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Miami Dade College Butyrophenone Antipsychotic Responses

Miami Dade College Butyrophenone Antipsychotic Responses


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Sharon LeeYesterdayAug 7 at 9:16amManage Discussion EntryHaloperidol, also known as Haldol, is a high potency conventional antipsychotic (Stahl, 2013, p. 68). This butyrophenone antipsychotic is a nonselective postsynaptic dopamine receptor antagonist (D-Ran), neuroleptic, and dopamine 2 antagonist. As haloperidol blocks dopamine 2 receptors, this reduces acute psychotic mania and schizophrenia symptoms, Tourette’s syndrome symptoms, as well as combative, explosive, and hyperactive behaviors (Stahl, 2021, p. 347). Off-label uses for Haldol include treating agitation/aggression, substance intoxication, bipolar disorder, delirium, hyperactivity, and terminal illness or chemotherapy-induced as well as postoperative nausea and vomiting (UpToDate, 2023).Haloperidol is commonly used for psychotic disorders, Tourette’s syndrome, schizophrenia, bipolar disorder, dementia, and delirium in combination with lorazepam. It is a second-line treatment for children above the age of three with severe behavior problems such as combativity, explosivity, and hyperexcitability. Haldol should be used with caution in those with renal impairment, hepatic impairment, cardiac impairment, as well as the elderly or pregnant. Haldol should not be used in those with CNS depression or in a comatose state, Parkinson’s disease, dementia with Lewy bodies, allergy to haloperidol, or breastfeeding (Stahl, 2021, p. 347-350).Haloperidol dosing is started at 1-15 mg/day orally and increased as needed to a max of 100 mg/day. It may also be given as a 2-5 mg immediate-release injection, or a decanoate injection 10-20 times the daily oral dose for chronic schizophrenia. Haldol takes on average one week to have onset of improvement in psychiatric conditions, but it may take several weeks for the full effect. Too low of a dose may not result in improvement of symptoms while too high of a dose may worsen schizophrenia symptoms and even lead to overdose. Addition of a mood-stabilizing anti-convulsant, augmentation with lithium, or addition of a benzodiazepine may be helpful to increase response in those with only partial response or treatment resistance. Once reaching a satisfactory plateau in symptom improvement, haloperidol should be continued for a year in first episode psychosis in schizophrenia; then treatment should be switched to a mood stabilizer and/or atypical antipsychotic. If no improvement in psychosis is noted, a first-line typical antipsychotic or an atypical antipsychotic may be tried. If this fails, clozapine may be an option. To discontinue haloperidol and/or switch to another antipsychotic, it is important to have a slow downward titration over a period of six to eight weeks to prevent rebound psychosis as well as withdrawal symptoms (Stahl, 2021, p. 347-349).Potential side effects of haloperidol include the following:Neuroleptic-induced deficit syndrome: If noting neutrophil count less than 1000/mm3, treatment should be discontinued.Metabolic syndrome with weight gain and increase in triglycerides: It is important to assess appropriate use in overweight, obese, pre-diabetic or diabetic, and dyslipidemia patients. If noting weight gain, metformin may help reduce this side effect.Akathisia: Use of beta blockers, benzodiazepines, or 5HT2A antagonists may reduce this side effect.Drug-induced parkinsonism: Use of an anticholinergic agent, benztropine, trihexyphenidyl, or amantadine may reduce this side effect.Tardive dyskinesia, tardive dystonia: Use of valbenazine or deutetrabenazine may reduce this side effect.Risk of potentially irreversible involuntary dyskinetic movements with higher doses and treatment timesSedation: Haldol is best given at night due to its sedating effects.Dry mouth, constipation, urinary retention, blurred vision, decreased sweatingHypotension, dizziness, tachycardia, hypertension, QTc prolongationEsophageal dysfunctionHyperprolactinemia, galactorrhea, amenorrhea, sexual dysfunctionTemperature dysregulationReducing the dose may improve side effects, but most of these side effects will subside over time.Life-threatening adverse effects of haloperidol include:Neuroleptic malignant syndrome (NMS): This may cause hyperpyrexia, muscle rigidity, delirium, autonomic instability with elevated creatine phosphokinase, myoglobinuria from rhabdomyolysis, and acute renal failure.SeizuresJaundice, agranulocytosis, and leukopeniaCerebrovascular events in elderly patients with dementiaSedation with respiratory depressionShock-like state from overdose(Stahl, 2021, p. 347-349; UpToDate, 2023)ReferencesUpToDate. (2023). Haloperidol: Drug information. UpToDate. Retrieved July 14, 2023, from…Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical application (4th ed.). New York, NY: Cambridge University Press.Stahl, S. M. (2021). Stahl’s essential psychopharmacology: Prescriber’s guide (7th ed.). New York, NY: Cambridge University Press. 

