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Cureus Aug 2021Since the declaration of coronavirus disease 2019 (COVID-19) as a pandemic, it remains a widespread infection with a major impact on global resources and health...
Since the declaration of coronavirus disease 2019 (COVID-19) as a pandemic, it remains a widespread infection with a major impact on global resources and health infrastructure. The hallmark of COVID-19 continues to be the well-documented effects it has on the respiratory system. With the passage of time, the involvement of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in other systems has become more apparent, with the increased incidence of thromboembolic events, cardiac involvement as well as gastrointestinal and neurological symptoms secondary to the infection. Our case report demonstrates a presentation of vertigo, hearing loss, tinnitus, and aural fullness. Our patient was diagnosed as positive for COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) nine days prior to developing these symptoms. Her COVID-19 infection was otherwise relatively mild, for which she did not seek any medical intervention. A careful assessment ruled out cerebrovascular causes and led us to the diagnosis of SARS-CoV-2-induced labyrinthitis. Our patient was successfully treated as an outpatient without unnecessary investigations and responded well to standard therapy for viral labyrinthitis as per National Health Service (NHS) guidelines. She eventually reported having made a full recovery within three weeks of the initial encounter. Audio-vestibular consequences of COVID-19 are less reported compared to other symptoms of neurological involvement, such as gustatory or olfactory dysfunction, which have become key indicators aiding in the diagnosis of the infection. Among these disorders, the commonly reported presentation is that of vestibular neuronitis. Our case report demonstrates that labyrinthitis is also among the neurological manifestations to be considered as a result of COVID-19, which can be safely managed in the community with the same strategies as those employed for other viral triggers. It also reveals the need for further research into the effects that COVID-19 may have on the audio-vestibular system.
PubMed: 34548960
DOI: 10.7759/cureus.17121 -
Journal of Medical Case Reports Aug 2021Dystonia is a known neurological complication of certain medications; however, the mechanism behind such effects is often undetermined. Similarly, the clinical...
BACKGROUND
Dystonia is a known neurological complication of certain medications; however, the mechanism behind such effects is often undetermined. Similarly, the clinical pharmacogenomic effects associated with various alleles of the cytochrome P450 family of proteins, and their role in acute dystonic reactions, are also presently unknown.
CASE PRESENTATION
We describe a woman presenting with acute dystonic reactions to ondansetron, prochlorperazine, and metoclopramide followed by persistent focal dystonia. A similar family history was reported in her siblings and her father to prochlorperazine, drugs all metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme. Pharmacogenomic testing indicated the patient was heterozygous for the intermediate metabolizer *41 allele (CYP2D6 2988G>A, NM_000106.6:c.985+39G>A, rs28371725). Her father was homozygous for this CYP2D6 *41 allele, and consequently, her siblings were obligate carriers.
CONCLUSIONS
The metabolism of ondansetron, metoclopramide, or prochlorperazine in patients with the *41 CYP2D6 allele has not been studied. In this family, clinical evidence implicates the *41 CYP2D6 allele as causing extrapyramidal adverse pharmacologic reactions. Patients with a family history of medication-induced dystonia involving these medications should be considered for pharmacogenomic testing, and patients carrying the *41 CYP2D6 allele should consider reduction or avoidance of CYP2D6-mediated medications to minimize the potential risk of adverse extrapyramidal effects.
Topics: Alleles; Cytochrome P-450 CYP2D6; Dystonia; Female; Genotype; Humans; Pharmacogenetics; Pharmacogenomic Testing
PubMed: 34407866
DOI: 10.1186/s13256-021-03022-x -
Headache Sep 2021We conducted a randomized trial among emergency department patients with migraine to determine the relative impact on migraine-associated symptoms of hydromorphone, an... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
We conducted a randomized trial among emergency department patients with migraine to determine the relative impact on migraine-associated symptoms of hydromorphone, an opioid, versus prochlorperazine, an antidopaminergic antiemetic.
METHODS
This was a post hoc analysis of data from a double-blind study registered at http://clinicaltrials.gov (NCT02389829). Patients who met International Classification of Headache Disorders, 3rd edition criteria for migraine without aura or for probable migraine without aura were eligible for participation. Participants received either hydromorphone 1 mg IV or prochlorperazine 10 mg IV plus diphenhydramine 25 mg IV and could receive a second dose of the same medication 1 h later if needed. The outcomes were sustained relief of nausea, photophobia, and phonophobia.
