Anti Tuberculosis Therapy
Anti Tuberculosis Therapy
Tuberculosis (TB)
Tuberculosis (TB)
Caused by mycobacterium tuberculosis
Caused by mycobacterium tuberculosis
The disease may have to be treated for
The disease may have to be treated for 66
months to
months to 22 years.
years.
Strains of M. Tuberculosis are resistant to a
Strains of M. Tuberculosis are resistant to a
particular agent emerge during treatment
particular agent emerge during treatment
with a single drug.
with a single drug.
Tuberculosis (TB)
Tuberculosis (TB)
Caused by mycobacterium tuberculosis
Caused by mycobacterium tuberculosis
The disease may have to be treated for
The disease may have to be treated for 66
months to
months to 22 years.
years.
Strains of M. Tuberculosis are resistant to a
Strains of M. Tuberculosis are resistant to a
particular agent emerge during treatment
particular agent emerge during treatment
with a single drug.
with a single drug.
Anti Tuberculosis Therapy
Anti Tuberculosis Therapy
First
First--line agents (
line agents (isoniazid
isoniazid,, rifampin
rifampin (or
(or
rifabutin
rifabutin or
or rifapentine
rifapentine),), ethambutol
ethambutol, and
, and
pyrazinamide
pyrazinamide are the principal or a first
are the principal or a first--line
line
drugs because of their efficacy and
drugs because of their efficacy and
acceptable degree of toxicity.
acceptable degree of toxicity.
Second
Second--line medications are either less
line medications are either less
effective, more toxic. They are useful in
effective, more toxic. They are useful in
patients :
patients :
Who cannot tolerate the first
Who cannot tolerate the first--line drugs
line drugs
Who are infected with
Who are infected with myobacteria
myobacteria that are
that are
resistant to the first
resistant to the first--line agents.
line agents.
Anti Tuberculosis Therapy
Anti Tuberculosis Therapy
First
First--line agents (
line agents (isoniazid
isoniazid,, rifampin
rifampin (or
(or
rifabutin
rifabutin or
or rifapentine
rifapentine),), ethambutol
ethambutol, and
, and
pyrazinamide
pyrazinamide are the principal or a first
are the principal or a first--line
line
drugs because of their efficacy and
drugs because of their efficacy and
acceptable degree of toxicity.
acceptable degree of toxicity.
Second
Second--line medications are either less
line medications are either less
effective, more toxic. They are useful in
effective, more toxic. They are useful in
patients :
patients :
Who cannot tolerate the first
Who cannot tolerate the first--line drugs
line drugs
Who are infected with
Who are infected with myobacteria
myobacteria that are
that are
resistant to the first
resistant to the first--line agents.
line agents.
Drug Resistance
Drug Resistance
Strains of M. Tuberculosis that are resistant to a
Strains of M. Tuberculosis that are resistant to a
particular agent during treatment with a single
particular agent during treatment with a single
drug.
drug.
Multidrug therapy is employed when treating
Multidrug therapy is employed when treating
tuberculosis to delay or prevent the resistant
tuberculosis to delay or prevent the resistant
strains.
strains.
A minimum of two drugs, preferably with both
A minimum of two drugs, preferably with both
being bactericidal
being bactericidal
Drug Resistance
Drug Resistance
Strains of M. Tuberculosis that are resistant to a
Strains of M. Tuberculosis that are resistant to a
particular agent during treatment with a single
particular agent during treatment with a single
drug.
drug.
Multidrug therapy is employed when treating
Multidrug therapy is employed when treating
tuberculosis to delay or prevent the resistant
tuberculosis to delay or prevent the resistant
strains.
strains.
A minimum of two drugs, preferably with both
A minimum of two drugs, preferably with both
being bactericidal
being bactericidal
Treatment regimens include
Treatment regimens include
The combination of drugs should prevent the
The combination of drugs should prevent the
emergence of resistant strains.
emergence of resistant strains.
The multidrug regimen is continued well beyond
The multidrug regimen is continued well beyond
the disappearance of clinical disease to eradicate
the disappearance of clinical disease to eradicate
any persistent organisms.
any persistent organisms.
