Miscellaneous treatments: thalidomide, potassium iodide, levamisole, clofazimine, colchicine, and d-Penicillamine

Sanchez, Miguel

doi:10.1016/s0738-081x(99)00103-0

Cited by 24 publications

(9 citation statements)

References 164 publications

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“…Further complexity may be inherent in the activity of CFM against intracellular M. tuberculosis: interactions that may enhance macrophage-mediated, antimicrobial mechanisms have been observed for CFM (2,3), suggesting that a combination of host-directed and antibacterial properties may affect growth inhibition of intracellular mycobacteria exposed to CFM. In addition, the clinically apparent anti-inflammatory properties of CFM, under investigation for the treatment of several autoimmune disorders (23,24,39,40), may also contribute to the in vivo action of this compound against TB. Our in vitro data suggest that, for most of these new analogs, the aspects of CFM's mechanism important to activity against extracellular and intracellular replicating bacteria and against extracellular nonreplicating bacteria have been preserved.…”

Section: Discussionmentioning

confidence: 99%

Clofazimine Analogs with Efficacy against Experimental Tuberculosis and Reduced Potential for Accumulation

Zheng

Wang

et al. 2011

Antimicrob Agents Chemother

157

149

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The global tuberculosis crisis urgently demands new, efficacious, orally available drugs with the potential to shorten and simplify the long and complex treatments for drug-sensitive and drug-resistant disease. Clofazimine, a riminophenazine used for many years to treat leprosy, demonstrates efficacy in animal models of tuberculosis via a novel mode of action. However, clofazimine's physicochemical and pharmacokinetic properties contribute to side effects that limit its use; in particular, an extremely long half-life and propensity for tissue accumulation together with clofazimine's dye properties leads to unwelcome skin discoloration. We recently conducted a systematic structure-activity study of more than 500 riminophenazine analogs for antiMycobacterium tuberculosis activity. We describe here the characteristics of 12 prioritized compounds in more detail. The new riminophenazine analogs demonstrated enhanced in vitro activity compared to clofazimine against replicating M. tuberculosis H37Rv, as well as panels of drug-sensitive and drug-resistant clinical isolates. The new compounds demonstrate at least equivalent activity compared to clofazimine against intracellular M. tuberculosis and, in addition, most of them were active against nonreplicating M. tuberculosis. Eleven of these more water-soluble riminophenazine analogs possess shorter half-lives than clofazimine when dosed orally to mice, suggesting that they may accumulate less. Most importantly, the nine compounds that progressed to efficacy testing demonstrated inhibition of bacterial growth in the lungs that is superior to the activity of an equivalent dose of clofazimine when administered orally for 20 days in a murine model of acute tuberculosis. The efficacy of these compounds, along with their decreased potential for accumulation and therefore perhaps also for tissue discoloration, warrants further study. Despite global efforts, tuberculosis (TB) remains responsible for the second greatest number of deaths due to an infectious disease with 1.7 million deaths reported due to TB in 2009 (45). Of particular concern, the increasing prevalence of TB caused by multidrug-resistant (MDR) and extensively drugresistant (XDR) strains of Mycobacterium tuberculosis puts at risk hard-won gains to public health. MDR-TB treatment regimens, where available, comprise multiple expensive drugs with limited efficacy and significant toxicity that must be administered by both oral and parenteral routes for up to 24 months (30). Treatment of drug-sensitive TB is also long and complex, requiring at least 6 months of a four-drug regimen to achieve a stable cure. The first-line TB drugs are poorly tolerated, reducing compliance and increasing the risk of resistance development. New TB drugs that are safe, orally available, have novel modes of action and efficacy sufficient to simplify and shorten the regimen required to cure TB would impact both patients and TB control by providing improved treatment for drug-resistant TB and by providing a faster, more tolerable cure for dr...

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Section: Discussionmentioning

confidence: 99%

Clofazimine Analogs with Efficacy against Experimental Tuberculosis and Reduced Potential for Accumulation

Zheng

Wang

et al. 2011

Antimicrob Agents Chemother

157

149

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“…Based on the patient's weight (13.5 kg), dosage ranged from 3 drops/d (150 mg/d) to 10 drops/d (500 mg/d). Treatment needs to be continued for 6 weeks after clinical cure . Hypothyroidism has been described in other cases, which appears after discontinuation of SSKI .…”

Section: Discussionmentioning

confidence: 99%

Potassium iodide in refractory, recurrent pediatric Sweet syndrome: Guidance in dosing and monitoring

Tangtatco

Drucker

et al. 2018

Pediatric Dermatology

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We describe a 5-month-old boy with clinical and histopathologic presentation of Sweet syndrome. He responded to systemic corticosteroids, with multiple flares on tapering; potassium iodide was added, which provided complete resolution of Sweet syndrome. Potassium iodide has been used in only a few cases, and no standard dosage has been established in children. We discuss calculation of a pediatric dosage for potassium iodide in Sweet syndrome.

