Antipsychotics - Lacher Flashcards
What are the 4 dopaminergic systems?
- Mesolimbic Pathway
- from tegmentum (midbrain) → nucleus accumbens (limbic system)
- Mesocortical Pathway
- from tegmentum (midbrain) → frontal and limbic cortex
- Nigrostriatal
- from substantia nigra (midbrain) → basal nuclei
- Tuberoinfundibular
- from hypothalamus → anterior pituitary
How is the mesolimbic pathway thought to contribute to the symptoms of psychoses?
- Mediates the positive symptoms of schizophrenia
- delusions
- hallucinations (auditory)
- disorganized speech
- grossly disorganized behavior
- catatonic (unresponsive stupor)
How is the mesocortical pathway thought to contribute to the symptoms of psychoses?
- Mediates negative symptoms of schizophrenia
- lack of emotion/interest in life
- social isolation
- affective flattening (blank facial expression)
- alogia (difficulty speaking)
- inability to keep friends
- and possibly mediates cognitive symptoms
- disorganized thinking
- slow thinking
- poor concentration
- poor memory
- difficulty integrating thoughts, feelings, and behavior
How is the nigrostriatal pathway thought to contribute to the symptoms of psychoses?
- Regulates posture and voluntary movement
How is the tuberoinfundibular pathway thought to contribute to the symptoms of psychoses?
- DA inhibits prolactin release
- hormone that prepares the breast for lactation in women
How is the mesolimbic pathway thought to contribute to the adverse side effects after treatment with antipsychotics?
- Block D2 DA receptors → decreases positive symptoms
- antipsychotic drugs
- Decreasing DA activity has been show to increase 5HT
- Increase in 5HT inhibits DA release
How is the mesocortical pathway thought to contribute to the adverse side effects after treatment with antipsychotics?
- Decreasing DA activity may produce or worsen negative symptoms
- likely due to increased 5HT → inhibits DA release here
- Helps explain why negative symptoms are unaffected or worsened by antipsychotics that ONLY block D2 receptors
How is the nigrostriatal pathway thought to contribute to the adverse side effects after treatment with antipsychotics?
- Therapeutically blocking the D2 receptors in striatum results in a Parkinsonism-like syndrome
- EPSE = extrapyramidal side effects
How is the tuberoinfundibular pathway thought to contribute to the adverse side effects after treatment with antipsychotics?
- DA inhibits prolactin
- Blocking D2 receptors here causes:
- galactorrhea
- amenorrhea
- sexual dysfunction
How does the proposed mechanism of action of first generation antipsychotic drugs account for both the therapeutic and extrapyramidal effects of this class of drugs?
- Block D2 receptors in limbic system (only D2)
- usually 5HT blocks DA release
- Actually blocks D2 receptors everywhere in the brain
- effective against positive symptoms (decrease DA)
- worsen negative symptoms (due to increased 5HT)
- causes Parkinsonism
What are the most common adverse effects of FGA?
- FGA
- Haloperidol → Severe EPSE (Parkinsonism)
- Chlorpromazine → autonomic dysfunction
- Tardive Dyskinesia (DA Receptor Disuse Supersensitivity)
What are the most common adverse effects of second generation antipsychotic drugs?
- SGA:
- Clozapine → Agranulocytosis, weight gain, DM2
- Olanzapine → weight gain, DM2
- Risperidone → EPS, hypotension with higher doses
- Tardive Dyskinesia possible in all SGA’s except Clozapine.
What is the MOA of Clozapine?
Block D2 receptors AND 5-HT2A receptors
- No D2 activation
- DA still released into the synapse, because it is not inhibited by 5-HT anymore
- No downstream G-protein activation
What ending (suffix) do all FGA’s have except Haloperidol?
-zine
Chlorpromazine
Thioridazine
Fluphenazine
Is Risperidone (Risperdal) a FGA or SGA?
SGA
