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.
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