treating the negative symtpoms of schizophrenia
due to their low affinity for D2 receptors and high affinity for D3, D4 and 5-HT2A receptors
why do we get a lot of adverse drug reactions with dopamine antagonists
due to importance of dopamine in brain
2 main distinctions between typical and atypical antipsychotics
- extrapyrimidal side effects more common in 1st gen
2. 2nd gen has a better efficacy against negative symptoms
side effects of antipsychotics on D2 receptors
extrapyrimmidal e.g parkinsons
galactorrhoea
side effects of antipsychotics on H1 receptors
sedation
side effects of antipsychotics on M1 receptors
dry mouth
blurred visison
constipation
side effects of antipsychotics on alpha 1 receptors
postural hypotension
