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Toxicology Reports Jun 2024Chlorpromazine (CPZ) is one of the most effective antipsychotic drugs used for managing psychotic related disorders owing to its dopamine receptor blocking action....
Chlorpromazine (CPZ) is one of the most effective antipsychotic drugs used for managing psychotic related disorders owing to its dopamine receptor blocking action. However, pharmacological investigations against CPZ's cytotoxic effect have remained scarce. Hence, this study investigated the preventive and reversal effects of taurine and coenzyme-Q10 (COQ-10), which are compounds with proven natural antioxidant properties, against CPZ-induced hematological impairments in male rats. In the preventive study, rats received oral saline (10 ml/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day) or in combination for 56 days, alongside CPZ (30 mg/kg, p.o.) between days 29-56. In the reversal protocol, rats had CPZ repeatedly for 56 days before taurine and COQ-10 treatments or their combination from days 29-56. Rats were also given taurine (150 mg/kg/day), and COQ-10 (10 mg/kg/day) alone for 56 days. Serums were extracted and assayed for hematological, with oxidative and inflammatory markers. CPZ induced decreased red/white blood cells, erythropoietin, platelet count, packed cell volume and hemoglobin, neutrophil, and lymphocyte, which were prevented and reversed by taurine and COQ-10, or their combination. Taurine and COQ-10 improved mean corpuscular volume, hemoglobin concentration, with increased erythropoietin levels relative to CPZ groups. CPZ-induced increased malondialdehyde, tumor necrosis factor-alpha and interleukin-6 levels with decreased interleukin-10, glutathione, and superoxide-dismutase were prevented and reversed by taurine and COQ-10 in comparison with CPZ groups. Taurine and COQ-10 alone notably improved the antioxidant/anti-inflammatory status relative to controls. Among other mechanisms, taurine and COQ-10 abated CPZ-induced hematological deficiencies, via decreased serum levels of oxidative stress, and pro-inflammatory cytokines release, with increased antioxidants and anti-inflammation function.
PubMed: 38693965
DOI: 10.1016/j.toxrep.2024.04.004 -
In Vivo (Athens, Greece) 2024Patients with pneumonia after prolonged neutropenia are at increased risk for acute respiratory distress syndrome (ARDS). The key molecule of endothelial barrier...
BACKGROUND/AIM
Patients with pneumonia after prolonged neutropenia are at increased risk for acute respiratory distress syndrome (ARDS). The key molecule of endothelial barrier breakdown in sepsis is lipopolysaccharide (LPS), which is a component of the outer membrane of gram-negative bacterial cell walls. Maintaining increased cyclic adenosine monophosphate (cAMP) levels in endothelial cells is effective in preventing endothelial dysfunction and microvascular permeability. The aim of this study was to elucidate whether roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor, is effective in LPS-induced acute lung injury (ALI) during neutropenia recovery in a murine model.
MATERIALS AND METHODS
To induce neutropenia, all mice were administered intraperitoneal cyclophosphamide. On day 2 after neutropenia, mice were administered LPS by intra-tracheal instillation. In the prevention group, roflumilast was given orally on day 0, when neutropenia was induced. In the treatment group, roflumilast was administered orally 1 hour after LPS injection.
RESULTS
Roflumilast attenuated histopathological changes associated with LPS-induced lung injury. The accumulation of neutrophils and the concentrations of inflammatory cytokines IL-1β, TNF-α, and IL-6 in bronchoalveolar lavage fluids were inhibited effectively by roflumilast. Also, MMP-9 and TGF-β expression was attenuated in the roflumilast group.
CONCLUSION
Roflumilast significantly attenuated LPS-induced ALI during neutropenia recovery.
Topics: Animals; Aminopyridines; Cyclopropanes; Acute Lung Injury; Lipopolysaccharides; Mice; Benzamides; Neutropenia; Disease Models, Animal; Phosphodiesterase 4 Inhibitors; Cytokines; Male; Bronchoalveolar Lavage Fluid; Neutrophils
PubMed: 38688656
DOI: 10.21873/invivo.13547 -
Journal of Integrative Neuroscience Apr 2024Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic... (Review)
Review
Parkinson's disease is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, including hallucinations. The use of antipsychotic medications is a common strategy to manage hallucinations associated with Parkinson's disease psychosis (PDP). However, careful consideration is necessary when selecting the most appropriate drug due to the potential risks associated with the available treatment options. Atypical antipsychotics (AAPs), such as Pimavanserin and Clozapine, have effectively controlled PDP symptoms. On the contrary, the support for utilizing quetiapine is not as substantial as other antipsychotics because research studies specifically investigating its application are still emerging and relatively recent. The broad mechanisms of action of AAPs, involving dopamine and serotonin receptors, provide improved outcomes and fewer side effects than typical antipsychotics. Conversely, other antipsychotics, including risperidone, olanzapine, aripiprazole, ziprasidone, and lurasidone, have been found to worsen motor symptoms and are generally not recommended for PDP. While AAPs offer favorable benefits, they are associated with specific adverse effects. Extrapyramidal symptoms, somnolence, hypotension, constipation, and cognitive impairment are commonly observed with AAP use. Clozapine, in particular, carries a risk of agranulocytosis, necessitating close monitoring of blood counts. Pimavanserin, a selective serotonin inverse agonist, avoids receptor-related side effects but has been linked to corrected QT (QTc) interval prolongation, while quetiapine has been reported to be associated with an increased risk of mortality. This review aims to analyze the benefits, risks, and mechanisms of action of antipsychotic medications to assist clinicians in making informed decisions and enhance patient care.
