Biomedical Engineering Reference
In-Depth Information
of six months or more. h e daily administration of antibiotics has side
ef ects like nephrotoxicity and ototoxicity and longer duration of treatment
has resulted in low patience adherence [37]. To improve the treatment and
reduction in death cases due to tuberculosis, various chemotherapeutic
strategies against TB include :- (1)-Derivatization of the existing Anti-
tubercular drugs (ATDs) into more potent compounds. (2)-Screening of
the compounds which are active against replicating as well as latent bacilli.
(3)-Identii cation of novel drug targets and designing of appropriate inhib-
itors. (4)-Targeting of host-pathogen related processes which are essential
for the survival in the human diseases [38].
h e currently used vaccine for the tuberculosis treatment is Bacillus-
Calmette-Guerin (BCG) which provides extremely limited protection.
Recently, several
Mycobacterium tuberculosis
antigens have been identi-
i ed for potential use as vaccine antigens, including three protein Antigen
85 complex (Ag85A, Ag85B and Ag85C), the surface exposed lipoproteins
PstS (PstS-1, PstS-2 and PstS-3) and early secretary antigenic target pro-
tein ESAT-6 [39-41]. Cationic liposomes entrapped antigenic tuberculosis
ESAT-6 protein, complexed with TLR agonists was evaluated as a prophylac-
tic vaccine system by Zaks research group [42]. h ese control measures for
TB such as BCG vaccination and chemoprophylaxis has proven to be unsat-
isfactory, so there come anti-TB drugs the only option for TB treatment. h e
goal of treatment with drugs is to cure without relapse, to prevent death, to
stop transmission, and to prevent the emergence of drug resistance [43]. As
suggested by WHO, treatment of TB and drug resistant cases required multi-
drug therapy, comprising (a): an initial intensive phase of rifampicin (RIF),
isoniazid (INH), pyrazinamide (PYZ), ethambutol (ETB) for 2 months; and
(b): a continuation phase of RIF and INH for further 4 months, either daily
or 3 times per week has to be administered [44]. (Figure 14.4)
14.3.1
Action of anti-TB drugs
Rifampicin (RIF)
-Inhibition of bacterial RNA synthesis by binding to
the β subunit of bacterial DNA dependent-RNA polymerase, as a result
it inhibits RNA synthesis. It is one of the most ef ective anti-tuberculosis
agents and is bactericidal for extra and intracellular bacteria [45, 46].
Isoniazid (INH)
- It is most active drug for treatment of TB caused by
susceptible strains. It is a prodrug activated by katG, which exerts its lethal
ef ects by inhibiting the synthesis of mycolic acids, an essential component
of mycobacterial cell walls through formation of covalent complex with
an acyl carrier protein (AcpM) and KasA, a beta-ketoacyl carrier protein
synthetase [45, 47].
