Antipsychotic drugs Flashcards
What is schizophrenia
Combination of environmental and genetic factors.
It is a disease of hypoglutaminergic and/or hyperdopaminergic function altering input to the cortex.
What are the positive symptoms of schizophrenia
Defusions (bizarre, persecutory
Hallucinations
Disorganized thought
Abnormal behaviours
What are the negative symptoms of schizophrenia
Blunted emotions Anhedonia – unable to experience pleasure form normal happy situations. Poverty of speech Attention impairment Loss of motivation
What are the mood symptoms of schizophrenia
Depression
Anxiety
Impulse control
What are the cognition symptoms of schizophrenia
New learning
Memory
Executive function
Give examples of first generation typical anti-psychotic drugs
Phenothiazines:
- ->Chlorpromazine
- ->Fluphenazine
- ->Thioridazine.
Butyrophenones:
- ->Haloperidol
- ->Pimozide
What is the function of typical anti-psychotic drug
Primary D2-receptor antagonists but multiple sites of action:
What are the mesolimbic actions of D2-receptor antagonism by typical anti-psychotic drugs
Reduces positive symptoms
no effect against negative symptoms
What are the Mesocortical actions of D2-receptor antagonism by typical anti-psychotic drugs
Increases negative symptoms, cognitive deficits
What are the Nigrostriatal actions of D2-receptor antagonism by typical anti-psychotic drugs
Induces motor side-effects (parkinsonian)
What are the Tuberoinfundibular actions of D2-receptor antagonism by typical anti-psychotic drugs
Effects on hormone secretion (hyperprolactinaemia)
What side effects does D2-receptor antagonism by typical anti-psychotic drugs have
good effect on positive symptoms:
- Defusions (bizarre, persecutory)
- Hallucinations
- Disorganized thought
- Abnormal behaviours
but major side effects
Give examples of second generation atypical anti-psychotic drugs
Clozapine Risperidone Quetiapine Zotepine Aripriprazole
What is the function of atypical anti-psychotic drugs
Serotonin (5-HT2) and dopamine (D2) antagonists
Why are atypical anti-psychotic drugs beter than typical drugs
fast off theory
5HT-2A antagonism - rich expression in cortical and hippocampal regions
What is the specific action of Aripriprazole
- D2-receptor partial agonist
2. 5-HT2A antagonist
What are the side effects of Aripriprazole
Extra pyramidal disturbances (blockade of DA2-receptors in nigrostriatal pathway) Parkinsonian: -Bradykinesia -Rigidity -Tremor
What is the first and then second line treatment for atypical drugs
1st - Risperidone, Quetiapine, and Zotepine
2nd - Clozapine
What is the risk associated with clozapine
Agranulocytosis
Describe the dopamine theory
Disease of hyperdopaminergic dysfunction.
Evidence of increased dopamine in the amygdala, and increased receptor number in postmortem brain (but drug treated)
Describe the 5HT theory
5-HT has important influences on DA pathways (particulary 5-HT2A receptors) – regulation
LSD causes schizophrenic symptoms → Hallucinations
Atypical antipsychotic drgus target serotonin and DA systems (rapid kinetics)
describe the Glutamate theory
-Disease of hypoglutamatergic function
NMDA antagonists produce/enhance psychotic symptoms – PCP, Ketamine
-Mutation of neuroegulin -1, a gene involved with synaptic development and plasticity.
-Reduced glutamate and glutamate receptor densities found in schizophrenic patients
-Possible genes linked to schizophrenia are mainly effect glutaminergic transmission
