The Pharmacokinetics and Pharmacogenetics of the Antiemetic Cyclizine in Palliative Care Patients

Vella-Brincat, Jane; Begg, Evan J.; Jensen, Berit Packert; Chin, Paul; Roberts, Rebecca; Fairhall, Mary; Macleod, Sandy; Reid, Kate

doi:10.1016/j.jpainsymman.2011.04.022

Cited by 9 publications

(6 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 Cyclizine also has antimuscarinic effects, which could induce adverse effects on neurofunction, including dry mouth, blurred vision, constipation, and reduced cognitive functions, particularly in the elderly. 1,2 In addition, cyclizine abuse may lead to addiction and hallucinations. 4,17 Teenagers constitute the main age group involved in illegal use of cyclizine and overdoses.…”

Section: Discussionmentioning

confidence: 99%

“…Cyclizine is an H1 antagonist primarily used to combat motion sickness and postoperative nausea and exhibits several notable effects on nerve cells, including sedation, impacting alertness and coordination 2 . Cyclizine also has antimuscarinic effects, which could induce adverse effects on neuro‐function, including dry mouth, blurred vision, constipation, and reduced cognitive functions, particularly in the elderly 1,2 . In addition, cyclizine abuse may lead to addiction and hallucinations 4,17 .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, it has proven efficacy in managing vertigo, commonly used to prevent and treat motion sickness (nausea, vomiting, and dizziness) and vertigo; the therapeutic effects of cyclizine are mediated through its antihistaminic and antimuscarinic activities. 1,2 The overuse or misuse of cyclizine induces various disorders, such as hallucinations, confusion, tachycardia, hypertension, bradypnea, hypersomnia, convulsions, and facial dyskinesia. 3,4 Macrophages are key players in innate immunity and also contribute to the homeostatic functions of the cardiovascular and nervous systems.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cyclizine induces cytotoxicity and apoptosis in macrophages through the extrinsic and intrinsic apoptotic pathways

Lu,

Chiang,

Hsu

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

Cyclizine, an over‐the‐counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine‐induced cytotoxicity and apoptosis remain unclear. During the 24 h incubation duration, RAW264.7 macrophages were exposed to different concentrations of cyclizine. Cytotoxicity was assessed through the lactate dehydrogenase assay. Flow cytometry employing annexin V‐fluorescein isothiocyanate and propidium iodide was utilized to evaluate apoptosis and necrosis. Caspase activity and mitochondrial dysfunction were evaluated through a fluorogenic substrate assay and JC‐1 dye, respectively. Flow cytometry employing fluorogenic antibodies was utilized to evaluate the release of cytochrome c and expression of death receptor, including tumor necrosis factor‐α receptor and Fas receptor. Western blotting was utilized to evaluate the expression of the Bcl2 and Bad apoptotic regulatory proteins. The findings unveiled from the present study demonstrated that cyclizine exerted a concentration‐dependent effect on RAW264.7 macrophages, leading to the induction of cytotoxicity, apoptosis, and necrosis. This compound further activated the intrinsic apoptotic pathway by inducing mitochondrial dysfunction, Bcl2/Bad exchange expression, cytochrome c liberation, and activation of caspases contained caspase 3, 8, and 9. Moreover, the activation of the extrinsic apoptotic pathway was observed as cyclizine induced the upregulation of death receptors and increased caspase activities. Based on our investigations, it can be inferred that cyclizine prompts cytotoxicity and apoptosis in RAW264.7 macrophages in a concentration‐dependent manner by triggering both the intrinsic and extrinsic apoptotic pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cyclizine induces cytotoxicity and apoptosis in macrophages through the extrinsic and intrinsic apoptotic pathways

Lu,

Chiang,

Hsu

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…Cyclizine is a piperazine-derived, first-generation histamine-1 receptor antagonist, first produced in 1952 1. The antiemetic mechanism of cyclizine is poorly understood, but is generally accepted to be related to its antihistaminergic and anticholinergic properties 2.…”

Section: Introductionmentioning

confidence: 99%

“…It has an oral bioavailability of 50% and is extensively metabolised to inactive metabolites, with a half-life in healthy volunteers of between 13 and 20 hours 3 4. The route of metabolism remains unclear 1…”

Section: Introductionmentioning

confidence: 99%

Cyclizine pharmacovigilance in hospice/palliative care: net effects for nausea or vomiting

McNeill

Prael

Hunt

et al. 2022

BMJ Support Palliat Care

View full text Add to dashboard Cite

ObjectivesTo describe the contemporary real-world use of cyclizine for nausea or vomiting, and the associated benefits and harms.MethodsThis was a prospective, consecutive case series of routine clinical use of cyclizine for nausea or vomiting in palliative care conducted across 19 sites in Australia, Aotearoa/New Zealand and the UK. Clinical outcomes were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline and 72 hours after initiation of cyclizine. Ad hoc safety reporting continued for 2 weeks.ResultsData were collected from 101 patients between May 2018 and December 2020. Cyclizine was mostly used in combination with another antiemetic. Overall, 79 patients benefited and 32 experienced harm (56 had benefit without harm; 9 had harm without benefit). The most common harms were constipation (13%), somnolence (9%) and confusion (7%), adding to the already high rates of these symptoms at baseline. For the four patients with serious harms (grade ≥3), these were exacerbations of existing symptoms. Nine patients stopped cyclizine at 72 hours and a further 20 patients within 2 weeks. The most common reasons for stopping were lack of benefit and symptom resolution; none stopped because of harms.ConclusionsWhen used as described in a palliative care setting, cyclizine benefits about three-quarters of patients, with about one-third experiencing tolerable harms.

show abstract

Medications Used for the Gastrointestinal System

Khan

2020

Understanding Pharmacology in Nursing Practice

View full text Add to dashboard Cite

The Pharmacokinetics and Pharmacogenetics of the Antiemetic Cyclizine in Palliative Care Patients

Abstract: Palliative care patients have similar cyclizine pharmacokinetics to those reported in other patient groups. Cyclizine metabolism to norcyclizine may include CYP2D6 as the metabolic ratio varied with CYP2D6 genotype in the SC group.

Cited by 9 publications

References 13 publications

Cyclizine induces cytotoxicity and apoptosis in macrophages through the extrinsic and intrinsic apoptotic pathways

Cyclizine induces cytotoxicity and apoptosis in macrophages through the extrinsic and intrinsic apoptotic pathways

Cyclizine pharmacovigilance in hospice/palliative care: net effects for nausea or vomiting

Medications Used for the Gastrointestinal System

Contact Info

Product

Resources

About