Sulfonamide side effects

Contraindications Anuria, hypersensitivity to sulfonamides Side Effects... 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

Among one of the more unusual side effects noticed as the use of the sulfonamides became widespread was the increased urine output of many patients treated with these drugs. The fact that the urine was unusually alkaline led to the suspicion, later (Confirmed by independent means, that these agents were responsible for partial inhibition of the enzyme carbonic anhydrase. Inhibition of this enzyme causes increased excretion of sodium and bicarbonate ions as well as water, in effect bringing about diure-... 

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... 

Because of bacterial resistance and unacceptable side effects in some patients, the antibacterial sulfonamides no longer enjoy the clinical vogue they once had. Still, their cheapness, undeniable efficacy in susceptible infections, and the hope of overcoming their deficiencies leads to a continuing interest despite thousands having been synthesized to date. 

The most common side effects include somnolence, dizziness, anorexia, headache, nausea, word-finding difficulties, oligohidrosis, modest weight loss, and irritability. Symptomatic kidney stones may occur in 2.6% of patients. Hypersensitivity reactions may occur in 0.02% of patients, and it should be used with caution if at all in patients with a history of allergy to sulfonamides. Monitoring of renal function may be advisable in some patients. 

Finally, some drugs widely used including lithium, ethionamide, sulfonamides carbutamide, p-aminobenzoic acid, p-aminosalycilic acid, ketoconazole, or phenylbutazone have adverse side effects on the thyroid [26]. 

One of the side effects noted in the clinical use of the sulfonamide antibacterial agents was a diuretic effect caused by inhibition of the enzyme carbonic anhydrase. Attempts to capitalize on this side effect so as to obtain agents with greatly enhanced diuretic activity first met success when a heterocyclic ring was substituted for the benzene ring of the sulfonamide. Treatment of the hydrazine derivative, 151, with phosgene leads... 

Minocycline is an effective alternative to rifampin for eradication of meningococci, including sulfonamide-resistant strains, from the nasopharynx. However, the high incidence of dose-related vestibular side effects renders it less acceptable. Although minocychne has good in vitro activity against Nocardia spp., further studies are necessary to confirm its clinical efficacy. 

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... 

The history of pharmacology revealed that certain drugs have been developed from the observation of their side effects for example sulfonamide produce hypoglycemia and acidosis as side effect, which further gave an idea for developing a new compound related to sulfona-mide - sulfonylurea as hypoglycemic agent and acetazolamide as diuretic. 

All those side effects seen with sulfonamides. 

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. 

Some 10,000 structurally dilferent sulfonamides have been synthesized as a result of the discovery of the antibacterial properties of sulfanilamide. The practice of synthesizing numerous structurally related compounds in an elfort to find some that are more efficient or have fewer side effects than those already available is very important to the pharmaceutical industry. However, as is usually the case, of the many known sulfonamides only about thirty have the proper balance of qualities to be clinically useful. 

The structural formulas of several cyclic compounds containing both nitrogen and sulfur are shown in Figure 17.4. Basic to the structures of these compounds is the simple ring structure of thiazole. It is a colorless liquid (bp, 117°C). One of its major uses has been for the manufacture of sulfathiazole, one of the oldest of the sulfonamide class of antibacterial drugs. The use of sulfathiazole is now confined to the practice of veterinary medicine because of its serious side effects. 

Commonly used drugs (other than isoniazid) affected by NAT2 polymorphism were procainamide, hydralazine, dapsone, and sulfonamides with an increase of side effects in all cases. A selective substrate of NATl is -aminosalicylic acid (PAS), but its genetic variation was never clinically important (52). Because of such lack of importance, more attention is often paid to the fact that various industrial chemicals with carcinogenic potential, and mutagenic heterocyclic amines, are substrates of both N-acetyltransferases (53). The presence or absence of these transferases will determine some incidences of cancer (54). Attempts have been made to ascribe cancer incidences in different populations to acetyltransferase differences (55). 

Adverse effects The side effects include gastrointestinal distress. At higher doses, albuminuria, hematuria and rashes may develop. Methenamine mandelate is contraindicated in treating patients with renal insufficiency, because mandelic acid may precipitate. Sulfonamides react with formaldehyde and must not be used concomitantly with methenamine. 

Another very prominent example of the development of dmgs for new indications, from the fortuitous observation of side effects, is that of the sulfonamides. Several sulfonamides of the first generation had, in addition to their antibacterial effect, either diuretic or hypoglycemic activities. Correspondingly, specific diuretics, antiglaucomics, antihypertensives, and antidiabetics could be developed in this group of compounds [11,14,16]. 

Upon systemic distribution, many drugs evoke skin reactions that are caused on an immunological basis. Moreover, cutaneous injury can also arise from nonimmunological mechanisms. Cutaneous side effects vary in severity from harmless to lethal. Cutaneous reactions are a common form of drug adverse reaction. Nearly half of them are attributed to antibiotics or sulfonamides, and one-third to nonsteroidal anti-inflammatory agents, with many other pharmaceuticals joining the list... 

Selective inhibitors of COX-II or 5-lipoxygenase (5-LO) consisting of oxazolyl-, (I), and pyrazolylbenzene sulfonamide derivatives, (II), prepared by Talley (1,2), respectively, and sulfonyl derivatives, (III), prepared by Ando (3) were effective as anti-inflammatory agents with only marginal gastrointestinal side effects. 

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