TETRACYCLINES

Dr. Md. Rageeb Md. Usman

(M. Pharm., Ph.D., FAPP, FICPHS, FSRHCP, FRSH, FSPER)
Associate Professor
Department of Pharmacognosy

Smt. Sharadchandrika Suresh Patil

College of Pharmacy,
Chopda, Maharashtra, India
 Tetracyclines:
-a broad-spectrum antibiotics.

-It is commonly used to treat acne,

infection, and other infections caused by
bacteria.

-The first of these compounds was

chlortetracycline followed by
oxytetracycline and tetracycline.
 Tetracycline divided into:
a) Naturally occurring:

1-tetracycline 2-chlortetracycline

3-oxytetracycline 4-demeclocycline
Semisynthetic occurring:

1-doxycycline 2-minocycline

3-meclocycline 4-lymecycline

5-methacycline 6-rolitetracycline
Total Synthesis of the
Tetracyclines:
 Structure and chemical characteristics

•
Structure activity relationship
•
R5 R4 R3 R2 R1.
Chlortetracycline H H OH CH3 Cl
Oxytetracycline H OH OH CH3 H
Tetracycline H H OH CH3 H
Demethylchlortetracycline H H OR H CI
Rolitetracycline + H OH CH3 H
Metacycline H OH CH2 H
Doxycycline H OH H CH3 H
Minocycline H H H N(CH3)2
• Retention of the configuration of the
asymmetric centres C-4, C-4a and C-12a is
essential, whereas the configurations at C-5,
C-5a and C-6 may be altered:

• 1- The amide hydrogen may be replaced

with a methyl group, but larger groups have
a deleterious effect except for those which
are eliIminated spontaneously in water .
• 2-The dimethyl amino group may be
replaced by a primary amino group
without loss of in vitro activity but all
other changes so far lead to decreased
bacteriostatic action .
• The hydrophobic part of the molecule
from C-5 to C-9 may be altered in
various ways:
• modifications at C-6 and C-7 in
particular afford products having
greater chemical stability.
• increased antibiotic activity and more
favourable pharmacokinetics
• Dehydrogenation to form a double
bond between C-5a and C-11a
markedly decreases activity

• Polar substituents at C-5 and C-6

contribute decreased lipid versus water
solubility to the tetracycline
• . The drugs are amphoteric, meaning
they will form salts with both strong
acids and bases. Thus, they may exist
as salts of sodium or chloride.
 Uses:
-treat cancer patients with SIADH.

-treat hyponatremia.

-combined with hydrocortisone in a paste used

by dentists .

-treat trachoma.
 Side effect:
Dermatological:-Skin reactions, photosensitivity

GIT:-nausea, vomiting, and diarrhea.

CNS:-Dizziness,visualdisturbances .

Immune System:-allergic reactions.

Other:-yellowish-grayish-brown discoloration of the

teeth.
 Pharmacodynamics/Kinetics:
-Absorption: ~50% to 80%.

-Protein binding: 41% to 50%

-Metabolism: Hepatic.

-Half-life elimination: 10-17 hours

-Time to peak, serum: 3-6 hours

-Excretion: Urine
 Side effects:
-Gastrointestinal: anorexia, nausea,
vomiting, diarrhea,
-Skin: rashes, dermatitis.
-Renal Toxicity
-Hepatic Cholestasis:
-Hypersensitivity
Reactions:Anaphylaxis,
Miscellaneous: Dizziness and headache
 Side effects:
-Hypersensitivity reactions:Urticaria,anaphylaxis.

-GI :Anorexia, nausea, vomiting, diarrhea.

-Hepatic toxicity: Hyperbilirubinemia.

-Respiratory:Cough, dyspnea.

-Blood:Agranulocytosis, hemolytic anemia.

-CNS: Convulsions, dizziness,sedation.

-Oral cavity discoloration.