Carlyn Bailey MasonYesterdayAug 7 at 7:07pmManage Discussion EntryAssignment Week 6                                                            QuetiapineQuetiapine is a second-generation (atypical) antipsychotic and is among the most frequently used psychiatric medications for the treatment of bipolar disorders, schizophrenia, general anxiety, and major depressive disorder. Quetiapine is only atypical antipsychotic approved in the US for use as a single therapy to treat bipolar disorders that often require life-long medication Quetiapine has the lowest risk for extrapyramidal symptoms and documented efficacy as compared to several other atypical antipsychotics. The downside of quetiapine, however, is its association with dyslipidemia, cardiovascular disease, diabetes type 2 and weight gain (Ortega, et al. 2020).There is no universal consensus on the mechanism of action of quetiapine. The prevailing theory seems to be “serotonin 5-HT2 receptor antagonist (HTR2) and dopamine D1 and D2 receptors, it is a serotonin 5-HT2 receptor antagonist (HTR2) and a dopamine D1 and D2 receptor (DRD1 and DRD2) antagonist with affinity for other receptors, such as histamine H1, muscarinic M1, M3 and M5, ?1-adrenergic and other serotonin receptors.” On the other hand, norquetiapine has moderate to high affinity for several muscarinic receptors, which may explain the anticholinergic effects (Hojland et al 2021). Quetiapine also inhibits the norepinephrine transporter (NET), mainly due to norquetiapine action. The blockade of DRD2 in the mesocortical and mesolimbic pathways is proposed as the interaction responsible for the treatment of schizophrenia, where increased dopamine levels are responsible for negative and positive symptoms, respectively. 5-HT2 and ?2 receptor antagonism is related to quetiapine’s antidepressant activity, as well as noradrenaline transporter blockage by norquetiapine.Dosing is as follows (all dosing is oral):For SchizophreniaIR: 150 to 750 mg daily in two or three divided doses; start at 25 mg twice daily, and titrate up to 300 to 800 mg daily in two or three divided doses, with daily increases of 50 to 150 mg. In elderly patients, increase 25 to 50 mg daily.ER: 400 to 800 mg each evening; start with 300 mg daily with up to 300 mg increases daily or as needed. In the elderly, start at 50 mg daily with 50 mg dose increments. Patients should not chew, crush, or cut the ER tablets.For Bipolar I Disorder (manic)IR: 200 to 400 mg twice daily. Start at 50 mg twice daily, increasing by 100 mg a day to 200 mg twice daily by the fourth day, then begin increasing by 200 mg each day as needed. The maximum dose is 800 mg daily.For Bipolar I Disorder (manic/mixed)ER: 400 to 800 mg each evening. Start at 300 mg daily for one day, then 600 mg in the evening for one day; adjust by 200 mg per day or as needed to a maximum dose of 800 mg daily. In the elderly, start with 50 mg in the evening with 50 mg increments daily for therapeutic effectiveness.For Acute Depressive Bipolar Disorder IR: 300 mg daily at bedtime; start at 50 mg at bedtime for one day, then 100 mg at bedtime for one day, 200 mg at bedtime for one day, then 300 mg at bedtime. The maximum dose is 600 mg daily, with doses over 300 mg daily rarely demonstrating effectiveness. For the elderly, start with 25 mg at bedtime, with 25 to 50 mg dose increases daily. ER: 300 at bedtime; start with 50 mg in the evening, then 100 mg each evening for one day, 200 mg in the evening for one day, then 300 mg in the evening. The maximum dose is 300 mg daily. In the elderly, start with 50 mg in the evening, with 50 mg daily dose increments. Patients should not chew, crush, or cut the ER tablets.As an adjunct treatment measure for various forms of major depressive disorder, the dose ranges from 50 to 300 mg daily with the IR form and 150 to 300 mg daily with the ER form, using similar titration schedules to a maximum of 300 mg daily.For efficacy, a range of 300 mg to 800 mg a day should be optimal, and for some patients, prescribers can try a non-FDA-approved dose of 1200 mg to 1600 mg per day for benefits, with QT interval monitoring (Stäuble et al. 2022)Common Side effectsFatigueAbnormal movementsHeadacheVertigoConstipationWeight gainGynecomastiaAmenorrheaTachycardiaHøjlund M, Lund LC, Andersen K, Correll C, Hallas J. (2021) Association of Low-Dose Quetiapine and Diabetes. JAMA Netw Open. ;4(5): e213209. doi:10.1001/jamanetworkopen.2021.3209Ortega-Ruiz M, Soria-Chacartegui P, Villapalos-García G, Abad-Santos F, Zubiaur P(2020). The Pharmacogenetics of Treatment with Quetiapine. Future Pharmacology.  2(3):276-286. to an external site.Stäuble C. Lampert M. Mikoteit T. Hatzinger M, Hersberger K, (2022) Severe Adverse Drug Reac tions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report. Int J Mol Sci. (12):6480. doi: 10.3390/ijms22126480. PMID: 34204223; PMCID: PMC8233787.

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