scholarly journals Peculiarities of penetration of anti-tuberculosis drugs into the foci of infection in patients with tuberculosis of the central nervous system and the choice of pharmacotherapy

2020 ◽  
pp. 252-253
Author(s):  
R. Ruslami

Background. Tuberculosis (TB) of the central nervous system (CNS) is the most severe and life-threatening form of TB. Diagnosis of TB of CNS is difficult, and treatment is suboptimal. At present, the treatment of tuberculous meningitis (TBM) involves the same drugs and doses as for pulmonary TB, however, the problem is that not all the drugs cross the blood-brain barrier. Objective. To describe the penetration of anti-TB drugs (ATBD) into the foci of infection in patients with TB of CNS and the choice of pharmacotherapy. Materials and methods. Analysis of literature sources on this issue. Results and discussion. Options for optimizing the TBM treatment include a non-pharmacological approach, treatment prolongation, and increasing the residence time of ATBD at the infection site. A meta-analysis of 17 observational studies found no significant benefits of 9-month treatment over 6-month regimens. To increase the residence time of the drug in CNS, you can increase the dose of drugs that poorly penetrate the CNS, add drugs with better brain penetration characteristics, modify drug delivery systems and physical and chemical properties of drugs. The optimal dose provides the maximum effectiveness of the active substance on the background of the minimum number of side effects, so increase of the dose without taking into account the risks of side effects is not advisable. One of the main ATBD rifampicin is characterized by poor penetration into the cerebrospinal fluid. The killer activity of rifampicin depends on its concentration. In our own study, it was found that the administration of a high dose of rifampicin (600 mg) intravenously for 14 days was characterized by lower mortality in patients with TBM than treatment with oral rifampicin (standardized risk ratio was 0.42). Intravenous high-dose treatment was safe and well tolerated by patients. The disadvantages of this treatment include its high cost, invasiveness and poor availability. A meta-analysis of Indonesian patient data confirmed that high doses of rifampicin were associated with lower mortality (Svensson E. et al., 2019). Other drugs that need research in TBM include a new drug bedaquiline, fluoroquinolones (levofloxacin), linezolid. Isoniazid, pyrazinamide, cycloserine, ethionamide, prothionamide are also characterized by the good permeability to cerebrospinal fluid. Therefore, in a strategy to optimize the TBM treatment high-dose rifampicin, high-dose isoniazid and pyrazinamide (?) are the first line, and cycloserine, ethionamide, linezolid, delamanide, pretomanide – the second line. Conclusions. 1. Diagnosis of TB of CNS is difficult, and treatment is suboptimal. 2. Not all the drugs cross the blood-brain barrier. 3. Options for optimization of the TBM treatment include a non-pharmacological approach, prolongation of therapy and increasing the residence time of ATBD in the infection focus. 4. Administration of high-dose rifampicin (600 mg) intravenously for 14 days was characterized by lower mortality in patients with TBM than treatment with oral rifampicin. 5. High-dose rifampicin, high-dose isoniazid and pyrazinamide (?) are the first line of TBM treatment.

2014 ◽  
pp. 29-31
Author(s):  
Seshadri Sekhar Chatterjee ◽  
Arnab Maji ◽  
Nitu Mallik

SSRI are the widely prescribed first line drugs for depression and as depression very commonly presents with insomnia SSRI are good at improving the sleep problems also. But though rare the occurrence of sleep related side effects like bruxism,it may cause significant distress and cause of nonadherence which easily may be overlooked. In this case we report a case of Paroxetine induced bruxism and subsequently treated with withdrawing the drug and buspirone. Though the aetiology of such bruxism remained unclear, the imbalances in dopaminergic and serotonergic activities in the central nervous system is mostly implicated.Key Words : Bruxism, Escitalopram, Parafunctional activity, Selective Serotonin Reuptake Inhibitors


Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 300
Author(s):  
Petr Kelbich ◽  
Aleš Hejčl ◽  
Jan Krejsek ◽  
Tomáš Radovnický ◽  
Inka Matuchová ◽  
...  

Extravasation of blood in the central nervous system (CNS) represents a very strong damaged associated molecular patterns (DAMP) which is followed by rapid inflammation and can participate in worse outcome of patients. We analyzed cerebrospinal fluid (CSF) from 139 patients after the CNS hemorrhage. We compared 109 survivors (Glasgow Outcome Score (GOS) 5-3) and 30 patients with poor outcomes (GOS 2-1). Statistical evaluations were performed using the Wilcoxon signed-rank test and the Mann–Whitney U test. Almost the same numbers of erythrocytes in both subgroups appeared in days 0–3 (p = 0.927) and a significant increase in patients with GOS 2-1 in days 7–10 after the hemorrhage (p = 0.004) revealed persistence of extravascular blood in the CNS as an adverse factor. We assess 43.3% of patients with GOS 2-1 and only 27.5% of patients with GOS 5-3 with low values of the coefficient of energy balance (KEB < 15.0) in days 0–3 after the hemorrhage as a trend to immediate intensive inflammation in the CNS of patients with poor outcomes. We consider significantly higher concentration of total protein of patients with GOS 2-1 in days 0–3 after hemorrhage (p = 0.008) as the evidence of immediate simultaneously manifested intensive inflammation, swelling of the brain and elevation of intracranial pressure.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuchen Wu ◽  
Xuefei Sun ◽  
Xueyan Bai ◽  
Jun Qian ◽  
Hong Zhu ◽  
...  

Abstract Background Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. Methods We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. Results Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0–44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). Conclusions These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.


Author(s):  
Sara Gredmark-Russ ◽  
Renata Varnaite

Tick-borne encephalitis (TBE) is a viral infectious disease of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is usually a biphasic disease and in humans the virus can only be detected during the first (unspecific) phase of the disease. Pathogenesis of TBE is not well understood, but both direct viral effects and immune-mediated tissue damage of the central nervous system may contribute to the natural course of TBE. The effect of TBEV on the innate immune system has mainly been studied in vitro and in mouse models. Characterization of human immune responses to TBEV is primarily conducted in peripheral blood and cerebrospinal fluid, due to the inaccessibility of brain tissue for sample collection. Natural killer (NK) cells and T cells are activated during the second (meningo-encephalitic) phase of TBE. The potential involvement of other cell types has not been examined to date. Immune cells from peripheral blood, in particular neutrophils, T cells, B cells and NK cells, infiltrate into the cerebrospinal fluid of TBE patients.


1927 ◽  
Vol 23 (11) ◽  
pp. 1183-1183

The adverse side effects of salvarsan injections include bleeding from the nose, gums, kidney, lung, etc. The reason for this is the permeability of the capillary walls to red blood cells due to irritation of the central nervous system in persons who are too sensitive to salvarsan. They are caused by the permeability of the capillary walls to red blood cells, caused by irritation of the central nervous system in persons over-sensitive to salvarsan.


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