Tetracylines

Tetracyclines
Obtained by fermentation procedures from
Streptomyces spp. or by chemical
transformation of the natural products
Octahydronaphthacene- an important
derivative of hydrocarbon system that
comprises four annulated six-membered
ring.
Close congeners of polycyclic
naphthacenecarboxamide
 Mechanism of Action

MOA: They bind to the 30S ribosomal

subunit, and thereby prevent the
binding of aminoacyl tRNA to the
mRNA-ribosome-complex.

Specific inhibitors of bacterial protein

synthesis
 Both the binding of aminoacyl tRNA and
the binding of tetracyclines at the
ribosomal binding site require magnesium
ions

Tetracycline also bind to mammalian

ribosomes but with lower affinities, and
they apparently do not achieve sufficient
intracellular concentrations to interfere
with protein synthesis
 Tetracyclines enter bacterial cells by
two processes:

Passive diffusion
Active transport

The active uptake of tetracyclines by bacterial

cells is an energy-dependent process that
requires adenosine triphosphate (ATP) and
magnesium ions
Tetracycline Components

Tetracycline Meclocycline
Rolitetracycline Methacycline
Oxytetracycline Doxycycline
Chlortetracycline Minocycline
Demeclocycline
 Tetracycline

Indication: for the treatment of the

infection, such as: acne, rosacea,
Rocky Mountain Spotted fever, typhus
fever, Q fever, rickettsial pox and fever
cause by Rickettsiae
 A/E: GI disturbances, Clostridium
difficile, candidiasis, photosensitivity,
bone & dental effects in children,
fatty liver

C/I: Allergy, renal insufficiency,

children <8 years old
Rolitetracycline
Indication: a broad spectrum antibiotic
high concentrations (oral; impractical)
C/I: hypersensitivity, SLE, Renal
impairment, pregnancy, lactation,
children 8 years old

S/E: nausea, vomiting, headache

Oxytetracycline
treatment for chest infection such as
pneumonia, mouth infection, bites, STI, and
skin conditions, such as acne and rosacea.
S/E: abdominal pain, diarrhea, headache,
allergy

C/I: hypersensitivity, Renal damage,

pregnancy, lactation, children 8 years old
Chlortetracycline
Indication: used in bacterial infection, for
ocular infection and minor skin infections
C/I: hypersensitivity, SLE, severe renal
impairement, pregnancy, and lactation

A/E: hypersensitivity and photosensitivity

reactions, abnormal pigmentation of the
eye, myopia
Demeclocycline (vs. chlor the methyl group on c-6)
Indication: used to treat a wide variety of
bacterial infections like that of
tetracyclines, but is slightly more active
C/I: Hypersensitivity to demeclocycline or
other tetracyclines, lactation, Concurrent
use with methoxyflurane

A/E: Photosensitivity, Reversible

nephrogenic, diabetes insipidus,
Permanent discoloration of the teeth
Metacycline
Indication: for acute bacterial
exacerbations of chronic bronchitis
C/I: hypersensitivity

S/E: hypersensitivity reactions,

urticaria, photosensitivity, fever,
epigastric pain, anorexia
Doxycycline
Indication: oral tetracycline of choice because
it is given twice daily, its absorption is not
significantly affected by food.
C/I: Allergies to tetracycline, Clostridium
difficile infection, Myasthenia Gravis,
Pregnancy, Problems with food passing
through the Esophagus

A/E: dizziness, vertigo, nausea, and vomiting

(>100 mg)
Minocycline(rifampicin is preffered)
Indication: 200 mg orally daily for 5 days,
can eradicate the meningococcal carrier
state
C/I: Hypersensitivity to minocycline and
other tetracyclines, concurrent use with
methoxyflurane, lactation

A/E: Hemolytic anemia,

thrombocytopenia, neutropenia
Resistance Mechanism to Tetracycline
and Glycylcyclines
tetracycline as a result of either decreased
antibiotic influx or acquisition of an
energy-dependent efflux pathway
Production of a ribosomal protection
protein that displays tetracycline from its
target, a protection that may occur by
mutation
Enzymatic inactivation of tetracyclines