Sulfonamides topical

A tetracycline (topical plus oral) a sulfonamide (topical plus oral)... 

Sulfanilamide (C) Sulfonamide Topical drug used to treat vulvovaginitis caused by Candida aibi-cans. 

Blood dyscrasias are quite uncommon, but if they occur may be serious enough to cause discontinuance of the therapy. Both topical and systemic adrninistration of sulfas can cause hypersensitivity reactions, such as urticaria, exfoHative dermatitis, photosensiti2ation, erythema nodosum, and in its most severe form, erythema multiformexudativum. (Stevens-Johnson syndrome). In general, however, use of sulfonamide therapy is considered relatively safe. 

The sulfonamides are often used to control urinary tract infections caused by certain bacteria such as Escherichia coli, Staphylococcus aureus, and Klebsiella-Enterobacter. Mafenide (Sulfamylon) and silver sulfadiazine (Silvadene) are topical sulfonamides used in the treatment of second- and third-degree bums. Additional uses of the sulfonamides are given in the Summary Drug Table The Sulfonamides. 

Viader MP, McKeever BM, Navia MA. Thienothiopyran-2-sulfonamides novel topically active carbonic anhydrase inhibitors for the treatment of glaucoma. J Med Chem 1989 32 2510-13. 

Local side effects include burning, stinging, itching, foreign body sensation, dry eyes, and conjunctivitis. Brinzolamide may have a lower incidence of these side effects since the drug is in a neutral pH solution. Dorzolamide has been reported to cause irreversible corneal decompensation. Taste abnormalities have been reported with each agent. Both topical carbonic anhydrase inhibitors are sulfonamides and are contraindicated in patients with history of sulfonamide hypersensitivity.10,13... 

Systemic effects These agents are sulfonamides and, although administered topically, are absorbed systemically. Therefore, the same types of adverse reactions attributable to sulfonamides may occur with topical administration of brinzolamide and dorzolamide. 

A number of infections caused by Chlamydia trachomatis, such as trachoma, inclusion conjunctivitis, pneumonia, and urethritis, can be treated with topical or systemic sulfonamides, although tetracycline or erythromycin is preferred. 

Topically active sulfonamides are useful in preventing infections in burn patients. Mafenide acetate... 

Orally administered carbonic anhydrase inhibitors lower the intraocular pressure of glaucoma patients, however they induce a number of intolerable side effects associated with extraocular inhibition of the enzyme [5,6]. Thus, much research has been directed towards the search for a topically effective agent. Several compounds have been synthesized since the 1980 s in Merck Sharp Dohme Research Laboratories, and have been found to be topically active in man [7]. Unfortunately, many of these compounds were not very soluble. Attempts to obtain an active carbonic anhydrase inhibitor with good solubility resulted in the synthesis of Dorzolamide hydrochloride [8,9], which was first made available for pharmacological evaluation in 1987. Like other carbonic anhydrase inhibitors sulfonamides (such as acetazolamide, ethoxzolaniide, and methazolamide) dorzolamide is an inhibitor of human carbonic anhydrase isoenzymes I, II, and IV. In contrast to the other sulfonamides, dorzolamide is a potent inhibitor of isoenzymes II and IV, and a weak inhibitor of isoenzyme I [ 10]. Isoenzyme II is thought to play a major role in aqueous humor secretion. 

Side effects characteristic of all sulfonamides may occur when systemically absorbed, e.g. when used topically over large exposed areas, such as extensive burn areas. Anorexia, nausea, vomiting, headache, diarrhea, dizziness, photosensitivity, joint pain Frequent... 

Sulfonamides can be divided into three major groups (1) oral, absorbable (2) oral, nonabsorbable and (3) topical. The oral, absorbable sulfonamides can be classified as short-, intermediate-, or long-acting on the basis of their half-lives (Table 46-1). They are absorbed from the stomach and small intestine and distributed widely to tissues and body fluids (including the central nervous system and cerebrospinal fluid), placenta, and fetus. Protein binding varies from 20% to over 90%. Therapeutic concentrations are in the range of 40-100 mcg/mL of blood. Blood levels generally peak 2-6 hours after oral administration. 

Sodium sulfacetamide ophthalmic solution or ointment is effective in the treatment of bacterial conjunctivitis and as adjunctive therapy for trachoma. Another sulfonamide, mafenide acetate, is used topically but can be absorbed from burn sites. The drug and its primary metabolite inhibit carbonic anhydrase and can cause metabolic acidosis, a side effect that limits its usefulness. Silver sulfadiazine is a much less toxic topical sulfonamide and is preferred to mafenide for prevention of infection of burn wounds. 