For example
For example
:: The initial short
The initial short--course
course
chemotherapy for tuberculosis
chemotherapy for tuberculosis
includes isoniazid, rifampin,
includes isoniazid, rifampin,
ethambutol
ethambutol,, and pyrazinamide for
and pyrazinamide for 22
months and then isoniazid and
months and then isoniazid and
rifampin for the next
rifampin for the next 44 months (the
months (the
continuation phase).
continuation phase).
Treatment regimens include
Treatment regimens include
The combination of drugs should prevent the
The combination of drugs should prevent the
emergence of resistant strains.
emergence of resistant strains.
The multidrug regimen is continued well beyond
The multidrug regimen is continued well beyond
the disappearance of clinical disease to eradicate
the disappearance of clinical disease to eradicate
any persistent organisms.
any persistent organisms.
For example
For example
:: The initial short
The initial short--course
course
chemotherapy for tuberculosis
chemotherapy for tuberculosis
includes isoniazid, rifampin,
includes isoniazid, rifampin,
ethambutol
ethambutol,, and pyrazinamide for
and pyrazinamide for 22
months and then isoniazid and
months and then isoniazid and
rifampin for the next
rifampin for the next 44 months (the
months (the
continuation phase).
continuation phase).
One of several recommended multidrug schedules for
One of several recommended multidrug schedules for
the treatment of tuberculosis
the treatment of tuberculosis
Isoniazid
Isoniazid
The most potent
The most potent antitubercular
antitubercular drugs
drugs
Isoniazid is bacteriostatic (for bacilli in the
Isoniazid is bacteriostatic (for bacilli in the
stationary phase), but it is bactericidal (for
stationary phase), but it is bactericidal (for
rapidly dividing organisms)
rapidly dividing organisms)
It is never given as a single agent in the
It is never given as a single agent in the
treatment of active tuberculosis
treatment of active tuberculosis
It inhibits cell wall synthesis by covalently binding
It inhibits cell wall synthesis by covalently binding
and inhibiting the enzymes, which are essential
and inhibiting the enzymes, which are essential
for the synthesis of
for the synthesis of mycolic
mycolic acid that is found in
acid that is found in
mycobacterial
mycobacterial cell walls.
cell walls.
Isoniazid
Isoniazid
The most potent
The most potent antitubercular
antitubercular drugs
drugs
Isoniazid is bacteriostatic (for bacilli in the
Isoniazid is bacteriostatic (for bacilli in the
stationary phase), but it is bactericidal (for
stationary phase), but it is bactericidal (for
rapidly dividing organisms)
rapidly dividing organisms)
It is never given as a single agent in the
It is never given as a single agent in the
treatment of active tuberculosis
treatment of active tuberculosis
It inhibits cell wall synthesis by covalently binding
It inhibits cell wall synthesis by covalently binding
and inhibiting the enzymes, which are essential
and inhibiting the enzymes, which are essential
for the synthesis of
for the synthesis of mycolic
mycolic acid that is found in
acid that is found in
mycobacterial
mycobacterial cell walls.
cell walls.
Pharmacokinetics of
Pharmacokinetics of Isoniazid
Isoniazid
Orally administered
Orally administered
Absorption is impaired if
Absorption is impaired if isoniazid
isoniazid is taken with
is taken with
carbohydrates, or with aluminum
carbohydrates, or with aluminum--containing antacids.
containing antacids.
It undergoes N
It undergoes N--acetylation and hydrolysis, resulting in
acetylation and hydrolysis, resulting in
inactive products (Chronic liver disease decreases
inactive products (Chronic liver disease decreases
metabolism).
metabolism).
Excretion is through
Excretion is through glomerular
glomerular filtration,
filtration,
predominantly as metabolites
predominantly as metabolites
Note:
Note:
Acetylation is genetically regulated.
Acetylation is genetically regulated.
The fast
The fast acetylators
acetylators
Slow
Slow acetylators
acetylators ((excrete more of the parent
excrete more of the parent
compound).
compound). so,Severely
so,Severely depressed renal
depressed renal
function results in accumulation of the drug,
function results in accumulation of the drug,
primarily in slow
primarily in slow acetylators
acetylators..
