PURPOSE: A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden decline in visual function. Despite the known complications of ethambutol treatment, it was discontinued after another three months. METHODS: In the case report, we highlight the damage to the dominantly peripheral visual pathways. Using electrophysiological examinations, we showed a significant alteration in the optic nerves. Optical Coherence Tomography (OCT) showed progressive loss of vessel density and nerve fibre layer of retinal ganglion cells. Perimetric examination showed both a central decrease in sensitivity and mainly scotomas in the temporal parts of the visual fields. Although there was improvement in visual fields over time, OCT findings indicated progression of ethambutol-induced optic neuropathy (EON). Magnetic Resonance Imaging confirmed the alteration in the peripheral part of the visual pathway (intraorbital, intracranial parts of optic nerves, chiasma, and optic tracts). CONCLUSION: Even though EON is not an unknown complication, new cases still occur and, unfortunately, with an irreversible course. Therefore, it is important to draw attention constantly to this complication and to consider it not only in ophthalmologists' surgeries.
- Klíčová slova
- ethambutol, magnetic resonance imaging, optic neuropathy, vessel density,
- MeSH
- antituberkulotika škodlivé účinky MeSH
- dospělí MeSH
- ethambutol škodlivé účinky MeSH
- lidé MeSH
- nemoci zrakového nervu * chemicky indukované diagnóza patologie MeSH
- nervus opticus diagnostické zobrazování patologie MeSH
- optická koherentní tomografie metody MeSH
- tuberkulóza * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- antituberkulotika MeSH
- ethambutol MeSH
- MeSH
- antituberkulotika farmakologie terapeutické užití MeSH
- bakteriální proteiny účinky léků MeSH
- ethambutol farmakologie terapeutické užití MeSH
- isoniazid farmakologie terapeutické užití MeSH
- katalasa účinky léků MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- multirezistentní tuberkulóza genetika MeSH
- Mycobacterium tuberculosis účinky léků izolace a purifikace MeSH
- rifampin farmakologie terapeutické užití MeSH
- streptomycin farmakologie terapeutické užití MeSH
- tuberkulóza farmakoterapie epidemiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- Geografické názvy
- Turecko MeSH
- Názvy látek
- antituberkulotika MeSH
- bakteriální proteiny MeSH
- ethambutol MeSH
- isoniazid MeSH
- katalasa MeSH
- katG protein, Mycobacterium tuberculosis MeSH Prohlížeč
- rifampin MeSH
- streptomycin MeSH
In order to provide a more detailed view on the structure⁻antimycobacterial activity relationship (SAR) of phenylcarbamic acid derivatives containing two centers of protonation, 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(dipropylammonio)propyl]pyrrolidinium oxalates (1a⁻d)/dichlorides (1e⁻h) as well as 1-[2-[({[2-/3-(alkoxy)phenyl]amino}carbonyl)oxy]-3-(di-propylammonio)propyl]azepanium oxalates (1i⁻l)/dichlorides (1m⁻p; alkoxy = butoxy to heptyloxy) were physicochemically characterized by estimation of their surface tension (γ; Traube's stalagmometric method), electronic features (log ε; UV/Vis spectrophotometry) and lipophilic properties (log kw; isocratic RP-HPLC) as well. The experimental log kw dataset was studied together with computational logarithms of partition coefficients (log P) generated by various methods based mainly on atomic or combined atomic and fragmental principles. Similarities and differences between the experimental and in silico lipophilicity descriptors were analyzed by unscaled principal component analysis (PCA). The in vitro activity of compounds 1a⁻p was inspected against Mycobacterium tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794, respectively), M. tuberculosis H37Ra ATCC 25177, M. kansasii CNCTC My 235/80 (identical with ATCC 12478), the M. kansasii 6509/96 clinical isolate, M. kansasii DSM 44162, M. avium CNCTC My 330/80 (identical with ATCC 25291), M. smegmatis ATCC 700084 and M. marinum CAMP 5644, respectively. In vitro susceptibility of the mycobacteria to reference drugs isoniazid, ethambutol, ofloxacin or ciprofloxacin was tested as well. A very unique aspect of the research was that many compounds from the set 1a⁻p were highly efficient almost against all tested mycobacteria. The most promising derivatives showed MIC values varied from 1.9 μM to 8 μM, which were lower compared to those of used standards, especially if concerning ability to fight M. tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 or M. avium CNCTC My 330/80. Current in vitro biological assays and systematic SAR studies based on PCA approach as well as fitting procedures, which were supported by relevant statistical descriptors, proved that the compounds 1a⁻p represented a very promising molecular framework for development of 'non-traditional' but effective antimycobacterial agents.
