CHLORAMPHENICOL First broad spectrum antibiotic. First broad spectrum antibiotic. Originally...

CHLORAMPHENICOLCHLORAMPHENICOL

First broad spectrum antibiotic.First broad spectrum antibiotic.

Originally isolated in 1947.Originally isolated in 1947.

Now produced synthetically. Now produced synthetically.

CHLORAMPHENICOLCHLORAMPHENICOL

Nitrobenzene Nitrobenzene structure is uniquestructure is unique

Derivative of Derivative of chloroacetic acidchloroacetic acid

ANTIBACTERIAL ANTIBACTERIAL ACTIVITYACTIVITY

Wide spectrum of antimicrobial activity. Wide spectrum of antimicrobial activity.

PHARMACOKINETICSPHARMACOKINETICS

Rapidly and completely absorbed when Rapidly and completely absorbed when given orally.given orally.

Widely distributed throughout body Widely distributed throughout body fluids and tissues.fluids and tissues.

Chloramphenicol

Chloramphenicol Glucuronide

Unchanged

Deacetylation &

Dehalogenation

Metabolism

Glomerular

Filtration

Tubular

Secretion

Excretion

90%

8%

2%

METABOLISMMETABOLISM

The immature liver of newborn and The immature liver of newborn and premature infants are deficient in the premature infants are deficient in the enzyme metabolizing the drug.enzyme metabolizing the drug.

Rapidly excreted in the urine.Rapidly excreted in the urine.

THERAPEUTIC USESTHERAPEUTIC USES

Limit use to infections for which the Limit use to infections for which the benefits outweigh the risks of toxicity.benefits outweigh the risks of toxicity.

Periodic blood tests.Periodic blood tests.

THERAPEUTIC USESTHERAPEUTIC USES

Serious anaerobic infections Serious anaerobic infections ((BacteroidesBacteroides).).

DRUG INTERACTIONSDRUG INTERACTIONS

Inhibits microsomal cytochrome P-450 Inhibits microsomal cytochrome P-450 enzymes.enzymes.

TETRACYCLINESTETRACYCLINES

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 General patterns of susceptibility and resistance are similar.resistance are similar.

ANTIBACTERIAL ANTIBACTERIAL ACTIVITYACTIVITY

Broadest spectrum of any group of Broadest spectrum of any group of antibiotics. antibiotics.

Less useful against gram-positive Less useful against gram-positive organisms.organisms.

ANTIBACTERIAL ANTIBACTERIAL ACTIVITYACTIVITY

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

ABSORPTIONABSORPTION

Most are adequately but incompletely Most are adequately but incompletely absorbed from the GI tract.absorbed from the GI tract.

Absorption is impaired by many Absorption is impaired by many substances. substances.

Hours after administrationOf tetracycline

0 5 10

Pla

sma

con

cen

trat

ion

of

tetr

acyc

line

On Empty Stomach

With Milk0

1

2

With Al(OH)3

DISTRIBUTIONDISTRIBUTION

Diffuse well into most body fluids and Diffuse well into most body fluids and tissues. tissues.

Penetration into the CNS is variable and Penetration into the CNS is variable and not very good. not very good.

Enterohepatic circulation

Tetracyclines

METABOLISM AND METABOLISM AND EXCRETIONEXCRETION

Primary route of excretion is the kidney. Primary route of excretion is the kidney.

Avoid tetracyclines in patients with renal Avoid tetracyclines in patients with renal dysfunction (except doxycycline).dysfunction (except doxycycline).

Intestine is also an important route of Intestine is also an important route of elimination for the tetracyclines.elimination for the tetracyclines.

THERAPEUTIC USESTHERAPEUTIC USES

MYCOPLASMA PNEUMONIA

CONTRAINDICATIONSCONTRAINDICATIONS

CONTRAINDICATIONSCONTRAINDICATIONS

Children 8-12 years of age.Children 8-12 years of age.

Renal insufficiency (except doxycycline).Renal insufficiency (except doxycycline).

DRUG-DRUG DRUG-DRUG INTERACTIONSINTERACTIONS

Divalent and trivalent cations.Divalent and trivalent cations.

Concurrent use with oral contraceptives.Concurrent use with oral contraceptives.

Warfarin.Warfarin.

DRUG-DRUG INTERACTIONSDRUG-DRUG INTERACTIONS

Tetracyclines and FQ’s with divalent and Tetracyclines and FQ’s with divalent and trivalent cations.trivalent cations.

Macrolides and drugs prolonging QT interval Macrolides and drugs prolonging QT interval and with drugs inhibiting CYP3A4.and with drugs inhibiting CYP3A4.

Tetracyclines with warfarin and oral Tetracyclines with warfarin and oral contraceptives.contraceptives.