Topics: Humans; Antipsychotic Agents; Clozapine; Hallucinations; Parkinson Disease; Piperidines; Quetiapine Fumarate; Urea
PubMed: 38682215
DOI: 10.31083/j.jin2304080 -
Journal of the American Animal Hospital... May 2024Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here,...
Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here, we report on a case in which a cat was prescribed methimazole but the medication was filled incorrectly with azathioprine tablets and the prescription label indicated a methimazole dosing regimen that was administered for three days before recognition of the error. On presentation, the cat's physical examinations were consistent with previous examinations before ingestion of azathioprine. A complete blood cell count revealed neutropenia and leukopenia. The cat later developed hyporexia, dehydration, and vomiting. Treatment included antinausea and appetite stimulant medications, filgrastim, and antibiotics. Filgrastim given as subcutaneous injections over the course of treatment increased neutrophil cell counts after suppression. The cat made a full recovery after responding to the treatment protocol. Based on the perceived response to filgrastim in this single feline case report, its use can be considered for the treatment of azathioprine-induced neutropenia in cats.
Topics: Animals; Cats; Filgrastim; Cat Diseases; Azathioprine; Neutropenia; Medication Errors; Immunosuppressive Agents; Male; Methimazole; Female
PubMed: 38662994
DOI: 10.5326/JAAHA-MS-7409 -
Infection and Drug Resistance 2024To investigate the clinical characteristics, etiology, and risk factors of bacterial bloodstream infection (BSI) in allogeneic hematopoietic stem cell transplantation...
PURPOSE
To investigate the clinical characteristics, etiology, and risk factors of bacterial bloodstream infection (BSI) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. This study also aimed to provide a clinical basis for early identification of high-risk patients and optimization of empirical antimicrobial treatment.
PATIENTS AND METHODS
This is a retrospective study of clinical data during agranulocytosis from 331 patients with hematological malignancies who underwent allo-HSCT at our institute between January 2016 and December 2022. The incidence, distribution and drug resistance patterns, and the risk factors of BSI were analyzed.
RESULTS
Among the 331 HSCT patients, 250 had febrile neutropenia and 45 cases were found to have BSI. The incidence of BSI in patients with agranulocytosis fever was 18% (45/250). A total of 48 pathogens were isolated during BSI episodes, gram-negative bacteria (GNB) accounted for 70.8% (34/48), gram-positive bacteria (GPB) for 29.2% (14/48). Multivariate analysis revealed that ≥grade 2 acute graft-versus-host disease (aGVHD) and previous BSI within 6 months before HSCT were independently associated with an increased occurrence of BSI. Coagulase-negative (CoNS) and were the most commonly isolated GPB and GNB, respectively. A total of 32 GNB were tested for drug susceptibility, the detection rate of carbapenem-resistant (CRE) was 12.5% (4/32), and extended-spectrum β-lactamase (ESBL) accounted for 56.3% (18/32).
CONCLUSION
BSIs are still a common and severe complication after allo-HSCT. In our center, BSIs in allo-HSCT patients are dominated by gram-negative bacteria and the resistance rate to carbapenem drugs is high. Risk factors for BSI during agranulocytosis were previous BSI within 6 months before HSCT and ≥grade 2 aGVHD.
PubMed: 38660056
DOI: 10.2147/IDR.S451781 -
International Journal of Clinical... Jun 2024Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparison between a single dose of PEG G-CSF and multiple doses of non-PEG G-CSF: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.
BACKGROUD
Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days.
METHODS
This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes.
RESULTS
Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/μL), quality of life, and pain, were not apparent.
CONCLUSIONS
A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.
Topics: Humans; Granulocyte Colony-Stimulating Factor; Polyethylene Glycols; Practice Guidelines as Topic; Febrile Neutropenia; Recombinant Proteins
PubMed: 38649648
DOI: 10.1007/s10147-024-02504-4 -
Cureus Mar 2024Psychiatric polypharmacy involves the use of two or more psychotropic medications to manage a mental and emotional condition. The prevalence of psychotropic...
