Sulfacetamide is a

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

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

commonly used in the treatment of bacterial infections, particularly those affecting the eyes and skin. It functions by inhibiting the 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 ...

in bacteria, which is essential for their growth and reproduction, thereby exerting a

bacteriostatic A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfec ...

effect. Available in various forms, including eye drops, topical solutions, and creams, sulfacetamide is often prescribed for conditions such as

conjunctivitis Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...

seborrheic dermatitis Seborrhoeic dermatitis (also spelled seborrheic dermatitis in American English) is a long-term skin disorder. Symptoms include flaky, scaly, greasy, and occasionally itchy and inflamed skin. Areas of the skin rich in sebum, oil-producing gland ...

, and

acne vulgaris Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

. Its efficacy, coupled with a relatively low risk of side effects, makes it a widely utilized agent in both ophthalmic and dermatologic care.

Medical uses

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 infections. 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. 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 Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

and

. When combined with

sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

, it is sold under the brand names Plexion, Clenia, Prascion, and Avar, which contain 10% sulfacetamide and 5% sulfur.

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 In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

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

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 and Erythema multiforme. 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), also known as Lyell's syndrome, 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 f ...

(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 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.

Pharmacology

Mechanisms of action

Sulfacetamide is a sulfonamide

. 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. The Gram stain is ...

and

gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

. It blocks the synthesis of dihydrofolic acid by inhibiting the enzyme

dihydropteroate synthase Dihydropteroate synthase (DHPS) 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 ...

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

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

Pharmacokinetics

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 ...

glucuronic acid Glucuronic acid (GCA, from ) is a uronic acid that was first isolated from urine (hence the name "uronic acid"). It is found in many natural gum, gums such as gum arabic ( 18%), xanthan, and kombucha tea and is important for the metabolism of ...

. However, there are some differences in biotransformation 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.

Chemistry

Structure and chemical properties

These are organic compounds containing an benzenesulfonamide moiety with an

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

group attached to the

benzene Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

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 A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfec ...

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

→ 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 Azo dyes are organic compounds bearing the functional group R−N=N−R′, in which R and R′ are usually aryl and substituted aryl groups. They are a commercially important family of azo compounds, i.e. compounds containing the C−N=N−C l ...

with a second order reaction.

Synthesis

Sulfacetamide is synthesized either by direct alkylation of acetamide with 4-aminobenzenesulfonyl chloride, or by reacting 4-aminobenzenesulfonamide with

acetic anhydride Acetic anhydride, or ethanoic anhydride, is the chemical compound with the chemical formula, formula . Commonly abbreviated , it is one the simplest organic acid anhydride, anhydrides of a carboxylic acid and is widely used in the production of c ...

and subsequent selective, reductive deacylation of the resultant acetamide using a system of zinc-sodium hydroxide.

Research

Sulfacetamide has been investigated for use in the treatment of pityriasis versicolor 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, en ...

. It also has

anti-inflammatory Anti-inflammatory is the property of a substance or treatment that reduces inflammation, fever or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs reduce pain by inhibiting mechan ...

properties when used to treat blepharitis or

(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 lesions, lumps. These are typically painful and break open, r ...

. Sulfacetamide has antibacterial activity and is used to control acne. Products containing sulfacetamide and sulfur (a keratolytic) 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 two-phase materials science, material systems where a gas is dispersed in a second, non-gaseous material, specifically, in which gas cells are enclosed by a distinct liquid or solid material. Note, this source focuses only on liquid ...

s, shampoos,

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 proces ...

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

References

{{Ophthalmological anti-infectives Sulfonamide antibiotics Anti-acne preparations Acetamides Acylsulfonamides 4-Aminophenyl compounds