Sulphonamides

Sulphonamides are the antimicrobial compoundings containing a sulphonamides group (-SO2NH2) and are the derivatives of sulphanilamide

Classification:-

    Chemotherapeutic agents that are contain -SO2NH3 (sulpamoyl) groups, can be placed into two groups.

A)  Synthetic antibacterial sulphonamides which are called as sulpha drugs.

B)  Non-antibacterial sulphonamides-

eg. a) Diuretics - Frusemide, Clorothiazole, Hedroclorothiazole.

             b) Hypoglycemic agent - eg. Clorpamide, tolbutamide.

1)  The synthetic antibacterial sulphonamides can be grouped as follows

   a) Sulphanilamide (aniline substituted) derivatives

eg. Sulphadiazine, sulphaguanide.

   b) Prodrugs that produce sulphanilamide in viva.

eg. sulphadiazine.

   c) Non-anilides ( non-aniline) sulphonamides. 

eg. Mefenide.

2) Chemical classification -

  1) N1- substituted sulphonamides

       a) With acyclic substituents

eg. Sulphacetamide, sulphaguanidine

       b) With heterocyclic substituents

eg. Sulphadiazine, sulphamethoxazole, sulphadiamethoxine, sulphamethoxypyridazine.

 2) N4 - substituted sulphonamides

eg. sulphasalazine

3) sulponamides with both N1 and N4 substituents

eg. phthalylsulphathiazole, succinylsulphathiazole.

3) Classification depending upon their therapeutic uses

  a) sulphonamides used for systemic infections-

   !) Those used in urinary tract infection

eg. sulphamethoxazole, sulpacetamide.

   !!) Those used in respiratory tract infection.

eg. cotrimoxazole, sulphadiazine.

   !!!) Those used in menimgeal infection

eg. Sulphadiazine.

b) Suphonamides used for local infection

!) Those used for intestinal infections

eg. sulphaguanidine, phthalylsulphathiazole, succinylsulphathiazole.

!!) Those used for opthalmic infection

eg. sulphacetamide.

!!!) Those used in burn therapy

eg. mefenide, silver sulphadiazine

Chemistry and nomenclature of sulpha drugs

    The general term 'sulpha drugs' or ' sulphonamides' has been used for antimicrobial agent. It is restricted to N- substituted derivatives of the parent substance sulphanilamide ( p-amino benzene sulphonamide) in which one hydrogen atom of sulphamoyl group ( -SO2NH2) is replaced by various substituents.

PABA-    P-amino benzoic acid

Physical properties of sulpha drugs:

They are white or yellowish white crystalline powder

They are odourless and very slightly soluble in water but soluble in aqueous alkali hydroxide solution and dilute mineral acid.

Taste--   eg. sulphadiazine, sulphaguanidine, sulphadimethoxine.

Acidic and saline taste - eg. Sulphacetamide.

Slightly bitter taste - eg. phthalylsulphathiazole, succinylsulphathiazole                                sulphamethoxypyridine

Bitter after taste- eg.sulphamethoxazole.

Stability and storage of sulpha drugs :

   They are affected by heat and light and the presence of air and moisture accelerates the effect. hence they are stored in tightly closed, light resistance containers.

1) Sulphadiazine -

2-(p-aminobenzenesulphanamido) pyrimidine

                         Or

2- sulphanilamido pyrimidine

                         Or

N1( pyrimidine- 2- yl ) sulphanilamide

Chemical properties :

1) Diazotisationrection:

when sulphadiazine is treated with sodium diazotisation giving diazo compound.

                                                             

a) NaNO2 + HCl

p -  pyrimid - 2 -yl amino sulphonyl benzene diazoniumcloride.

thisrection is used for its assay.

when sulphadiazine is dissolved in 0.1 N sodium hydroxide and to this 1% copper sulphate solution is added purple browencolouredppt is obtained. This is the teste for identification.

Uses::

It has an antibaccterial activity hence it is used in treatment of:

1.Meningitis

2.Urinary tract infection

3.Toxoplasmosis combination with pyrimethanamine.

3.Its silver salts silver sulphadiazine is used topically in the treatment of burn therapy.

Pharmaceutical preparation :

1.      Sulphadiazine tablets

2.      Sulphadiazine injection or sulphadiazine sodium injection

3.      Trisulphapyrimidine tablets           

Brand name:

Atrina , cotrizine , trimozine.

2)  Sulphaguanidine :

    Structure:

Chemical name :

                N-(p - aminobenzenesulphonyl )guanme guanidine monohydrate or 1- ( 4 - aminobenzenesulphonyl ) guanidine monohydrate or N1 - amino sulphanilamide monohydrate.

Chemical Properties :

   1. When sulphaguanidine is treated with sodium nitrite in presence of conc. hydrocloride acid at 0* C to 10* C diazotisationrectionoccures in which aromatic primery amino group is converted into diazo group.

p - ( guanidinesulphonyl ) benzene diazonium cloride

 2. As under sulphadiazine it gives blue coloured precipitate.

This test for identification.

