Sulfacetamide is a sulfonamide antibiotic.

Uses

Sulfacetamide 10% topical lotion, sold under the brand name Klaron or Ovace, is approved for the treatment of

acne Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...

and

seborrheic dermatitis Seborrhoeic dermatitis, sometimes inaccurately referred to as seborrhoea, is a long-term skin disorder. Symptoms include red, scaly, greasy, itchy, and inflamed skin. Areas of the skin rich in oil-producing glands are often affected including the ...

. When combined with sulfur, it is sold under the brand names Plexion, Clenia, Prascion, and Avar, which contain 10% sulfacetamide and 5% sulfur. Sulfacetamide has been investigated for use in the treatment of

pityriasis versicolor Pityriasis commonly refers to flaking (or scaling) of the skin. The word comes from the Greek πίτυρον "bran". Classification Types include: * Pityriasis alba * Pityriasis lichenoides chronica * Pityriasis lichenoides et varioliformis ac ...

and

rosacea Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, enlarg ...

. It also has

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as o ...

properties when used to treat blepharitis or

conjunctivitis Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The ...

(in eye-drop solution). It is believed to work by limiting the presence of folic acid which bacteria need to survive. It has been suggested that sulfacetamide may also serve as a treatment for mild forms of

hidradenitis suppurativa Hidradenitis suppurativa (HS), sometimes known as acne inversa or Verneuil's disease, is a long-term dermatological condition characterized by the occurrence of inflamed and swollen lumps. These are typically painful and break open, releasing ...

. Sulfacetamide has antibacterial activity and is used to control acne. Products containing sulfacetamide and sulfur (a

keratolytic Keratolytic () therapy is a type of medical treatment to remove warts, calluses and other lesions in which the epidermis produces excess skin. In this therapy, acidic topical medicines, such as Whitfield's ointment or Jessner's solution, are ap ...

) are commonly promoted for the treatment of acne rosacea (rosacea with papules, pustules, or both). There are several prescription topical products containing sulfacetamide, such as

foam Foams are materials formed by trapping pockets of gas in a liquid or solid. A bath sponge and the head on a glass of beer are examples of foams. In most foams, the volume of gas is large, with thin films of liquid or solid separating the ...

shampoo Shampoo () is a hair care product, typically in the form of a Viscosity, viscous liquid, that is used for cleaning hair. Less commonly, shampoo is available in solid bar format. Shampoo is used by applying it to wet hair, massaging the product ...

cream Cream is a dairy product composed of the higher-fat layer skimmed from the top of milk before homogenization. In un-homogenized milk, the fat, which is less dense, eventually rises to the top. In the industrial production of cream, this process ...

and washes. Some research indicates that sulfacetamide derivatives may act as antifungals by an CYP51A1-independent mechanism.

Structure and chemical properties

These are organic compounds containing an benzenesulfonamide moiety with an

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

group attached to the

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...

ring. The molecular formula is C₈H₁₀N₂O₃S. Its scientific name is N-(4-aminophenyl)sulfonylacetamide. At room temperature, it appears as a white powder.

Degradation reactions and stability

Sulfacetamide is stable under normal temperatures and pressures. No dangerous reactions occur under known conditions of normal use. It is an important bacteriostatic agent that is commonly used in human and veterinary medicine. Therefore it can accumulate in the environment (mostly surface water). It has a long lifetime in the environment so different degradation reactions are researched: The photocatalytic degradation of sulfacetamide in water solutions during illumination of UV radiation with TiO₂ was examined. It was found that sulfacetamide is resistant to

biodegradation Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegrada ...

and that it is toxic to the green alga ''

Chlorella vulgaris ''Chlorella vulgaris'' is a species of green microalga in the division Chlorophyta. It is mainly used as a dietary supplement or protein-rich food additive in Japan. Description ''C. vulgaris'' is a green eukaryotic microalga in the genus ...

''. It undergoes photocatalytic degradation and the toxicity of the intermediate products is significantly lower than the initial toxicity. The intermediates can be mineralized in contrast to sulfacetamide. Sulfonamide → organic intermediate products (degradation) (in presence of OH⁻). Sul2

At higher temperatures sulfacetamide solutions degrade to its hydrolysed product, sulphanilamide with a first-order rate constant. Also oxidation of sulfacetamide by in an aqueous alkaline medium can occur. Copper(III) is used, as it is involved in many biological electron transfer reactions. The sulphanilamide can oxidise to a blue product with a first order reaction and it can form azo dye with a second order reaction.

Available forms

Sulfacetamide as a medicine is available as solution, eye drops, lotion, and powder. It can also be found in the form of the sodium

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

, sulfacetamide sodium. It is available in fixed-dose combinations with prednisolone.

Mechanisms of action

Sulfacetamide is a sulfonamide antibiotic. Sulfonamides are synthetic bacteriostatic antibiotics, that are active against

gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

and

gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

. It blocks the synthesis of dihydrofolic acid by inhibiting 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 antibiotics, which compete with the PA ...

