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44 Cards in this Set
- Front
- Back
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What is the mechanism of action of Isoniazid?
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Competitive inhibiton of inhA; can't synthesize mycolic acid
Bacteriacidal |
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What is the activity of inhA in this bacterium?
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M. tuberculosis
Synthesis of mycolic acid |
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What drug requires activation by katG to be effective against this bacteria?
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Isoniazid
M. tuberculosis |
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What are the mechanisms of resistance to Isoniazid?
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Mutation in katG
Mutation in inhA: overexpression, can't bind isoniazid Mutation in ahpC promoter |
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What is the activity of katG?
What drug does it activate? |
Catalase/peroxidase
Isoniazid |
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What is the absorption of isoniazid?
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Oral bioavailability
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What is the distribution of isoniazid?
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Widely distributed
Penetrates CSF |
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What is the metabolism of Isoniazid?
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ACETYLATION IN LIVER;
RATE IS GENETICALLY DETERMINED |
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What is the excretion of isoniazid?
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Renally
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What drug is isoniazid typically administered with?
Why? |
Pyridoxine
Solves the problem of the slow acetylators |
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What are the adverse effects of Isoniazid?
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Dose-dependent neuritis (solved by administration with pyridoxine)
Hepatotoxicity Inhibition of metabolism of phenytoin, carbamazepine |
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What Tb drug is given with pyridoxine?
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Isoniazid
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What is Rifampin's mechanism of action?
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Inhibition of MYCOBACTERIAL RNA Polymerase
Bactericidal |
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What bacteria are Rifampin active against?
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Broad activity
Gram positive Gram negative |
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What is the mechanims of resistance to rifampin?
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Alteration of the mycobacterial RNA Pol
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What is the absorption of Rifampin?
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Orally
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What is the distribution of Rifampin?
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Widely distributed
penetrates CSF |
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What is the metabolism of Rifampin?
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Deacetylated in the liver
T1/2: 1-5 hr. |
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What is the excretion of rifampin?
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Bile
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What are the adverse effects of rifampin?
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GI Irritatin
Rash, fever Jaundice Hepatotoxicity Reddish discoloration to body fluids |
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What enzymes not directly related to the killing of Mycobacterium does Rifampin interact with?
What is its effect? |
P450 enzymes in the liver
Induction |
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What are some examples of drugs that Rifampin can effect the metabolism of?
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Anticoagulants
Glucocorticoids Ketoconazole Sulfonylureas Oral contraceptives |
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What is the mechanism of action of pyrazinamide?
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Inhibition of Fatty Acid Synthase I in mycobacterium.
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Is Pyrazinamide itself an active compound?
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NO!
It has to be converted to pyrazinoic acid by pyrazinamidase. |
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What is the enzyme responsible for the activation of pyrazinamide?
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Pyrazinamidase
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What is the active form of pyrazinamide?
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Pyrazinoic acid
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What is the absorption of pyrazinamide?
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Orally
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What is the distribution of pyrazinamide?
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Widely distributed
Penetrates the CSF |
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Problems with what enzymes would result in problems in metabolism of pyrazinamide?
What is the half life of pyrazinamide? |
Deamidases; it's metabolized by deamidation.
T1/2 = 6-10 hrs |
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What is the excretion of pyrazinamide?
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Renally
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What are the adverse effects of pyrazinamide?
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GI irritation
Hepatotoxicity Hyperuricemia |
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What is the mechanism of action of ethambutol?
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Inhibition of the polymerization of arabinan
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What is the enzyme targeted by ethambutol?
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The embB gene; arabinosyltransferases
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What is the mechanism of resistance to ethambutol?
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Mutation to the embB gene
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What is the way that ALL TB drugs are taken?
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Orally
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What is the distribution of ALL TB drugs?
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Widely distributed
Penetrates the CSF |
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Where is the metabolism of ethambutol?
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Liver
T1/2 = 4 hrs. |
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What is the excretion of ethambutol?
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Renally
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What are the adverse effects of ethambutol?
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Optic neuritis: loss of acuity, red/green problems. Reversible
GI Irritation Hyperuricemia: ureate excreted |
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What is the mechanism of action of Streptomycin?
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Inhibition of elongation through binding to the 30S ribosomal subunit
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What is the mechanism of resistance to Streptomycin in Tb?
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ALTERATION OF THE RIBOSOME (not acetylation like in the regular bacteria)
RpsL gene encoding the S12 protein rrs gene encoding the 16S rRNA |
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What are the adverse effects of Streptomycin?
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Ototoxic
Nephrotoxic Teratogenic - don't give to pregnant women! |
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What drugs are MDR TB resistant to?
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Isoniazid
Rifampin |
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What are the adverse effects of rifampin?
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Jaundice
Flushing/Fever Hepatotoxicity GI upset Reddish-colored body fluids |
