Sulphonamide interaction

Sulphonamides interact with warfarin (anticoagulant) and sulphonylureas (oral hypo-glycaemics) by enhancing the actions of these drugs. 

The procedure is not usually applicable to aminosulphonic acids owing to the interaction between the amino group and the phosphorus pentachloride. If, however, the chlorosulphonic acid is prepared by diazotisation and treatment with a solution of cuprous chloride in hydrochloric acid, the crystalline chloro-sulphonamide and chlorosulphonanilide may be obtained in the usual way. With some compounds, the amino group may be protected by acetylation. Sul-phonic acids derived from a phenol or naphthol cannot be converted into the sulphonyl chlorides by the phosphorus pentachloride method. 

Accordingly, the spectrum of applicability of these CSPs can be derived. It appears that cellulose- and amylose-carbamate CSPs are excellent for the enantioseparation of SAs with hydrogen donor and/or acceptor sites (amides, carbamates, sulphonamides, hydroxy groups) as well as aromatic moieties, advantageously in combination with bulky groups close to the interaction sites. Due to the broad range of applicability a more detailed list of resolvable SAs would extend this report. However, further information is available from the application guide [172], from review articles [47,99,1(X), and from recently published enantioseparations (Table 9.4). 

The action of sulphonylureas is intensified by heavy sulphonamide dosage and some sulphonamides increase free tolbutamide concentrations, probably by competing for plasma protein binding sites. These examples suffice to show that the possibility of interactions of practical clinical importance is a real one. 

Clinically important, potentially hazardous interactions with beta andrenergic blocking agents, chloramphenicol, cimetidine, dofibrate, coumarin deriveratives, disopyramide, MAO inhibitors, miconazole, phenylbutazone, salicylates, sulphonamides, tetracycline... 

The mechanism differs from that underlying the sulfamethoxazole/trimethoprim interaction. Sulphonamides such as co-trimoxazole and sulfadiazine are known to cause renal dysfunction - interstitial nephritis and renal failure, which may -L excretion of methotrexate. Sulphonamides are also known to compete with methotrexate for renal elimination. Displacement from protein-binding sites of methotrexate is a minor contribution to the interaction... 

What is the name of the intermediate product obtained by the interaction of Tolu-ene-p-sulphonamide and sodium h3rpochlorite ... 

The interaction between toluene-p-sulphonamide with freshly prepared sodium hypochlorite solution (2 M) in the presence of 10% NaOH solution results into the formation of chloramine-T, and a mole of H2O gets eliminated. 

The interaction betweenparo-chlorobenzenesulphonamide and propylisocyanate in the presence of N, N-dimethyl formamide (DMF) and triethylamine gives rise to the formation of chlorpropamide. This is a simple condensation reaction whereby one active H-atom from the sulphonamide function gets attached to the N-atom of the isocyanate to result in the formation of the desired product without any loss of an entity separately. However, triethylamine acts as a catalyst to facilitate the above cited reaction. 

Where some of the cases of hypoglycaemia cannot be predicted on pharmacokinetic grounds, it is worth noting that hypoglycaemia induced by co-trimoxazole, in the absence of a conventional antidiabetic,and sometimes associated with renal failure, high dose of sulphonamide, advanced age, - or malnutrition, has been described. Note that trimethoprim alone may cause interactions mediated via inhibition of CYP2C8 and CYP2C9, see Antidiabetics + Trimethoprim , p.510. 

UK manufacturer lists carbamazepine (see also Clozapine + Anti epileptics , p.744), chloramphenicol, cytotoxics, penicillamine, pyrazolone analgesics (e.g. phenylbutazone), sulphonamides (e.g. co-trimoxazole) and, because they cannot be stopped if an adverse reaction occurs, they advise against the use of depot antipsychotics. There are several cases that confirm the clinical significance of these predicted interactions. 

Not established. The pharmaeokinetie and pharmacodynamic evidence in-dieates that eo-trimoxazole is not likely to reduce the effectiveness of combined oral eontraeeptives. Although there are a number of reports of contraceptive failure attributed to co-trimoxazole, these are anecdotal and unconfirmed, whereas the studies suggest increased contraceptive efficacy (but see below). It is possible that the cases are coincidental, and fit within the normal failure rate of combined oral contraceptives. The UK Family Planning Authority considered that it was almost certain that co-trimoxazole and sulphonamides did not interact with combined oral contraceptives. However, the Faculty of Family Planning and Reproductive Health Care (FFPRHC) Clinical Effectiveness Unit has issued guidance on the use of antibacterials with hormonal contraceptives. Although they recognise that there is poor evidence for contraceptive failure, they recommend that additional contraceptives, such as condoms, should be used for short courses of antibacterials, see Hormonal contraceptives + Antibacterials Penicillins , p.981, for more detailed information. This applies to both the oral and the patch form of the combined contraceptive. This advice has usually been applied to only broad-spectrum antibacterials that do not induce liver enzymes but the FFPRHC notes that some confusion has occurred over which antibacterials are considered to be broad-spectrum , and thus they recommend that this advice is applied to all antibacterials that do not induce liver enzymes, which would include co-trimoxazole, sulfonamides and trimethoprim. ... 

The documentation is only moderate, and these interaetions are not firmly established. Be aware that intravenous sulfadimidine with trimethoprim may cause a marked reduetion in serum eielosporin levels with aeeompa-nying inadequate immunosuppression. Sulfadiazine may also reduce ciclosporin levels. The evidenee suggests that oral sulfadimidine with trimethoprim, suifametoxydiazine, and eo-trimoxazole do not interact adversely and are normally safe and effeetive, although toxicity can apparently oeeur in a small number of patients. Until more information is available it would be prudent to keep a elose eheck on ciclosporin levels if any sulphonamide is added to established treatment with ciclosporin. The manufaeturer reeommends elose monitoring of renal function when ciclosporin is used with eo-trimoxazole. 

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