First Lectures Flashcards
Inhibitors of Nucleic Acid Synthesis:
Sulfonamides
Bacteriostatic
Mechanism: competitive inhibitor of Dihydropteroate synthase
Selectivity: humans use dietary folate (don’t have enzyme)
Spectrum: gram - & + but narrow
Uses: UTI, P jirovecii in AIDS, Malaria, toxoplasmosis
Absorption: oral
distribution: wide
excretion: renal (drink a lot)
Toxicity: crysalluria, anemia, GI, Kernicterus- causes encephalitis (never give infants), hypersensitivity (Stevens-Johnson syndrome), photosensitivity
Inhibitors of Nucleic Acid Synthesis:
Trimethoprim
Bacteriostatic Mechanism: inhibits dihydrofolate reductase Selectivity: higher concentrations hurt us (we have the enzyme) Spectrum: broader than sulfa (+ &-) Take with sulfamethoxazole = CIDAL uses: UTI, P jarovicii in AIDS Absorption: oral Distribution: wide (BBB) Renal excretion toxicity: blood dyscrasias or anemia Has lower MICs than sulfa
Inhibitors of Nucleic Acid Synthesis:
Rifampin
Semisynthetic analog of Streptomyces
CIDAL
mechanism: inhibits RNA polymerase
selectivity: can’t bind our enzyme
spectrum: good against tuberculosis and resistant staphs
uses: tuberculosis, resistant staph, meningitis prophylaxis
Distribution: wide (BBB)
Metabolism: p450 in liver causes its excretion (remains active during the process
excretion: 30% renal, rapid in bile
Toxicity: deactivates HIV drugs so use Rifabutin instead
DNA Damaging Agents:
Quinolones
CIDAL
Mechanism: inhibit DNA Gyrase A (ahead of fork) and Topoisomerase IV (behind fork)
selectivity: our topoisomerase II isn’t really affected
spectrum: + & -
uses: UTI, RTI, tuberculosis, Ciprofloxacin+ Levofloxacin can kill Psuedomonas, Cipro can’t kill gram + anymore b/c resistance –> thats why 3rd and 4th gen have been made (moxifloxacin = 4th gen = can’t be cleared renally)
Absorption: oral, don’t take with cations (milk)
rapid renal excretion
toxicity: don’t give kids Cipro (tendon rupture)
DNA Damaging Agents:
Nitrofurantoin
static to cidal pending conc. mechanism: free radical selectivity: we don't activate the drug as much as bacteria Uses: exclusively UTI spectrum: broad (+&-) oral renal excretion Toxicity: don't give to compromised kidneys, can lead to pulmonary fibrosis
DNA Damaging Agents:
Methenamine
Only used for UTI prophylaxis
forms formaldehyde in acid
needs to be enterically coated to get to urine and be active
oral
spectrum: gram - only
Toxicity: GI, bladder irritation, crystallize out
DNA Damaging Agents
Metonidazolepp
PRODRUG FOR ANAEROBIC INFECTIONS CIDAL mechanism: reductive activation leads to free radicals spectrum: anaerobic gram + and - spectrum: wide (crosses BBB) oral Excretion: renal Toxicity: nausea, vomiting, disulfiram-like effects (BOOZE you LOSE)
Inhibitors of Cell Wall Synthesis:
Beta-lactams
Penicillins
Cidal (when growing)
mechanism: mimics D-Ala-D-Ala and ties up transpeptidase
selectivity: humans have no cell wall
narrow spectrum (gram + and some -)
amino penicillins have the broadest spectrum
uses: strep pneumoniae, H. influenza, STDs, UTI
poor oral absorption , dont eat
cant cross BBB unless meningitis inflammation
renal excretion (very fast)
TIME DEPENDENT DRUG (dose frequently)
4 mechanisms of Beta-Lactam resistance
- B-Lactamases
- Altered PBPs (MRSA)
- Altered porins (gram -)
- Efflux pumps
Inhibitors of Cell Wall Synthesis:
Beta-lactams
Cephalosporins
CIDAL
same mechanism as penicillin but usually more resistant to lactamases
4 generation (higher = better @ gram - worse at +
1st gen - must inject (cefazolin)
3rd gen - ceftazidime (effective agains psuedomonas), ceftiaxone
4th gen - cefepime
5th gen new - ceftolozane, ceftobiprole, ceftaroline (kills mrsa)
oral and parenteral
wide (cross BBB)
Renal excretion (ceftrixone biliary)
hypersensitivity
Inhibitors of Cell Wall Synthesis:
Beta-lactams
Carbapenems (Imipenem)
ONLY used for nosocomial infections spectrum is wide - gram + and - effective against pseudo carbapenem resistant enterobacteriaceae important clnically IV only renal Cilastatin increases imipenems half life can cause CNS toxicity
Inhibitors of Cell Wall Synthesis:
Beta-lactams
Monobactams (Aztreonam)
ONLY nosocomial use
gram (-) only (can kill pseudo)
IV only
renal
Beta-Lactamase Inhibitors- clavulanic acid, subactam, tazobactam, sucide inactivators of B-lactamases
mechanism: inhibits B-lactamases
IV (except Augmentin)
Used to augment beta-lactams
Inhibitors of Cell Wall Synthesis:
Beta-lactams
Vancomycin
large tricyclic glycopeptide from strep orientalis
CIDAL but becoming static
mechanism: binds carboxy terminus D-Ala-D-Ala, inhibits transpeptidation, inhibits peptidoglycan snthase
Resistance: due to changing D-Ala-D-Ala
narrow spectrum - only gram - b/c size
Only IV
use to treat severe C. diff (oral admin) infection and MRSA
renal excretion with no metabolism
hearing loss and renal toxicity possible
Inhibitors of Cell Wall Synthesis:
Beta-lactams
Bacitracin
binds the isoprenyl-phosphate lipid carrier and inhibits dephosphorylation and utilization (stops the thing that carries peptidoglycan to cell wall)
spectrum: gram positive, some negative
uses: superficial skin and eye infections
topical use only (severe renal damage if IV)
