Tetracyclines are a class of broad-spectrum antibiotic drugs derived from soil actinomycetes. They work by inhibiting bacterial protein synthesis and have activity against many gram-positive and gram-negative bacteria. Common adverse effects include gastrointestinal upset, tooth discoloration in children, and risk of liver toxicity or nephrotoxicity in high doses. Tetracyclines have a wide range of clinical uses including treatment of respiratory infections, urinary tract infections, and certain other bacterial infections.

1. Tetracyclines
AMIR SOHAIL

2. Tetracyclines
• History
• Chemistry
• Classification
• Mechanism of action
• Spectrum of activity
• Bacterial Resistance
• Pharmacokinetics
• Adverse Effects
• Clinical uses

3. History:
• Broad spectrum antibiotics
• Naturally from soil actinomycetes or
prepared semi-synthetically
• In 1948, first member introduced was
chlortetracycline derived from soil
actinomycetes streptomyces aureofacens
• Followed by oxytetracycline.

4. • Removal of chlorine atom from
chlortetracycline produced semi-synthetic
tetracycline introduced in 1952.
• Semisynthetic are methacycline,
doxycycline, rolitetracycline etc.
• Doxycycline and minocycline are newer
tetracyclines with high lipid solubility and
longer duration of action.

5. Chemistry
• The basic tetracycline structure consists of
four benzene rings with various
constituents on each ring.
(Naphthacenecarboxamide Nucleus)
• The crystalline bases are faintly yellow,
odorless, slightly bitter compounds. They
are only slightly soluble in water at pH 7
but they can form soluble sodium and
hydrochloride salts .

7. Other Properties:
• Acidic
• Hygroscopic
• In aqueous solution form salts with both acids
and bases.
• Stable as powder, aqueous solutions are not
stable
• Available in injections, bolus, capsules, powder,
feed additives, ointments.

8. Classification:
Short acting: t1/2=<8 hrs.
• Oxytetracycline, tetracycline,
chlortetracycline
Intermediate acting:t1/2=8-16 hrs.
• Demeclocycline, methacycline
Long acting:t1/2= >16 hrs.
• Doxycycline, minocycline

10. Mechanism of Action:
• Inhibit bacterial protein synthesis
• Two steps
1.Passage into bacterial cell
2. Interaction with bacterial ribosomes.
Tetracycline bind to the 30 S ribosomal
subunit and prevent the binding/access of
aminoacyl t-RNA to acceptor (A) site on
the mRNA-ribosome complex.This
prevents addition of amino acids to the
growing peptide chain resulting in

11. Tetracyclines binds to the 30S ribosomal subunit, thus
preventing the binding of aminoacyl-tRNA
to the ribosome. aa = amino acid.

12. Antimicrobial Spectrum:
• Bacteriostatic
• Broad spectrum
• Active against mycoplasma, rickettsia,
chlamydia, and some protozoa like
anaplasma, amoebae etc.
• Pseudomonas, aeruginosa, proteus,
klebsiella, salmonella, staph.,
corynebacterium are resistant.

13. Typical therapeutic applications of tetracyclines.

14. Microbial resistance:
• Decrease penetration of drug
• Increased activity of efflux pumps
• Enzymatic inactivation of drug
• Production of proteins by bacteria that
protect ribosomes by binding with
tetracyclines

15. Pharmacokinetics:
Absorption:
• Minocycline and doxycycline being 100%
bio available.
• All produce varying degree of tissue
irritation on parenteral administration.

16. • All tetracyclines are adequately but
incompletely absorbed from the G.I. tract.
• The % of an oral dose that is absorbed
(when the stomach is empty) is lowest for
chlortetracycline (30%) and highest for
minocycline (~98-100%).
• Most absorption takes place from the
stomach and upper small intestine (greater
in a fasting state).

17. • Absorption of tetracyclines is impaired by
food in the stomach, milk products,
aluminum OH gels, Na+ bicarbonate,
Ca++ & Mg++, and Fe++ preparations.
• Thus milk,antacids or iron salts should be
avoided 3 hrs before and after oral
administration.

