Sulfonamides are a group of synthetic antibiotics dating back to the 1930es. They were not isolated from microorganisms, in contrast to many antibiotics of the early era. All sulfonamides share a core structure derived from para-aminobenzoic acid (PABA), a naturally occurring substance essential for bacterial folate synthesis. Trimethoprim is not a sulfonamide but belongs to the class of diaminopyrimidine drugs. It is often grouped with sulfonamides because of a similar mechanism of action (see below).
Bacterial growth depends on folate as it is required for DNA replication. Sulfonamides reduce bacterial folate synthesis by competitively inhibiting an essential substrate of the folate pathway, para-aminobenzoic acid (PABA). Antibiotics of this class are bacteriostatic. Trimethoprim works by inhibiting dihydrofolate reductase, another enzyme of the bacterial folate pathway. Resistance to sulfonamides and trimethoprim is widespread and often mediated by modifications of various enzymes involved with folate synthesis.
Sulfonamides are active against a variety of gram-positive and gram-negative organisms. Due to widespread antibiotic resistance, sulfonamide use has become less frequent. Sulfamethoxazole is most commonly given with trimethoprim. This combination drug (known as 'Cotrim' or 'Bactrim') has synergistic effects and is used to treat and prevent Pneumocystis jiroveci infections in immunocompromised patients (i.e. patients living with AIDS).
Elimination half-life of sulfonamides varies greatly, but all drugs of this class are usually well absorbed from the gastrointestinal tract. Tissue penetration as well as penetration of the blood-brain barrier is good. Sulfonamides are metabolised by the liver and for the most parts, cleared by the kidneys.
Allergic reactions to sulfonamide therapy are not uncommon but usually mild. More severe adverse effects associated with sulfonamides are Stevens-Johnson syndrome, bone marrow depression and haemolytic anaemia.