RESULTS
A total of 127 patients were enrolled, of whom 63 received prochlorperazine and 64 received hydromorphone. Of 49 patients in the prochlorperazine arm who reported nausea at baseline, 34 (69.4%) reported complete resolution without relapse versus 15/49 (30.6%) in the hydromorphone arm (absolute risk reduction [ARR] = 38.8%, 95% CI: 20.5%-57.0%, p < 0.001). Of 55 patients in the prochlorperazine arm who reported photophobia at baseline, 23 (41.8%) reported complete resolution without relapse versus 13/62 (20.9%) patients treated with hydromorphone (ARR = 20.8%, 95% CI: 4.3%-37.3%, p = 0.014). Of 56 patients in the prochlorperazine arm who reported phonophobia at baseline, 25 (44.6%) reported complete resolution without relapse versus 16/59 (27.1%) in the hydromorphone arm (ARR = 17.5%, 95% CI: 0.3%-34.8%, p = 0.049). For adverse events, three patients in the prochlorperazine arm reported anxiety or restlessness, and nine patients in the hydromorphone arm reported dizziness or weakness.
CONCLUSIONS
Prochlorperazine plus diphenhydramine is more efficacious than hydromorphone for the treatment of migraine-associated symptoms.
Topics: Administration, Intravenous; Adult; Analgesics, Opioid; Antiemetics; Diphenhydramine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hydromorphone; Hyperacusis; Male; Middle Aged; Migraine Disorders; Nausea; Outcome Assessment, Health Care; Photophobia; Prochlorperazine
PubMed: 34363617
DOI: 10.1111/head.14185 -
Biological & Pharmaceutical Bulletin 2021The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease,...
The clinical applications of antipsychotics for symptoms unrelated to schizophrenia, such as behavioral and psychological symptoms, in patients with Alzheimer's disease, and the likelihood of doctors prescribing antipsychotics for elderly people are increasing. In elderly people, drug-induced and aging-associated urinary disorders are likely to occur. The most significant factor causing drug-induced urinary disorders is a decrease in urinary bladder smooth muscle (UBSM) contraction induced by the anticholinergic action of therapeutics. However, the anticholinergic action-associated inhibitory effects of antipsychotics on UBSM contraction have not been sufficiently assessed. In this study, we examined 26 clinically available antipsychotics to determine the extent to which they inhibit acetylcholine (ACh)-induced contraction in rat UBSM to predict the drugs that should not be used by elderly people to avoid urinary disorders. Of the 26 antipsychotics, six (chlorpromazine, levomepromazine (phenothiazines), zotepine (a thiepine), olanzapine, quetiapine, clozapine (multi-acting receptor targeted antipsychotics (MARTAs))) competitively inhibited ACh-induced contractions at concentrations corresponding to clinically significant doses. Further, 11 antipsychotics (perphenazine, fluphenazine, prochlorperazine (phenothiazines), haloperidol, bromperidol, timiperone, spiperone (butyrophenones), pimozide (a diphenylbutylpiperidine), perospirone, blonanserin (serotonin-dopamine antagonists; SDAs), and asenapine (a MARTA)) significantly suppressed ACh-induced contraction; however, suppression occurred at concentrations substantially exceeding clinically achievable blood levels. The remaining nine antipsychotics (pipamperone (a butyrophenone), sulpiride, sultopride, tiapride, nemonapride (benzamides), risperidone, paliperidone (SDAs), aripiprazole, and brexpiprazole (dopamine partial agonists)) did not inhibit ACh-induced contractions at concentrations up to 10 M. These findings suggest that chlorpromazine, levomepromazine, zotepine, olanzapine, quetiapine, and clozapine should be avoided by elderly people with urinary disorders.
Topics: Acetylcholine; Aging; Animals; Antipsychotic Agents; Chlorpromazine; Cholinergic Antagonists; Clozapine; Dibenzothiepins; Male; Mental Disorders; Methotrimeprazine; Muscle Contraction; Muscle, Smooth; Olanzapine; Quetiapine Fumarate; Rats, Wistar; Urinary Bladder; Urologic Diseases; Rats
PubMed: 34334499
DOI: 10.1248/bpb.b21-00363 -
General Dentistry 2021This case report describes an adverse reaction (phenothiazine reaction) to prochlorperazine (Compazine), a commonly prescribed drug. The patient had been referred to a...