18. • After a single oral dose peak plasma
concentrations are achieved in 2-4 hours.
• The mechanisms responsible for
decreased absorption appear to be
chelation.

19. • CSF levels are 10 -20% of the serum
levels.
• Tetracyclines are stored in the
reticuloendothelial cells of liver, spleen, &
bone marrow
• They can cross the placental barrier and
can accumulate in fetal bones, thus
delaying bone growth. They are also
excreted in breast milk.
• Binding action with Ca++ is the result of

20. Effect of antacids and milk on the absorption of
tetracyclines.

21. Distribution:
• Widely distributed in kidneys, liver, lungs,
bile, bones.
• With exception of lipid soluble members
like doxycycline and minocycline,
tetracyclines do not penetrate the brain
and CSF.
• Cross placenta.

22. • They are bound to plasma protein in
varying degree.
• Penetration of these drugs into most
tissues and body fluids is excellent.
• All tetracyclines are concentrated in the
liver and excreted by way of the bile into
the intestine from which they are partially
reabsorbed (enterohepatic circulation)

23. Biotransformation:
• With exception of lipid soluble tetracycline,
they are not metabolized to a significant
extent in the body

24. Excretion:
• All the tetracyclines are excreted in the
urine and the feaces, the primary route for
most being the kidney.
• The mechanism of renal exertion is
glomerular filtration.
• They will accumulate in the body in
patients with depressed renal function;
EXCEPT doxycycline -not eliminated via
the same pathways as other tetracyclines.
• Intestinal excretion is the major route of
elimination for doxycycline

25. • The drug is excreted in the feces, largely
as an inactive conjugate.

26. Administration and fate of tetracyclines.

27. Adverse Effects
• Have relatively low toxicity at normal
dosage levels
• TET can produce a variety of adverse
effects ranging from minor inconvenience
to life-threatening.
Gastrointestinal upsets:
• All produce GI irritation, mostly after oral
administration

28. • Anorexia, abdominal pain, diarrhoea,
nausea and vomiting may occur

29. • Effect on Bones:
• Deposited in growing teeth and bones due
to chelating properties with calcium
• Form tetracycline-calcium orthophosphate
complex which inhibits calcification
• So permanent discoloration of the teeth.
• Delay fracture healing

30. • Children receiving long-or short term
therapy with TET may develop brown
discoloration of the teeth.
• The drug deposits in the teeth and bones
probably due to its chelating property and
the formation of a TET -calcium
orthophosphate complex.
• Avoid giving to pregnant.

31. • Hepato toxicity:
• Acute hepatic necrosis with fatty changes
is common in patients receiving high
doses.
• Nephrotoxicity:
• Potentially nephrotoxic particularly in renal
insufficiency

32. Hypersensitivity reaction:
• Not common.
• Skin rashes, urticaria, pruritis, dermatitis
etc.
Cardio vascular effects:
• Rapid IV inj. results in hypotension,
collapse and sudden death.
• Due to rapid chelation of blood calcium

33. Other Effects:
• Cause irritation on parenteral
administration
• Swelling, necrosis, yellow discoloration at
inj. site.
• Drug fever, photoallergic dermatitis etc.
• Prolong blood coagulation

34. Some adverse effects of tetracycline

35. Contra indications/Precautions:
• Contra indicated in hepatic insufficiency,
renal diseases and in hypersensitive
patients.

36. Drug Interactions:
• Antacids, iron preparations, saline
purgatives, kaolin, pectin, sodium bi
carbonate decrease absorption of
tetracyclines from GI tract.
• May interfere with bactericidal activity of
penicillins, cephalosporins and
aminoglycosides.

37. Clinical Uses:
• Bronchopneumonia
• UTI
• Metritis
• Mastitis
• Prostatitis
• Cholangitis etc.
• Actinomycosis and actinobacillosis also
respond to TET.
• Chlortetracycline used in food producing
animals as growth promoters

38. Administration:
• Oral, Parenteral, Topical, Intramammary
• All can be given IV or IM