China
Africa
Explore chapters and articles related to this topic
Linear IgA disease
Published in Lionel Fry, Atlas of Bullous Diseases, 2020
If patients are unable to take dapsone then either sulfapyridine or sulfamethoxypyridazine may be given. The initial dose of the former for an adult is 2 g per day, and 1 g per day for the latter. The dose may then be titrated up or down to achieve control of the eruption on the smallest possible dose. The maximum dose for sulfapyridine is 4 g per day, and is 1.5 g per day for sulfamethoxypyridazine. Side-effects of sulfonamides include drug eruptions and agranulocytosis.
Classifications
Published in Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani, Pharmacology in 7 Days for Medical Students, 2018
Fazal-I-Akbar Danish, Ahmed Ehsan Rabbani
Long acting (well absorbed by GIT and slowly eliminated)SulfadoxineSulfametopyrazineSulfamethoxypyridazineSulfaphenazole
Sulfonamides
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Natasha E. Holmes, M. Lindsay Grayson
The degree of sulfonamide protein binding influences the rate of renal excretion of these drugs (see section 5d, Excretion). The protein-bound drug does not penetrate into some body compartments, such as the subarachnoid space, but this may not apply if the meninges are inflamed. Madsen et al. (1963) compared the sulfonamide concentration and the antibacterial activity in serum of two long-acting sulfonamides (sulfadimethoxine and sulfamethoxypyridazine) with sulfadiazine. These authors found that these three sulfonamides all produced about the same antibacterial activity in the serum. There appeared to be a close correlation between the total sulfonamide concentration and the antibacterial activity regardless of the degree of protein binding. The highly protein-bound long-acting sulfonamides also penetrated well into extravascular fluids and exudates, particularly when these were of a high protein content. There are many considerations in assessing the effect of protein binding on antibacterial activity (Rolinson, 1980). A protein-bound drug is essentially without antibacterial effect and is nondiffusible, but this is only a temporary state, because when a protein-bound drug dissociates, the drug is available again in active form. The free unbound plasma levels of a drug dictate the free levels in extravascular fluids. The level of free drug after therapeutic doses and how this relates to the MIC of the organism are important factors in determining therapeutic efficacy.
Development of small-molecule immune checkpoint inhibitors of PD-1/PD-L1 as a new therapeutic strategy for tumour immunotherapy
Published in Journal of Drug Targeting, 2019
Researchers at Jilin University in China used resorcinol and 3-hydroxythiophenol as the core and linked them with N,N-dimethylcarbamate and other alkyl-substituted amines to afford 13 amine-appended phenyl dimethylcarbamates (AAPDs), which exhibited the potential to inhibit PD-1/PD-L1 signalling pathways [70]. Based on the PD-1/PD-L1 complex structure reported by Lin et al. [71] and Zak et al. [72] and on the results reported by Harvard et al. [69] on sulfamoxol and sulfamethoxypyridazine, these researchers used V-type domain complete resorcinol and mercapto-substituted resorcinol as the raw materials to synthesise 13 compounds. Then, activity screening was performed to obtain amino- or dimethylcarbamate-substituted resorcinol with the ability to bind to PD-1, thereby efficaciously blocking the binding of PD-1 to PD-Ll. One of the most active structures was Compound 9 (Figure 2).
