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Pharmacology Exam I
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Tuberculosis no longer contagious after
two weeks of therapy
Those suceptible to tuberculosis infections
older
malnurished
HIV
% of Tb patients that are HIV positive
18-40%
TB may be difficult to diagnose in aids pt due to
decreased immune response to skin test antigens
Targets of TB therapeutic agents
cell wall mycolic acid
cell wall polysaccharides
cell wall peptidoglycan
First line treatments for TB
Isoniazid
Rifampin
Pyrazinamide
Ethambutol
Streptomycin
Drug resistant TB is no longer killed by the agents
isoniazid
rifampin
Isoniazid
most active drug against sensitive strains
Isoniazid MoA
inhibition of Mycolic Acid synthesis
Mutations resulting in Isoniazid resistance
inhA
KatG
KasA
Possibility of a mutation when using 1 drug
1 in 10
6
possibility of a mutation when using 2 drugs
1 in 10
12
Kinetics of Isoniazid
fast absorption
20-100% CSF distribution
metabolized by acetylation
3hr HL in slow acetylators
If peripheral neuropathy developes with isoniazid use, use:
pyridoxine
Isoniazid toxicity
fever and rash
hepatitis
peripheral neuropathy
Avoid isoniazid with this ARV
stavudine
Bacteriocidal agent against M. Tuberculosis and M. Leprae
Rifampin
Rifamycin MoA
binds beta subunit of RNA polymerase
Rifampin clinical use
atypical mycobacterium
latent infection
meningococcal carriage
prophylaxis against hemophilus influenza B
Rifampin toxicity
orange body fluids
flu-like symptoms
liver toxicity
induction of CYP450 pathway
Rifampin increases metabolism of
PIs
NNRTIs
Ethambutol inhibits
arabinoglycan
arbinosyl transferase encoded by emb
Isoniazid + ethambutal would have a _____ effect
synergistic
Ethambutol kinetics
good bioavailability
HL = 2-4 hr
Ethamutol is contraindicated in
children
Pyrazinamide
active in lysosomes
unknown mechanism
resistance occurs by mutation in pncA
Pyrazinamide kinetics
t1/2 = 8-11 hr
metabolism in liver
Side effects of pyrazinamide
hepatotoxicity (1-5%)
hyperuricemia (gouty attack)
Streptomycin
aminoglycoside
binds bacterial ribosome
Side effects of streptomycin
n/v
rash
fever
ototoxic
nephrotoxic esp. in elderly
Minimum duration of therapy for TB
6 months
duration of therapy with isoniazid + rifampin + pyrazinamide
6 months
duration of therapy with isoniazid + rifampin
9 months
Duration of therapy for rifamipn + ethambutol + pyrazinamide
6 months
Isoniazid target
mycolic acid
Rifamycin target
RNA polymerase
Ethambutol target
arabinoglycan synthesis
Pyrazinamide target
unknown
Streptomycin target
protein synthesis (ribosome)
Second line agens for TB
ethionamide
capreomycin
cycloserine
aminosalicylic acid
rifabutin
Ethionamide
inhibits mycolic acid synthesis
poor OB
hepatotoxic and neurotoxic
Capreomycin
protein synthesis inhibitor
nephro and oto toxic
contraindicated in pregnancy
Cycloserine
inhibitor of cell wall synthesis
nephro and oto toxic
peripheral neuropathy
Aminosalicylic acid
folate synthesis antagonist
hepatosplenomegaly
hepatitis
Rifabutin
cross resistance with rifamycins
less potent inducer of CYP450 therefore recommended in HIV pt
Keys to successful treatmet
at least 6 months of therapy
treatment within 4 days of diagnosis
monthly monitoring
compliance is crutial
clinical improvemnt should be observed in
10-14 days
Sputum AFB performed
every 2 weeks until negative
Sputum cultures performed
monthly until negative
Treatment is continued for _____ beyond 1st negative culture
3 months
If cultures remain positive >4 months
suspect resistance
Drugs used in leprocy
dapsone (used with rifampin)
clofazimine (2 month half life)
Author
Rx2013
ID
61324
Card Set
Pharmacology Exam I
Description
Anti-Mycobacterial Agents
Updated
2011-01-22T21:18:23Z
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