-Where do negative symptoms originate? - -Mesocortical dopamine
pathway. May also involve mesolimbic regions such as nucleus
accumbens
-Medications to treat negative symptoms - -Vraylar, amisulpride
-Hypotheses of Schizophrenia - --Mesolimbic pathway is hypothesized to
be hyperactive resulting in excess dopamine at the synapse.
-The gluatamate activity at NMDA receptors is hypofunctional
-Mesolimbic Pathway Theory of Schizophrenia - -Mesolimbic pathway is
hyperactive, resulting in excess dopamine at the synapse which leads to
positive symptoms. Hyperactivity of mesolimbic dopamine neurons may
also play a role in aggression and hostile symptoms.
-Five Different Dopamine Pathways in the brain - --Nigrostriatal
Dopamine Pathway
-Mesolimbic dopamine pathway
-Mesocorticol dopamine pathway
-Tuberoinfundibular dopamine pathway
-Thalamic dopamine pathway
-Nigrostriatal pathway - -Projects from the substantia nigra to the basal
ganglia or striatum.
-Part of the extrapyramidal nervous system
-Controls motor function and movement
-When dopamine is deficient, can cause parkinsonism with tremor,
rigidity, and akinesia/bradykinesia
-Excess dopamine- can cause hyperkinetic movements, such as tics and
dyskinesias
, -Mesolimbic dopamine pathway - -Projects from the midbrain ventral
tegmental area to the nucleus accumbens (part of limbic system) where
many behaviors such as pleasurable sensations, the powerful euphoria
of drug abuse as well as delusions and hallucinations.
-Mesocortical pathway - -Projects from the ventral tegmental area to
the prefrontal cortex and is important for cognition
-Tuberofundibular pathway - -Projects from the hypothalamus to the
anterior pituitary gland and controls prolaction secretion
-Thalamic pathway - -Arises from multiple sites.
-Function not well known, may be involved in sleep and arousal
mechanisms
-Major neurotransmitters involved in schizophrenia - --Dopamine
-Glutamate
-Dopamine and Schizophrenia - -Major neurotransmitter in
schizophrenia
Some atypical psychotics block dopamine receptors
Increased in schizophrenia
-Glutamate and schizophrenia - -Considered the "master switch" of the
brain. Glutamate is the major excitatory neurotransmitter of the CNS as
it can turn on nearly all of the CNS neurons
Decreased in schizophrenia
-Neuroleptic Malignant Syndrome - --Adverse reaction to antipsychotics
with severe "lead pipe" rigidity, FEVER, and mental status changes
-Lab findings- increased CK, leukocytosis, low serum iron
-Caused by dopamine antagonists
-Slower in onset, 1-2 weeks after starting/changing therapy.
-Manage by stopping causative agent, supportive care, ECT, Dantrolene,
bromocriptine, and amantadine.
-Serotonin Syndrome - --Caused by serotonergic agents
-Hyperreflexia, myoclonus, ocular clonus
-Manage by stopping all serotonergic agents, supportive care aimed at
normalization of vitals, sedation with benzos, administration of
serotonergic antagonists, and antidote therapy with cyproheptadine
-Assess need to resume use of causative serotonergic meds after
resolution of symptoms
-Symptoms seen within 24 hours of starting/changing therapy.
-The "-pine" family - -Have 5-HT2A and D2 antagonism.
Strong potency for H1 and muscarinic receptors
Clozapine, Olanzapine, Quetiapine,
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