Lecture 9: Antipsychotics Flashcards
Flow chart of psychotic disorders
See figure
What is schizophrenia?
Chronic psychosis with deterioration of functional capacity
Inability to interact mentally and emotionally with other people
Diagnosis symptom groups
Positive symptoms
Negative symptoms
Cognitive symptoms
Affective symptoms
What are positive symptoms of schizophrenia
Excess cognition
Hallucinations (50%)
Delusions (65%)
Disorganized speech (50%)
What are negative symptoms of schizophrenia
Deficits in behaviour
Avolition
Alogia (poverty of speech)
Anhedonia
Blunted affect
Cognitive symptoms of schizophrenia
Declines in attention, language, memory, executive function
Probably present from birth
Affective symptoms of schizophrenia
Blunted, inappropriate, odd expression
Often lead to social stigmatization
Dopamine hypothesis of schizophrenia
Too much mesolimbic dopamine pathway activity leads to positive symptoms
Negative symptoms result from low dopaminergic activity in the mesocortical pathway
Dopamine systems and their relation to symptoms
Mesolimbic pathway responsible for positive symptoms
Mesocortical pathway responsible for negative symptoms
See figure
Dopaminergic systems
Substantia nigra to stratium
Tegmentum (VTA) to prefrontal cortex
Tegmentum to nucleus accumbent
Hypothalamus
Support for dopamine hypothesis?
Drugs that increase dopaminergic activity can produce psychosis
Mechanism of typical antipsychotics
Thought to be antagonism of D2 receptors in mesolimbic pathway (decrease positive symptoms)
Also block nigrostriatal (EPS) and tuberoinfundibulnar (hyper-prolactin) pathways
Typical antipsychotics (FGAs)
Chlorpromazine (Thorazine)
Fluphenazine (Permitil, Prolixin)
Haloperidol (Haldol)
Thiothixene (Navene)
What are the adverse effects of antipsychotics related to?
Receptor non-selectivity
Blokage of non-mesolimbic D2 dopaminergic pathways
Drugs targeting nigostriatal pathway - what do they block? Side effects?
Block dopamine D2
Extrapyramidal side effects (EPS)
Parkinson’s syndrome
Akathisia
Acute dystonic reactions
Tardive dyskinesia (no reliable treatment; can be irreversible)
Tuberoinfundibular pathway - what do they block? Side effects?
Block dopamine D2
Increased prolactin production
Women: lactation, amenorrhea, infertility
Men: lactation, impotence, decreased libido, gynecomastia
Advantages of atypical antipsychotics
Block D2 in Nucleus accumbens: decreases positive symptoms (also less EPS and prolactin)
Reduced D2 affinity: Nigostriatal = decreased EPS
Block 5HT2 receptors = decreased negative symptoms
How do atypical antipsychotics decrease negative symptoms?
They have increased serotonin 5HT2 affinity
5HT2 receptors suppress dopamine in the mesocortical pathway, so if they are blocked, we get increased dopamine activity
Relief of negative symptoms of schizophrenia
Comparison of adverse effects of typical and atypical
See figure
Typical are associated with more EPS and hyper-prolactin
Atypical are associated with less WPS and less prolactin, but more weight gain and hyperglycaemia
Important enzymes in metabolism of atypical antipsychotics
Cyp3A4, 1A2, 2D6 are common
Inducers and inhibitors can affect these enzymes
Drug interactions with antipsychotics
Excess sedation (anxiolytics, alcohol, antidepressants, antihistamines)
Additive antimuscarinic effects
Metoclopramide - D2 antagonist, EPS
SSRI antidepressants - dopamine suppression in NGS and EPS
Progression of selection of anti-psychotics
SGA: second generation antipsychotics
FGA: first generation antipsychotics
