Sulphonamides

Subodh Dhakal

Sulphonamides

• The first clinically important derivative was prontosil which was a prodrug.
• Prontosil can be metabolized to sulphonamide in vivo.

Definition

• Sulphonamides are the compounds that contain –SO₂NH₂ (sulphamoyl group).
• These are the derivatives of sulphanilamide.

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• Sulphonamides are the structural analogue of para amino benzoic acid (PABA).

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Classification

1. N₁ substituted sulphonamide
• With acyclic substituent: Sulphacetamide, sulphaguanidine
• With heterocyclic substituent: Sulphadiazine, Sulphamethoxazole, Sulphadimethoxine
2. N₄ substituted sulphonamide: Sulphasalazine
3. Sulphonamide with N₁ and N₄ substituent: phthalyl sulphathiazole, succinyl sulphathiazole

Sulphaguanidine

Chemistry

• It is the derivative of sulphanilamide.
• The structure consist of guanidino group.
• The structure also contains para amino benzene group.

Physical properties

• It occurs as white crystalline powder.
• It is odorless.
• It possess slightly bitter taste.
• Its melting point is 190-193 ºC.
• It is slightly soluble in water. Solubility: 1g/1000ml It is also slightly soluble in ethanol or acetone and easily soluble in dilute hydrochloric acid.

Note: Solubility Classification as per Indian Pharmacopoeia

Stability/Storage

• It slowly darkens on exposure to light hence it is stored in well closed light resistant container.

Uses

• In veterinary, it can be used for enteric fever.
• It is poorly absorbed through the GI tract, hence it is used in the treatment of local intestinal infection.

Sulfadiazine*

• Chemistry
• It is the derivative of sulfanilamide.
• H atom of N1 is replaced by pyrimidine group.
• Physical properties
• It occurs as white or slightly yellow crystalline powder.
• It is odorless.
• It is tasteless or has slightly bitter taste.
• It is insoluble in water and alcohol but soluble in mineral acids and solution of alkali hydroxide.
• Its melting point is 252-256 degree celsius.
• It is affected by heat and light.

Stability/Storage

• It darkens on exposure to light. In presence of air and moisture, activity of light is accelerated. Hence it should be stored in tightly closed light resistant container.

Uses

• Pneumococcal infection
• Meningococcal infection
• UTI
• Bacillary dysentery
• Prophylaxis of Malaria

Silver sulfadiazine*

• Chemistry
• It is the derivative of sulfanilamide.
• H atoms of N1 are replaced by Silver cation and pyrimidine group.
• Physical properties
• It is white to creamy white crystalline powder.
• It is odorless or possesses slight odor.
• It is stable in air but turns yellow on exposure to light.
• It is insoluble in water. It is practically insoluble in alcohol. It is freely soluble in 30% ammonium solution.
• Its melting point is 285 °C,

Stablity/Storage

• Since it is sensitive to light, it should be stored in well closed containers protected from light.

Uses

• Burn wound infections

Cotrimoxazole

• It is the mixture of 5 parts of Sulphamethoxazle and 1 part of trimethoprim

Chemistry

Sulphamethoxazole:

• It is the derivative of sulfanilamide.
• 5-methyl oxazole group is attached as position N1.

Trimethoprim:

• It is the pyrimidine derivative.
• Two amino groups are present at position 2 and 4.
• Trimethoxy benzyl group is attached at position 5.

Physical properties

Sulphamethoxazole

• It occurs as white crystalline powder.
• It is odorless.
• It has bitter taste.
• It is very slightly soluble in water.
• Its melting point is 169 °C

Trimethoprim

• It is white to yellowish white crystalline powder.
• It is odorless.
• It has very bitter taste.
• It is very slightly soluble in water, slightly soluble in alcohol.
• Its melting point is 199-203ºC.

Storage

• On exposure to light, cotrimoxazole becomes discolored. So it should be stored in a well closed light resistant container.

Uses

• Chronic bronchitis
• Urinary tract infection
• Bacterial meningitis
• Pneumonia
• Sepsis
• Shigellosis (infection caused by Shigella bacterium)
• Traveller’s Diarrhea
• Acne vulgaris (off label)

Note

• Off label
• Off-label" means the medication is being used in a manner not specified in the FDA's approved packaging label, or insert.

Sulfacetamide*

Chemistry

• It is the derivative of sulfanilamide.
• Acetyl group is present at N1

Physical properties

• It occurs as white or yellowish white crystalline powder.
• It is odorless.
• It has characteristic sour taste.
• It is slightly soluble in water; soluble in alcohol.
• Its aqueous solution is sensitive to light.
• Its melting point is 182-184 degree celsius.

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• Stability/Storage
• It should be stored in well closed container protected from light.
• Uses
• Conjunctivitis
• Trachoma (infectious disease caused by Chlamydia trachomatis)
• Acne vulgaris
• Seborrheic Dermatitis