Term
|
Definition
alter cellular metabolism because they structurally resemble endogenous compounds
eg: sufonamides & trimethoprim |
|
|
Term
| Sulfonamides & trimethoprim are examples of: |
|
Definition
|
|
Term
| Sufonamides are derived from: |
|
Definition
|
|
Term
| Sunfonamides combine with: |
|
Definition
| para-amine benzoic acid (PABA) |
|
|
Term
| para-amine benzoic acid (PABA) |
|
Definition
|
|
Term
| folic acid is required by bacteria to synthesize: |
|
Definition
| thymidine, purines, methionine, glycine, formylmethionine |
|
|
Term
|
Definition
| processes sulfonamides & --> their incorporation into dead-end products & inhibits formation of dihydropteroic acid |
|
|
Term
| Why are sulfonamides selectively toxic for bacteria? |
|
Definition
| mammilian cells can't synthesize folic acid from PABA |
|
|
Term
| Sulfonoamides are bacteriostatic against: |
|
Definition
|
|
Term
| Sulfonamides are used to treat: |
|
Definition
| uncompliated urinary tract infections (sulfisoxazole), inflammatory bowel disease (sulfasalazine), and burns (silver sulfadiazine) |
|
|
Term
| Resistance to sulfonamides is due to: |
|
Definition
altered target (plasmid based)
decreased permeability of bacterial pathogens for the drugs
increased PABA synthesis by the bacteria |
|
|
Term
| adverse effects of sunfonamides include: |
|
Definition
hypersensitivity reactions (rash, fever, photosensitivity)
cross-allergenicity with chemically related drugs (thiazides, sufonylureas, actezolamide)
can cause kernicterus: displace uncojugated bilirubin from plasma proteins
RBC hemolysis (in G6PD deficiency)
GI disturbances |
|
|
Term
| Sulanomides are contraindicated: |
|
Definition
| during the 3rd trimester & in the neonate |
|
|
Term
| Sulfonamides are delivered: |
|
Definition
|
|
Term
| Do sulfonamides enter the CNS? |
|
Definition
|
|
Term
| Are sulfonamides distributed widely? |
|
Definition
|
|
Term
| How are sulfonamides metabolized? |
|
Definition
|
|
Term
| How are sulfonamides eliminated? |
|
Definition
|
|
Term
|
Definition
| the structure of pteridine (another precursor of folic acid) |
|
|
Term
|
Definition
| competitively inhibits dihydrofolate reductase --> blocking synthesis of tetrahydrofolic acid (FAH4) |
|
|
Term
| Trimethoprim is selectively toxic because: |
|
Definition
| it inhibits bacterial DHFR >>> than mammalian DHFR |
|
|
Term
| Trimethoprim is bacteriostatic against: |
|
Definition
|
|
Term
| Trimethoprim is used to treat: |
|
Definition
| uncomplicated urinary tract infections due to Gram - organisms |
|
|
Term
| Resistance to trimethoprim is usually due to: |
|
Definition
altered target (plasmid-based)
or: overproduction of DHFR |
|
|
Term
| Adverse effects of trimethoprim: |
|
Definition
bone marrow depression --> megloblastic anemia, leucopenia, granulocytopenia
*can be overcome by giving folic acid |
|
|
Term
| Trimethoprim is orally bioavailable? |
|
Definition
|
|
Term
| Trimethoprim distribtuion: |
|
Definition
| distributed widely in tissues |
|
|
Term
| Trimethoprim elimination: |
|
Definition
|
|
Term
| Trimethoprim-Sulfamethoxazole (TMP-SMX) inhibit: |
|
Definition
| sequential steps in folic acid synthesis --> drugs have a synergistic effect in combo |
|
|
Term
| Trimethoprim-Sulfamethoxazole (TMP-SMX) combo is bactericidal against: |
|
Definition
|
|
Term
| Trimethoprim-Sulfamethoxazole (TMP-SMX) is used to treat: |
|
Definition
| urinary tract infections, Shigella infections, travelers' diarrhea, otitis media, bronchitis, Pneumocystis cariniii pneumonia |
|
|
Term
