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29 Cards in this Set
- Front
- Back
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Why is tuberculosis difficult to treat?
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Organism multiplies slowly
Intracellular Quickly develops resistance |
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What are the 4 main tuberculosis drugs?
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Isoniazid
Rifampin Ethambutol Streptomycin |
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What are the basics of treating tuberculosis?
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Always treat with a combination (because of resistance)
Treatment lasts for at least 6 months |
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What about tuberculosis allows for its selectivity by specific drugs?
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The mycotic acid layer of its cell wall
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How does Isoniazid work?
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It competitively inhibits inhA (isoniazid is INH), which is an enzyme that synthesizes mycolic acid for the mycobacterial (tuberculosis) cell wall
It has to be activated by an enzyme encoded by katG before it can bind inhA Bactericidal |
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What is katG?
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Gene that codes for the catalase/peroxidase that activates isoniazid
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What are the mechanisms of resistance to isoniazid? Which is the main one?
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The main method is a mutation in the katG gene (accounts for 60-70% of resistance)
Mutation in inhA gene |
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How is Isoniazid absorbed? Distributed? Metabolized? Excreted?
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Absorbed: orally
Distributed: widely, including CSF Metabolized: acetylated in liver Excreted: renal |
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What are the adverse effects of isoniazid?
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Peripheral neuritis - higher dose or slower acetylation of drug makes it worse. Administering isoniazid with pyridoxine eliminates this
Hepatotoxic Inhibits metabolism of phenytoin and carbamazepine |
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How does Rifampin work?
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Inhibits mycobacterial RNA polymerase
Bactericidal Broad spectrum against Gram positive and negative bacteria |
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What is the main mechanism of resistance to Rifampin?
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Alteration of RNA polymerase which prevents binding
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How is Rifampin absorbed? Distributed? Metabolized? Excreted?
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Absorbed: orally
Distributed: widely, penetrates CSF Metabolized: deacteylated in liver Excreted: bile |
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What are the adverse effects of Rifampin?
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Hepatotoxicity
GI irritation Rash, fever Jaundice Reddish discoloration to body fluids (eg urine) KNOW Affects metabolism of other drugs (warfarin) |
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Which drugs can cause hepatitis?
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Isoniazid and Rifampin
Even worse if used together |
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How does Rifampin affect metabolism of other drugs?
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Activates cytochrome P450 enzymes, which accelerates inactivation of other drugs (warfarin)
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What is pyrazinamide used to treat?
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Tuberculosis
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How does pyrazinamide work?
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Inhibits synthesis of fatty acids required for mycobacterial cell wall
Target enzyme: FASI (fatty acid synthetase I) Requires conversion in cell |
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What is the mechanism of resistance to pyrazinamide?
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Mutation in pyrazinamidase (pncA gene), resulting in decreased activation of drug
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How is pyrazinamide absorbed? Distributed? Metabolized? Excreted?
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Absorbed: orally
Distributed: widely, including CSF Metabolized: deamidated Excreted: renal |
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What are the adverse effects of pyrazinamide?
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Hepatotoxicity
GI irritation Hyperuricemia |
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What does ethambutol treat?
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Tuberculosis
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How does ethambutol work?
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Inhibits polymerization of arabinan, which is necessary for mycobacterial cell wall
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How does ethambutol resistance work?
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Mutation in enzyme that the drug blocks
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How is ethambutol absorbed? Distributed? Metabolized? Excreted?
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Absorbed: orally
Distributed: widely, including CSF Metabolized: in liver Excreted: renal |
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What are the adverse effects of ethambutol?
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Optic neuritis (goes away after drug stopped)
GI irritation Hyperuricemia |
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How does streptomycin work?
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Inhibits protein synthesis through binding to 30S ribosomal subunit
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How do bugs develop resistance to streptomycin?
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Alteration in ribosome
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What are the adverse effects of streptomycin?
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Ototoxic
Nephrotoxic |
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Which bug was streptomycin the first to treat?
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Tuberculosis
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