ANTITUBERCULAR DRUGS

TUBERCULOSIS
• Chronic granulomatous disease
• Mycobacterium tuberculii
• 1/3rd of world’s population
• 40% of adults in India
• Mycobact.avium complex(MAC)
• Multidrug resistant(MDR)
 DIAGNOSIS
• CLINICAL

• BACTERIOLOGICAL

• RADIOLOGICAL
• Thiacetazone
-static,
-given orally,primarily excreted unchanged in urine.
S/E-anorexia,abd discomfort,loose motions,rashes
PAS
-static, inhibits synthesis of PABA
-orally administered, acetylated,
- anorexia,nausea,epigastric pain, liver dysfunction
etc
Ethionamide
-static ,extra/intracellular,atypical
-orally absorbed,pentrates cavities,
anorexia,nausea,abdupset,aches,pains,rashes,hepatitis,
neuritis
Cycloserine
-static, inhibits CW synthesis
-well absorbed orally, diffuses all over
-sleepiness, headache,tremor,psychosis,convulsions
Kanamycin,Amikacin,Capreomycin
-Reserve drugs, given only im
-no good penetration
-For resistance cases and atypical TB
• NEWER DRUGS
Ciprofloxacin,Ofloxacin,moxi,spar
-fluoroquinolones,effective against MAC
-effective in MAC ,MDR TB,in place of H,R,Z
-1500 mg/day
Clarithromycin,Azithromycin
-macrolides,MAC,atypical
Rifabutin
-Against myco.TB,MAC
-weak enzyme inducer
Principles of ATT Drug
therapy
 Kill dividing bacilli
 Kill persisting bacilli
 Prevent emergence of resistance
 Drug combinations (2 or 3 drugs must be used.
I& R are most efficacious and synergistic
combination ) are selected to maximize the above
actions
 Duration of Rx is reduced from 12 to 6 months.
 The DOTS (directly observed treatment short
course) was recommended by WHO in 1995.
 SHORT COURSE CHEMOTHERAPY
These are regimens of 6 to 9 months duration by
WHO & is applicable to both adults and children.
REGIMENS

Initial intensive phase Continuation phase

(2 to 3 months) (4 to 6 months)
Aimed to rapidly kill TB During which remaining
bacilli, sputum conversion & bacilli are eliminated so no
symptomatic relief. relapse.

Treatment of TB is categorized by : Site of disease

& severity, Sputum smear positivity or negativity,
History of previous treatment.
 RNTCP- DOTS(thrice weekly regimen)

TB category Initial Continu Duration

phase . phase
I: New smear +ve pulm TB, 2H3R3Z3E3 4H3R3 6 Months
new smear –ve pulm TB with
parenchymal invol & new
cases of extarpulm TB.
II: RX failure, relapse and RX 2H3R3Z3E3S3 8 Months
after interruption. +1H3 R3 Z3 E3 5H3R3E3

III: Cases of smear–ve pulm 2H3R3Z3 4H3R3 6 Months

TB with limited parenchymal
involvement/extrapulm TB.

Category IV: Mainly MDR cases. For H resistance-RZE for 12 mths.

For H+R resistance-ZE+S/Etm+Cipro/ofl
Directly Observed Treatment
Short course (DOTS)
 Alternative grouping of antitubercular
drugs

Group I First line oral anti-TB Isoniazid, Rifampin, Pyrazinamide, Ethambutol

drugs

Group II Injectable anti-TB drugs Streptomycin, Kanamycin, Amikacin, Capreomycin

Group III Fluroquinolones Ofloxacin, Levofloxacin, Moxifloxacin,

Ciprofloxacin
Group IV Second line anti-TB drugs Ethionamide, Prothionamide, Cycloserine,
Terizidone, Para-aminosalicyclic acid

Group V Drugs with unclear Thiacetazone, Clarithromycin, Clofazimine,

efficacy Linezolid, Amoxicillin/ Clavulanate,
Imipenem/Cilastatin
Multidrug resistant (MDR)
TB
 Extensively drug resistant TB

• Resistant to FQs & injectable 2nd line drugs

• Bacilli resistant to 4 cidal drugs – H, R, FQ &
one of Km/Am/Cm
• Difficult to treat high mortality
• Standard MDR regimen must be stopped
• Start with category V drugs
 MANAGEMENT OF ANTI-TB
ADR
 Symptomatic Rx without altering
medication if mild
 If severe, offending drug stopped.
 If possible, H&R should be continued
 Reintroduced after reaction has subsided by
challenging with small doses.
 H, R and Z all cause hepatotoxicity; if
develops, stop all and S+E may be started
or continued ; Fluoroquinolone added.
CHEMOPROPHYLAXIS OF TB
Indications:
 Household members and other close
contacts of a patient with active TB.
 A positive PPD test in childrens/adults
 A positive PPD test in the
immunocompromized persons with
leukemia, DM, silicosis and HIV + ve
patients
 Neonate of tubercular mother
 H/o TB but currently disease is inactive/ no
apparent symptoms
Drugs :
 H - 300mg (childrens -10mg/kg) daily for 6 -12
months
 R-10mg/kg daily for 4months (Hepatic diseases)
 H (5mg/kg) + R (10mg/kg) daily for 6months
 E + Z with or without FQ for MDR –TB

Main risk / contraindication for chemoprophylaxis :

Hepatic injury/ Active hepatic diseases

Pregnancy with TB : Drug treatment should never be

interrupted /postponed . H + R + Z for 6months
Except streptomycin
 TB IN AIDS PATIENTS
 More severe & serious problem , drug
regimen is same as for category I pts but the
continuation phase lasts for 7 months instead
of 4 months
 ADR’s more common
 MAC is more common – most effective
regimen is Clarithromycin (500mg bd) +
Ethambutol (15mg/kg/d) + Rifabutin (300mg
od ) or ciprofloxacin (750mg bd ) – all are
given orally
 Lifelong Rx is required
 Prophylaxis of MAC is afforded by
Clarithromycin/ Azithromycin
Regimen for MAC infection
 Newer Drugs for MDR TB
• Linezolid
• is used in combination with other drugs for
MDR/XDR
• Though bacteriostatic it achieves adequate
intracellular concentration
• ADR : anemia/ neuropathy /myelosupression
 • Bedaquiline (TMC 207)

• Diarylquinoline compound

• Acts by inhibiting mycobacterial ATP synthase

 • Delamanid
• Is an nitro-dihydro-imidazo-oxazole derivative

• It is a mycolic acid synthesis inhibitor

• 200- 400mg for 2 to 4 months

• ADR : QT prolongation

• Under evaluation