Novel avenues for identification of new antifungal drugs and current challenges
Published in Expert Opinion on Drug Discovery, 2022
Different groups of drugs may have their own antifungal activity, but more often, it is more appropriate to combine them with existing clinically used antifungals. These ‘newly discovered’ drugs are able to resensitize existing antifungals or act synergistically with them [111–116]. The most commonly studied groups are tricyclic antipsychotics, local anesthetics, anti-inflammatory drugs/antirheumatics, and other enzyme inhibitors such as statins and disulfiram. Thus, these diverse molecules involve all sorts of mechanisms of action, such as interactions with the fungal cell wall, membranes, modulation of proteosynthesis, metabolic processes, and proliferation. Table 1 provides an overview of repurposed drugs with in vitro proven antifungal activity. Table 1 does not list drugs from the class of antiseptics and disinfectants such as hexachlorophene, chloroxine, iodoquinol, clioquinol, chlorhexidine, cetrimonium bromide, thonzonium bromide, and benzethonium chloride, because their antifungal activity is not surprising. These agents are able to damage the fungal cell wall and membranes, chelate metal enzyme cofactors, and inhibit biofilm formation and mature biofilm. They show synergism with azoles and most often act against Candida sp., Aspergilus sp., Fusarium sp., C. neoformans and R. oryzae [94,101,117–124]. Antibacterial chemotherapeutics are not listed. Their antifungal effect is minimal except for tetracyclines (doxycycline) and macrolides (clarithromycin, azithromycin), that showed in vitro activity against Pythium insidiosum [115,125], and sulfonamides (sulfadiazine, sulfapyridine, sulfametoxydiazine, sulfamethoxazole, sulfadoxine, sulfamonomethoxine, sulfamethoxypyridazine) including dapsone, which inhibited the biofilm formation of C. albicans and C. auris and showed synergism with azoles [126].
An update on the cutaneous manifestations of coeliac disease and non-coeliac gluten sensitivity
Published in International Reviews of Immunology, 2018
The cornerstone of DH treatment is strict adherence to a GFD [2]. This is the most important behaviour for managing this skin condition and associated CD. Improvements in skin can be slow, taking months or even years [5]. Patients need to avoid all exposure to wheat, barley and rye, and effective gluten avoidance may also decrease their long-term risk of developing lymphoma [39]. In the short to medium term, pharmacological intervention may be required to control DH. Dapsone and the related sulphonamide drugs are useful for suppressing the itch, reported to be effective within days of initiating treatment [2]. Dapsone is considered a valid treatment for patients with DH during the 6- to 24-month period until the GFD is effective. The mechanism of action of dapsone (25–150 mg daily dose) in DH is through its effects on neutrophil function and recruitment [2]. Dapsone has anti-inflammatory features similar to those of non-steroidal anti-inflammatory drugs (NSAIDs), with effects on inflammatory effector cells, cytokines and/or mediators, such as reactive oxygen species, the myoloperoxidase-/halogenid system, adhesion molecules, chemotaxis, membrane-associated phospholipids, prostaglandins, leukotrienes, IL-8, tumour necrosis factor α, lymphocyte function and tumour growth [44]. Haematological effects such as haemolysis, methaemoglobinaemia and agranulocytosis can sometimes occur [45]. Adverse non-haematological effects include dapsone hypersensitivity syndrome and peripheral neuropathy [44]. Patients with glucose-6-phosphatase (G6PD) deficiency are more prone to the adverse effects of dapsone [2]; thus, G6PD activity should be assessed before treatment. Consequently, patients require regular blood monitoring. Before starting the therapy, patients should undergo a complete blood count in addition to liver and renal function, G6PD and methaemoglobinaemia tests. After therapy, they should be revaluated every week for the first month to monitor anaemia, methaemoglobinaemia and symptoms of neuropathy, as well as a complete blood count and liver and renal function testing twice a month for the following two months and then every three months after that [46]. Other drugs include sulphamethoxypyridazine (0.25–1.5 g/day), sulphapyridine (SP; 2–4 g/day) and sulphasalazine (SSZ; 1–2 g/day) [47]. The mode of action of SSZ and its metabolites, 5-aminosalicylic acid (5-ASA) and SP, are still under investigation, but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal and in vitro models [48]. All of these drugs have similar side effects, including gastrointestinal upset (nausea, anorexia and vomiting), hypersensitivity drug reactions, haemolytic anaemia, proteinuria and crystalluria [49]. Systemic and topical corticosteroids are of little benefit, but they may be of use in the short term [5].