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“…4 Levamisol bekerja pada limfosit B dan T, walaupun efeknya terhadap limfosit T lebih bermakna berupa aktivasi dan peningkatan motilitas limfosit T, juga meningkatkan fagositosis makrofag, meningkatkan perlekatan dan kemotaksis neutrofil, serta meningkatkan pembentukan antibodi terhadap berbagai antigen. 4,5 Levamisol dapat menstimulasi reaksi hipersensitivitas tipe lambat, melalui proliferasi sel T helper (Th)1 dan produksi interleukin 12 (IL-12), interferon-γ (IFN-γ) dan atau penurunan jumlah produksi Th 2 dengan efek pada IL-4, IL-5 dan IL-10. 4 Aktivitas IL-2 yang meningkat akan memengaruhi IL-18 untuk menstimulasi produksi IFN-γ sehingga terjadi pergeseran keseimbangan respons imun kearah Th1.…”

Section: Jenis-jenis Imunostimulan Dan Penggunaannya Dalam Bidang Derunclassified

Penggunaan Imunostimulan Dalam Bidang Dermatovenereologi

Martinus¹,

Agustin²,

Dachlan³

et al. 2019

MDVI

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ABSTRAKImunitas terdiri atas 2 jenis yaitu imunitas alamiah dan imunitas didapat. Imunomodulator adalah semua obat yang dapat memodifikasi respons imun, menstimulasi mekanisme pertahanan alamiah dan adaptif, dan dapat berfungsi baik sebagai imunosupresan maupun imunostimulan. Imunostimulan atau imunostimulator adalah substansi (obat dan nutrien) yang menstimulasi sistem imun dengan meningkatkan aktivitas komponen sistem imun untuk melawan infeksi dan penyakit. Terdapat beberapa imunostimulan yang digunakan dalam bidang dermatologivenereologi, meliputi levamisol, simetidin, isoprinosin, talidomid, sitokin rekombinan, dan vaksin BCG. Masing-masing obat memiliki mekanisme kerja, indikasi dan efek simpang yang berbeda, baik sebagai monoterapi maupun terapi kombinasi dengan terapi lain. Talidomid memiliki peran sebagai antiinflamasi, imunomodulator, dan antiangiogenik, tergantung dari komponen respons imun yang dipengaruhi. Pengunaan talidomid harus mempertimbangkan rasio manfaat berbanding risiko bagi pasien, khususnya dalam penggunaan jangka panjang. Beberapa obat telah disetujui penggunaannya oleh badan yang berwenang di beberapa negara. Namun masih tetap dibutuhkan penelitian lebih lanjut mengenai efektivitas imunostimulan pada berbagai penyakit kulit dan efek simpang yang ditimbulkan dalam penggunaan jangka panjang. Kata kunci: Imunostimulan, sistem imun IMMUNOSTIMULANTS IN DERMATOVENEROLOGY ABSTRACTImmunity consists of two types; innate and adaptive immunity. Immunomodulators are all drugs that modify immune response. They can stimulate innate and adaptive defence mechanisms, and can be used both an immunosuppressant and immunostimulant. Immunostimulants, also known as immunostimulators, are substances (drugs and nutrients) that stimulate the immune system by inducing activation or increasing activity of any of its components, to fight infection and diseases. There are several immunostimulants that have been used in dermatovenereology, such as levamisole, cimetidine, isoprinosine, thalidomide, recombinant cytokines, and BCG vaccine. Each immunostimulants has mechanisms, indications and adverse effects, both as monotherapy and combination therapy. Thalidomide has roles as anti-inflammatory, immunomodulator, and antiangiogenic, depending on immune response's components that are affected. Long term use of thalidomide in patients must consider benefit versus risk ratio. Some drugs have been approved for use by food and drug administration in several countries. However, we still have to conduct many researchs in order to know their efficacy for dermatological uses, and adverse effects from long term use.

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Miscellaneous treatments: thalidomide, potassium iodide, levamisole, clofazimine, colchicine, and d-Penicillamine

Cited by 24 publications

References 164 publications

Clofazimine Analogs with Efficacy against Experimental Tuberculosis and Reduced Potential for Accumulation

Clofazimine Analogs with Efficacy against Experimental Tuberculosis and Reduced Potential for Accumulation

Potassium iodide in refractory, recurrent pediatric Sweet syndrome: Guidance in dosing and monitoring

Penggunaan Imunostimulan Dalam Bidang Dermatovenereologi

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