Olanzapine

Olanzapine is an atypical antipsychotic agent of the thienobenzodiazepine class. Olanzapine blocks multiple neurotransmitter receptors, including dopaminergic (D1, D2, D3, and D4), serotonergic (5-hydroxytryptamine 2A [5-HT2A], 5-HT2C, 5-HT3, and 5-HT6), adrenergic (α1), histaminic (H1), and muscarinic (M1, M2, M3, and M4) receptors. Olanzapine has a high affinity for the 5HT2A receptor, which is up to 5 times greater than the dopamine receptor, resulting in less propensity to the development of extrapyramidal side effects. The affinity of olanzapine for multiple receptors has lead to the identification of olanzapine as an important agent in the treatment of delirium, nausea, and vomiting. Olanzapine has been demonstrated to have opioid-sparing properties. Olanzapine is principally metabolized by glucuronidation, with a smaller metabolic contribution from the cytochrome oxidase system. Adverse effects of olanzapine include somnolence, postural hypotension, constipation, dizziness, restlessness, and weight gain. The purpose of this article is to outline the pharmacodynamics, pharmacology, and evidence for the use of olanzapine in palliative care.

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Dopamine Blockers (“Antipsychotics”)

Clinical Psychopharmacology ◽

10.1093/med/9780199995486.003.0010 ◽

2018 ◽

pp. 101-126

Author(s):

S. Nassir Ghaemi

Keyword(s):

Metabolic Syndrome ◽

Clinical Pharmacology ◽

Weight Gain ◽

Side Effects ◽

Tardive Dyskinesia ◽

Drug Class ◽

Acute Mania ◽

Psychotic Symptoms ◽

Extrapyramidal Side Effects ◽

Bipolar Illness

The drug class of dopamine blockers includes agents called antipsychotics. It consists of dopamine blockers, often with serotonin blockade. Dopamine blockers are agents used to treat psychotic symptoms such as delusions and hallucinations. These medications have been developed mostly for use in schizophrenia, but they always have been found to be effective in acute mania as well. For the latter reason, they have been used in bipolar illness as well. Several of these agents have been proven effective in the depressive phase of bipolar illness, not just the manic phase. Also, some of them have been shown to be effective in the depressive phase of unipolar mood illness. The clinical pharmacology of specific agents within each class of dopamine blockers, including efficacy and side effects, is explored. Specific phenomena surveyed include metabolic syndrome, weight gain, extrapyramidal side effects, Parkinsonism, akathisia, and tardive dyskinesia.

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Cross-sectional examination of extrapyramidal side effects in a specialist palliative care inpatient unit

BMJ Supportive & Palliative Care ◽

10.1136/bmjspcare-2018-001504 ◽

2018 ◽

Vol 9 (3) ◽

pp. 271-273

Author(s):

Hannah O'Brien ◽

Fiona Kiely ◽

Aileen Barry ◽

Sarah Meaney

Keyword(s):

Palliative Care ◽

Side Effects ◽

Rating Scale ◽

Demographic Data ◽

Previous History ◽

Inpatient Unit ◽

Screening Tools ◽

Screening Tests ◽

Extrapyramidal Side Effects ◽

Inclusion Criteria

ObjectivesExtrapyramidal side effects (EPSEs) are serious potentially reversible side effects of antipsychotic and other medications that can cause distress for patients. A core principle of palliative care involves optimising quality of life. If side effects of medications are burdensome, it is imperative that we address this issue. The aim of the study was to determine and describe the burden of EPSEs in a specialist inpatient unit.MethodsConsenting patients who met inclusion criteria were assessed for EPSE with two validated screening tests, the Modified Simpson-Angus Scale (MSAS) and Barnes Akathisia Rating Scale (BARS). Additional demographic data were collected including medications associated with EPSE, previous history of EPSE and known risk factors that may predispose a patient to EPSE.Results43% inpatients met inclusion criteria. At least 66% of patients were taking regular medications associated with EPSE. Of those, 25% were taking ≥2 medications associated with EPSE. The MSAS revealed 50% scored <3, 44% scored 3–5% and 6% scored 6–11. Seven patients had at least one ‘not rateable score’. In the BARS (sitting±standing), 94% scored 0/5 and 6% scored 1/5. 12.5% of participants were able to stand for 2 min to complete the BARS.Conclusions50% screened positive for EPSE. The complete BARS was unsuitable for most participants. The MSAS, while allowing a not rateable score, may underestimate EPSE. The frailty of an inpatient unit population impacts on applicability of screening tools and may therefore underestimate the burden of the problem in this population. Development of a population-specific screening tool warrants further investigation.

