366 Section 9/ Chemotherapyof tuberculosis are classified as in table
9.11.1.
FIRST LINE OR STANDARD DRUGSISONIAZID
It is the most active drug used in the
treatment of tuberculosis. It is a hydrazide of
isonicotinic acid. It is a bactericidal drug,
effective against Mycobacterium tuberculosis
and ineffective against atypical mycobacteria.
Isoniazid possibly exerts its action by
inhibiting the synthesis of mycolic acid
which is an essential component of
mycobacterial cell wall. It is also postulated
that the ability of isoniazid to suppress the
formation of DNA and RNA and also
inhibition of various oxidative mechanisms
may be responsible for its action.
Isoniazid is completely absorbed on oral
administration and penetrates all tissues of the
body. Peak plasma levels are reached within
one hour and persists for 24 hours. It penetrates
intracellularly and diffuses into macrophages
and the necrotic centres. It is metabolized in
liver by acetylation and isoniazid metabolites
and a small amount of unchanged drug is
excreted mainly by kidney.
Adverse effects include skin rash, fe-
ver, peripheral neuritis, nausea, vomiting,
weakness, dizziness, lethargy, slurred
speech, blurred vision, agranulocytosis,
hepatitis (which is dose related, common
in old people but rare in children), optic
neuritis, optic atrophy and convulsions.
RIFAMPICIN
It is a semisynthetic derivative of rifa-
mycin isolated from Streptomyces mediter-
ranei. It is bactericidal against Mycobacteri-
um tuberculosis and also against many
gram positive and negative organisms such
as Staph. aureus, pneumococci, Bacillus an-
thracis, N. gonorrhoeae, C. diphtheriae, men-
ingococci, H. influenzae and Streptococcus
faecalis.
It acts by inhibiting DNA-dependent
RNA polymerase and stopping the
expression of bacterial genes.
After oral administration, it is absorbed
well and distributed to different body
tissues and penetrates meninges, caseous
masses and placental barrier. It is
metabolized in liver to active deacylated
metabolite and induces the microsomal
enzymes in liver. It is excreted mainly in bile
and urine.
Adverse effects include skin rash, drug
fever, nausea, vomiting, peripheral neuropathy,
fatigue, hepatitis and jaundice, haemolytic
anaemia, diarrhoea, drowsiness, ataxia,
headache, flu like syndrome and stomatitis.
Apart from its main use in tuberculosis,
it is also used in leprosy and prophylaxis
of meningitis due to H. influenzae and
meningococci. It is also used with
doxycycline in treatment of brucellosis.STREPTOMYCIN
Detailed pharmacology is discussed in
chapter ‘Aminoglycoside antibiotics’.PYRAZINAMIDE
It is chemically related to nicotinamide
and thiosemicarbazone. It is bactericidal.
It is effective against Mycobacterium tuber-
culosis resistant to INH and streptomycin.
It is converted to pyrazinoic acid (active