Tetracyclines
·
Chemistry.
·
Pharmacokinetics.
·
Adverse reactions.
·
Therapeutic
indications.
Chemistry
1.
A family of closely related antibiotics sharing a common 4-benzene ring
structure.
2.
Bacteriostatic in action.
3.
Inhibit protein synthesis by binding to receptors on 30S subunit of
bacterial ribosome.
Pharmacokinetics
1.
Absorption:
a.
Most tetracyclines are only partially absorbed from the GI tract.
b.
Doxycycline and minocycline are almost completely absorbed.
c.
Absorption is impaired in the presence of calcium, aluminium, magnesium
or iron compounds due to chelation.
2.
Distribution:
a.
Widely distributed throughout the body and cross the placenta.
b.
Half-life of tetracycline: 6 – 9h.
c.
Half-life of doxycycline and minocycline: 16 – 20h.
3.
Excretion:
a.
Excreted mainly unchanged in the urine and should be avoided when renal
function is impaired.
b.
Doxycycline and minocycline are excreted into the bile and may be used in
patients with impaired renal function.
Adverse effects
1.
Gastrointestinal discomfort:
a.
Abdominal discomfort.
b.
Nausea and vomiting.
c.
Diarrhea.
2.
Photosensitization and other rashes.
3. Liver
and pancreatic damage can occur, especially in pregnancy and with renal disease.
4.
Renal toxicity: may aggravate established renal insufficiency.
5. Bony
structures and teeth:
a.
Selectively taken up in the teeth and growing bones of the fetus and of
children.
b.
Cause staining of teeth, dental enamel hypoplasia with pitting, cusp
malformation and increased susceptibility to caries.
c.
Retardation of growth.
6.
Increased intracranial pressure in infants.
7.
Vesticular disturbance with dizziness, tinnitus and vertigo: minocycline.
Therapeutic indications
1.
Tetracyclines are active against nearly all Gram-positive and
Gram-negative bacteria.
2.
Drugs of first choice for infection with:
a.
Chlamydiae.
b.
Mycoplasma.
c.
Rickettsiae.
d.
Vibrio cholerae.
e.
Borreliae.
3.
Doxycline: chemoprophylaxis for malaria.
4.
Minocycline: used for meningococcal prophylaxis.