Pharmacotherapy of Tetracyclines

1. Presented By
Dr. Manoj Kumar
Assistant Professor
Department of Pharmacology
Adesh Medical College & Hospital Ambala Can’t

2.  4 rings fused with each other
◦ Shorter acting (t1/2: 6-10hrs): Tetracycline,
Chlortetracycline, Oxytetracycline
◦ Intermediate acting (t1/2: 12-13hrs): Demeclocycline,
Methacycline
◦ Long acting (t1/2: 18-20 hrs): Doxycycline, Minocycline
 Obtained from actinomycetes
 Bacteriostatic
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3. 3
Inhibit protein synthesis
• Bind to 30S ribosome
• Blocks access of
aminoacyl tRNA to A-
site of mRNA template
• Peptide chain fails to
grow

4.  Gram positive: S.aureus, S.pneumoniae, B.anthracis
 Gram negative: Brucella, Vibrio
 Anaerobes: Clostridia
 Spirochetes: Borrelia burgdorferi
 Chlamydia: Urethritis, PID, LGV
 Rickettsia
 Mycoplasma: M.pneumoniae
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5.  Mg+2 dependent
active efflux
 Enzymatic inactivation
 Decreased cell
permeability
 Ribosomal protection
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6.  Available as HCl salts
 Entry through passive transport
 Concentrate intracellularly
 Interference with food
◦ Good absorption empty stomach
◦ Impaired absorption: Dairy foods, Fe preparations,
Antacids: Mg+2, Al+3
 Distribution in liver, kidney, skin, CNS
◦ Deposited in teeth, bone
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7.  Enterohepatic circulation
 Cross placental barrier, Secreted in milk
◦ CI in pregnancy, nursing mothers
 ROA: IM, IV, Oral, topical, eye/ear drops
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8. Cholera, plague
Rickettsia: Rocky mountain spotted fever, Typhus fever
Chlamydia: LGV, Pneumonia
Calymmatobacterium granulomatis: Granuloma inguinale
Ureaplasma: Nonspecific urethritis
M.pneumoniae: atypical pneumonia
Borrelia: Lyme’s disease
B.recurrentis: Relapsing fever
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9. 1. Brucella: Brucellosis (along with gentamycin)
2. F.tularensis: Tularemia
3. Y.pestis: Plague
4. Bacteremia, abscesses
5. Trachoma, NSU/cervicitis
6. Syphilis, Gonorrhoea
7. Anthrax
8. Tetanus
9. Chancroid
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10.  Amoebiasis (with metronidazole)
 Malaria (for chloroquine resistant malaria)
 Acne
◦ Anti-oxidant effect on degranulated neutrophils in acidic contents of
sebaceous material
 Peptic ulcer due to H.pylori
Doxycycline: longer t1/2, no nephrotoxicity, can be given IV
Demeclocycline: inhibits ADH action on renal tubules
◦ Used in SIADH
Minocycline: swimming pool granuloma (M.marinum)
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11.  Irritant
◦ On GIT: epigastric pain, nausea, vomiting,
diarrhea
 Most commonly involved in super
infection
◦ Marked suppression of flora
◦ Oral thrush, pseudomenbranous colitis
◦ Discontinue therapy
 Pain on IM inj: not recommended
 Hepatotoxicity
 Nephrogenic D.insipidus: Demeclocycline
 Pseudotumour cerebri, bulging fontanelle
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12.  Chelating property: form insoluble, unabsorbable
complexes with Ca+2
 Bind to connective tissue
 Decidual teeth affected (3-6 yrs): tetracycline teeth
 Permanent teeth
 Stained (Brown color), ill-formed, susceptible to caries
 Retarded bone growth: Suppression of growth
 CI in pregnancy, children <10yrs
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13.  Photosensitivity: Demeclocycline, Doxycycline
◦ Sunburn type of reaction to sun/UV light
 Renal toxicity
◦ On prolonged use, expired drugs
◦ Dose needed to be decreased in renal failure
◦ Doxycycline, minocycline safe
 Minocycline: vestibular toxicity, induce skin
pigmentation
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14.  Synthetic derivative of minocycline
 Glycylcycline
 More potent, IV infusion
 No resisitance
 MDR S.pneumoniae, VRE, MRSA
 Uses
◦ cSSTIs, cIAIs, CAP
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