- Klíčová slova
- Mycobacterium spp., dibasic phenylcarbamates, electronic properties, lipophilicity, surface tension,
- MeSH
- antituberkulotika chemická syntéza farmakologie MeSH
- azepiny chemická syntéza farmakologie MeSH
- ciprofloxacin chemie terapeutické užití MeSH
- ethambutol chemie terapeutické užití MeSH
- fenylkarbamáty chemická syntéza farmakologie MeSH
- isoniazid chemie terapeutické užití MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium avium účinky léků MeSH
- Mycobacterium kansasii účinky léků MeSH
- Mycobacterium smegmatis účinky léků MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- Mycobacterium účinky léků MeSH
- ofloxacin chemie terapeutické užití MeSH
- oxaláty chemie farmakologie MeSH
- počítačová simulace MeSH
- pyrrolidiny chemická syntéza farmakologie MeSH
- racionální návrh léčiv MeSH
- rozpustnost MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antituberkulotika MeSH
- azepiny MeSH
- ciprofloxacin MeSH
- ethambutol MeSH
- fenylkarbamáty MeSH
- isoniazid MeSH
- ofloxacin MeSH
- oxaláty MeSH
- pyrrolidiny MeSH
The authors give an account of a 57-year-old male patient who was regularly dialyzed for two years and treated because of suspect TB of the spine with antituberculotics, incl. ethambutol. In the course of 8-9 months he was given 17.9 mg/kg ethambutol per day. Because of the practically zero excretion by the damaged kidney the drug cumulated in the serum and reached toxic levels before dialysis. Gradual deterioration of eyesight developed (central acuity and colour sense) which resulted in bilateral atrophy of the optic nerves with concentric narrowing of the visual field.
- MeSH
- chronické selhání ledvin terapie MeSH
- dialýza ledvin * MeSH
- ethambutol škodlivé účinky farmakokinetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- tuberkulóza páteře farmakoterapie MeSH
- zánět zrakového nervu chemicky indukované MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- ethambutol MeSH
A 22 years old woman suffering from renal insufficiency has been treated for 4 years by means of regular dialysis. Two years after the beginning of this therapy the renal transplantation was performed, but the graft was removed after 3 weeks. The hypertonic neuropathy was diagnosed. Patient was treated with antituberculotics, Imuran and Prednisone. After Ethambutol treatment indicated for pulmonar tbc (daily dose 11 mg per kg, the total dose of 33,6 g) the ocular side effects were pronounced: the toxical damage of both optical nerves, bilateral decrease of vision for distance and near, minute scotoma in the retinal centre of the left eye, deterioration of the vision of colours in the sense of deuteranopia. Complications were reversible, when the therapy with Ethambutol was discontinued and patient was treated with vitamins and Prednison in the total dose of 1,420 g. Authors mention also some other signs of ocular toxicity of antituberculotics.
- MeSH
- chronické selhání ledvin komplikace terapie MeSH
- dialýza ledvin * MeSH
- dospělí MeSH
- ethambutol škodlivé účinky MeSH
- lidé MeSH
- oční nemoci chemicky indukované MeSH
- plicní tuberkulóza komplikace farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- ethambutol MeSH
On the basis of a mathematical analysis of the time course of the drug distributed in the organism there were studied pharmacokinetics of antituberculosis drugs after an isolated oral administration of doses used in daily treatment of tuberculosis, in INH, RMP, EMB, PZA, ETA, CS and TZ, and after a simultaneous--single and repeated--administration of INH, RMP, EMB in a triple combination, after the usual daily doses and after increased intermittent doses administered twice weekly. At first there were determined, with the use of chemical methods, blood concentrations of the antituberculosis drugs studied and their excretion with urine in an unchanged form. The results were analyzed pharmacokinetically by means of a one- compartment model with absorption. By an iteration process, based on non-linear regression analysis, the following pharmacokinetic parameters were calculated: Vd, Ka, Ke, T0.5 abs, T0.5 el, Tmax, Cmax, Clp tot and AUC. Their comparison revealed the following facts: The microbiologically most effective antituberculosis drugs--INH and RMP--are comparable even from the point of view of pharmacokinetics on account of similar pharmacokinetic parameters; in comparison with them EMB has half the size of the AUC, characterizing the efficacy of the drug. In this parameter PTA exceeds more than twice ETA; CS and TZ have a low Ke as well as Clp tot and a high T0.5 el, which is indicative of an insufficient excretion of both drugs. Pharmacokinetic parameters of PZA confirm the possibility of using the dose of 25 mg/kg in the treatment of tuberculosis. A simultaneous administration of the triple drug combination under study influences pharmacokinetic parameters of all the three antituberculosis drugs--it significantly decreases Ka as well as Ke, increases T0.5 el, Tmax, Vd and in INH also Clp tot, but only after a repeated administration. An intermittent administration of the mentioned triple drug combination significantly increases the area under the curve AUC in all the three antituberculosis drugs. This explains the same efficacy of higher doses of antituberculosis drugs, administered twice weekly, in comparison with a daily administration of lower doses of the same combination. The pharmacokinetic process of orally administered antituberculosis drugs can be analyzed according to a one-compartment model of pharmacokinetics, although the kinetics of certain antituberculosis drugs probably proceed in the organism in a more complicated way.