Pharmacokinetics of
Pharmacokinetics of Isoniazid
Isoniazid
Orally administered
Orally administered
Absorption is impaired if
Absorption is impaired if isoniazid
isoniazid is taken with
is taken with
carbohydrates, or with aluminum
carbohydrates, or with aluminum--containing antacids.
containing antacids.
It undergoes N
It undergoes N--acetylation and hydrolysis, resulting in
acetylation and hydrolysis, resulting in
inactive products (Chronic liver disease decreases
inactive products (Chronic liver disease decreases
metabolism).
metabolism).
Excretion is through
Excretion is through glomerular
glomerular filtration,
filtration,
predominantly as metabolites
predominantly as metabolites
Note:
Note:
Acetylation is genetically regulated.
Acetylation is genetically regulated.
The fast
The fast acetylators
acetylators
Slow
Slow acetylators
acetylators ((excrete more of the parent
excrete more of the parent
compound).
compound). so,Severely
so,Severely depressed renal
depressed renal
function results in accumulation of the drug,
function results in accumulation of the drug,
primarily in slow
primarily in slow acetylators
acetylators..
Adverse effects of Isoniazid
Adverse effects of Isoniazid
1.
1. Peripheral neuritis:
Peripheral neuritis: due to pyridoxine deficiency.
due to pyridoxine deficiency.
This side effect can be corrected by
This side effect can be corrected by
supplementation of
supplementation of 25
25 to
to 50
50 mg per day of
mg per day of
pyridoxine (vitamin B
pyridoxine (vitamin B
66
))
2.
2. Hepatitis
Hepatitis
3.
3. Mental abnormalities,
Mental abnormalities, convulsions and optic
convulsions and optic
neuritis.
neuritis.
4.
4. Hypersensitivity reactions (rashes and fever).
Hypersensitivity reactions (rashes and fever).
5.
5. Drug interactions:
Drug interactions: isoniazid
isoniazid inhibits metabolism of
inhibits metabolism of
phenytoin
phenytoin
Adverse effects of Isoniazid
Adverse effects of Isoniazid
1.
1. Peripheral neuritis:
Peripheral neuritis: due to pyridoxine deficiency.
due to pyridoxine deficiency.
This side effect can be corrected by
This side effect can be corrected by
supplementation of
supplementation of 25
25 to
to 50
50 mg per day of
mg per day of
pyridoxine (vitamin B
pyridoxine (vitamin B
66
))
2.
2. Hepatitis
Hepatitis
3.
3. Mental abnormalities,
Mental abnormalities, convulsions and optic
convulsions and optic
neuritis.
neuritis.
4.
4. Hypersensitivity reactions (rashes and fever).
Hypersensitivity reactions (rashes and fever).
5.
5. Drug interactions:
Drug interactions: isoniazid
isoniazid inhibits metabolism of
inhibits metabolism of
phenytoin
phenytoin
Rifamycins
Rifamycins::
(Rifampin,
(Rifampin, Rifabutin
Rifabutin and
and Rifapentine
Rifapentine))
They are first
They are first--line drugs for tuberculosis
line drugs for tuberculosis
Used in combination with at least one other
Used in combination with at least one other
antituberculosis
antituberculosis drug
drug
Rifampin
Rifampin
Has a broader antimicrobial activity than
Has a broader antimicrobial activity than
Isoniazid
Isoniazid
It is bactericidal for M. tuberculosis
It is bactericidal for M. tuberculosis
Rifampin
Rifampin blocks transcription by interacting with
blocks transcription by interacting with
the bacterial DNA
the bacterial DNA--dependent RNA polymerase
dependent RNA polymerase
Resistance to
Resistance to Rifampin
Rifampin can be caused by :
can be caused by :
Mutation in the affinity of the bacterial DNA
Mutation in the affinity of the bacterial DNA--
dependent RNA polymerase for the drug
dependent RNA polymerase for the drug
Decreased permeability.
Decreased permeability.
