Antipsychotics Flashcards
structural abnormalities associated with schizophrenia
enlarged cerebral ventricles atrophy of cortical layers reduced volume of basal ganglia -reduced CBF reduced glucose utilization in prefrontal cortex
positive schizophrenia symptom
presence of inappropriate behaviors:
- hallucinations
- delusion
- paranoid delusions
- mood disturbances
- confusion & suicidal thoughts
negative schizophrenia symptoms
absence of appropriate behaviors: -loss of normal function -social w/d reduced speech and thought loss of energy inability to experience pleasure
dopamine hypothesis of schizophrenia
- symptoms are in part due to increase in the activity of dopaminergic neurons
evidence: typical antipyschotics block d2 receptors (mesolimbic and striatal-frontal) - drugs that increase dopa activity aggrevate schizo
- dopa receptor density is increased in schizo brains
- dopa levels and d2 receptor density increased in nucleus accumbens, caudate, putamen
mesolimbic p’way
role: motivation, reward, emo behaviors
- auditory hallucinations, delusions, thought d/o with hyperactivity (schizo)
- INCREASED d2 receptor interaction shuts off downstream cascade
mesocortical p’way
cognition, executive fxn, emo
-hypoactivity in this pway causes negative symptoms of schizophrenia (less D2 receptor interaction)
nigrostriatal p’way
motor planning, purposeful movement
-normal during schizophrenia
but hyperactivity from rx can lead to hyperkinetic movement d/o (dyskinesias, chorea) - often irreversible
tuberoinfundibular pathway
inhib prolactin release normally
-normal in schizophrenia, but hypoactivity from meds can cause galactorrhea, amenorrhea, sexual dysfxn
Typical antipsychotics (chlorpromazine, fluphenazine, haloperidol, thiothixene)
- inhibit D2 receptors, regardless of p’way
- return mesolimbic p’way to normal, but exacerbate the mesocortical p’way
neuroleptic malignant syndrome
- rare but lifethreatening, idiosyncratic reaction to neuroleptic meds
- often begins 4-14 d after start of drug or dose increase
sym: hyperthermia, rigidity, mental status changes, autonomic instability - 0.2-3.2% of patients
- manifests in parkinson’s patients
rx: supportive: -d/c use, circ/vent support, bromocriptine (DA agonist), dantrolene (muscle rigidity)
serotonin hypothesis of schizophrenia
-either increased release of serotonin or serotonin receptors are more sensitive; either way, more signals than normal
serotonin regulates dopamine release via GABA interneuron
-shuts of dopaminergic neuron
atypical antipsychotics (risperidone, quetiapine, olanzapine, paliperidone, ariprazole, clozapine)
block 5HT 2A (some 2C), inhibits serotonin receptors, only sends small amt GABA to dopa neuron (targeting mesocortical p’way -decreased)
-also antagonize D2 receptors, but with much less affinity than typical meds
5HT 2A receptors also regulate glutamate release
glutamate p’way to schizophrenia
5HT 2A receptors also regulate glutamate release, dampen it, stabilizes cognitive p’ways
-non-NMDA receptor interaction
atypical antipsychotics SE (risperidone, quetiapine, olanzapine, paliperidone, ariprazole, clozapine)
lower likelihood (compared to typical) of: extrapyramidal symptoms (debatable), neuroleptic malignant syndome
increased risk of: metabolic syndrome (esp clozapine and olanzapine), obesity, DM II, granulocytosis and leukopenia (clozapine – delayed)
sedation
sexual dysfunction
postural hypertension
CV arrhythmia/SCD
Typical antipsychotics (chlorpromazine, fluphenazine, haloperidol, thiothixene) SE
sedation
sexual dysfunction
postural hypertension
CV arrhythmia/SCD