This case report describes an adverse reaction (phenothiazine reaction) to prochlorperazine (Compazine), a commonly prescribed drug. The patient had been referred to a dental clinic for an oral evaluation because of muscle spasms in the oral musculature. He had severe muscle spasms, a reduced range of motion, difficulty registering a repeatable maximum intercuspation, facial grimacing, and difficulty speaking because of the spasms. The dental examination revealed no history of trauma to the musculature or the temporomandibular joints and no previous history of seizures. The patient was a young, healthy man who had recently been hospitalized for an upper respiratory infection and sinusitis. The drug regimen used to treat the sinusitis and respiratory infection caused some nausea and vomiting, and the patient received a prescription for prochlorperazine to control the symptoms. When questioned in the dental clinic about his medical and drug use history, he reported taking only amoxicillin for the infections. His symptoms worsened, necessitating a referral to a co-located emergency department. When he was asked specifically if he was taking Compazine, the patient reported that he had taken it earlier in the day. A tentative diagnosis of a phenothiazine reaction was made, and 50 mg of diphenhydramine was administered intramuscularly. The patient showed a marked alleviation of symptoms. Although the patient's reaction to the prochlorperazine is common, many dental care providers may never treat a patient with such symptoms. The phenothiazines are a common class of drugs, and some, such as prochlorperazine, are often prescribed by dentists. This case highlights the importance of taking an accurate history and being aware of possible adverse effects of medications.
Topics: Humans; Male; Prochlorperazine; Vomiting
PubMed: 34185669
DOI: No ID Found -
Journal of Child and Adolescent... Jun 2021Antipsychotic prescribing in children and adolescents increased sharply beginning in the 1990s, but recent reports among Medicaid enrollees suggest declining trends....
Antipsychotic prescribing in children and adolescents increased sharply beginning in the 1990s, but recent reports among Medicaid enrollees suggest declining trends. However, few studies have included both commercially and publicly insured patients or focused on trends in new antipsychotic medications in children without documented psychotic disorders or other indicated conditions. The objective of the study was to report trends in new antipsychotic prescribing for pediatric patients (age 3-17 years) in a large children's health care system. Data were abstracted from electronic medical records (January 1, 2013 to December 31, 2017). New antipsychotic medication orders were defined as antipsychotic orders for patients without an order in the 180 days prior. Patients were excluded if the order was initiated in an emergency department or inpatient setting; they were diagnosed with psychotic disorder, mania, autism spectrum disorder, or intellectual disability; or the order was for prochlorperazine. The crude rate of new antipsychotic prescribing is reported quarterly with Poisson 95% confidence intervals in the total sample and by demographic subgroups (child vs. adolescent, female vs. male, public vs. private insurance, and white vs. nonwhite). Antipsychotic orders decreased from 54.9 prescriptions per 10,000 person months in the first quarter of 2013 to 34.1 per 10,000 person months in the last quarter of 2017. Rates of antipsychotic prescribing were significantly higher for adolescents compared with children, patients who were commercially insured compared with Medicaid insured, and at most time points for white compared with non-white patients. However, prescribing rates did not differ significantly based on gender. Antipsychotic prescribing declined for both commercially and Medicaid-insured children in a pediatric hospital-based system, although white and commercially insured patients were more likely to be prescribed antipsychotics. More attention may be needed for reducing potentially avoidable prescribing of antipsychotics in previously understudied subgroups, such as commercially insured patients. Clinical Trial Registration Number: NCT03448575.
Topics: Adolescent; Age Factors; Antipsychotic Agents; Child; Child, Preschool; Delivery of Health Care; Drug Prescriptions; Female; Humans; Insurance, Health; Male; Medicaid; Practice Patterns, Physicians'; United States
PubMed: 34143677
DOI: 10.1089/cap.2020.0190 -
The Journal of Dermatology Sep 2021
Topics: Dermatitis, Photoallergic; Humans; Patch Tests; Prochlorperazine
PubMed: 34109659
DOI: 10.1111/1346-8138.16017 -
Biomedicine & Pharmacotherapy =... Aug 2021Metastasis is the main cause of cancer morbidity and mortality. Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that can drive metastasis. The...
