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What do Antipsychotic Medications Do? Reduce neurotransmission of dopamine
Mechanism of Action The exact unknown.
According to the dopamine theory of schizophrenia, positive symptoms are the result of an overactivity in the mesolimbic dopamine pathway.
Based on the observation that drugs that increase dopaminergic availability (L-DOPA, cocaine, amphetamines) can trigger psychotomimetic effects in individuals not affected by schizophrenia.
first-generation antipsychotics are D2 antagonists. As a result, they reduce dopaminergic neurotransmission in the four dopamine pathways.
people stop taking their meds/FGA because of Dysfunction associated w/cognitive impairments and disturbances of emotions and affect (negative symptoms)Blockade of the mesocortical pathway by high doses of FGA can cause secondary negative symptoms and cognitive effects.
Blockade of D2 receptors in the mesolimbic pathway has been proposed as a possible mechanism of antipsychotic action of first-generation agents overactivity of this pathway is thought to decrease positive symptoms of schizophrenia.
Nigrostriatal pathway antagonism and drugs used in this pathway may cause Extrapyramidal Symptoms
Tuberoinfundibular pathway: Hyperprolactinemia- D2 blockade increases prolactin levels by promoting its release in the pituitary gland.
First Generation Antipsychotics(still used in clinical practice) Haloperidol, Chlorpromazine (Thorazine), Fluphenazine (prolixin)
FGA Side Effects think Parkinson’s Dyskinesia –movement d/o (nigrostriatal DA pathway), TD – permanent, Dystonia, neck (torticollis), arms, legs –painful – benztropine, diphenhydramine tx – IM, Akisthesia , hyperprolactinemia, amenorrhea, galactorrhea (lower dose)
Hyperprolactinemia D2 blockade (tubuloinfundibular dopamine pathway)
Second Generation Antipsychotic Medications 5HT2A Antagonism, Increases dopamine neurotransmission in the nigrostriatal pathway, Reduces risk of extrapyramidal symptoms.Theoretically improves negative and cognitive symptoms in schizophrenia by I increasing dopamine release in the prefrontal cortex.
SCA Example Iloperidone (Fanapt) has antagonist action at D2 and 5HT2A receptors
The Schizophrenia Patient Outcomes Research Team (PORT) recommended treating first episodes with antipsychotics other than clozapine or olanzapinemay be used depending on need to clear psychosis)- associated with more weight gain, insulin resistance and dyslipidemia than other antipsychotics . In addition, clozapine can cause agranulocytosis.
Know phases of schizophrenia Prodrome phase- late adolescence- withdrawn- poor affect, flat, not engaging, anhedonia, poor ADLs- CBT good in this stage- ANCC wants us to know the stages
ACUTE PHASE- The Schizophrenia PORT recommended that first-episode patients receive antipsychotic doses in the lower half of the recommended dose range. Ie; a first-episode pt would be tx with 1-3 mg of risperidone or 10 mg of aripiprazole daily-exception; quetiapine, may require titration to 500 to 600 mg daily.
STABILIZATION PHASE The stabilization phase covers the first 6 months or more after the onset of an acute phase, during which acute psychotic symptoms decrease in severity.
The treatment goals during the stabilization phase are to minimize stress and provide support to prevent relapse, enhance the patient's adaptation to life in the community, facilitate continued reduction of symptoms, and consolidate remission.
During the stabilization phase, monitor the patient for at least 6 months on the same medications at the same dose used in acute phase. Prematurely lowering the dose or discontinuing medication can lead to relapse.
According to the APA Guideline, the overall goal of the stable phase is "to optimize functioning and minimize the risk and consequences of relapse."
The goal of maintenance antipsychotic treatment of schizophrenia is to minimize symptoms and functional impairments, avoid relapses, and promote recovery that allows self-determination, full integration into society, and pursuit of personal goals.
Indications for Use of antipsychotics Schizophrenia, Schizophreniform, Schizoaffective Disorder, Delusional Disorder, Medical Conditions with Psychotic Symptoms, Mood Disorders(Bipolar/Major Depressive Disorder) with Psychotic Symptoms
The FDA reported in a public health advisory that the use of SGAs is associated with increased mortality ***BLACK BOX WARNING*** .(nursing homes- linked to stroke and MI)
For each patient, an individual assessment and documentation of risks and benefits of therapy is necessary The use should be assessed in a case-by-case basis.
Long-acting Injectable SGAs Risperdal Consta- every 2 weeks, Invega Sustenna, monthly, Abilfy Maintena monthly, Zyprexa Relprevv monthly - Post-Injection Delirium Sedation Syndrome (PDSS) risk: 3 hour watch Clozapine (Clozaril)
SGA used in treatment resistant patients and can be life saving for those who respond last resort d/t agranulocytosis, Weekly CBC x 6 months, then q 2 weeks, Only registered pharmacies may dispense & must have CBC at pharmacy, (ANC) >2000uL, Therapeutic level ~ 200 – 400 ng/ml
FGA also block which receptors, other than D2 histamine-1, muscarinic-1 and alpha-1
prescribing guideline for FGA haldol (2mg), prolixin (2mg) and thorazine (100mg)
MOA of SGA through fx activation of 5-HT(1A) receptors by 5-HT(2A) and D(2) receptor-mediated interaction,is basis for neurocognitive effects. Abilify may not only be a simply partial D(2) agonist but also a 5-HT(1A) agonist and 5-HT(2A) antagonist.
some SGA do what are 5ht1 agonists (prefrontal cortex) and block glutamate- seroquel and clozapine,
antipsychotics with low weight gain Asenapine (saphris) , Amisulpride, Aripiprazole, Lurasidone (latuda) , Ziprasidone, Haloperidol
Created by: arsho453
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