Tetracyclines

Tetracyclines 

First Generation :( 1948 to 1963):

·        Chlortetracycline

·        Oxytetracycline

·        Tetracycline

·        Demeclocycline

·        Rolitetracycline

·        Limecycline

Second Generation (1965 to 1972):

·        Methacycline

·        Doxycycline

·        Minocycline

Third Generation: Tigecycline (2005)

According to duration of action:

·        Short-acting (Half-life is 6-8 hrs)

–       Tetracycline

–       Chlortetracycline

–       Oxytetracycline

·        Intermediate-acting (Half-life is ~12 hrs)

–       Demeclocycline

–       Methacycline

·        Long-acting (Half-life is 16 hrs or more)

–       Doxycycline

–       Minocycline

–       Tigecycline

Mechanism of action:

Bacteriostatic against many G-ve &G+ve bacteria. It bind to the 30S subunite of the bacterial ribosome, thus inhibitory bacterial protein synthesis.

Pharmacokinetic

·        Incompletely absorbed after oral administration.

·        If taken with the diet, it can decreases the absorption, because of the formation of non-absorbable chelates with calcium ions (this is not a problem with doxycycline & minocycline).

·        Non- absorabable chelates are also formed with other divalent and trivalent cations (Mg, AL-Antacid & iron preparation).

·        Distribution : tetracycline concentrate in liver , kidney , spleen & skin and bind to tissues undergoing calcification ( e.g bone & teeth )  all tetracycline enter CSF but levels are insufficient  for therapeutic efficacy except minocycline ( useful in eradicating  meningococcal  carrier state ).

·        All crosses placental barrier and concentrate in fetal bones and dentition.

·        Excretion in part metabolized in liver by conjugation, the parent drug & its metabolites are secreted into the bile, most tetracyclines are reabsorbed in the intestine and enter the glomerular filtration except doxycycline where it is excreted in the bile and with fecal material.

So Doxycycline can be used in treating infections in renally compromised patients.

Side Effects:

·        GI discomfort. irritation to gastric mucosa

·        Deposition in the bone and primary dentition occurs during calcification in growing children this causes discolouration and hypoplasia of the teeth, a temporary stunting of growth, and increase liability to caries.

·        Prolonged tetracycline therapy can also stain the fingernails at all ages.

·        Since tetracycline act by inhibitory bacterial protein synthesis, the same effect occurring in man causes blood urea to rise (antianabolic effect) the increased nitrogen load can be clinically important in renal failure and in the elderly.

·        Allergy, photosensitivity and skin rashes.

·        Hepatic damage esp during pregnancy, with renal disease and when the drug is given i.v.

·        Benign intracranial hypertension 

·        Superinfection, overgrowth of candida, resistant Staph can occur.

·        Vestibular problems as dizziness, nausea, vomiting occurs with minocycline.

Note: Fanconi Syndrome The breakdown products of tetracyclines are toxic and can cause Fanconi Syndrome It is a potentially fatal disease affecting proximal tubular function in the nephrons of the kidney Prescriptions of these drugs should be discarded once expired.

Clinical uses:

1.     Chlamydial infection as Psittacosis, Trachoma, Plevic inflammatory diseases.

2.     Mycoplasmal infections as mycoplasmal pneumonia.

3.     Rickettsial infection as Q-fever.

4.     Cholera

5.     Acne

6.     Inappropriate antidiuretic hormone secretion (Demeclocycline).

7.     Brucellosis

8.     Malaria

9.     Minocycline for eradication of meningococcal carrier state (but rifampicin is preferred).

10.       In the combination therapy of peptic ulcer for eradication of H.Pylori.