Tetracyclines

Tetracyclines are broad spectrum

antibiotics with activity against aerobic
and anaerobic Gram positive and Gram
negative organisms, rickettsiae,
mycoplasma and chlamydia
There is high incidence of development
of resistance against these drugs
Classification
Tetracyclines and its Congeners
 Tetracycline
 Chlortetracycline
 Oxytetracycline
 Demeclocycline
 Methacycline
 Doxycycline
 Minocycline
 According to Generations
First Generation Third Generation
(Dose intervals shorter)  Glycylcycline
 Chlortetracycline Are synthetic glycylamido
 Oxytetracycline derivatives of
 Tetracycline minocycline
 Demeclocycline (Not currently Available)
Second Generation
(Dose interval longer)
 Minocycline
 Methacycline
 Doxycycline
Spectrum Of Tetracyclines

Bacteria:
 In general Tetracyclines are more active
against Gram positive organisms than
Gram negative organisms.
 Due to superior anti-microbial activity they
are usually used in treatment of infections
caused by gram +ve organisms
 S. pneumonia, H. influenzae (Doxycycline)
 Pseudomonas pseudomallei, brucella
 Haemophilus ducreyi (chancroids), vibrio
cholera, ligionella pneumophila,
campylobacter jejuni,
 Helicobacter pylori, yersinia pestis, yersinia
enterocolitica, francisella tularensis,
pasteurella multocida
Rickettsiae
 Rocky mountain spotted fever, murine
typhus, epidemic typhus, scrub typhus,
rickettsial pox, Q. fever
Miscellaneous:
 Spirochetes – Borrelia recurrentis, borrelia
burgdorferi, treponema pallidum (syphilis),
treponema pertenue, mycobacterium
marinum.
The activity against chlamydia and
Mycoplasma has become particularly
important.
Strains of Mycobacterium marinum also
are susceptible.
Effects on intestinal flora. (important
feature)
 Incompletely absorbed from GIT.
 High concentrations reach the bowel
therefore intestinal flora is markedly
altered.
 They give yellow-green discolouration to
stool and soft consistency.
 May also cause pseudomembranous colitis
(Toxin from Clostridium defficile)
Mechanism Of action:
The drug enters the microorganisms
through channels in the cell wall – The
Porins (protein channels) through
energy dependent transport ( as
described in aminoglycosides). The
entry into gram positive organisms is
not clear but it is definitely through
porins and energy dependant.
Once inside the cell:
 The tetracyclines (tetracycline, doxycycline,
demeclocycline, minocycline, etc.) block
bacterial translation by binding reversibly to
the 30S subunit and distorting it in such a
way that the anticodons of the charged
tRNAs cannot align properly with the
codons of the mRNA.
Mechanism of development of
resistance against tetracyclines

Decreased accumulation as a result of

decreased antibiotic influx or acquisition
of energy dependent pathway
Decreased access of tetracyclines to
ribosomes because of presence of
ribosome protection proteins
Enzymatic inactivation of tetracyclines
Tetracyclines [Tetra-cycles]
Inhibit 30S ribosomal unit [4 wheels parked inside 30S]
Effective against:
oChlamydia [Clam]
oLime disease [Severed Lime]
oSpirochetes [Spiral]
oRickettsia [Racket]
oMycoplasma [My cop plasma amorphous shape]
oVibrio [Comma shaped bacillus from clams]
Eliminated first into bile, reabsorbed and then excreted by kidney [hungry kidney first
licking with a green tongue]
Causes tooth and bone discoloration in children [spotted tooth]
Calcium and Magnesium (e.g. antacids, dairy) decrease absorption from GI [California
surfer with a magnet pulling back the tetra-cycle]
Hepatotoxic [Severed liver]
Phototoxicity [Burning sun]
Blurry vision [Blurred eye] due to increased intracranial pressure
Doxycycline [Dog is cycling] is eliminated exclusively in bile [Sinking into bile puddle]
Minocycline [mine cycle] enters the brain and endolymph, causing vertigo and vomiting
Pharmacokinetics
Absorption:
 Incomplete absorption from GIT
 The percentage of oral dose absorbed empty
stomach:
 Chlortetracycline 30 %
 Oxytetracycline

 Demeclocycline 60% -- 80%

 Tetracycline

 Doxycycline 95 %
 Minocycline 100 %
They are more absorbed when taken empty stomach
Impaired absorptions with dairy products. Aluminum hydroxide
gel, calcium, magnesium, iron, zinc salts, bismuth subsalicylates
Distribution:
 Widely distributed throughout the body into the
tissue secretions, including urine and prostate.
 Accumulation in the reticuloendothelial cells of
liver, spleen, bone marrow and in the bones,
dentine and enamel of un-erupted teeth.
 They cross placental barrier

 They are found in the breast milk.

Excretion:
 The primary route of elimination is through kidneys
 Minocycline is significantly metabolized in the liver.

Route of Administration:
 Oral
 Parenteral

 Local
Therapeutic uses
Rickettsial infections:
 Life saving drugs in rickettsial infections
like Rocky Mountain spotted fever,
recrudescent epidemic typhus, murine
typhus, scrub typhus, rickettsial pox, Q.
fever.
Mycoplasma Infections:
 Mycoplasma pneumoniae
Chlamydia:
 Lymphogranuloma Venereum ( 1 st
line. Doxy. Drug of
choice)

 Pneumoniae, bronchitis or sinusitis caused

by chlamydia pneumoniae
 Trachoma (contraindicated in early childhood – azythromycin is
indicated)

 Non specific urithritis – usually due to

chlamydia trachomatis.
Sexually Transmitted Diseases:
 Effective for uncomplicated gonococcal infections
( although ceph. 3rd gen. Are more prescribed)
Bacillary Infections:
 Brucellosis
 Tularemia
 Cholera

Acne:
 Used for treatment of acne. These drugs may act
by inhibiting propionibacteria which reside in the
sebaceous follicles and metabolize lipids into
irritating free fatty acids.
Adverse Effects:
GIT:
 Epigastric burning, distress, abdominal discomfort,
nausea, vomiting, diarrhea
 Pseudomembranous colitis

Photosensitivity
Hepatic toxicity
 Oxytetracycline and tetracycline are less
hepatotoxic.
Renal Toxicity
Discolouration of teeth in children (brown-
yellow)
Hypersensitivity reactions
 Urticaria, fixed drug eruptions, exfoliative
dermatitis, burning eyes
Increased Intracranial pressure (psuedotumor
cereberi)
Biological effects other than Allergic
reactions:
 Superinfection
 Pseudomembranous colitis
Miscellaneous
 Thrombophlebitis often followed by I/V injections
 Long term therapy may produce changes in the
peripheral blood picture
 Increase intracranial pressure leading to tense
bulging fontanels in young infants.
 Minocycline may cause vestibular toxicity,
dizziness, ataxia, nausea and vomiting.
Contraindications:
 Pregnant ladies
 Children under 8 years

 Unused Drug should be discarded