Antipsychotics Flashcards
(30 cards)
What are antipsychotics used for?
They are primarily used in the treatment of schizophrenia, but are also indicated in other disorders – bipolar, agitation, psychosis, Touette’s, etc.
What is an additional indication for the second generation antipsychotics?
Mood stabilization; they may also be used as an adjunct in refractory depression or anxiety.
All antipsychotics (first and second generation) work via this mechanism:
All antipsychotics block D2 dopamine receptors.
What are the four dopamine pathways?
(1) Nigro-striatal; (2) mesolimbic; (3) mesocortical; and (4) tuberoinfundibular.
Describe the nigro-striatal pathway:
Dopamine here acts as an inhibitory neurotransmitter in the extra-pyramidal system; it filters extraneous stimuli to allow fine motor movements.
Describe the mesolimbic pathway:
This pathway communicates with the amygdala and hypothalamus to process sensory stimuli.
Describe the mesocortical pathway:
This pathway branches into the cerebral cortex; dopamine here is responsible for the learning response, attention, decreasing distractibility, and for the awakening response.
Describe the tuberoinfundibular pathway:
This pathway communicates to the pituitary gland; dopamine here acts as an inhibitory neurotransmitter to inhibit/diminish the secretion of prolactin.
What is schizophrenia?
A disorder characterized by two types of symptoms – positive symptoms (hallucinations, delusions, paranoia); and negative symptoms (apathy, anhedonia, etc.)
What causes the positive symptoms of schizophrenia?
Hyper-dopaminergic activity in the mesolimbic system (improper processing of sensory stimuli).
What causes the negative symptoms of schizophrenia?
Hypo-dopaminergic activity in the mesocortical system (these symptoms are progressive).
Describe why the first-generation antipsychotics treat the positive symptoms while worsening the negative symptoms:
These drugs indiscriminately block dopamine in both the mesolimbic system and the mesocortical system.
Describe the relationship between dopamine and serotonin:
They have an inverse relationship; the second generation antipsychotics take advantage of this fact to treat both the positive and negative symptoms of schizophrenia.
How do the second generation antipsychotics work?
They block dopamine receptors in the mesolimbic system to treat the positive symptoms; they block serotonin receptors in the mesocortical system to selectively increase dopamine here and treat the negative symptoms.
Why does blocking serotonin receptors have no effect on dopamine levels in the mesolimbic system?
Because there are no serotonin receptors; there are only serotonin receptors in the mesocortical system.
What are the effects of dopamine blockade in the nigro-striatal pathway?
Dopamine blockade here can precipitate Parkinsonian effects; however, the inverse relationship between dopamine and serotonin exists here as well.
Why do the second generation antipsychotics have fewer Parkinsonian side-effects than the first-generation antipsychotics?
Because they block serotonin in the nigro-striatal pathway in order to prevent loss of dopamine here.
What is the relationship between dopamine and ACh?
This is also an inverse relationship (although the effect is not as robust).
Describe the efficacy of the second generation antipsychotics:
They are relatively weak dopamine blockers; while a low dose can provide effective mood stabilization, a much higher dose would be needed to treat hallucinations.
What causes the wide range of ADRs seen with antipsychotics?
These drugs block other receptors as well – histamine receptors; acetylcholine receptors; and alpha-1 receptors.
What ADRs occur as a result of histamine-receptor blockade?
Sedation and weight gain.
What ADRs occur as a result of acetylcholine receptor blockade?
Anticholinergic ADRs – dry mouth, blurred vision, tachycardia.
What ADR occurs as a result of alpha-1 blockade?
Orthostatic hypotension.
What ADRs occur as a result of serotonin receptor blockade?
Weight gain; carbohydrate craving.
