The Sulfa Drugs

L. MEYER JONES.

THE SULFONAMIDES were discovered in 1935. They have been as important in controlling bacterial diseases in animals as in man.

Despite the subsequent introduction of the more effective and less toxic antibiotics, the sulfonamides continue to be widely used in the treatment of certain animal diseases because many domestic animals individually are of low economic value and must be treated as members of a herd or flock. Mass treatment in most instances involves giving the drug in water or ground feed. The sulfonamides possess greater physical and chemical stability than do the antibiotics and are more adaptable to mass treatment in the control of diseases in animals.

The sulfonamides are produced by chemical synthesis, and are stable white powders, which may be mixed in animal feeds or compressed readily into tablets for administration by mouth. They are sparingly soluble in water and in the fluids of the body. The low solubility sometimes leads to difficulty in eliminating the drug in the urine.

Sulfanilamide was the first of the sulfa drugs to be synthesized. It was followed by sulfapyridine, sulfathiazole, sulfadiazine, sulfamerazine, and sulfamethazine. Other sulfonamides--phthalylsulfathiazole and phthalylsulfacetamide have been synthesized for slow release in the digestive tract to control infections. Sulfasoxizole is admirably adapted to treatment of urinary infections because of a broad antibacterial activity and a high solubility in the urinary system.

The sulfonamides inhibit bacterial multiplication during the growth phase. A therapeutic dose of sulfonamide does not kill the micro-organisms but prevents further bacterial multiplication until the body defenses can destroy the invading organisms. Early treatment of an infected animal is therefore necessary if the sulfas are to be effective.

The sulfonamides have little value in treating prolonged sickness, because the body defenses already have been exhausted by the chronic infection and cannot dispose of the invading disease germs. Prolonged use of sulfonamides in a chronic infection tends to make the disease germs more resistant to the drugs.

The sulfonamides must be administered at regular intervals throughout the 24 hours for greatest effectiveness. The objective in sulfonamide therapy is to maintain an antibacterial concentration of sulfonamide continuously in all tissues of the body where the disease germs might multiply.

The sulfonamides are excreted primarily by way of the urine. Large amounts of the poorly absorbed sulfonamides are excreted in the feces. They are excreted also in milk and in bile in concentrations approaching that of the blood stream.

Chronic toxicity from sulfonamides is more important than acute toxicity. The most significant form is kidney toxicity, which occurs after several days of therapy because the kidneys fail to excrete the sulfonamides properly.

The sulfonamides have a low solubility in the body fluids. After filtering out of the blood into the urinary fluid of the kidney, the sulfonamides normally are concentrated five times or more through the reabsorption of water from the filtrate by the kidneys. The sulfonamides may exceed their solubility and precipitate in the urinary system. The tendency for crystallization to occur is increased by the normal reabsorption of the alkali ions by the kidneys, which lowers the acidity of the urine and the solubility of the sulfas.

The needlelike crystals of a precipitated sulfonamide puncture and tear the lining of the kidneys. The crystals may become numerous enough to conglomerate and to form stones, which obstruct the urinary tract. After the obstruction, waste products that normally are eliminated in the urine accumulate in the body. The accumulation of wastes is progressive until it leads to the death of the animal.

Other toxic reactions are noted. In poultry, for example, sulfanilamide causes a hen to lay eggs with soft shells or without shells. Other sulfonamides may not interfere with the formation of shells but will lower egg laying. Large amounts of sulfonamides cause a marked interference with the structure and the function of the nerves to the legs so that walking becomes difficult or impossible. The continuous use of sulfonamides at therapeutic levels suppresses the bacteria in the digestive tract that the animal needs to synthesize certain nutrients.

Sulfonamides may be prescribed for any generalizing disease that is caused by a susceptible organism, if there is no impairment of kidney function that handicaps excretion.

Virus infections are not susceptible to sulfonamides, although secondary bacterial invaders may be.

Water must be available at all times to the patient receiving sulfonamide. If necessary, forced intake of water is indicated to insure a nearly normal consumption. Water is the vehicle for excreting sulfonamides, which will precipitate and block the kidney if there is too little fluid.

Signs of sulfonamide toxicity, especially bloody and frequent urination, must be recognized promptly and the treatment stopped immediately.

Sulfonamides should be administered no longer than absolutely necessary. The maximum period is 4 days. The dose should be decreased soon after the patient shows improvement. Therapy should be stopped 24 to 36 hours after the patient appears vigorous or after the 4-day maximum.

L. MEYER JONES, professor of veterinary pharmacology in Iowa State College, holds degrees of doctor of veterinary medicine from Iowa State College and doctor of philosophy from the University of Minnesota. He is author of a textbook, Veterinary Pharmacology and Therapeutics.