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Antipsychotic Medications. Illnesses in which a client might experience Psychosis.
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Illnesses in which a client might experience Psychosis • Schizophrenia, Substance-induced psychosis, schizophreniform, schizoaffective, delusional disorder, brief psychotic, shared psychosis, psychosis due to a medical condition, Mania, depression, cognitive disorders, and Alzheimer’s dementia
Types of Psychosis • Paranoid Psychosis: Paranoid projections, hostile belligerence and grandiose expansiveness • Disorganized-Excited Psychosis: Conceptual disorganization (giving answers that are irrelevant, drifting off subject, etc), Disorientation (time, place…), Excitement (expression of feeling without restraint, excess speech, restlessness, etc>)
Type of Psychosis (cont) • Depressive Psychosis: Retardation, apathy (Slowed speech/Movements, indifference to future, poor recent memory and blocking speech), anxious self-punishment and blame (feeling fully unworthy and sinful, guilt and remorse, etc.).
As we will see… • There are four main pathways for Dopamine (Draw page 375 on Board) • The Mesolimbic Pathway #1 • The Mesocortical Pathway #2 • The Nigrostriatal Pathway #3 • The Tuberoinfundibular Pathway #4
Symptoms • Positive Symptoms: Delusions, hallucinations, disorganized speech, disorganized/catatonic/agitated behavior • Schizophrenia, bipolar, schizoaffective, psychotic depression, Alzheimers • Seems to occur from EXCESS activity of Dopamine in the Mesolimbic dopamine pathway #1 • Negative Symptoms: Affective flattening, alogia (restricted thought and speech), avolition (restriction in initiating goal related behavior), anhedonia (lack of pleasure), attentional impairment • Schizophrenia, depression • Seems to occur from TOO LITTLE dopamine in the mesocortical pathway #2
Thorazine and Conventional Neuroleptics • Used in 1952 as postoperative sedative • Blocks Dopamine D2 Receptors (causing upregulation of receptors, thus less dopamine in synapse) • However, the D2 receptors in the mesolimbic pathway #1 are not the only ones that get blocked, all D2 receptors get blocked in the entire brain. Thus the D2 receptors in the mesocortical pathway #2 also get blocked (where DA may already be deficient) Thus negative symptoms can worsen with tx
Side effects of Neuroleptics • Due to blocking D2 in the nigrostriatal DA pathway #3 cause Extrapyramidal Side Effects (EPS) • Parkinson’s like: slowed movements, decreased facial expressions, tremor and shuffling gate • Dystonic effects: Sustained muscle spasms • Akathisia: Intense feelings of restlessness • Due to blocking D2 in the Tuberoninfundibular pathway #4 • Breast secretions and irregular periods • Due to muscarinic cholinergic receptor blocking • Anticholinergic, Antiandrenergic, Tardive Dyskinesia, weight gain, seizures, Temperature disregulation • Fever, confusion and rigidity are cluster of symptoms that may lead to coma or death
If these occur, get physician Involved • Confusion • Falls • Inability to Urinate • Severe constipation • Rash • High Fever • Involuntary movement • Jaundice • Severe Sedation • Severe restlessness • Muscle spasms
Atypical Antipsychotics • Clozapine, risperidone, olanzapine, quetiapine, and ziprasidone • Strong 5HT 2A receptor and weaker Dopamine D2 blockers (SDAs) thus • Low extrapyramidal symptoms • Efficacy with negative symptoms as well as positive symptoms • 5HT inhibits dopamine release to different degrees in the four different dopamine pathways
We can’t go into each pathway….but please refer to chapter11 of Essential Psychopharmacology if you want the specifics. But to sum it up… • In conventional neuroleptics…dopamine blockade occurs at every pathway resulting in improved positive symptoms, but worsened negative symptoms and tough side effects • In atypical antipsychotics….Dopamine blockade wins the “tug of war” where it must win (improved positive symptoms) and Dopamine release occurs where needed due to the interaction of 5HT and Dopamine • Due to the chemistry of the 5 most common atypical drugs, each has its “benefits” and “drawbacks” concerning which side effects are best managed
Clozapine-MOST EFFECTIVE • Few EPS, no TD, no elevated prolactin • Can cause life threatening Agranulocytosis (blood count lowers) and risk of seizures at higher doses • Is sedating and causes weight gain • Greatest efficacy, but highest side effects of atypical antidepressants
Risperidone • Good at low doses, but mimics conventional neuroleptics at higher doses • Used with elderly, children and adolescents due to low dose needs • Elevates Prolactin • May improve cognitive functioning in Alzheimer’s and may improve mood in schizophrenia, manic and depressive phases of bipolar • Does not block histamine 1 receptors, so less weight gain
Olanzapine • Usually no EPS- even at high doses • So used with more severe cases • Expensive • Weight gain, moderate sedation, low prolactin, low TD • Improved mood in bipolar and improved cog functioning in schizophrenia and dementia
Quetiapine • Virtually no EPS at any dose, no Prolactin • Thus good for patients with Parkinson’s and Psychosis • Weight gain, may cause cataracts (animal studies) • Mood and Cog func. Bipolar, Dementia, Schizophrenia
Ziprasidone • Low EPS, low Prolactin • No weight gain • Antidepressant and anxiolytic properties due to additional inhibition of 5HT and NE reuptake • Cog and Mood: Bipolar, schizophrenia, Dementia
Additional Facts • Atypical Antipsychotics • Seem to act differently in different patients, unlike the more conventional drugs • Optimal doses change dependent on patient • May not work as fast as conventional neuroleptics for acutely psychotic, aggressive, agitated patients that require rapid sedation • So use conventional or use benzos as adjuncts • Consider use of conventionals in intravenous injections • Monthly injections available for conventionals (no atypical injections available at this time) • Most patients receive more than one antipsychotic in clinical treatment
So how do you choose • Match drug effects and side effects to symptoms and comorbid disorders • Match enzyme metabolizing properties with desired effects and other drugs being taken • Consider time needs • What has worked in the past; with family members