- MeSH
- antituberkulotika aplikace a dávkování metabolismus MeSH
- aplikace orální MeSH
- dospělí MeSH
- ethambutol aplikace a dávkování MeSH
- isoniazid aplikace a dávkování MeSH
- kinetika MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- plicní tuberkulóza farmakoterapie metabolismus MeSH
- rifampin aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antituberkulotika MeSH
- ethambutol MeSH
- isoniazid MeSH
- rifampin MeSH
- MeSH
- dospělí MeSH
- ethambutol aplikace a dávkování metabolismus MeSH
- kinetika MeSH
- lidé MeSH
- tablety MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- ethambutol MeSH
- tablety MeSH
Two groups of patients suffering from extensive pulmonary tuberculosis treated with daily or twice-weekly regimens of isoniazid (INH) plus rifampicin (RMP) plus ethambutol (EMB) were formed by random selection. The effectiveness of treatment was expressed by the slope of regression line calculated for each patient in terms of quantitative time dependent decrease of mycobacteria isolated by culture per 1 ml of sputum. Chemically serum concentrations of drugs in five time intervals following simultaneous administration were established. It was shown that the rate of decrease of mycobacteria did not significantly vary in the compared groups. Negativity was reached in 48 day on the average. The mean regression line with double standard deviation allocated patients with rapid, normal or slow sputum conversion. Rapid convertors were the youngest, excreted largest amounts of mycobacteria before the start of treatment, and their x-ray showed predominantly changes of exudative character. Slow convertors excreted least amounts of mycobacteria. In the group of slow convetors with daily regimen was significantly higher number of rapid INH inactivators compared with groups of rapid and normal convertors. Analysis of multiple correlation and variance of the ratio of mycobacterial decrease rate and of the parameters of the biological availability of drugs as expressed by the area under the curve of drug serum levels reveal the rate of mycobacterial decrease to be dependent always on the drug out of the combination. In daily regimen the decrease rate was controlled by INH, in the intermittent regimen by RMP. The speed of negativization could therefore be increased in daily regimen by increased doses of INH, chiefly in rapid INH inactivators. The most important share of RMP in the mycobacterial decrease rate during intermittent administration can be judged from dependence of biological availability on the dose of RMP. Under the experimental circumstances of this study the pharmacological means for speeding up negativization were best utilized. Further shortening of time necessary for obtaining negativity would be practicable only when residual factors are involved presumably existing beyond the region of pathogen and drug relationship.
- MeSH
- dospělí MeSH
- ethambutol aplikace a dávkování MeSH
- isoniazid aplikace a dávkování krev MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- plicní tuberkulóza krev farmakoterapie mikrobiologie MeSH
- rifampin aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- klinické zkoušky MeSH
- Názvy látek
- ethambutol MeSH
- isoniazid MeSH
- rifampin MeSH
- MeSH
- antibakteriální látky farmakologie MeSH
- antibiotická rezistence MeSH
- cykloserin farmakologie MeSH
- ethambutol farmakologie MeSH
- ethionamid farmakologie MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- pyrazinamid farmakologie MeSH
- rifampin farmakologie MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- antibakteriální látky MeSH
- cykloserin MeSH
- ethambutol MeSH
- ethionamid MeSH
- pyrazinamid MeSH
- rifampin MeSH
- MeSH
- dospělí MeSH
- ethambutol škodlivé účinky terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- oční nemoci chemicky indukované MeSH
- senioři MeSH
- spondylitida farmakoterapie MeSH
- tuberkulóza farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- ethambutol MeSH