Rifampin
Rifampin
Has a broader antimicrobial activity than
Has a broader antimicrobial activity than
Isoniazid
Isoniazid
It is bactericidal for M. tuberculosis
It is bactericidal for M. tuberculosis
Rifampin
Rifampin blocks transcription by interacting with
blocks transcription by interacting with
the bacterial DNA
the bacterial DNA--dependent RNA polymerase
dependent RNA polymerase
Resistance to
Resistance to Rifampin
Rifampin can be caused by :
can be caused by :
Mutation in the affinity of the bacterial DNA
Mutation in the affinity of the bacterial DNA--
dependent RNA polymerase for the drug
dependent RNA polymerase for the drug
Decreased permeability.
Decreased permeability.
Pharmacokinetics of
Pharmacokinetics of Rifampin
Rifampin
Oral administration
Oral administration
The drug is taken up by the liver and
The drug is taken up by the liver and
undergoes
undergoes enterohepatic
enterohepatic cycling
cycling
It is inducer of cytochrome P
It is inducer of cytochrome P450
450 enzymes.
enzymes.
Cause orange
Cause orange--red color of the urine,
red color of the urine,
feces,Tears
feces,Tears and other secretions, stain soft
and other secretions, stain soft
contact lenses
contact lenses
Pharmacokinetics of
Pharmacokinetics of Rifampin
Rifampin
Oral administration
Oral administration
The drug is taken up by the liver and
The drug is taken up by the liver and
undergoes
undergoes enterohepatic
enterohepatic cycling
cycling
It is inducer of cytochrome P
It is inducer of cytochrome P450
450 enzymes.
enzymes.
Cause orange
Cause orange--red color of the urine,
red color of the urine,
feces,Tears
feces,Tears and other secretions, stain soft
and other secretions, stain soft
contact lenses
contact lenses
Adverse Effects of Rifampin
Adverse Effects of Rifampin
1.
1. Nausea, vomiting,
Nausea, vomiting, and rash
and rash
2.
2. Hepatitis (specially in alcoholic, elderly or have
Hepatitis (specially in alcoholic, elderly or have
chronic liver disease)
chronic liver disease)
3.
3. A flu
A flu--like syndrome (fever, chills, and
like syndrome (fever, chills, and myalgias
myalgias))
4.
4. Acute renal failure
Acute renal failure
5.
5. Hemolytic anemia
Hemolytic anemia
6.
6. Shock.
Shock.
Adverse Effects of Rifampin
Adverse Effects of Rifampin
1.
1. Nausea, vomiting,
Nausea, vomiting, and rash
and rash
2.
2. Hepatitis (specially in alcoholic, elderly or have
Hepatitis (specially in alcoholic, elderly or have
chronic liver disease)
chronic liver disease)
3.
3. A flu
A flu--like syndrome (fever, chills, and
like syndrome (fever, chills, and myalgias
myalgias))
4.
4. Acute renal failure
Acute renal failure
5.
5. Hemolytic anemia
Hemolytic anemia
6.
6. Shock.
Shock.
Rifabutin
Rifabutin
Use in tuberculosis
Use in tuberculosis--infected with the human
infected with the human
immunodeficiency virus (HIV) patients who
immunodeficiency virus (HIV) patients who
are concomitantly treated with protease
are concomitantly treated with protease
inhibitors or
inhibitors or nonnucleoside
nonnucleoside reverse
reverse
transcriptase inhibitors,
transcriptase inhibitors,
It is a less potent inducer of cytochrome P
It is a less potent inducer of cytochrome P450
450
enzymes.
enzymes.
Rifabutin
Rifabutin has adverse effects similar to those
has adverse effects similar to those
of
of Rifampin
Rifampin but can also cause
but can also cause uveitis
uveitis, skin
, skin
hyperpigmentation
hyperpigmentation, and
, and neutropenia
neutropenia..
Rifabutin
Rifabutin
Use in tuberculosis
Use in tuberculosis--infected with the human
infected with the human
immunodeficiency virus (HIV) patients who
immunodeficiency virus (HIV) patients who
are concomitantly treated with protease
are concomitantly treated with protease
inhibitors or
inhibitors or nonnucleoside
nonnucleoside reverse
reverse
transcriptase inhibitors,
transcriptase inhibitors,
It is a less potent inducer of cytochrome P
It is a less potent inducer of cytochrome P450
450
enzymes.
enzymes.