Topical sulfacetamide is available alone as a 10% lotion (Klaron) and as a 10% wash (Ovace), and in several preparations in combination with sulfur for the treatment of acnevulgaris and acne rosacea. The mechanism of action is thought to be inhibition of P acnes by competitive inhibition of p-aminobenzoic acid utilization. Approximately 4% of topically applied sulfacetamide is absorbed percutaneously, and its use is therefore contraindicated in patients having a known hypersensitivity to sulfonamides. 

Aminosalicylates, eg, mesalamine in many formulations Mechanism uncertain t may be inhibition of eicosanoid inflammatory mediators Topical therapeutic action systemic absorption may cause toxicity Mild to moderately severe Crohn s disease and ulcerative colitis Sulfasalazine causes sulfonamide toxicity and may cause GI upset, myalgias, arthralgias, myelosuppression other aminosalicylates much less toxic... 

Administration of streptomycin intramuscularly is the method of choice for treating systemic infections. Oral forms of streptomycin or dihydrostreptomycin, frequently combined with sulfonamide drugs and other compounds, are also used in animals for treatment of enteric infections. In addition, streptomycin is used as a feed additive for growth promotion purposes. In some countries, the combination of streptomycin with procaine penicillin is used as an initial nonspecific therapy in farm animals, and in intramammary applications for treatment of mastitis. Intramuscular dosages are in the range 5-10 mg/kg bw, while oral dosages are 20 mg/kg bw. Dihydrostreptomycin is also used in veterinary medicine in intramammary and topical treatments. 

In addition, specific testing was performed for chloramphenicol in muscle, nitrofurans in muscle and serum, dimefridazole in muscle of pigs and poultry, and sulfonamides in liver. In Australia, chloramphenicol is not registered for use in food animals and nitrofurans are only available as a topical preparation for use in companion animals. No residues of either of these compounds were detected. No residues of dimefridazole were detected in pig and poultry samples. Sulfonamide residues were monitored in cattle and pigs. No residues were detected in 613 cattle samples. In 594 pig liver samples analyzed, 9 residues of sulfamethazine (sulfamethazine) were detected, 4 of which were above the MRL. 

Sulfonamides have been extensively used in medicine for their antibacterial properties. Silver sulfadiazene (Af-pyrimidin-2-ylsulfanilamide, 41), when applied topically, has proved effective in preventing infections in bums victims.335,336... 

Several sulfonamides, including co-trimoxazole in high doses, can produce hyperchloremic metabolic acidosis. This has even been seen in patients with extensive burns receiving topical mafenide (1077). Mafenide (Sulfamylon) and its metabolite para-sulfamoylbenzoic acid inhibit carbonic acid anhydrase, resulting in reduced reabsorption of bicarbonate and thus bicarbonate wasting. 

The thieno[2,3-Z ]furan-2-sulfonamides (346) (Scheme 28) have been prepared and evaluated as topical carbonic anhydrase inhibitors <91JMC1805>. 

The thieno[2,3-6]furan-2-sulfonamides (11), thieno[2,3-6]thiophene-2-sulfonamides, and thieno-[3,2-6]thiophene-2-sulfonamides were prepared and found to be a new class of topically active ocular hypotensive carbonic anhydrase inhibitors (91JMC1805,92JMC3027). 

Administration Most sulfa drugs are well absorbed after oral administration. Sulfasalazine [sul fa SAL a zeen], when administered orally or as a suppository, is reserved for treatment of chronic inflammatory bowel disease (for example, Crohn s disease or ulcerative colitis), because it is not absorbed. Similarly, succinylsulfathiazole [suks in ill sul fa THI a zole] is used for the treatment of salmonella and shigella carriers. Intravenous sulfonamides are generally reserved for patients who are unable to take oral preparations. Because of the risk of sensitization, sulfas are not usually applied topically. In burn units, creams of mafenide acetate (p-aminomethylbenzensulfonamide) or silver sulfadiazine have been effective in reducing burn sepsis. However, superinfections with resistant bacteria or fungi may occur. 

Maestrclli, E, Mura, R, Casini, A., Mincione, F., Scozzafava, A., and Supuran.C.T. (2002), Cyclodextrin complexes of sulfonamide carbonic anhydrase inhibitors as long-lasting topically acting antiglaucoma agents,/. Pharm. Sci., 91(10), 2211-2219. 

Barboiu M, Supuran CT, Menabuoni L, Scozzafava A, Mincione F, Briganti F, Mincione G (1999) Carbonic anhydrase inhibitors, synthesis of topically effective intraocular pressure lowering agents derived from 5-(aminoalkyl-carboxamido)-l,3,4-thiadiazole-2-sulfonamide. J Enz Inhib 15 23 -6... 

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