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The prospects of new antipsychotic principles

Acta Neuropsychiatrica ◽

10.1017/s0924270800036838 ◽

1997 ◽

Vol 9 (2) ◽

pp. 68-70

Author(s):

A. Carlsson

Keyword(s):

Side Effects ◽

Dopamine Receptor ◽

Muscarinic Receptors ◽

Research Field ◽

Receptor Subtypes ◽

Extrapyramidal Side Effects ◽

Dopamine Receptor Subtypes ◽

High Affinity ◽

Drug Companies ◽

Dopamine Hypothesis

Biological schizophrenia research has been dominated by the dopamine hypothesis for decades, but in recent years a more diversified view has gained increasing attention. Several neurotransmitters are now being discussed, and especially their interaction in complex circuitries.The demonstration of an atypical profile of clozapine (Leponex®), with lessened extrapyramidal side effects and somewhat increased efficacy, has stimulated this research field considerably. This agent has high affinity not only for the different dopamine receptor subtypes, but also for serotonergic, alpha-adrenergic and muscarinic receptors. Different workers have stressed one or more of these sites as being of major importance for the atypical profile of clozapine, and several drug companies have made attempts to mimic the profile of clozapine by developing molecules with affinity for these receptors in varying proportions. A number of such agents have reached or will soon reach the market and appear to be promising, even though they may not match clozapine in terms of atypicality.

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Efficacy of clozapine in treatment-resistant psychosis and neuroleptic sensitivity: results of the Dutch open multi-center project

European Psychiatry ◽

10.1017/s0924933800003321 ◽

1992 ◽

Vol 7 (2) ◽

pp. 77-84 ◽

Cited By ~ 4

Author(s):

WMA Verhoeven ◽

WH Doesburg ◽

R Snoej ◽

AJMP Rutgers ◽

PHM van Dongen

Keyword(s):

Side Effects ◽

Marked Reduction ◽

Antipsychotic Agent ◽

Percentage Reduction ◽

Extrapyramidal Side Effects ◽

Treatment Resistant ◽

Schizophrenic Patients ◽

Multi Center Study ◽

Center Study

SummaryIn an open multi-center study, 57 schizophrenic patients were treated with clozapine for indications of treatment-resistant psychosis or severe extrapyramidal side-effects caused by conventional neuroleptics. In 58% of the patients a clinical relevant improvement, expressed as percentage reduction of at least 50 from baseline BPRS scores was observed. With respect to extrapyramidal side-effects, a marked reduction was found upon treatment with clozapine. No major side-effects occurred, particularly agranulocytosis. It was concluded that clozapine is a potent antipsychotic agent that can be used safely when treatment is accompanied by frequent clinical and hematological monitoring.

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Clozapine-Induced Cardiotoxicity Presenting as Sepsis: A Case Report and Literature Review

Case Reports in Medicine ◽

10.1155/2019/3435108 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Mazin Khalid ◽

Oluwole Jegede ◽

Vijay Gayam ◽

Ying Chi Yang ◽

Binav Shrestha ◽

...

Keyword(s):

Case Report ◽

Side Effects ◽

Postural Hypotension ◽

Systolic Function ◽

Antipsychotic Agent ◽

Elevated Troponin ◽

Medical Unit ◽

Psychiatric Illnesses ◽

Intravenous Antibiotics ◽

Life Threatening

Clozapine is an atypical antipsychotic agent indicated in the treatment of medication-resistant schizophrenia. It is often reserved as a last line of treatment owing to the potential for serious and potentially life-threatening side effects, the most serious being agranulocytosis requiring close hematological monitoring and possible discontinuation of the medication from further use in the patient even when the agranulocytosis resolves. Other complications of clozapine include sedation, weight gain, elevated triglyceride levels, postural hypotension, and tachycardia. However, the potentially serious complication of myocarditis, though rare (with an incidence of 3%), may lead to cardiomyopathy as described in our present case. We present a 21-year-old patient who was started on clozapine for management of schizophrenia. He developed fever and tachycardia and was admitted to the medical unit on intravenous antibiotics for management of sepsis as he met the criteria for systemic inflammatory response syndrome. His labs revealed an elevated troponin and trending eosinophilia, which, in the context of clozapine use, raises the suspicion of clozapine cardiotoxicity. Echocardiogram showed reduced systolic function (45%). Clozapine was immediately discontinued, and his repeat echocardiogram showed normalization of his systolic function. In view of the increased prevalence of psychiatric illnesses, internists should be aware of rare but potentially life-threatening side effects.

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Role of α1 adrenergic antagonism in the mechanism of action of iloperidone: reducing extrapyramidal symptoms

CNS Spectrums ◽

10.1017/s1092852913000850 ◽

2013 ◽

Vol 18 (6) ◽

pp. 285-288 ◽

Cited By ~ 16

Author(s):

Stephen M. Stahl

Keyword(s):

Side Effects ◽

Atypical Antipsychotic ◽

Mechanism Of Action ◽

Adrenergic Receptors ◽

Extrapyramidal Side Effects ◽

Binding Profile ◽

High Affinity ◽

Low Incidence ◽

Serotonin 2A

ISSUE:The low incidence of extrapyramidal side effects associated with the atypical antipsychotic iloperidone may be linked to its unique binding profile of high affinity antagonism of both α1 adrenergic receptors and serotonin 2A receptors.

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