ANTIMYCOBACTERIALS

(ANTI-TBs)
 Antimycobacterials

1ST line 2nd line

Isoniazid Streptomycin
Rifampicin Amikacin
Pyrazinamide Ethionamide
Ethambutol Cycloserine
Streptomycin Capreomycin
Dapsone
1ST LINE DRUGS

1. ISONIAZID -
Mxn: disrupts metabolism in mycobacteria;
 structure similar to pyridoxine
Adm: oral
Abs: readily
Distribution: all body tissues and fluids including
CSF, placenta, breast milk

Elimination:
• Metabolism – liver
• Renal excretion
S/E
1. Peripheral neuropathy. May also lead to pyridoxine
deficiency
2. Hepatotoxicity – most severe S/E effect – (discontinue the
drug)
3. Hypersensitivity rxns – rash, fever
4. GIT disturbance

Drug interactions: (phenytoin)

Uses: TB
2. RIFAMPICIN–
Mxns:
1. Binds and inhibits bacterial DNA-dependent RNA
polymerase
2. Inhibits RNA synthesis

► Very Rapid development of resistance by mycobacteria,

never use alone
Adm: oral Abs: adequate
Distribution:
wide- into most tissues and fluids, inflamed meninges

Elimination:
Liver metabolism; some into bile,
Renal excretion - Minor

► Is a powerful enzyme inducer & induces its own

metabolism
S/E:
1. GIT irritation
2. Hypersensitivity – fever, itching, rash
3. Hepatitis – esp in those with hepatic insufficiency
4. Renal damage

Drug interactions
• Anticoagulants, anticonvulsants, chloramphenicol

Uses:
1. Mycobacterial infection Rx – first line
2. Mycobacterial prophylaxis – those at risk of TB
4. Leprosy
5. Brucellosis
3. PYRAZINAMIDE
Mxn: unknown
Adm: oral
Abs: well
Distribution: wide including CSF
S/E
• Hepatotoxicity
• GIT irritation
• Anemia
• Urticaria (An itchy skin eruption)
4. ETHAMBUTOL
Mnxs: inhibits a mycobacterial enzyme involved in cell wall
synthesis
Adm: oral
Abs: well
Distribtn: effective conc. in most tissues, inflamed meninges
Elimination: some metabolism, biliary and Renal excretion

S/E
• optic neuritis –(uni or bilateral, decreased visual aquity,
red-green color blindness, (discontinue drug –
reversible if prompt)
2ND LINE DRUGS

• More serious toxicities

1. STREPTOMYCIN (AMINOGLYCOSIDE)
USES:
• Severe tuberculosis (life threatening)
• disseminated TB
• resistant TB

2. AMIKACIN (AMINOGLYCOSIDE) – when the mycobacteria

are resistant to streptomycin and other drugs
3. ETHIONAMIDE
Adm: oral
Abs: effectively
Distribution: wide including CSF
Elimination: metabolized extensively
• Renal excretion
S/E
-GIT irritation: Intense
-Peripheral neuropathy: (pyridoxine helps)
-Optic neuritis
-hepatotoxic
4. CAPREOMYCIN:
Mxn: protein syn inhibitor
Adm: parenteral

S/E
1. Nephrotoxic
2. CnVIII damage – ototoxic – deafness,
imbalance, tinnitus
3. Pain and abscess at injection site

Uses: Drug resistant TB

5. CYCLOSERINE
• Mxn: cell wall syn inhibitor
• Adm: oral
• Abs: rapid
• Distribution: wide – tissues and fluids including
the CSF
• Elimination: Largely renal

• S/E
• Neurotoxic – improved by pyridoxine
(neuropathy)
 Regimens
H - Isoniazid RHZE
R - Rifampicin RHZ
RH
Z - Pyrazinamide
EH
E - Ethambutol
S - Streptomycin
ATYPICAL MYCOBACTERIA

LEPROSY (M. leprae)

1. SULFONES: e.g. dapsone

• Mnx: structural analogues of PABA, folate syn inhibitor

• Adm: oral
• Abs: well
• Distribution: wide – tissues and fluids

• S/E
• GIT disturbance (anorexia, nausea, vomiting)
• Hypersensitivity
• Neuropathy
2. RIFAMPICIN
• Uses: In combination with dapsone to stop
resistance
3. Ethionamide,
4. Thalidomide (teratogenic)

Regimen
• Tuberculoid leprosy- Dapsone & rifampicin for 6
months
THANK YOU