Psychiatric polypharmacy involves the use of two or more psychotropic medications to manage a mental and emotional condition. The prevalence of psychotropic polypharmacy has been increasing since the 1990s and has been attributed to the rise in multiple psychiatric conditions presenting in one patient. However, as the prevalence of polypharmacy increases to maximize therapeutic advantages, so does the adverse effect profile of those drugs used in combination, leading to very life-threatening effects such as agranulocytosis. Thus, we report a case of agranulocytosis secondary to polypharmacy in a patient with a history of multiple complex psychiatric conditions. The patient is a 20-year-old female with a past medical history of major depressive disorder, borderline personality disorder, post-traumatic stress disorder, anxiety disorder, hypothyroidism, and ulcerative colitis. Her psychiatric conditions were managed with multiple medications including chlorpromazine, and clozapine was recently added a month prior to admission. Upon admission, the patient was hemodynamically stable and febrile, with complaints of generalized body aches and myalgia. Laboratory results showed profound leukopenia with a white blood cell count of 1.0x10/uL and a neutrophil number of 0.02x10/uL. The patient was admitted to the hospital for neutropenic sepsis and was aggressively treated with intravenous antibiotics. Her clozapine and chlorpromazine were discontinued. In this report, we discuss the association between chlorpromazine and clozapine use and agranulocytosis, emphasizing the importance of regular monitoring and heightened awareness for patients on these medications. This case also underscores the necessity for cautious polypharmacy medication management in individuals with complex psychiatric conditions, highlighting the potential life-threatening consequences of polypharmacy in this population.
PubMed: 38646228
DOI: 10.7759/cureus.56701 -
Blood Advances Apr 2024Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug-induced neutropenia (IDIN) that may put them at risk of infection....
Patients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug-induced neutropenia (IDIN) that may put them at risk of infection. The purpose of this analysis was to examine the rates of severe IDIN and risk of serious infections at different ANC levels in patients treated with deferiprone. Events of severe IDIN (ANC <0.5×109/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by 3 discrete ANC levels: Group 1, 0.2-0.5×109/L; Group 2, 0.1-0.199×109/L; Group 3, <0.1×109/L. In clinical trials, 22 events of severe IDIN were observed (Group 1, n=9; Group 2, n=3; Group 3, n=10); total deferiprone exposure was 1990.26 patient-years; and rates of severe IDIN per 100 patient-years were 0.45 in Group 1, 0.15 in Group 2, and 0.50 in Group 3. All serious infections were in Group 3 (3/10, 30.0%). In the postmarketing setting, 176 events of severe IDIN were reported (Group 1, n=65; Group 2, n=20; Group 3, n=91); total deferiprone exposure was 111,570.24 patient-years; and rates of severe IDIN per 100 patient-years were 0.06 in Group 1, 0.02 in Group 2, and 0.08 in Group 3. Rates of serious infection were 7.7% (n=5/65) in Group 1, 10% (n=2/20) in Group 2, and 13.2% (n=12/91) in Group 3. Our findings suggest that in patients receiving deferiprone, ANC below 0.2×109/L carries a high risk of serious infections, consistent with the recent neutropenia guidelines that agranulocytosis with ANC <0.2×109/L is associated with a high risk of serious infections.
PubMed: 38640437
DOI: 10.1182/bloodadvances.2023012316 -
Pediatric Transplantation May 2024
Topics: Child; Humans; Valganciclovir; Neutropenia; Organ Transplantation
PubMed: 38623879
DOI: 10.1111/petr.14754 -
Clinical Laboratory Apr 2024Infection may lead to agranulocytosis due to bone marrow suppression. However, a rare case with infection presented with morphological features of acute myeloid leukemia...
BACKGROUND
Infection may lead to agranulocytosis due to bone marrow suppression. However, a rare case with infection presented with morphological features of acute myeloid leukemia (AML).
METHODS
We report a case of extreme agranulocytosis due to severe infection mimicking acute myeloid leukemia. The case was definitively diagnosed by subsequent morphology, flow cytometry, and bone marrow biopsy, and subsequent successful anti-infective treatment confirmed the diagnosis.
CONCLUSIONS
To date, no case of a patient diagnosed with severe infection mimicking AML has been reported. The case emphasizes the importance of an integrated diagnostic work-up, especially careful clinical observation and differential diagnosis.
Topics: Humans; Bone Marrow; Leukemia, Myeloid, Acute; Diagnosis, Differential; Flow Cytometry; Agranulocytosis
PubMed: 38623673
DOI: 10.7754/Clin.Lab.2023.231002