Broad spectrum Antibiotics

“Broad Spectrum Antibiotics” is traditionally a very specific term. It means only TETRACYCLINES AND CHLORAMPHENICOL.

It is interesting that their spectrum of activity is broad, but they are not bactericidal. They are bacteristatic. They inhibit protein synthesis in the organisms. Tetracyclines does this by binding to 30 S ribosomal subunit, while Chloramphenical does it by binding to 50 S ribosomal subunit.

Both – Tetracyclines and Chloramphenicol have a narrow therapeutic index; which means the margin of their therapeutic safety is low.

Their important negative points / drawbacks are:

  1. Bacteristatic effect
  2. Longer time needed for cure
  3. Relapse is possible because the organisms may remain dormant and may multiply later.
  4. Many common organisms have already developed resistance to the broad spectrum antibiotics.
  5. Narrow therapeutic index, hence toxicity.
  6. Wide range of commensals may be suppressed; which may lead to superinfection.

Important Tetracyclines are

(A) Older / Short Acting: Tetracycline hydrochloride, Oxytetracycline, Chlortetracycline (Remember – it produces cholestatic jaundice)

(B) Newer / Longer acting: Doxycycline (Safer in renal failure), Minocycline (Safer in hepatic failure, but produces photosensitivity and ototoxicity), Demeclocycline (Produces photosensitivity)


LAQ/SAQ/Viva

Mention adverse effects of tetracyclines:

Tetracyclines are classical broad spectrum antibiotics with bacteristatic effect . Their therapeutic index is low, so they may be toxic. Adverse effects are as follows:

1. Superinfection: Due to the broad spectrum, they inhibit the commensals and may produce superinfection by organisms such as Staph, Strepto, Proteus, Clostridium difficile, and candida.

2. Teeth: Tetracyclines chelate the calcium and form an insoluble chelate complex (Tetracycline Calcium Orthophosphate). Given to the pregnant women, it may affect the deciduous dentition in the fetus. Similarly, given to an infant upto 5 years of age, it affects the deciduous denttion. Administered to the children above 5 months of age, it may affect the permanent dentition. The harmful effects on teeth include –

  1. Teeth become weak and fragile.
  2. Brown black discoloration of teeth
  3. Enamel dysplasia
  4. Teeth become more susceptible to caries

3. Nephrotoxicity is common to most of the tetracyclines. Doxycycline is not much excreted through urine; it is excreted through feces, hence Doxycycline is considered safer in patients with renal failure.

4. Hepatotoxicity: Many of the tetracyclines do exhibit hepatotoxicity. Chlortetracycline is most susceptible to cause cholestatic jaundice. Whereas Minocycline is considered safer in hepatic failure.

5. Bones: Calcium chelation may lead to weakness and fragility of bones and stunted growth.

6. Antianabolic effects and weight loss.

7. Photosensitivity is known with many tetracyclines including minocycline, demeclocycline, doxycycline, and tetracycline hydrochloride.

8. Ototoxicity especially Vestibular toxicity is known with many tetracyclines such as minocycline and doxycycline.

9. Tetracyclines may increase the intracranial pressure.

10. Fanconi-like syndrome is an adverse effect due to ingestion of OUTDATED (EXPIRED) TETRACYCLINES. These form degradation products such as epitetracycline, anhydrotetracycline, and epianhydrotetracycline, which lead to proximal tubular atrophy and tubular dysfunction in the renal tubules. Manifestations may include anemia, stunted growth, excess thirst and urination, weakness in bones and muscles, slow growth, low muscle tone, rickets, vomiting, and failure to thrive


 

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