. It is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA). PABA is required for 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 and ...

and it is an essential component for bacterial growth. The multiplication of bacteria is therefore inhibited by the action of sulfacetamide.

Biotransformation

Sulfacetamide is absorbed orally. The oral absorption of sulfacetamide is found to be 100% and the plasma protein binding is 80–85%. In the liver it is metabolized to inactive metabolites. Plasma half-life is 7 – 12.8 hours. Sulfonamides are usually metabolized by several oxidative pathways, acetylation, and conjugation with

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

or glucuronic acid. However, there are some differences in

biotransformation Biotransformation is the biochemical modification of one chemical compound or a mixture of chemical compounds. Biotransformations can be conducted with whole cells, their lysates, or purified enzymes. Increasingly, biotransformations are effected w ...

between certain species. Acetylation, which reduces the solubility of sulfonamides, is for example poor developed in dogs. The acetylated, hydroxylated, and conjugated forms have little antibacterial activity. Furthermore, the hydroxylated and conjugated forms are less likely to precipitate in urine. The hydrolysis takes place by the action of amidases. It is excreted primarily in the urine. Secretory routes of less significance are bile, feces, milk and sweat. Glomerular filtration, active tubular secretion, and tubular reabsorption are the main processes involved.

Efficacy

Sulfacetamide is a sulfonamide antibiotic, that is used as a cream to treat skin infections and as eye drops to treat eye infections. On the skin it is used to treat acne and

. In cream form it is used to treat bacterial infections on the skin. It can also be used orally to treat

urinary tract infection 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 kidne ...

s. It kills the bacteria by restricting the production of folic acid, which is essential for bacterial growth. It mainly inhibits the multiplication of bacteria as it acts in a competitive inhibitor.

Side effects

The most common side effects are irritation, stinging or burning of the skin. Other side effects include nausea, vomiting, dizziness, tiredness and headache. There are however also severe side effects including severe allergic reactions, like (nettle) rash, itch, tightness in chest, difficult breathing and swelling in either the face, mouth, lips or tongue. Other severe side effects include bloody or severe diarrhea, fever, joint pain, red, blistered or swollen skin and stomach pain. In the eye, it can cause

. There are also life-threatening conditions which can be produced by the antibiotic, like

Stevens Johnson syndrome Stevens may refer to: People * Stevens (surname), including a list of people with the surname Given name * Stevens Baker (1791–1868), farmer and member of the Legislative Assembly of Lower Canada * Stevens T. Mason (1811–1843), territorial g ...

and

Erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in th ...

. Higher exposure can also cause unconsciousness. One case showed that sulfacetamide eyedrops can very rarely cause life-threatening skin condition

toxic epidermal necrolysis Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later ...

(TEN). These are however not all side effects. For more information the health care provider can be contacted. Sulfacetamide should not be used by individuals who have a sensitivity to sulfur or sulfa.

Toxicity

The acute oral toxicity (LD₅₀) in a mouse is 16.5 g/kg. As this falls within Toxicity Category IV of the

toxicity category rating In , the EPA established four Toxicity Categories for acute hazards of pesticide products, with "Category I" being the highest toxicity category ( toxicity class). Most human hazard, precautionary statements, and human personal protective equipme ...

for oral administration, it is practically non-toxic and also not an irritant when taken in orally. However, it is very hazardous in case of skin contact (irritant), ingestion and inhalation. Research proved that it is more toxic in the presence of light than in the dark. Sulfacetamide is slightly irritant when UV-A light is present. In the presence of light sulfacetamide gets sensitized and degraded which might cause irritation which will lead to toxicity when it is used continuously. In the dark only slight irritation has been shown. Therefore it should be stored in the dark. There are no known carcinogenic and mutagenic effects. It has a moderate toxicity according to the Chemwatch hazard ratings.

First aid measures

First aid measures:

Effects on organisms

Sulfonamides are generally effective against most gram-positive and many gram-negative organisms. Specifically enteric bacteria and other eubacteria are affected by the antibiotic as it kills the bacteria by restricting the production of folic acid, which is essential for their growth. However strains of bacteria can be resistant to the antibiotic. If a bacterium is resistant to a sulfonamide, it is resistant to all the forms. Furthermore, sulfacetamide is toxic to soil organisms.

Synthesis

Sulfacetamide is synthesized either by direct alkylation of

acetamide Acetamide (systematic name: ethanamide) is an organic compound with the formula CH3CONH2. It is the simplest amide derived from acetic acid. It finds some use as a plasticizer and as an industrial solvent. The related compound ''N'',''N''-dimet ...

with 4-aminobenzenesulfonyl chloride, or by reacting 4-aminobenzenesulfonamide with acetic anhydride and subsequent selective, reductive deacylation of the resultant acetamide using a system of zinc-sodium hydroxide.

References

{{SulfonamideAntiBiotics Sulfonamide antibiotics Anti-acne preparations Acetamides