Sulfadimethoxine (or sulphadimethoxine, trade names Di-Methox or Albon) is a long-lasting

sulfonamide In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactiv ...

antimicrobial medication used in veterinary medicine. It is used to treat many infections, including respiratory, urinary tract, enteric, and soft tissue infections and can be given as a standalone or combined with ormetoprim to broaden the target range. Like all sulfamides, sulfadimethoxine inhibits bacterial synthesis of

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing a ...

by acting as a competitive inhibitor against PABA. It is the most common drug prescribed to dogs who have

coccidiosis Coccidiosis is a parasitic disease of the intestinal tract of animals caused by coccidian protozoa. The disease spreads from one animal to another by contact with infected feces or ingestion of infected tissue. Diarrhea, which may become bloody ...

Mechanism

Like other sulfonamides, sulfadimethoxine is a

dihydropteroate synthase inhibitor Dihydropteroate synthase inhibitors are drugs that inhibit the action of dihydropteroate synthase. They include Sulfonamide (medicine), sulfonamides, dapsone, and para-aminosalicylic acid. In bacterium, bacteria, antibacterial sulfonamides act a ...

. Bacteria and some protozoa are unable to obtain

from the environment, and must instead synthesize it by converting PABA ( ''para''-aminobenzoate) to dihydropteroate using the enzyme

dihydropteroate synthase Dihydropteroate synthase is an enzyme classified under . It produces dihydropteroate in bacteria, but it is not expressed in most eukaryotes including humans. This makes it a useful target for sulfonamide In organic chemistry, the sulfona ...

. Sulfonamides act as a

competitive inhibitor Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected b ...

; being structurally similar to PABA, they are able to bind to the enzyme's active site and prevent the synthesis of folic acid from progressing. Folic acid is necessary for these organisms to produce nucleic acids (i.e. DNA and

RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...

), which are required for cell division. Thus, it has a microbiostatic effect rather than a microbiocidal one (it prevents pathogen growth rather than killing them), and has the strongest effect in the beginning stages of an infection, when the pathogen is rapidly dividing. Since it is microbiostatic, sulfadimethoxine still requires the animal to still be able to mount an

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

to kill the pathogen.

With ormetoprim

Sulfadimethoxine can either be given alone (such as under the commercial name Albon) or in combination with ormetoprim to as a "potentiated sulfonamide" to increase antimicrobial activity. Ormetoprim is a diaminopyridine, inhibiting

dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. ...

, which is further along the pathway for synthesizing folic acid. Though the optimum ratio of sulfadimethoxine to ormetoprim has been found to be 20:1, it is sold pharmaceutically as a 5:1 mixture.

Pharmacokinetics

Sulfadimethoxine, like all sulfonamides, diffuses easily when it is in its unionized, lipid-soluble form, and easily reaches many tissues. The relative amounts are determined by both its pKa and by the pH of each tissue. Therefore, levels tend to be higher in less acidic tissue and body fluids or in diseased tissues having high concentrations of

leucocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multi ...

. Its ability to bind to plasma proteins is very high, leading sulfadimethoxine to maintain higher blood levels than most other long-acting sulfonamides. Comparatively low doses can give rapid and sustained therapeutic blood levels. Most animals for which sulfadimethoxine is marketed acetylate sulfadimethoxine in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

to form acetylsulfadimethoxine, which is secreted in the

bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver b ...

. Dogs are the exception – since they are unable acetylate sulfonamides, they excrete sulfadimethoxine mostly unchanged in the urine (their inability to transform sulfadimethoxine also makes them more susceptible to negative side effects). Sulfadimethoxine has a relatively high solubility at the pH normally occurring in the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

s, and is easily reabsorbed into the

renal tubules The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a Nephron#Renal tubule, renal tubule. The renal corpuscle consists of a tuft of capillary, capillaries called a glomeru ...

, adding to its long half-life. The use of sulfadimethoxine raises concerns that it will precipitate in the kidneys, leading to

crystalluria Crystalluria refers to crystals found in the urine when performing a urine test. Crystalluria is considered often as a benign condition and as one of the side effects of sulfonamides and penicillins. The main reason for the identification of urin ...

. Though crystallization is not actually a common occurrence in veterinary medicine, it can be avoided entirely by adding a diaminopyrimidine such as ormetoprim. Having the animal stay well-hydrated also is advised.

Usage

Sulfadimethoxine is the only FDA-approved drug for treating intestinal coccidioisis in cats and dogs. It is also used for: *Treating skin and soft-tissue infections in dogs caused by ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...

'' or '' E. coli'' *Treating cattle for bovine respiratory disease complex ("shipping fever complex"), necrotic pododermatitis (foot rot), pneumonia when caused by ''

Pasteurella __NOTOC__ ''Pasteurella'' is a genus of Gram-negative, facultatively anaerobic bacteria. ''Pasteurella'' species are nonmotile and pleomorphic, and often exhibit bipolar staining ("safety pin" appearance). Most species are catalase- and oxidase- ...

'', and calf diphtheria caused by ''

Fusobacterium necrophorum ''Fusobacterium necrophorum'' is a species of bacteria responsible for Lemierre's syndrome and other medical problems. Biology ''F. necrophorum'' is a rod-shaped species of Gram-negative bacteria. It is an obligate anaerobe and is a common inha ...

'' *When combined with ormetoprim: **Treating soft tissue infections, skin infections,

urinary tract infections A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney ...

, and intestinal coccidia infections in dogs **Prevention of fowl cholera and coccidioisis by ''

Eimeria ''Eimeria'' is a genus of apicomplexan parasites that includes various species capable of causing the disease coccidiosis in animals such as cattle, poultry and smaller ruminants including sheep and goats. ''Eimeria'' species are considered to be ...

'' in poultry **Treating salmon and trout for furunculosis It is also one of the only sulfonamides allowed for treating lactating dairy cattle (the others being sulfabromethazine and sulfathoxypyridazine).

Notes

{{Sulfonamides and trimethoprim Sulfonamide antibiotics Pyrimidines Veterinary drugs