Rifabutin
Rifabutin has adverse effects similar to those
has adverse effects similar to those
of
of Rifampin
Rifampin but can also cause
but can also cause uveitis
uveitis, skin
, skin
hyperpigmentation
hyperpigmentation, and
, and neutropenia
neutropenia..
Rifampin induces cytochrome P
Rifampin induces cytochrome P450
450, which can decrease the half
, which can decrease the half--
lives of
lives of coadministered
coadministered drugs that are metabolized by
drugs that are metabolized by this system
this system
Pyrazinamide
Pyrazinamide
It is bactericidal to actively dividing organisms
It is bactericidal to actively dividing organisms
Orally effective
Orally effective
Used in combination with
Used in combination with isoniazid
isoniazid,, rifampin
rifampin,,
and
and ethambutol
ethambutol..
Pyrazinamide
Pyrazinamide distributes throughout the body,
distributes throughout the body,
penetrating the CSF.
penetrating the CSF.
It undergoes extensive metabolism (may cause
It undergoes extensive metabolism (may cause
liver dysfunction).
liver dysfunction).
Urate
Urate retention can also occur and may
retention can also occur and may
precipitate a gouty attack .
precipitate a gouty attack .
Pyrazinamide
Pyrazinamide
It is bactericidal to actively dividing organisms
It is bactericidal to actively dividing organisms
Orally effective
Orally effective
Used in combination with
Used in combination with isoniazid
isoniazid,, rifampin
rifampin,,
and
and ethambutol
ethambutol..
Pyrazinamide
Pyrazinamide distributes throughout the body,
distributes throughout the body,
penetrating the CSF.
penetrating the CSF.
It undergoes extensive metabolism (may cause
It undergoes extensive metabolism (may cause
liver dysfunction).
liver dysfunction).
Urate
Urate retention can also occur and may
retention can also occur and may
precipitate a gouty attack .
precipitate a gouty attack .
Pyrazinamide
Pyrazinamide and
and ethambutol
ethambutol may cause
may cause urate
urate
retention and gouty attacks
retention and gouty attacks
Ethambutol
Ethambutol
It is bacteriostatic
It is bacteriostatic
Ethambutol
Ethambutol inhibits the enzyme that is important
inhibits the enzyme that is important
for the synthesis of the mycobacterial cell wall.
for the synthesis of the mycobacterial cell wall.
Ethambutol
Ethambutol can be used in combination with
can be used in combination with
pyrazinamide
pyrazinamide,, isoniazid
isoniazid, and
, and rifampin
rifampin to treat
to treat
tuberculosis.
tuberculosis.
Oral administration
Oral administration
It used for
It used for tuberculous
tuberculous meningitis (Penetrate into
meningitis (Penetrate into
the central nervous system).
the central nervous system).
The drug and its metabolites are excreted by kidney
The drug and its metabolites are excreted by kidney
The most important adverse effect is optic neuritis
The most important adverse effect is optic neuritis
Urate
Urate excretion is decreased by the drug
excretion is decreased by the drug
Ethambutol
Ethambutol
It is bacteriostatic
It is bacteriostatic
Ethambutol
Ethambutol inhibits the enzyme that is important
inhibits the enzyme that is important
for the synthesis of the mycobacterial cell wall.
for the synthesis of the mycobacterial cell wall.
Ethambutol
Ethambutol can be used in combination with
can be used in combination with
pyrazinamide
pyrazinamide,, isoniazid
isoniazid, and
, and rifampin
rifampin to treat
to treat
tuberculosis.
tuberculosis.
Oral administration
Oral administration
It used for
It used for tuberculous
tuberculous meningitis (Penetrate into
meningitis (Penetrate into
the central nervous system).
the central nervous system).
