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 10⁶
possibility of a mutation when using 2 drugs

1 in 10¹²
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

61324

Card Set

Pharmacology Exam I

Description

Anti-Mycobacterial Agents

Updated

2011-01-22T21:18:23Z

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