Download Chloramphenicol

CHLORAMPHENICOL

First broad spectrum antibiotic.

Originally isolated in 1947.

Now produced synthetically.
CHLORAMPHENICOL

Nitrobenzene
structure is unique

Derivative of
chloroacetic acid
ANTIBACTERIAL
ACTIVITY

Wide spectrum of antimicrobial activity.
PHARMACOKINETICS

Rapidly and completely absorbed when
given orally.

Widely distributed throughout body
fluids and tissues.
Chloramphenicol
Unchanged
Glomerular
Filtration
8%
90%
Chloramphenicol
Glucuronide
2%
Tubular
Deacetylation & Secretion
Dehalogenation
Metabolism
Excretion
METABOLISM

The immature liver of newborn and
premature infants are deficient in the
enzyme metabolizing the drug.

Rapidly excreted in the urine.
THERAPEUTIC USES

Limit use to infections for which the
benefits outweigh the risks of toxicity.

Periodic blood tests.
THERAPEUTIC USES

Serious anaerobic infections
(Bacteroides).
DRUG INTERACTIONS

Inhibits microsomal cytochrome P-450
enzymes.
TETRACYCLINES

Systematic soil screening.

Chlortetracycline introduced in 1948.

Doxycycline and minocycline- 1962.

General patterns of susceptibility and
resistance are similar.
ANTIBACTERIAL
ACTIVITY

Broadest spectrum of any group of
antibiotics.

Less useful against gram-positive
organisms.
ANTIBACTERIAL
ACTIVITY

Minocycline and doxycycline are usually
more effective than the other
tetracyclines.
ABSORPTION

Most are adequately but incompletely
absorbed from the GI tract.

Absorption is impaired by many
substances.
Plasma concentration of
tetracycline
2
On Empty Stomach
1
With Al(OH)3
With Milk
0
0
5
10
Hours after administration
Of tetracycline
DISTRIBUTION

Diffuse well into most body fluids and
tissues.

Penetration into the CNS is variable and
not very good.
Tetracyclines
Enterohepatic circulation
METABOLISM AND
EXCRETION

Primary route of excretion is the kidney.

Avoid tetracyclines in patients with renal
dysfunction (except doxycycline).

Intestine is also an important route of
elimination for the tetracyclines.
THERAPEUTIC USES
MYCOPLASMA PNEUMONIA
CONTRAINDICATIONS
CONTRAINDICATIONS

Children 8-12 years of age.

Renal insufficiency (except doxycycline).
DRUG-DRUG
INTERACTIONS

Divalent and trivalent cations.

Concurrent use with oral contraceptives.

Warfarin.
DRUG-DRUG INTERACTIONS

Tetracyclines and FQ’s with divalent and
trivalent cations.

Macrolides and drugs prolonging QT interval
and with drugs inhibiting CYP3A4.

Tetracyclines with warfarin and oral
contraceptives.