The drug and its metabolites are excreted by kidney
The drug and its metabolites are excreted by kidney
The most important adverse effect is optic neuritis
The most important adverse effect is optic neuritis
Urate
Urate excretion is decreased by the drug
excretion is decreased by the drug
Alternate second
Alternate second--line Drugs
line Drugs
(Streptomycin,
(Streptomycin, para
para--aminosalicylic
aminosalicylic acid,
acid,
ethionamide
ethionamide,, cycloserine
cycloserine,, capreomycin
capreomycin,,
fluoroquinolones
fluoroquinolones, and
, and macrolides
macrolides))
They are particularly active against atypical strains
They are particularly active against atypical strains
of
of mycobacteria
mycobacteria
They are no more effective than the first
They are no more effective than the first--line
line
agents toxicities
agents toxicities
They are often more serious toxicities
They are often more serious toxicities
Alternate second
Alternate second--line Drugs
line Drugs
(Streptomycin,
(Streptomycin, para
para--aminosalicylic
aminosalicylic acid,
acid,
ethionamide
ethionamide,, cycloserine
cycloserine,, capreomycin
capreomycin,,
fluoroquinolones
fluoroquinolones, and
, and macrolides
macrolides))
They are particularly active against atypical strains
They are particularly active against atypical strains
of
of mycobacteria
mycobacteria
They are no more effective than the first
They are no more effective than the first--line
line
agents toxicities
agents toxicities
They are often more serious toxicities
They are often more serious toxicities
Streptomycin
Streptomycin
Its action is directed against extracellular
Its action is directed against extracellular
organisms.
organisms.
Infections due to streptomycin
Infections due to streptomycin--resistant organisms
resistant organisms
may be treated with
may be treated with kanamycin
kanamycin or
or amikacin
amikacin, to
, to
which these bacilli remain sensitive.
which these bacilli remain sensitive.
Capreomycin
Capreomycin: it inhibits protein
: it inhibits protein synthesis,it
synthesis,it isis
administered
administered parenterally
parenterally..
Capreomycin
Capreomycin is primarily reserved for the
is primarily reserved for the
treatment of multidrug
treatment of multidrug--resistant tuberculosis.
resistant tuberculosis.
Careful monitoring of the patient is necessary to
Careful monitoring of the patient is necessary to
prevent its
prevent its nephrotoxicity
nephrotoxicity and
and ototoxicity
ototoxicity
Streptomycin
Streptomycin
Its action is directed against extracellular
Its action is directed against extracellular
organisms.
organisms.
Infections due to streptomycin
Infections due to streptomycin--resistant organisms
resistant organisms
may be treated with
may be treated with kanamycin
kanamycin or
or amikacin
amikacin, to
, to
which these bacilli remain sensitive.
which these bacilli remain sensitive.
Capreomycin
Capreomycin: it inhibits protein
: it inhibits protein synthesis,it
synthesis,it isis
administered
administered parenterally
parenterally..
Capreomycin
Capreomycin is primarily reserved for the
is primarily reserved for the
treatment of multidrug
treatment of multidrug--resistant tuberculosis.
resistant tuberculosis.
Careful monitoring of the patient is necessary to
Careful monitoring of the patient is necessary to
prevent its
prevent its nephrotoxicity
nephrotoxicity and
and ototoxicity
ototoxicity
Cycloserine
Cycloserine
Orally effective agent
Orally effective agent
Antagonize bacterial cell wall synthesis.
Antagonize bacterial cell wall synthesis.
The drugs and its metabolite are excreted in
The drugs and its metabolite are excreted in
urine.
urine.
Adverse Effects of
Adverse Effects of Cycloserine
Cycloserine
1.
1. CNS disturbances
CNS disturbances
2.
2. Exacerbation of epileptic seizure .
Exacerbation of epileptic seizure .
3.
3. Peripheral neuropathies, but respond to
Peripheral neuropathies, but respond to
pyridoxine.
pyridoxine.
Cycloserine
Cycloserine
Orally effective agent
Orally effective agent
Antagonize bacterial cell wall synthesis.
Antagonize bacterial cell wall synthesis.
The drugs and its metabolite are excreted in
The drugs and its metabolite are excreted in
urine.
urine.
Adverse Effects of
Adverse Effects of Cycloserine
Cycloserine
1.