Uses:

        It is antibacterial and it is poorly absorbed through gastrointestinal tract. Hence it is used in the treatment of local intestinal infections like bacillary dysentry.

Pharmaceutical Preparation :

1.Sulphaguanidine tablet.

2. Sulphadiazine injection or sulphadizine sodium injection.

Brand name:

Ganidan , Guanimycine , Entrogen.

3. Phthalylsulphathiazole:

Chemical Properties :

     1. Aromatic amino group is substituted and hence the compound is hydrolysed by boiling with sodium hydroxide to get primary aromatic amino group and then the diazotisationrection is done as discussed in sulphadiazine.

 2.  Refer chemical property no.2 under sulphadiazine :: green colouredppt is obtained.

3.  when phthalylsulphathiazole is heated for 1 min with resorcinol and in aq. NaOH solution a distinct green fluorenscence is produced which dissapear when the solution is acidifide

Uses :

     It is antibacterial and is not absorbed through G.I tract hence it is used in

     !) in the treatment of bacillary dysentry

      !!) to reduce bacterial flora of the large intestine before surgery

Pharmaceutical preparation :

        1.  Phthalylsulphathiazole tablets

Brand Name :    colicitina ,   Talidine

4.Succinylsulphathiazole:

                                                 It differs from phthalylsulphathiazole, in having N4 - succinyl (- co - ch2- ch2 - cooh ) group instead of N4 - phthalyl group.

Uses :: as under phthalylsulphathiazole

Pharmaceutical preparation :

  Succinylsulphathiazole tablet

Brand name ::

Bensulpha , Sulphadren , K- prim.

5: Sulphadimethoxin  --

In this -H of sulphamoyl group is replaces by 2,6-dimethoxy pyramidin—4- ylhetrocycle.

Chemical properties::

1.      Due to presence of free primary aromatic amino group, it gives diazotisation reaction described under sulphadiazine.

2.      Refer chemical property no. 2 under sulphadiazine, gives yellowish green reaction put.

Uses ::                       

It is long acting antimicrobial agent and it is used in the treatment of urinary track infection.

Pharmaceutical preparation::

Sulphadimethoxine tablets

Brand name :: bensulpha, sulphadren, k-prim.

6. Sulphamethoxypyridazine ::

In this ,  substituent present at sulphamoyl nitrogen is

6-methoxy – pyridazin -3 – yl.

Chemical properties::

1.      See chemical property no. 1 as under sulphadiamethoxin.

2.      Refer chemical property no 2 as under sulphadiazine. Gives greenish brown pot.

Uses::

As under sulphadiamethoxine.

Pharmaceutical preparation::

Sulphamethoxypyridazine tablets.

Brand name::

Dyrasul, Confin.

7.Contrimozole:

CO-trimoxazole is a mixture of 5 parts of sulphamethoxazole and I part of trimethoprim.

The two components of co-trimoxazole interfere with the blphamethoxazole and I part of trimethoprim.

The two components of co-trimoxazole interfere with the bacterial synthesis of acterial synthesis of tetrahytetrahydrofolic acid whdrofolic acid which is an essential stage in the production of nucleic acids. Sulphamethoxazole inhibits the synthesis of dihydrofolic acid from PABA and trimethoprim inhibits the action of dihydrofolite reductase and prevents the synthesis of tetrahydrofolic acid from dihydrofolic acid.

Sulphamethoxazole

1)     It is a sulphanilamide derivative.

2)     It is a white crystalline powder.

3)     It is odourless and has bitter taste.

4)     It is very slightly in water.

Trimethoprism

1)     It is a pyrimidine derivative.

2)     It is a white to yellowish powder.

3)     It is odourless and has bitter taste.

4)     It is very slightly soluble in water.

Uses of CO-trimozole

1)     Genito urinary tract infections.

2)     Respiratory tract infections like bronchitis pneumonia

3)     Meningitis

4)     Enteric infections like typhoid and paratyphoid.

Storage-

 It should be stored in well closed light resistant container.

Official preparation

1)     Co-trimoxazole tablet.

2)     CO-trimoxazole injection.

3)     Dispersible Co-trimoxazole tablet.

4)     Paediatric Co-trimoxazole tablet.

5)     Paediatric Co-trimoxazole mixture.

Brand names

Ciplin-Ds, Septran, Bacterin-Ds

                 

8.Sulphacetamide                                           

It is N acetyl derivatives of p –aminobenzene sulphonamide

Chemical name

 N1 – acetyl p – aminobenzine sulphonamide.

Structure   

Properties

1.      It occurs as a white crystalline powder.

2.      It is soluble in water and alcohol.

3.      Aqueous solutions are acidic to litmus.

4.      It has saline taste.

Uses

It is an antibacterial hence it is used

1.      It is used to treat eye infections.

2.      It is used to treat urinary tract infection.

Pharmaceutical preparation

1.      Sulphacetamide eye drops.

2.      Sulphacetamide eye ointment.

3.      Sulphacetamide tablet.

Brand name

albucid , sulamyd.