Antimycobacterial Drugs
Mechanism of action
• It is activated by mycobacterial catalase peroxidase.
• It targets enzymes Acyl carrier protein reductase and
beta ketoacyl-ACP-synthase and inhibits mycolic acid
synthesis
Isoniazid is a structural congener
of
Pharmacokinetics
• Liver metabolism of INH by acetylation
• INH halflife in “fast acetylators” is 60–90 min
• In “slow acetylators” it may be 3–4 h
Clinical use
• 1st line treatment for T.B
• Treatment of latent infection(close contact
patient)
Toxicity(S.H.A.N)
• SLE (lupus like syndrome)
• Hepatotoxic(abnormal LFT,jaundice,hepatitis and
inhibitors of hepatic metabolism)
• Anemia(hemolysis in G6PD)
• Neurotoxic(peripheral neuritis)
• First, INH metabolites directly inactivate pyridoxine species.
• Secondly,It also acts by inhibiting the enzyme pyridoxine
phosphokinase which is a necessary enzyme to convert
pyridoxine to its active form of pyridoxal 5' phosphate which
is a very important cofactor in many reactions.
Rifampicin
Mechanism of action
Mechanism of resistance
• Resistance via changes in drug sensitivity of
the polymerase often emerges rapidly if the
drug is used alone
Clinical uses
• Treatment of TB
• Treatment of latent TB in INH intolerant patients
• In leprosy
• Vancomycin + rifampin for MRSA and PRSP
• Prophylaxis of H.Influenza
• For meningococcal and staphylococcal carrier state
Toxicity (RANA has Red tissue for Flu)
• Rash
• Anemia
• Nephritis
• Hepatic dysfunction
• Sweat,urine,tear color is orange
• Flue like syndrome
Rifabutin Less likely to cause drug interaction
Preferred for TB coinfected with HIV who
are receiving protease inhibitor and
NNRTIs.less potent inducer than rifampin.
Rifapentin More potent than rifampin.used one in a
weekly with Isoniazid in TB
Rifaximin Don’t absorb from GI tractt and use for
Travellers diarrhea
Ethanbutol
• Ethambutol inhibits Arabinosyltransferase
involved in synthesis of arabinogalactan(a
component of mycobacterial cell wall
Toxicity
• Visual disturbance(dec visual acquity,red
green color blindness ,optic neuritis and
retinal damage)
• Hyperuricemia
• Headache
Drug Interactions Should be used
• Confusion in caution in
• Peripheral neuritis
Pyrazinamide
Mechanism of Action
• bacteriostatic action appears to require
metabolic conversion via pyrazinamidases to
Pyrazinoic Ac
Mechanism of resistance
• Mutation
• Increase efflux
Toxicity(3PM2 GHQ)
• Porphyria
• Photosenstivity
• Avoid in pregnancy
• Myalgia
• Macopopular rash
• GI irritation
• Hepatic dysfunction
Streptomycin
• Already discussed in aminoglycoside
Alternative drugs
• Amikacin
• Cipro and Ofloxacin
• Ethionamide
• P Amino salicylic acid
• Capreomycin
• Cycloserine
• Bedaquiline
Drug Regieme
Standard Regieme
Empric treatment
If INH resistance less than 4% INH,Rifampin,pyrazinamide
If person is suspectible and patient is HIV pyrazinamide can be discontinued after 2
negative month
treatment continued for a further 4 mo
with a 2-drug regimen
Alternative
INH+Rifampin 9 month
INH+ethanbutol 18 month
Resistance
• If higher than 4% resistance to INH
• Rifampin+pyrazinamide+ethanbutol or streptomycin for 6
months
• MDR→ resitant to both isoniazid and rifampin
• Treat with 3 or more drug →18 month
• 9 month Theray : INH + rifampin for 9 month
• 18 month Theray :INH+ ethambutol for 18
month
Drugs for leprosy
Dapsone
• mechanism of action of sulfones may involve
inhibition of folic acid synthesis
• It is recommended that the drug be used in
combinationswith rifampin and/or clofazin
Clinical Use
• most active drug against M leprae
Toxicity
• gastrointestinal irritation
• Fever
• skin rashes
• Methemoglobinemia
• Hemolysis may occur, especially in patients
with G6PDH deficiency
DRUGS FOR ATYPICAL MYCOBACTERIAL
INFECTIONS
• Mycobacterium avium complex (MAC) is a cause of
disseminated infections in AIDS patients.
• Currently, clarithromycin or azithromycin with or without
rifabutin is recommended for primary prophylaxis in
patients with CD4 counts less than 50/μL.
• Treatment of MAC infections requires a combination of
drugs, one favored regimen consisting of azithromycin or
clarithromycin with ethambutol and rifabutin.
• Infections resulting from other atypical mycobacteria (eg, M
marinum, M ulcerans), though sometimes asymptomatic, may
be treated with the described antimycobacterial drugs (eg,
ethambutol, INH, rifampin) or other antibiotics (eg, amikacin,
cephalosporins, fluoroquinolones, macrolides, or
tetracyclines).