1. CNS disturbances
CNS disturbances
2.
2. Exacerbation of epileptic seizure .
Exacerbation of epileptic seizure .
3.
3. Peripheral neuropathies, but respond to
Peripheral neuropathies, but respond to
pyridoxine.
pyridoxine.
Ethionamide
Ethionamide (a structural analog of
(a structural analog of isoniazid
isoniazid))
It inhibit
It inhibit acetylation
acetylation of
of isoniazid
isoniazid..
Oral administration
Oral administration
Widely distributed throughout the body, including
Widely distributed throughout the body, including
the CSF.
the CSF.
Metabolism is extensive,
Metabolism is extensive,
The main route of excretion is the urine .
The main route of excretion is the urine .
Adverse effects of
Adverse effects of Ethionamide
Ethionamide
1.
1. Gastric irritation
Gastric irritation
2.
2. Hepatotoxicity
Hepatotoxicity
3.
3. Peripheral neuropathies
Peripheral neuropathies
4.
4. Optic neuritis
Optic neuritis
Note:
Note:
Supplementation with pyridoxine decrease
Supplementation with pyridoxine decrease
severity of the neurologic side effects.
severity of the neurologic side effects.
Ethionamide
Ethionamide (a structural analog of
(a structural analog of isoniazid
isoniazid))
It inhibit
It inhibit acetylation
acetylation of
of isoniazid
isoniazid..
Oral administration
Oral administration
Widely distributed throughout the body, including
Widely distributed throughout the body, including
the CSF.
the CSF.
Metabolism is extensive,
Metabolism is extensive,
The main route of excretion is the urine .
The main route of excretion is the urine .
Adverse effects of
Adverse effects of Ethionamide
Ethionamide
1.
1. Gastric irritation
Gastric irritation
2.
2. Hepatotoxicity
Hepatotoxicity
3.
3. Peripheral neuropathies
Peripheral neuropathies
4.
4. Optic neuritis
Optic neuritis
Note:
Note:
Supplementation with pyridoxine decrease
Supplementation with pyridoxine decrease
severity of the neurologic side effects.
severity of the neurologic side effects.
Aminosalicylic
Aminosalicylic acid and
acid and ethionamide
ethionamide can inhibit the
can inhibit the
acetylation
acetylation of
of isoniazid
isoniazid
Fluoroquinolones
Fluoroquinolones::
Moxifloxacin
Moxifloxacin and
and levofloxacin
levofloxacin, have an
, have an
important place in the treatment of multidrug
important place in the treatment of multidrug--
resistant tuberculosis.
resistant tuberculosis.
Macrolides
Macrolides::
Azithromycin
Azithromycin and
and Clarithromycin
Clarithromycin, are part of the
, are part of the
regimen that includes
regimen that includes ethambutol
ethambutol and
and rifabutin
rifabutin
used for the treatment of infections by M.
used for the treatment of infections by M.
avium
avium--intracellulare
intracellulare complex.
complex.
Note:
Note:
Azithromycin is preferred for HIV
Azithromycin is preferred for HIV--infected
infected
patients because it is least likely to interfere
patients because it is least likely to interfere
with the metabolism of antiretroviral drugs.
with the metabolism of antiretroviral drugs.
Fluoroquinolones
Fluoroquinolones::
Moxifloxacin
Moxifloxacin and
and levofloxacin
levofloxacin, have an
, have an
important place in the treatment of multidrug
important place in the treatment of multidrug--
resistant tuberculosis.
resistant tuberculosis.
Macrolides
Macrolides::
Azithromycin
Azithromycin and
and Clarithromycin
Clarithromycin, are part of the
, are part of the
regimen that includes
regimen that includes ethambutol
ethambutol and
and rifabutin
rifabutin
used for the treatment of infections by M.
used for the treatment of infections by M.
avium
avium--intracellulare
intracellulare complex.
complex.
Note:
Note:
Azithromycin is preferred for HIV
Azithromycin is preferred for HIV--infected
infected
patients because it is least likely to interfere
patients because it is least likely to interfere
with the metabolism of antiretroviral drugs.
with the metabolism of antiretroviral drugs.