C H A P T E R 9
Antibiotics
115
not only the undesired bacteria, but also bacteria of the
normal flora, which increases the risk for exacerbation
of the ocular infection that is being treated.
Tetracyclines should be used with caution in children
younger than 8 years of age
because they can potentially
damage developing bones and teeth
; and in people with
hepatic or renal dysfunction
because they are concen-
trated in the bile and excreted in the urine.
Adverse effects
The major adverse effects of tetracycline therapy involve
direct irritation of the GI tract and include nausea,
vomiting, diarrhoea, abdominal pain, glossitis and
dysphagia. Fatal hepatotoxicity related to the drug’s irri-
tating effect on the liver has also been reported. Skeletal
effects involve damage to the teeth and bones. Because
tetracyclines have an affinity for teeth and bones, they
accumulate there, weakening the structure and causing
staining and pitting of teeth and bones. Dermatological
effects include photosensitivity and rash. Superinfec-
tions, including yeast infections, occur when bacteria
of the normal flora are destroyed. Local effects, such as
pain and stinging with topical or ocular application, are
fairly common. Haematological effects are less frequent,
such as haemolytic anaemia and bone marrow depres-
sion secondary to the effects on bone marrow cells that
turn over rapidly. Hypersensitivity reactions reportedly
range from urticaria to anaphylaxis and also include
intracranial hypertension.
Clinically important drug–drug interactions
When penicillin G and tetracyclines are taken concur-
rently, the effectiveness of penicillin G decreases. If
this combination is used, the penicillin dose should be
increased.
When oral contraceptives are taken with tetra
cyclines, the effectiveness of the contraceptives decreases,
and women who take oral contraceptives should be
advised to use an additional form of birth control while
receiving the tetracycline. (See Critical thinking scenario.)
When methoxyflurane is combined with tetra-
cycline, the risk of nephrotoxicity increases. If at
all possible, this combination should be avoided. In
addition, digoxin toxicity rises when tetracyclines are
taken concurrently. Digoxin levels should be moni-
tored and dose adjusted appropriately during treatment
and after tetracycline therapy is discontinued. Finally,
decreased absorption of tetracyclines results from oral
combinations with calcium salts, magnesium salts, zinc
salts, aluminium salts, bismuth salts, iron, urinary alka-
linisers and charcoal.
Clinically important drug–food interactions
Because oral tetracyclines are not absorbed effectively
if taken with food or dairy products, they should be
administered on an empty stomach 1 hour before or 2 to
3 hours after any meal or other medication.
Prototype summary: Doxycycline
Indications:
Treatment of various infections caused
by susceptible strains of bacteria; acne; when
penicillin is contraindicated for eradication of
susceptible organisms.
Actions:
Inhibits protein synthesis in susceptible
bacteria, preventing cell replication.
Pharmacokinetics:
Route
Onset
Peak
Oral
Varies
2–4 hours
Topical
Minimal absorption occurs
T
1/2
:
6 to 12 hours; excreted unchanged in the urine.
Adverse effects:
Nausea, vomiting, diarrhoea,
glossitis, discolouring and inadequate
calcification of primary teeth of fetus when used
in pregnant women or of secondary teeth when
used in children, bone marrow suppression,
photosensitivity, superinfections, rash, local
irritation with topical forms.
CRITICAL THINKING SCENARIO
Antibiotics and oral contraceptives
THE SITUATION
G.S., a 27-year-old married female postgraduate student,
is seen in the student health clinic a few weeks into the
autumn semester. She has developed a severe sinusitis
and complains of head pressure, difficulty sleeping, fever,
and muscle aches and pains. A culture is done, and the
next day the culture and sensitivity report identifies the
infecting organism as a strain of
Klebsiella
that is sensitive to
doxycycline. G.S. returns to the clinic to get the prescription
for doxycycline.
In talking with you, G.S. tells you that she began
university with plans to start a family in 2 years, after
completing her program. She is a very organised person
and has carefully planned her rigorous course work and
her non-academic activities so that almost every hour
