Azulfidine Sulfonamide

Sulfonamide is derived from prontosil (prodrug) and it is the structural analogue of P-aminobenzoic acid (PABA). It inhibits bacterial folic acid synthesis ( a competitor of PABA).

Folate is necessary for the synthesis of bacterial DNA or RNA. Thus, sulfonamide inhibits bacterial growth. That’s why it is bacteriostatic in action and not so effective in the presence of pus.

Sulfonamides that are still of clinical interest can be classified into 4 major groups:

• Short acting sulfonamide ( 4-8 hours) : Sulfadiazine.
• Intermediate acting sulfonamide (8-12 hours): Sulfamethoxazole.
• Long acting sulfonamide (~ 7 days): Sulfadoxine, Sulfamethopyrazine.
• Special purpose sulfonamides: Sulfasalazine, Silver sulfadiazine, Mafenide.

Sulfonamide is indicated in following medical conditions:

• Acute urinary tract infection
• Meningococcal meningitis
• Topical application for infected burn
• Chloroquine resistance malaria
• Ulcerative colitis, inflammatory bowel disease
• Opportunistic lung infection
• Lymphogranuloma venereum and chancroid
• Bacillary dysentery
• Trachoma and inclusion conjunctivitis

Before you start any drug therapy you should know all about the risks and benefits of such medications.

Always try to give the appropriate information regarding your past and present illness to your doctor. You should arrange adequate visits to your doctor in order to have proper monitoring.

Never forget to tell about the diseases like asthma, diabetes, myocardial infarction, heart failure, renal impairment etc. if you have had.

The term sulfonamide is employed for derivatives of para-amino benzenesulfonamide (sulfanilamide).

The - SO₂ NH₂ group present in sulfonamide is not essential but the important feature is that the sulfur is directly linked to the benzene ring.

The para – NH₂ group is essential for the antimicrobial activity of sulfonamide. A human does not synthesize folic acid inside the body but use preformed folate from leafy vegetables.

Their cells are thus unharmed by the metabolic effects of sulfonamides.

Sulfonamides are primarily bacteriostatic against much gram-positive, and gram-negative bacteria. However, bactericidal concentrations may be attained in urine.

Sensitivity patterns among microorganisms have changed from time-to-time and place-to-place.

Those still sensitive are many Strep. pyogenes, Haemophilus influenzae, H. ducreyi, Calymmatobacterium granulomatis, Vibrio cholera, Actinomyces, Nocardia, Toxoplasma etc.

• Route of administration: oral – well absorbed from the upper GIT
• Distribution: CSF, Placenta, metabolism: liver
• Excretion: kidney (tubular secretion and glomerular filtration)
• Sulfonamide is contraindicated in any hypersensitivity, pregnancy, and renal failure. In pregnancy it displaces bilirubin from albumin, so free bilirubin enters into fetal brain and leads to kernicterus which is a fatal condition.
• Resistance to sulfonamides: most bacteria are capable of developing resistance to sulfonamides. Prominent among these are- gonococci, pneumococci, Staph. aureus, meningococci, E. coli, Shigella and some Strep. pyogenes, Strep. viridans, and anaerobes. Resistance developed in vivo is quite persistent. Sensitivity patterns have changed depending on the extent of use.

Medicines should be used following the directions were given by a doctor.

The dose of this medicine will vary according to patient’s condition or requirements. You should follow the doctor's directions and advice.

The amount of medicine that you take must not exceed the maximum therapeutic dose.

Also, the frequency of your daily drug administration and the duration of drug therapy depend on the particular medical problem for which you are taking the medicine.

Systemic use of sulfonamides alone is narrow now.

Though they can be employed for suppressive therapy of chronic urinary tract infection, for streptococcal pharyngitis and gum infection, such uses are outmoded. Certain sulfonamides are widely used still nowadays. They are:

Sulfadiazine is the prototype of the general purpose sulfonamides that is rapidly absorbed orally and rapidly excreted in urine. This drug is preferred for meningitis. Dose: 0.5 g QID to 2 g TDS.

Sulfamethoxazole: having slower oral absorption and urinary excretion resulting in an intermediate duration of action. Dose: 1 g BD for 2 days, then 0.5 g BD.

Sulfadoxine, Sulfamethopyrazine: because of ultralong-acting action lasting 7 days and low plasma these are not suitable for treatment of acute pyogenic infections, but used in combination with pyrimethamine in the treatment of malaria, especially chloroquine-resistant P. falciparum , Pneumocystis jiroveci pneumonia in AIDS patients and in toxoplasmosis.

Sulfasalazine: used in ulcerative colitis and rheumatoid arthritis.

Although sulfonamide is well tolerated by most of the patients, but it may bring unwanted effects. You may need to consult with the doctor if you feel any of these discomforts excessively.

Firstly, you have to stop using this drug and then consult with your physician immediately. In the case of children, be careful not to exceed the optimum therapeutic dose.

You should not take certain medicines during this drug therapy. It is safe to consult with your doctor if you are in need of some drugs for another health problem.

On the other hand, you should be aware of drug interactions associated with such medication. Sulfonamide inhibits the metabolism of phenytoin, tolbutamide and warfarin by displacing them from protein binding sites.

It also displaces methotrexate from binding sites and decreases its renal excretion resulting in severe toxicity.

Precipitation in urine can be minimized by taking plenty of fluids and by alkalinizing the urine in which sulfonamides and their acetylated derivatives are more soluble.

By this way, you can avoid crystalluria which is a severe adverse effect found in patients receiving sulfonamide. 

Each drug comes with little or more side effects, but most of the time remains subtle. Usual side effects need no medical attention but in some conditions may demand emergency resolution.

However, toxicity may be influenced by the relative rates of absorption and metabolism.

You should seek medical help when the following problems become significant:

• Hypersensitivity reactions occur in 2-5% patients. These are mostly in the form of rashes, urticaria, and drug fever.
• Renal toxicity: crystalluria, spasmodic pain (renal colic), haematuria ( passage of bigger crystal ruptures the blood vessels), renal tubular necrosis etc.
• Haematological changes : haemolytic anemia in G6PD deficient individuals, bone marrow depression (aplastic anaemia).
• GIT upsets: nausea, vomiting, diarrhea, and epigastric pain.
• CNS (Basal ganglia): kernicterus (displace bilirubin from albumin in newborn) may be precipitated in the newborn, especially premature, whose blood-brain barrier is more permeable, by displacement of bilirubin from plasma protein binding sites.
• Long-term use may cause hepatitis and stomatitis. Hepatitis occurs in 0.1% patients.
• Stevens-Johnson syndrome and exfoliative dermatitis are serious reactions reported with long-acting agents.
• Anaphylactic shock and photosensitivity.