Transcript In The Name Of Allah

In The Name Of God
Antimycobacterial Drugs
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Mycobacterial infections are among
the most difficult infections to cure
because:
1.Slowly growing nature
2.Substantial proportion of bacteria
is intracellular (phagocytes)
3.Lipid rich cell wall
4.Rapid emerge of resistance
Drugs are used in
Tuberculosis
First line drugs
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Isoniazid (INH)
Rifampin (Rifamycin)
Ethambutol
Pyrazinamide
Streptomycin
Isoniazid
 Structurally similar to pyridoxine
 Bactericidal activity against M.
tuberculosis and less activity
against atypical strains
 Inhibit mycolic acid synthesis in cell
wall
 It is activated by catalaseperoxydase enzymes
Pharmacokinetics
• It is small (MW 137) and has Well
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absorption from GI and readily diffuses to
all body tissues and fluids
Acetylation by liver enzymes
In CSF reaches to 20~100 % of blood levels
Half life is about 1-3hrs
Dose adjustment is necessary in hepatic
insufficiency(1/2 to 1/3) while the dose
need not be adjusted in renal failure
Clinical Uses
• As single agent for prevention of
active tuberculosis (TB) in high risk
groups
• In active TB, only in combination
with other drugs is recommended
• Supplementation therapy with Vit.B6
(30mg/d) is recommended to prevent
central and peripheral neuropathy
Adverse Drug Reactions
• Depends to dose and duration of
treatment
• Allergic reactions (fever, rashs, SLE)
• Hepatotoxicity
• Central and peripheral neuropathy
• Isoniazid can reduce the metabolism
of phenytoin, increasing its blood
level and toxicity.
Predisposing conditions
for Neuropathy
• Slow acetylators
• Elderly patients with
malnutrition
• Alcoholism
• Diabetes
• AIDS
• Uremia
Rifampin
• A large complex derivative (Mw=823)
of rifamycin produced from St.
mediterenri
• Broad activity against gram – and +
bacteria, enterobacteriacea,
Chlamydia and Mycobacterium
Species.
• Has no cross resistance with other
antituberclosis drugs except for
Rifabuten
Antibacterial Activity
• Inhibits DNA –dependent RNA
polymerase
• Penetrates well to the infected cells
and kills the intracellular proportion
of Mycobacterium
• A great activity against
microorganisms have been
sequestered within abscesses and
lung cavities
Pharmacokinetics
• Well absorption from GI
• Widely distributes to body tissues
and fluids, but its penetration to CSF
require BBB inflammation (e.g.
meningitides)
• Undergone billiary excretion and
enterohepatic recirculation
• Dosage adjustment for renal or
hepatic insufficiency is not
necessary
Clinical Uses
• Mycobacterial infections
(Tuberculosis and Leprosy)
• Elimination of meningococcal and
staphylococcal carriage (2 days)
• Prophylaxis of H. influenza type b
infection in children (4 days)
• Staphylococcal osteomyelitis and
endocarditis in patients with
prosthetic valve or instruments
• Pneumococcal (highly penicillin
resistant) meningitidis (in
combination with ciprofloxacine)
Adverse Drug Reactions
• Coloring the fluids and discoloring
the soft lenses
• Cholestatic jaundice and
occasionally hepatitis
• Light chain proteinuria
• Flu-like syndrome
• Induction of metabolism for
anticoagulants, anticonvulsants and
OCP drugs
Ethambutol
• A synthetic , water soluble
antimycobacterial agent
• Inhibits arabinosyl transferase
which is necessary for cell wall
polymerization
• Enhances penetration of
lipophylic antimycobacterial
drugs to the microorganism
Pharmacokinetics
• Well absorption from the GI.
• Crosses the BBB if the
meningial inflammation has
been occurred.
• 20% is eliminated in feces and
50% in urine.
• Renal failure needs dose
adjustment.
Adverse Drug Reactions
• Depends strongly to dose and
duration of use.
• GI adverse effects.
• Loss of visual acuity due to
retro-bulbar neuritis
• Red – green blindness.
Pyrazinamide
• A nicotinamide derivative which is
activated in acidic pH.
• Readily penetrates to phagocytes
and sterilized the infected cells.
• In combination with INH and
Rifampin, reduces the course of
treatment to 6 months.
• In the case of multi drug resistant
TB, it is used in combination with
fluoroquinolones for prevention of
infection.
Pyrazinamide
• It has no cross resistance with
other antimycobacterial drugs.
• Liver toxicity (1-5%) and
hyperuricemia are main adverse
drug reactions
Streptomycin
• M. avium Intercellular and M.
kansassi are resistant to
Streptomycin.
• Only active against extra-cellular
bacteria.
• Only in inflamed meninges , could
penetrates to CSF.
• It is a useful drug when sever and
disseminated infection or meningitis
exists.
• ADRs are similar to other amino
glycosides
Drugs Used In Leprosy
• Similar to TB, only combination
of drugs should be used.
• Dapson, Rifampin and
Clofazimine are three main
effective drugs in the treatment
of leprosy
Dapson
• Inhibits folate synthesis
• Widely distributed in body
tissues specially skin, muscle,
kidney and liver
• In infected skin, drug level may
reach to several fold greater
than blood
• It is also used to prevent or
treat the pneumonia due to P.
Jiroveci in AIDS patients
Dapson
• It is excreted mainly by bile and
undergone
enterohepatic
recirculation.
• Hemolysis (G6PD deficiency)
and methemoglobinemia are
common blood disorders caused
by dapson.
• Erythema nodosume leprosume
may be occurred by using the
drug.
Clofazimine
• It is a synthetic dye commonly used
with other antileprosy drugs or as
alternative for dapson
• Binds to the DNA and this may
explain its antileprosy effect
• Has variable absorption from GI and
mainly excreted in feces
• The serum half life is about 2 months
due to its deposition in
reticloendothelial tissues.
• Skin discoloring is the most
prominent adverse reaction