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TB Pharmacotherapy
tb pharmacotherapy
27
Accounting
Pre-School
10/02/2014

Additional Accounting Flashcards

 


 

Cards

Term
First Line Drugs of TB
Definition

Rifampin

Isoniazide

Pyrazinamide

Ethambutol 

Term
Second Line drugs of TB
Definition

Streptomycin, Fluoroquinolones (Moxifloxacin, gatifloxacin), Amikacin, Kanamycin, Capreomycin, Ethionamide, P-aminosalicylic acid

 

Toxic, lack of data, many are IV only

Term
Order of Mycobacterial Cell wall from cytoplasm up
Definition

Cytoplasm, cell membrane, peptidoglycan, arabinogalactan, mycolic acid, superficial lipids (cord factor) 

 

LAM extends the length

Term
Rifamycins
Definition

Rifampin, Rifabutin, Rifapentine

Rifaximin (used in C diff infections; not mycobacterium infections) 

All inhibit DNA dependent RNA polymerase 

Inhibits Transcription

Highly bioavailable (except rifaximin) - highly distributed (including to CNS) 

Color secretions are orange red 

Metabolized in liver by de-acetylation -- VERY STRONG P450 CYTOCHROME INDUCER

Largely excreted by biliary tract (enterohepatic circulation) 

Very active against M tub, staphylococci, enteric GNRs

Don't use as monotherapy; resistance is usually through altered DNA dependent RNA polymerase

Term
Rifamycin SE
Definition

very strong cytochrome P450 inducer

Color secretions turn orange-red

Not common - nausea/vomiting, rash, hypersensitivity, hepatotoxicity

Term
Rifabutin
Definition

Less cytochrome P450 inducer

Common component of M avium-intracellurae complex

Alternative for TB

Can be used in other bacterial infections; never as a monotherapy 

Term
Isoniazid MOA
Definition

Metabolized to active drug that inhibits synthesis of mycolic acids 

Specific to mycobacteria 

Term
Isoniazid Pharmacokinetics
Definition

Very well distributed and highly absorbed - including to CNS and TB lung consolidations

Variable metabolism via acetylation by NAT2 

Genetically variable slow and rapid acetylators 

Metabolites eliminated renally 

Term
Isoniazid active against, cidal or static, resistance?
Definition

Most important drug in TB pharmacotherapy

Active only against MT and M. kansasii

Bacteriostatic for organisms not growing; bactericidal for dividing organisms 

Resistance is due to several mechanisms (decreased fitness in mutants)

 

Term
Isoniazid drug interactions and adverse effects
Definition

Phenytoin (not P450 related, monitor phenytoin concentrations)

Adverse effects: rash, fever, hepatotoxicityperipheral neuropathy (treat with pyridoxime - B6), drug induced lupus, optic neuritis/seizures

Term
Ethambutol MOA
Definition

MOA: inhibits arabinosyl transferase, preventing cell wall synthesis 

Inactive against non-mycobacteria 

Term
Ethambutol PK
Definition
Highly absorbed (75-80%), widely distributed including to CSF, some hepatic metabolism (non P450), largely renally eliminated so you would need to renally adjust it
Term
Ethambutol active against
Definition

Active against many species of mycobacteria

1st line drug in both TB and MAC infections

Resistance not common, but occurs when given as monotherapy 

Term
Ethambutol AE
Definition

Optic neuritis (decrease vision, loss of red green differentiation, test visual acuity during long term therapy)

GI effects

CNS effects possible, but rare 

Term
Pyrazinamide MOA
Definition

Inhibits FAS1, which blocks production of fatty acid precursors of mycolic acids


Active only at a acidic pH

 

May be bacteriostatic or bacteriocidal 

Term
Pyrazinamide PK
Definition

highly absorbed, widely distributed, including to CSF

Metabolized hepatically but not by P450 

Renally eliminated, but mostly metabolites, so you would not have to renally adjust

Would be most hepatotoxic 

Term
Pyrazinamide active against and SE
Definition

Pyrazinamide is only active against M. tuberculosis

Adverse effects: hepatotoxicity, arthralgias, hyperuricemia, GI effects 

Term

Streptomycin MOA

 

Bactericidal or bacteriostatic

Definition

Aminoglycoside antibiotic - inhibits protein synthesis by binding to 30S ribosomal bunit, causing misreading of mRNA 

 

Bactericidal for most organisms; bacteriostatic for M tuberculosis 

 

Term
Streptomycin Absorption
Definition

Poorly absorbed (must be given IV or IM for systemic treatment) 

Moderate distribution (Poor to CNS, moderate to lungs, inactive in acidic environments) 

No metabolism 

Entirely renally eliminated -- can be nephrotoxic 

Term
Streptomycin and TB
Definition

Streptomycin is active against TB, but not intracellularly 

Active against many GNRs and GPC

- GPC activity greatly enhanced in the presence of other agents 

Term
Streptomycin Adverse Reactions
Definition

Nephrotoxicity (related to elevated trough concentrations - monitor urine output, serum creatinine, streptomycin concentrations)

Ototoxicity (auditory and vestibular) - idiosyncratic, possibly related to overall exposure 

Term
Other aminoglycosides for TB
Definition

Kanamycin, Amikacin

AEs similar to streptomycin (ototoxicity, nephrotoxicity)

Other aminoglycosides are not active against TB

Term
Cycloserine
Definition

Inhibits D-ala-D-ala synthetase and alanine racemase, preventing peptidoglycan monomer synthesis at 2 different steps 

 

Second line agent 

 

Resistance is common

 

AE: psychosis and peripheral neuropathy (somewhat preventable with pyridoxine) 

Term
Fluoroquinolones
Definition

Monifloxacin, gatifloxacin (not used - hypo/hyper glycemia), most active; levofloxacin also used

Also active against M. avium intracellulare 

Currently second line agents but may move up

Term
p-Aminosalicylic acid
Definition

resembles PABA, blocks folate synthesis

Relatively safe but high incidence of hypersensitivity 

Term
Ethionamide
Definition
Similar to isoniazid but less effective
Term
Capreomycin
Definition

Peptide antibody that functions like aminoglycoside

 

Ototoxic and nephrotoxic 

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