Antimicrobial Therapy: Tetracyclines and Nitroimidazoles Flashcards
Tetracyclines
Originally isolated from streptomyces spp and subsequently modified for semisynthetic tetracyclines
Chlortetracycline, Tetracycline, Oxytetracycline, Doxycycline, Minocycline
Tetracyclines:
MOA
30s bacterial ribosomal inhibitor
Absorption through outer cell membrane by diffusion / pores
Penetration of inner cytoplasmic membrane by active transport
Tetracyclines:
Phramacokinetics
Bacteriostatic
Time dependnet (T>MIC)
Tetracyclines:
Absorption
Species / drug specific
Di- and Trivalent cations can chelate and inhibit oral absorption
Also be skeptical of compounded chewable and liquid forms
Oral bioavailability: chlotetracycline (30%) < ocytetracycline / minocycline (50-80%) < doxycycline (95%)
Tetracyclines:
Distribution
lipophilic - penetrates many tissues well, including bronchi
fair penetration into CNS, and prostate
Protein binding vairable (Doxycycline high, less penetration into CNS/prostate vs minocycline)
Tetracyclines:
Elimination
Primarily as intact drug in urine (CTC, OTC)
Hepatic metabolism (minocycline)
Intact drug in bile and urine (Doxycycline)
Even through smaller percentages of doxycycline and minocycline are eliminated as intact drugn in the urine, the can be clinically effective
Tetracyclines:
Adverse Effects
- Nausea, vomiting, diarrhea
- GI flora disturbances
- Esophageal strictures
- cats may be more prone, but any species is posisble
- Allergic / immune reactions
- Photosensitivity
- Rapid IV admin can cause weakness and collapse
- OTC, TC, CTC have been associated with tooth discoloration prior to complete eruption in humans
- th effects in animals are not well described
- Renal tubular necrosis associated with excessive doses / duration of oxytetracycline
- Hepatic disease has occurred in humans,
- Cautious use of high and prolonged doses
