1. CHLORAMPHENICOL First broad spectrum antibiotic. First broad spectrum antibiotic. Originally isolated in 1947. Originally isolated in 1947. Now produced synthetically. Now produced synthetically.

2. CHLORAMPHENICOL Nitrobenzene structure is unique Nitrobenzene structure is unique Derivative of chloroacetic acid Derivative of chloroacetic acid

3. ANTIBACTERIAL ACTIVITY Wide spectrum of antimicrobial activity. Wide spectrum of antimicrobial activity.

4. PHARMACOKINETICS Rapidly and completely absorbed when given orally. Rapidly and completely absorbed when given orally. Widely distributed throughout body fluids and tissues. Widely distributed throughout body fluids and tissues.

5. Chloramphenicol

6. Glucuronide Unchanged Deacetylation & Dehalogenation Metabolism Glomerular Filtration Tubular Secretion Excretion 90% 8% 2%

7. METABOLISM The immature liver of newborn and premature infants are deficient in the enzyme metabolizing the drug. The immature liver of newborn and premature infants are deficient in the enzyme metabolizing the drug. Rapidly excreted in the urine. Rapidly excreted in the urine.

8. THERAPEUTIC USES Limit use to infections for which the benefits outweigh the risks of toxicity. Limit use to infections for which the benefits outweigh the risks of toxicity. Periodic blood tests. Periodic blood tests.

9. THERAPEUTIC USES Serious anaerobic infections (Bacteroides). Serious anaerobic infections (Bacteroides).

10. DRUG INTERACTIONS Inhibits microsomal cytochrome P-450 enzymes. Inhibits microsomal cytochrome P-450 enzymes.

12. TETRACYCLINES Systematic soil screening. Systematic soil screening. Chlortetracycline introduced in 1948. Chlortetracycline introduced in 1948. Doxycycline and minocycline- 1962. Doxycycline and minocycline- 1962. General patterns of susceptibility and resistance are similar. General patterns of susceptibility and resistance are similar.

14. ANTIBACTERIAL ACTIVITY Broadest spectrum of any group of antibiotics. Broadest spectrum of any group of antibiotics. Less useful against gram-positive organisms. Less useful against gram-positive organisms.

15. ANTIBACTERIAL ACTIVITY Minocycline and doxycycline are usually more effective than the other tetracyclines. Minocycline and doxycycline are usually more effective than the other tetracyclines.

16. ABSORPTION Most are adequately but incompletely absorbed from the GI tract. Most are adequately but incompletely absorbed from the GI tract. Absorption is impaired by many substances. Absorption is impaired by many substances.

17. Hours after administration Of tetracycline 0 5 10 Plasma concentration of tetracycline On Empty Stomach With Milk 0 1 2 With Al(OH) 3

18. DISTRIBUTION Diffuse well into most body fluids and tissues. Diffuse well into most body fluids and tissues. Penetration into the CNS is variable and not very good. Penetration into the CNS is variable and not very good.

19. METABOLISM AND EXCRETION Tetracyclines are concentrated in the liver and excreted via the bile and then pass into the intestine. Tetracyclines are concentrated in the liver and excreted via the bile and then pass into the intestine. Metabolized in the liver (use cautiously in liver disease). Metabolized in the liver (use cautiously in liver disease).

20. Enterohepatic circulation Tetracyclines

21. METABOLISM AND EXCRETION Primary route of excretion is the kidney. Primary route of excretion is the kidney. Avoid tetracyclines in patients with renal dysfunction (except doxycycline). Avoid tetracyclines in patients with renal dysfunction (except doxycycline). Intestine is also an important route of elimination for the tetracyclines. Intestine is also an important route of elimination for the tetracyclines.

22. THERAPEUTIC USES

24. MYCOPLASMA PNEUMONIA

29. CONTRAINDICATIONS

31. CONTRAINDICATIONS Children 8-12 years of age. Children 8-12 years of age. Renal insufficiency (except doxycycline). Renal insufficiency (except doxycycline).

32. DRUG-DRUG INTERACTIONS Divalent and trivalent cations. Divalent and trivalent cations. Concurrent use with oral contraceptives. Concurrent use with oral contraceptives. Warfarin. Warfarin.

33. DRUG-DRUG INTERACTIONS Tetracyclines and FQ’s with divalent and trivalent cations. Tetracyclines and FQ’s with divalent and trivalent cations. Macrolides and drugs prolonging QT interval and with drugs inhibiting CYP3A4. Macrolides and drugs prolonging QT interval and with drugs inhibiting CYP3A4. Tetracyclines with warfarin and oral contraceptives. Tetracyclines with warfarin and oral contraceptives.