DRUGS
TYPICAL MYCOBACTERIA
M tuberculosis ACID FAST BACILLI
M bovis ZIEHL NEELSEN STAINING
ATYPICAL MYCOBACTERIA
M kansasii
M marinum
M scrofulaceum
M avium complex
M chelonae
M fortuitum
M ulcerans
M leprae
Selman Abraham Waksman
ANTI MYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSIS
FIRST LINE DRUGS
ISONIAZID
RIFAMPICIN
PYRAZINAMIDE
ETHAMBUTOL
STREPTOMYCIN
SECOND LINE DRUGS
AMIKACIN, THIACETAZONE
PARA AMINO SALICYLATE
ETHIONAMIDE & PROTHIONAMIDE
CIPROFLOXACIN/OFLOXACIN/MOXIFLOXACIN
RIFABUTIN
RIFAPENTIN
RIFAXIMIN
CLARITHROMYCIN
CYCLOSERINE & TERIZIDONE
CAPREOMYCIN
DRUGS FOR ATYPICAL MYCOBACTERIA
ERYTHROMYCIN
CLARITHROMYCIN
AZITHROMYCIN
RIFAMPICIN
QUINOLONES
RIFABUTIN
CONHNH2
INH
CH2OH
OH
H3C CH2OH
N
PYRIDOXIN
ADVANTAGES OF ISONIAZID
HIGHLY SELECTIVE AGAINST MYCOBACTERIA
BACTERICIDAL ACTION
COST- EFFECTIVE/EASILY AVAILABLE
ORALLY ADMINISTERED
WELL ABSORBED
WIDELY DISTRIBUTED IN BODY TISSUES/ FLUIDS
ENTERS MACROPHAGES
PENETRATES CASEOUS MATERIAL
CORSSES BLOOD BRAIN BARRIER
ONCE DAILY ADMINISTRATION
WELL TOLERATED
ADVERSE EFFECTS ISONIAZID
PERIPHERAL NEUROPATHY
HEPATOTOXICITY
HYPERSENSITIVITY REACTIONS
HEMATOLOGICAL REACTIONS
VASCULITIS
ARTHRALAGIA
METNAL DISTURBANCES (CNS TOXICITY)
GIT UPSETS
METHAEMOGLOBINAEMIA
INCORDINATION
SLE
MECHANISM OF ACTION OF ISONIAZID
INHIBITION OF MYCOLIC ACID SYNTHETASE
INHIBITION OF NUCLEIC ACID SYNTHESIS
INHIBITION OF LIPID SYNTHESIS
INHIBITION OF GLYCOLYSIS
MECHANISM OF RESISTANCE
MUTATION/DELETION OF CATALASE PEROXIDASE
(KATG)
MUTATION OF ACYL CARRIER PROTEINS
OVER EXPRESSION OF ENOYL ACYL CARRIER
PROTEIN REDUCTASE (INHA) ENZYME
USES OF ISONIAZID
ACTIVE T.B
TUBERCULIN +VE CONVERTERS OF
CLOSE CONTACT WITH ACTIVE CASES
TUBERCULIN +VE CASES ON IMMUNO
SUPPRESSIVE OR ANTINEOPLASTIC
CHEMOTHERAPY
DOSE: 300mg/d
SPECTRUM OF ACTIVITY RIFAMPICIN
M. tuberculosis
M. leprae
Atypical mycobacteria
Gram negative microorganism e.g. E.coli,
pseudomonas, Proteus, Klebsiella, Brucella
H.Influenzae, N.meningitidis
Staphylocci
Meningococci
Legionella
Chlamydia
Anti viral activity (pox virus)
Therapeutic uses of Rifampicin
Tuberculosis
Atypical mycobacterial infections
Chemoprophylaxis for meningococcal
disease and meningitis due to H. influenzae
Staph. endocarditis or osteomyelitis
Eradication of staph. nasal carrier state in
chronic furunculosis
Brucellosis
Legionnaires disease
Dose: 450 - 600mg/d or 10-20mg/kg
ADVERSE EFFECTS RIFAMPIN
HEPATOTOXICITY
THROMBOCYTOPENIA
CUTANEOUS REACTIONS
DISCOLORATION OF SECRETIONS
ON INTERMITTENT DOSING
FLU LIKE SYNDROME
ACUTE HEMOLYTIC ANEMIA
ACUTE RENAL FAILURE
DRUG INTERACTIONS
RIFABUTIN
HALF LIFE 36 HRS
LESS DRUG INTERACTIONS
REVERSIBLE UVEITIS
DRUG INTERACTIONS
FLUCONAZOLE
HIV PROTEASE INHIBITORS:INDINAVIR &
RITONAVIR, NON NUCLEOSIDE REVERSE
TRANSCRIPTASE INHIBITORS
Dose: 300mg o.d
RIFAPENTIN
HALF LIFE 13 HRS
POTENT ENZYME INDUCER
ACTIVE METABOLITE DESACETYLRIFAPENTIN
Dose: 600 mg once or twice weekly
ETHAMBUTOL
L isomer toxic
D isomer active
isomer no antibacterial activity
Mechanism of Action
Inhibit incorporation of mycolic acid
Inhibit RNA synthesis
Inhibit mycobacterial arabinogalactan synthesis in
cell wall
Adverse Effect
Retrobulbar neuritis
Red green colour blindness
Increase plasma uric acid
GIT
CNS
Dose: 15mg/kg to 25mg/kg
PYRAZINAMIDE
Bactericidal
Pro drug: active metabolite pyrazinoic acid by
enzyme pyrazinamidase
Kill persisters
Adverse effects
Arthralgia
Hepatitis
GIT
Allergy
Dysuria
Sideroplastic anaemia
Dose:20-30mg/kg or 1.5 -2.5g/d upto 3gm
STEROIDS IN TB
Massive pleural effusion
Pericardial effusion
Tuberculous meningitis
Miliary tuberculosis with involvement of
adrenal cortex
ANTITUBERCULOUS THERAPY
New Case
Induction Phase
RIF
INH
EMB
PZA
Continuation Phase
REGIMENS OF ANTITUBERCULOSIS DRUGS
New Cases
Patients who have not received treatment
For T.B previously
Patients who have taken the treatment for
less than 4 weeks
Initial Intensive Phase
Isoniazid
Rifampicin
Pyrazinamide For 02 months
Ethambutol
Continuation Phase
Isoniazid
Ethambutol For 06 months
Re- Treatment Cases
Relapse
Treatment failure
Non compliance after more than one month
Intensive Phase
Rifampicin
Isoniazid
Pyrazinamide For three months
Ethambutol
Streptomycin For first two months
Continuation Phase
Rifampicin
Isoniazid For five months
Ethambutol
INTERMITTENT REGIMENS
INH 15 mg/KG
TWICE WEEKLY
ETHAMBUTOL 50 mg/KG
DIRECTLY OBSERVED THERAPY (DOT)
Induction Phase & Continuation Phase
MULTIPLE DRUG RESISTANT TUBERCULOSIS (MDR-TB)
Cost 10 times & duration of treatment 3 times
EXTENSIVELY DRUG RESISTANT TUBERCULOSIS (XDR-TB)
PAN DRUG RESISTANT TUBERCULOSIS (PDR-TB)
TOTALLY DRUG RESISTANT TUBERCULOSIS (TDR-TB)
Treatment of tuberculosis during
pregnancy and lactation