UNTOWARD REACTONS OF SULFONAMIDES

Up to 5% of patients experience untoward reactions. Certain types of toxic reactions are related to individual difference in Sulfonamide metabolism. The commonly observed side effects are:

1. DISTURBANCE OF URINARY TRACT:

Sulfonamide may precipitate in urine at neutral or acidic pH producing crystal urea, haemeturia and even obstruction. Though this risk was high with older less soluble Sulfonamides, the incidence of this problem is very low with most soluble drugs. Crystal urea occurs in dehydrated patients and in those whose fluid intake is low. Thus there should be enough fluid intakes to ensure a daily volume of urine at least 1200 ml in adults.

Crystal urea is treated by alkalinizing with the administration of sodium bicarbonate and monitoring adequate hydration with large intake of fluid. Drug belonging to sulfonamide group should be avoided during the month of fasting.

2. HAEMATOPOIETIC DISTURBANCE:

a. Acute haemolytic anemia:

In some cases, the acute haemolytic anemia is thought to occur due to sensitizatization phenomenon while in other instance it is related to the deficiency of glucose-6-phosphate dehydrogenase enzyme in RBCs. The frequency of occurrence of this side effect is very low with the Sulfadiazine.

b. Agranulocytosis:

It occurs in about 0.1 percent of the patients receiving Sulfonamide therapy. After stopping the use of drug it may take weeks or even months for grannulocytes to return to normal level but supportive therapy hasten the recovery.

c. Aplastic anemia:

Complete bone marrow suppression with profound anemia, granulocytopenia and thrombocytopenia occurs extremely rarely with Sulfonamide therapy. This probably is caused by direct myelosuppresive effect of Sulfonamides and may be fatal.

3. HYPERSENSITIVITY REACTIONS:

Sulfonamides produce variety of hypersensitivity reactions. All Sulfonamides and their derivatives including Carbonic anhydrase inhibitors, Thiazides, Frusemide and Sulfonamide hypoglycemic agents are cross-allergic.

Among hypersensitivity reactions, all types of skin rashes, dermatitis, Steven Johnson syndrome (severe form of erythema multiform) and photosensitivity. Drug eruptions appear after one week of therapy and may occur earlier in sensitive individuals.

Necrosis of liver may be localized or diffused, occur in 0.1 percent patients due to direct sulfonamide sensitization or toxicity. Headache, nausea, vomiting, fever, hepatomegaly, and jaundice have been observed in patients receiving sulfonamide therapy.

4. MISCELLANEOUS REACTIONS:

Anorexia, nausea and vomiting may occur in 1.2% patients treated with sulfa drugs. Drug should not be given to pregnant women near term because drug can pass through placenta and may cause Kerniterus in newborn especially in premature infants due to increased bilirubin accumulation level in the brain.

Also administration of drug in newborns especially in premature infants may displace bilirubin from serum albumin and free bilirubin may deposit in brain causing encephalopathy known as kerniterus. All sulfonamides are secreted in milk, so they are contraindicated in lactating mothers.

DRUG INTERACTIONS:

Sulfonamides can potentiate effects of oral anticoagulants, Sulfonylurea hypoglycemic, hydantoin anticonvulsants by 2 mechanisms.

1. Inhibition of metabolism of these drugs

2. Displacement of these drugs from albumin.

Thus dose adjustment is necessary when Sulfonamides are given in presence of above-mentioned group of drugs.

Compiled By:

“THE PHARMACISTS”

Majid Bashir &

Noshad Akhtar