Tetracyclines are a class of broad-spectrum bacteriostatic antibiotics that work by binding to the 30S subunit of bacterial ribosomes and inhibiting protein synthesis. They are effective against many gram-positive and gram-negative bacteria, as well as anaerobes, rickettsiae, chlamydiae, mycoplasmas, and protozoa. Tetracyclines have a range of pharmacokinetic properties from short-acting to long-acting drugs. They are subject to resistance via efflux pumps, ribosomal protection proteins, and enzymatic inactivation. Common adverse effects include gastrointestinal issues, staining of teeth and bones, and photosensitivity.

1. TETRACYCLINES
By
Dr.Riffat Farooqui
Assistant Professor

2. Bacterial Protein Synthesis
Inhibitors
• Tetracyclines
• Macrolides
• Clindamycin
• Chloramphenicol
• Streptogramins

3. Tetracyclines
Inhibit bacterial protein synthesis by binding to
and interfering with ribosomes
1) Short-acting (6-8 hours)
Chlortetracycline, Tetracycline, Oxytetracycline
2) Intermediate-acting (12 hours)
Demeclocycline and Methacycline
3) Long-acting (16-18 hours)
Doxycycline and Minocycline

4. Antimicrobial Activity
• Broad-Spectrum Bacteriostatic Antibiotics
• Active against many gram-positive and gram-negative
bacteria, including
Anaerobes
Rickettsiae
Chlamydiae
Mycoplasmas
Protozoa, e.g. amebas

5. Pharmacodynamics(MOA)
The Tetracyclines bind to the 30S subunit and prevent binding
of the incoming charged tRNA unit (Inhibit step 1 in bacterial
protein synthesis).
Tetracyclines enter microorganisms
Susceptible cells concentrate the drug intracellularly
Tetracyclines bind to 30S subunit of the bacterial ribosome
Blocking the binding of tRNA to the acceptor site on the mRNA-
ribosome complex
This prevents addition of amino acids to the growing peptide

7. RESISTANCE
Three mechanism of resistance to
tetracycline analogs
(1) Impaired influx or increased efflux by
an active transport protein pump
(2) Ribosome protection due to
production of proteins that interfere
with tetracycline binding to the
ribosome
(3) Enzymatic inactivation

8. • Tet (AE) efflux pump-expressing gram-negative species
Resistant to
Older Tetracyclines
Doxycycline
Minocycline.
Susceptible to
Tigecycline
• Tet (K) efflux pump of staphylococci
Resistance to
Tetracyclines
Susceptible to
Doxycycline,
Minocycline,
Tigecycline
• Tet (M) ribosomal protection protein expressed by gram-positives
Resistance to
Tetracyclines,
Doxycycline,
Minocycline,
Susceptible to
Tigecycline,

9. PHARMACOKINETICS
Absorption
• 60-70% tetracycline, oxytetracycline,
demeclocycline, and methacycline
• 95-100% doxycycline and minocycline
• Tigecycline is poorly absorbed orally and must be
administered intravenously.
Absorption occurs in upper small intestine and is
impaired by
• Food (except doxycycline and minocycline)
• Divalent cations (Ca2+, Mg2+, Fe2+) or Al3+
• Dairy products
• Antacids

10. PHARMACOKINETICS
• 40-80% bound by serum proteins
• Distributed widely to tissues and body fluids
except for CSF(10-25%)
• Tetracyclines cross the placenta to reach the fetus
and are also excreted in milk Chelation with
calcium, damage growing bones and teeth
• 10 – 50 % excreted into the urine
10 - 40 % excreted in feces
• Doxycycline and Tigecycline eliminated by
nonrenal mechanisms do not accumulate in
renal insufficiency

11. DRUG INTERACTION
• Antacid Impaired absorption
• Carbamazepine
• Phenytoin
• Barbiturates
• Chronic alcohol ingestion
• Diuretics Nitrogen retention
Decreases the
half-life of
Doxycycline

12. INDICATIONS ( Clinical uses)
Tetracycline
• Drug of choice in infection with
Mycoplasma pneumoniae
Chlamydiae
Rickettsiae
Some spirochetes
• Used in PEPTIC ULCER caused by H.pylori
• Vibrio infections( Cholera)
• Chlamydial infections, including sexually transmitted
diseases
• In combination with an aminoglycoside, indicated for
plague, tularemia, and brucellosis

13. • Treatment of acne
• Exacerbations of bronchitis
• Community-acquired pneumonia
• Lyme disease
• Relapsing fever
• Leptospirosis
• Nontuberculous mycobacterial infections (e.g.,
Mycobacterium marinum)
Minocycline Meningococcal carrier state
Demeclocycline Inhibits the action of ADH So
used in inappropriate secretion of ADH

14. Tigecycline
• Tetracycline-resistant strains are susceptible to Tigecycline.
• Methicillin& Vancomycin-resistant Staphylococci
• Penicillin-susceptible and – resistant streptococci
• Vancomycin-resistant enterococci
• Gram-positive rods
• Enterobacteriaceae
• Multidrug-resistant strains of Acinetobacter sp
• Gram-positive and gram-negative anaerobes
• Rickettsiae, chlamydia, and legionella
• Rapidly growing mycobacteria
• Proteus and P aeruginosa, are intrinsically resistant.

15. ADVERSE EFFECTS
1) GASTROINTESTINAL ADVERSE EFFECTS
• Nausea, vomiting, anorexia and diarrhea
• Anal Pruritus
• Vaginal or oral candidiasis
• Enterocolitis
2) BONY STRUCTURES AND TEETH
When a tetracycline is given during pregnancy
Deposited in the fetal Teeth& Bones
Fluorescence, Discoloration, and Enamel Dysplasia;
Bone deformity or Growth inhibition

16. 3) LIVER TOXICITY
• Impair hepatic function
• Hepatic necrosis (4 g)
4) KIDNEY TOXICITY
Administration of outdated tetracycline
Damage to renal proximal tubule
Renal tubular acidosis
(Fanconi-like syndrom)

17. 5) LOCAL TISSUE TOXICITY
I/V injection Venous Thrombosis
I/M injection Painful local irritation
6) PHOTOSENSITIZATION
Demeclocycline Sensitivity to sunlight or ultraviolet light
7) VESTIBULAR REACTIONS
Dizziness
Vertigo
Nausea
Vomiting