| Trimethoprim-Sulfamethoxazole (TMP-SMX) resistance: |
|
Definition
same as for the individual drugs;
clinically: altered DHFR |
|
|
Term
| Half-lives of Trimethoprim-Sulfamethoxazole (TMP-SMX): |
|
Definition
| similar (9-12h), so drugs can be given in combo pill |
|
|
Term
| Ratio optimal for killing in vitro for Trimethoprim-Sulfamethoxazole (TMP-SMX): |
|
Definition
| 1:20; however, the volume of distribution of TMP is 5x that of SMX, so dosing TMP:SMX in a 1:5 ratio --> 1:20 ratio in the plasma |
|
|
Term
| Fluoroquinolones inhibit: |
|
Definition
DNA gyrase & topoisomerase 4 --> prevents unwinding of supercoiled DNA & inhibits DNA and RNA synthesis
(but not mammalian counterparts to these enzymes) |
|
|
Term
| Fluoroquinolones are bactericidal/ bacteriostatic? |
|
Definition
|
|
Term
| Do Fluoroquinolones have a PAE? |
|
Definition
|
|
Term
| Fluoroquinolones have what type of killing? |
|
Definition
| concentration-dependent killing |
|
|
Term
| Fluoroquinolone drug generations differ in: |
|
Definition
|
|
Term
| Lead compound for Fluoroquinolones: |
|
Definition
|
|
Term
| 1st generation Fluoroquinolone: |
|
Definition
|
|
Term
| 2nd generation Fluoroquinolone: |
|
Definition
ciprofloxacin:
Gram - > Gram + |
|
|
Term
| 3rd generation Fluoroquinolone: |
|
Definition
| gatifloxacin: Gram + > Gram - |
|
|
Term
| 4th generation Fluoroquinolone: |
|
Definition
| moxifoxacin: like 3rd generation drugs (Gram + > Gram -), but also active against anaerobes |
|
|
Term
| Fluoroquinolones are used for: |
|
Definition
meningococcal prophylaxis
TB (in combination with other drugs) |
|
|
Term
| Resistance to Fluoroquinolones is usually due to: |
|
Definition
altered target or efflux pumps
cross-resistance is present among Fluoroquinolones |
|
|
Term
| Is cross-resistance present across Fluoroquinolones? |
|
Definition
|
|
Term
| Adverse effects of Fluoroquinolones: |
|
Definition
GI disturbances
damage to developing cartilage (not recommended in pregnant/nursing women, ppl under 18 y/o) |
|
|
Term
| Fluoroquinolones have good bioavialability: |
|
Definition
|
|
Term
| How are Fluoroquinolones eliminated? |
|
Definition
|
|
Term
| Fluoroquinolones have wide distribution in the body? |
|
Definition
|
|
Term
| Synergistic drug combos are important in treating: |
|
Definition
bacterial endocarditis (esp. due to enterococci)
Gram - infections in neutropenic patients
Systemic infections due to Pseudomonas aeruginosa |
|
|
Term
| Mycobacteria may have _______ in their cell wall, making them extremely hydrophobic |
|
Definition
|
|
Term
| Mycolic acids & arabinoglycas are molecular compounds unique to: |
|
Definition
mycobacteria (components of the cell wall)
these components form the basis for selective toxicity for anti-mycobacterial drugs |
|
|
Term
|
Definition
| acyl carrier protein & carrier protein synthase (both are required for mycolic acid synthesis) |
|
|
Term
| What is required for activation of Isoniazid? |
|
Definition
| Oxidative deamination by KatG |
|
|
Term
| Isoniazid is bactericidal for: |
|
Definition
|
|
Term
| This drug is used for growing and latent TB: |
|
Definition
|
|
Term
| Resistance to Isoniazid is due to mutation of: |
|
Definition
| the target protein or mutation of KatG |
|
|
Term
| Adverse effects of Isoniazid include: |
|
Definition
| hepatitis & peripheral neuropathy (prevented by pyridoxine) |
|
|
Term
| How are side effects of Isoniazid prevented? |
|
Definition
|
|
Term
| Does Isoniazid enter the CNS? |
|
Definition
| yes: penetrates caseous lesions & enters phagocytes |
