Tetracycline hydrochloride is also available in ointments for topical and ophthalmic administration. A topical solution is used for the management of acne vulgaris.

Oxytetracycline Hydrochloride

Oxytetracycline hydrochloride is a pale yellow, bitter, crystalline compound. The amphoteric base is only slightly soluble in water and slightly soluble in alcohol. It is odorless and stable in air but darkens on exposure to strong sunlight

The hydrochloride salt is a stable yellow powder that is more bitter than the free base. It is much more soluble in water, 1 g dissolving in 2 mL, and more soluble in alcohol than the free base. Both compounds are inactivated rapidly by alkali hydroxides and by acid solutions below pH 2. Both forms of oxytetracycline are absorbed rapidly and equally well from the digestive tract, so the only real advantage the free base offers over the hydrochloride salt is that it is less bitter. Oxytetracycline hydrochloride is also used for parenteral administration (intravenously and intramuscularly).

Doxycycline A more recent addition to the tetracycline group of antibiotics available for antibacterial therapy is doxycycline, α-6-deoxy-5-oxytetracycline.

Absence of the 6-hydroxyl group produces a compound that is very stable in acids and bases and that has a long biological half-life. In addition, it is absorbed very well from the GI tract, thus allowing a smaller dose to be administered.

High tissue levels are obtained with it, and unlike other tetracyclines, doxycycline apparently does not accumulate in patients with impaired renal function. Therefore, it is preferred for uremic patients with infections outside the urinary tract. Its low renal clearance may limit its effectiveness, however, in urinary tract infections.

Doxycycline is available as a hydrate salt, a hydrochloride salt solvated as the hemiethanolate hemihydrate, and a monohydrate. The hydrate form is sparingly soluble in water and is used in a capsule; the monohydrate is water insoluble and is used for aqueous suspensions, which are stable for up to 2 weeks when kept in a cool place.

UNCLASSIFIED ANTIBIOTICS

Among the many hundreds of antibiotics that have been evaluated for activity, several have gained significant clinical attention but do not fall into any of the previously considered groups. Some of these have quite specific activities against a narrow spectrum of microorganisms. Some have found a useful place in therapy as substitute.

\\ Chloramphenicol The first of the widely used broad-spectrum antibiotics, chloramphenicol (Chloromycetin, Amphicol).

Chloramphenicol is a white, crystalline compound that is very stable. It is very soluble in alcohol and other polar organic solvents but only slightly soluble in water. It has no odor but has a very bitter taste. Chloramphenicol possesses two chiral carbon atoms in the acylamidopropanediol chain. Biological activity resides almost exclusively in the D-threo isomer; the L-threo and the D- and L-erythro isomers are virtually inactive.

Chloramphenicol is very stable in the bulk state and in solid dosage forms. In solution, however, it slowly undergoes various hydrolytic and light-induced reactions. The rates of these reactions depend on pH, heat, and light. Hydrolytic reactions include general acid–base-catalyzed hydrolysis of the amide to give 1-(p-nitrophenyl)-2-aminopropan- 1,3-diol and dichloroacetic acid and alkaline hydrolysis (above pH 7) of the α-chloro groups to form the corresponding α,α-dihydroxy derivative.

Metabolism of chloramphenicol

The metabolism of chloramphenicol has been investigated thoroughly. The main path involves formation of the 3-O-glucuronide. Minor reactions include reduction of the p-nitro group to the aromatic amine, hydrolysis of the amide, and hydrolysis of the α- chloracetamido group, followed.by reduction to give the corresponding α-hydroxyacetyl derivative.

Resistant

Strains of certain bacterial species are resistant to chloramphenicol by virtue of the ability to produce chloramphenicol acetyltransferase, an enzyme that acetylates the hydroxy groups at the positions 1 and 3. Both the 3-acetoxy and the 1,3-diacetoxy metabolites lack antibacterial activity.

SAR