C H A P T E R 9
Antibiotics
119
Isoniazid specifically affects the mycolic acid coat
around the bacterium. Although many of the anti
mycobacterial agents are effective against other species
of susceptible bacteria, their primary indications are in
the treatment of tuberculosis or leprosy (as previously
indicated). The antituberculosis drugs are always used
in combination to affect the bacteria at various stages
and to help decrease the emergence of resistant strains.
See Table 9.8.
Pharmacokinetics
The antimycobacterial agents are generally well
absorbed from the GI tract. These drugs, given orally,
are metabolised in the liver and excreted in the urine;
they cross the placenta and enter breast milk, placing the
fetus or child at risk for adverse reactions (see contra
indications and cautions).
Contraindications and cautions
Antimycobacterials are contraindicated for people with
any known allergy to these agents; in those with severe
renal or hepatic failure,
which could interfere with the
metabolism or excretion of the drug
; in those with
severe CNS dysfunction,
which could be exacerbated
by the actions of the drug
; and in pregnancy
because
of possible adverse effects on the fetus.
If an anti
tuberculosis regimen is necessary during pregnancy, the
combination of isoniazid, ethambutol and rifampicin is
considered the safest.
Adverse effects
CNS effects, such as neuritis, dizziness, headache,
malaise, drowsiness and hallucinations, are often
reported and are related to direct effects of the drugs on
neurons. These drugs also are irritating to the GI tract,
TABLE 9.8
DRUGS IN FOCUS Antimycobacterials
Drug name
Dosage/route
Usual indications
Antituberculosis drugs
First-line drugs
ethambutol (Myambutol)
Adult: 15 mg/kg/day PO as a single dose
Paediatric: not recommended for children
<13 years
Treatment of Mycobacterium tuberculosis
isoniazid (INH)
(generic)
Adult: 5 mg/kg/day PO
Paediatric: 10–12 mg/kg/day PO
Treatment of M. tuberculosis
rifampicin (Rifadin,
Rimycin)
Adult: 600 mg PO or IV as a single daily dose
Paediatric: 10–20 mg/kg/day PO or IV
Treatment of M. tuberculosis
Second-line drug
rifabutin (Mycobutin)
Adult: 300 mg PO daily
Second-line treatment of M. tuberculosis
Leprostatic drugs
clofazimine (Lamprene)
Adult: 50 mg PO daily and 300 mg PO monthly
Treatment of multibacillary forms of leprosy
dapsone (generic)
Adult: 50–100 mg/day PO
Paediatric: adjust dosage according to
bodyweight
Treatment of leprosy, Pneumocystis
carinii pneumonia in people with AIDS,
and a variety of infections caused by
susceptible bacteria and brown recluse
spider bites
In the 1950s, the drug thalidomide became
internationally known because it caused serious
abnormalities (e.g. lack of limbs, defective limbs) in
the fetuses of many women who received the drug
during pregnancy to help them sleep and to decrease
stress. This tragedy led to the recall of thalidomide
in the US and the establishment of more stringent
standards for drug testing and labelling. In 2010, the
TGA approved the use of this controversial drug for the
treatment of erythema nodosum leprosum, which is a
painful inflammatory condition related to an immune
reaction to dead bacteria that occurs after treatment
for leprosy. It is also approved for use in the treatment
of multiple myeloma, brain tumours, Crohn’s disease,
human immunodeficiency virus–wasting syndrome and
graft–host reaction in bone marrow transplant.
To take thalidomide, a woman must have a negative
pregnancy test, receive instruction in using birth control
and sign a release stating that she understands the risks
associated with the drug. These limits on the use of a
drug were the first such restrictions ever ordered by the
TGA.
Thalidomide (
Thalomid
) is given in doses of 100 to
400 mg/day PO at bedtime for at least 2 weeks, followed
by tapered dose in 50-mg increments over the next 2 to
4 weeks.
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BOX 9.6
New indication for thalidomide