|
|
Term
| Isoniazid is inactivated by: |
|
Definition
| hapatice N-acetyltransferase (polymorphic in humans) |
|
|
Term
| The oral bioavailabilty of Isoniazid is: |
|
Definition
|
|
Term
|
Definition
| fatty acid synthase I, which is required for mycolic acid synthesis |
|
|
Term
| Pyrazinamide is activated by: |
|
Definition
| oxidative deamination by pyrazinamidase (pcnA) |
|
|
Term
| Pyrazinamide is bactericidal towards: |
|
Definition
| actively-growing mycobacteria |
|
|
Term
|
Definition
|
|
Term
| Resistance to Pyrazinamide is usually due to: |
|
Definition
|
|
Term
| Adverse effects of Pyrazinamide include: |
|
Definition
| hepatotoxicity & arhralgias |
|
|
Term
| The oral bioavialability of Pyrazinamide is: |
|
Definition
|
|
Term
| Pyrazinamide is metabolized: |
|
Definition
|
|
Term
| Pyrazinamide is eliminated: |
|
Definition
|
|
Term
|
Definition
| arabinosyltransferase, which is required for mycobacterial cell wall biosynthesis |
|
|
Term
| Ethambutol is bactericidal/bacteriostatic? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Resistance to Ethambutol is due to: |
|
Definition
| mutations in target protein/ overproduction of the target protein (arabinosyltransferase) |
|
|
Term
| Adverse effects of Ethambutol include: |
|
Definition
| retrobulbar neuritis (affects vision & color discrimination( |
|
|
Term
| Oral bioavailability of Ethambutol is: |
|
Definition
|
|
Term
| Ethambutol is eliminated: |
|
Definition
|
|
Term
|
Definition
bactericidal RNA polymerase (beta subunit)
does not bind to human RNAP |
|
|
Term
| Rifampin is bactericidal against: |
|
Definition
actively growing mycobacteria
some Gram + and - |
|
|
Term
|
Definition
latent & active TB
prophylaxis for N. meningiditis & H. flu contacts
used in combo with other drugs for serious infections from MRSA & PRSP |
|
|
Term
| Resistance to Rifampin is due to: |
|
Definition
|
|
Term
| Adverse effects of Rifampin: |
|
Definition
| flu-like syndrome with fever, chills, and myalgias |
|
|
Term
| How does Rifampin affect the metabolism of other drugs? |
|
Definition
increases their metabolism (Ca++ channel blockers, B blockers, immunosuppressives, steroids, warfarin, anticancer drugs, benzodiazepines, sedatives, opiods, anti-convulsants, HMG-CoA reductase inhibitors, HIV protease inhibitors, non-nucleoside RT inhibitors) by inducing CYP34A and other CYP enzymes
HIV/AIDS patients should use Rifabutin insteasd (less CYP enzyme induction) |
|
|
Term
| HIV/AIDS patients should use ______ instead of Rifampin because _________ won't activate their CYP enzymes as much (CYP enzyme activation = more metabolism of HIV protease inhibitors, making them less effective) |
|
Definition
| Rifabutin should be used instead! |
|
|
Term
| Rifampin's oral bioavailability: |
|
Definition
|
|
Term
| Rifampin does/ does not enter the CNS: |
|
Definition
|
|
Term
| What happens to Rifampin in the liver? |
|
Definition
|
|
Term
| Resistance to anti-TB drugs arises: |
|
Definition
| spontaneously; mutations occur frequently so multiple drugs are used for treatment |
|
|
Term
| To start treatment for TB, how many drugs are used? |
|
Definition
|
|
Term
| If multi-drug resistant TB is suspected, how many drugs are used? |
|
Definition
|
|
Term
| How long must treatment for TB be continued? Why? |
|
Definition
| >6 months because mycobacteria are slow growing & become dormant |
|
|
Term
| Why is directly observed treatment recommended for TB? |
|
Definition
| poor adherance is common and --> drug resistant strains of TB |
|
|