Metastasis is the main cause of cancer morbidity and mortality. Cancer stem cells (CSCs) are a rare subpopulation of cancer cells that can drive metastasis. The identification of CSC inhibitors and CSC-related genes is an alluring strategy for suppressing metastasis. Here, we established a simple and repeatable high-throughput CSC inhibitor screening platform that combined tumor sphere formation assays and cell viability assays. Human lung cancer cells were cocultured with 1280 pharmacologically active compounds (FDA-approved). Fifty-four candidate compounds obtained from our screening system completely or partially inhibited tumor sphere formation. A total of 5 of these 54 compounds (prochlorperazine dimaleate, thioridazine hydrochloride, ciproxifan hydrochloride, Ro 25-6981 hydrochloride, and AMN 082) completely inhibited the self-renewal of CSCs without cytotoxicity in vitro via their targets and suppressed lung cancer metastasis in vivo, suggesting that our screening platform is selective and reliable. DRD2, HRH3, and GRIN2B exhibited potent genes promoting CSCs in vitro experiments and clinical datasets. Further validation of the top hit (DRD2) and previously published studies demonstrate that our screening platform is a useful tool for CSC inhibitor and CSC-related gene screening.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; High-Throughput Screening Assays; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Mice, Inbred BALB C; Mice, Nude; Neoplastic Stem Cells; Small Molecule Libraries; Mice
PubMed: 34044271
DOI: 10.1016/j.biopha.2021.111748 -
Headache Apr 2021To compare the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency... (Randomized Controlled Trial)
Randomized Controlled Trial
A prospective, randomized, double-blind trial of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department.
OBJECTIVE
To compare the efficacy of intravenous chlorpromazine versus intravenous prochlorperazine for the treatment of acute migraine in adults presenting to the emergency department (ED).
BACKGROUND
Migraine is a common, incapacitating neurological condition. Although chlorpromazine and prochlorperazine are known to be safe, efficacious treatments for migraine, they have never been directly compared.
DESIGN
We performed a prospective, randomized, double-blind clinical trial at a tertiary hospital in Melbourne, Australia. Adults aged 18-65 years, who presented with migraine, were eligible for recruitment. Sixty-six patients were randomized to either chlorpromazine 12.5 mg or prochlorperazine 12.5 mg, both infused in 500 ml of sodium chloride 0.9% over 30 min. Headache severity score, nausea severity score, and the presence of photophobia and phonophobia were assessed at 0, 30, 60, and 120 min. Adverse effects and the need for rescue therapy were recorded. The primary outcome was a reduction in headache severity score from baseline at 60 min post-commencement of the study medicine infusion.
RESULTS
Sixty-five patients were included in the analysis. There was a median reduction in headache severity score at 60 min of 3.0 (interquartile range 1.0-4.0) in the chlorpromazine arm versus 2.0 (1.0-4.0) in the prochlorperazine arm (median difference -0.5 (95% confidence interval, -1.9 to 0.9)). We saw no evidence of a difference in secondary outcomes at 30, 60, or 120 min. Side effects were reported in 16/32 (50%) patients in the chlorpromazine group versus 7/33 (21%) in the prochlorperazine group (p = 0.020). Rescue therapy was required in 7/32 (22%) patients in the chlorpromazine group versus 12/33 (36%) in the prochlorperazine group (p = 0.277).
CONCLUSIONS
Both chlorpromazine and prochlorperazine are efficacious treatments for acute migraine in adult patients presenting to the ED. This trial found no evidence of superiority of either agent over the other. Caution should be used when prescribing these medicines in the borderline hypotensive patient; in that circumstance, prochlorperazine should be preferentially used.
Topics: Administration, Intravenous; Adolescent; Adult; Aged; Australia; Chlorpromazine; Dopamine Antagonists; Double-Blind Method; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Migraine Disorders; Prochlorperazine; Prospective Studies; Tertiary Care Centers; Treatment Outcome; Young Adult
PubMed: 33797074
DOI: 10.1111/head.14091 -
Frontiers in Neurology 2021Polypharmacy in abortive medications is often inevitable for patients with refractory headaches. We seek to enumerate an exhaustive list of headaches abortive...
Polypharmacy in abortive medications is often inevitable for patients with refractory headaches. We seek to enumerate an exhaustive list of headaches abortive medications that are without drug-drug interactions. We updated a list of acute medications based on the widely used Jefferson Headache Manual with novel abortive medications including ubrogepant, lasmiditan, and rimegepant. Opioids and barbiturate-containing products are excluded. From this resultant list of medications, we then conducted an exhaustive search of all pair-wise interactions via DrugBank's API. Using this interaction list, we filtered all possible two, three, and four drug combinations of abortive medications. The list of medications was then reapplied to DrugBank to verify the lack of known drug-drug interactions. There are 192 medication combinations that do not contain any drug-drug interactions. Most common elements in these combinations are ubrogepant, prochlorperazine, followed by tizanidine. There are 67 three-drug combinations that do not contain interactions. Only two of the four-drug combinations do not yield some form of drug-drug interactions. This list of headaches abortive medications without drug-drug interactions is a useful tool for clinicians seeking to more effectively manage refractory headaches by implementing a rational polypharmacy.
PubMed: 33679591
DOI: 10.3389/fneur.2021.632830