Thursday, November 29, 2007

Chap 44: Bacterial protein synthesis inhibitors - tetracyclines, chloramphenicol

Tetracycline, macrolide, clindamycin, chloramphenicol, streptogramin - all inhibit protein synthesis

TETRACYCLINE
General
- bacteriostatic
- g+ve and g-ve
- anaerobes, rickettsia, chlamydia, mycoplasma, protozoa
- most tetracyclines has similar antibacterial activity --> resistant ones can use doxy
- differences in clinical efficacy are minor - only differences are due to pharmacokinetics
- MOA
  • partly passive diffusion; partly active transport into cell
  • binds reversibly to 30S subunit of bacterial ribosome
  • inhibit protein synthesis
- resistance
  1. reduced influx/increased efflux of drug by active transport protein pump
  2. ribosomal protection
  3. enzymatic inactivation
Pharmacokinetics
- differences in excretion
  • minocycline excreted in tears - eradicate carrier state of meningococcal infection
- excreted mainly in bile and urine --> enterohepatic circulation may contribute to maintenance of serum concentration level
- classified by serum T1/2
  • short acting - chlortetracycline, tetracycline, oxytetracycline
  • intermediate - demeclocycline, methacycline
  • long acting - doxy, minocycline
Clinical uses
- drug of choice in atypical infections - mycoplasma, chlamydia, rickettsia, spirochetes
- H. pylori - in combination with other regimens
- Vibrio - cholera
- combined with aminoglycosides --> to treat plague, tularemia, brucellosis
- protozoal infection - E. histolytica, Plasmodium falciparum

SE
- GIT - N/V/D
- Bony structures and teeth - binds to Ca in newly formed bone and teeth - enamel dysplasia + retardation in bone growth - hence never give in <8 yo
- Liver
- Nephrotoxic - renal tubular acidosis, renal injury
- Photosensitization
- Vestibular reaction - dizziness, vertigo, n/v

CHLORAMPHENICOL
- binds to 50S ribosomal subunit - inhibit protein synthesis
- bacteriostatic
- active against rickettsia, NOT chlamydia, also g+ve, g-ve aerobic and anaerobic

Clinical use
- rarely used due to resistance, other alternatives, toxicity
- serious rickettsial infection - typhus, rocky mountain spotted fever
- alternative to B-lactams for meningococcal meningitis for pt with serious allergy
- eye infections - cos of its broad spectrum, penetration of ocular tissue + aqueous humor (*ineffective for chlamydial infection)

SE
- BM suppresion - reversible, dose-related - aplastic anemia (idiosyncratic, irreversible)
- newborn infants lack effective glucoronic acid conjugation mechanism --> accummulate drugs in serum --> grey baby syndrome (vomit, flaccid, hypotherm, gray, shock, collapse)
- GIT - N/V/D

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