7. Agents Targeting the Cell Wall Machinery

Question 1

doxycycline, minocycline, tetracycline, tigecycline

Answer 1

aminoglycosides

Question 2

amikacin, gentamycin, kanamycin, neomycin, streptocmycin, tobramycin

Answer 2

aminoglycosides

Question 3

azithromycin, clarithromycin, erythromycin

Answer 3

macrolides

Question 4

clindamycin, chloramphenicol, linezolid

Answer 4

other protein synthesis inhbitors

Question 5

include aminoglycosides, macrolides, tetracyline, and some others, some bacteriostatic but can also be bactericidal, disrupt process of translation by targeting molecular machinery ribosomal subunit 50s and 30s needed to translate mRNA to protein

Answer 5

protein synthesis inhibitors

Question 6

charged tRNA binds to A site > peptidyl tRNA and peptide bond form between growing aminao acid chain and amino acid in A site > newly uncharged tRNA exits > amino acid chain elongates +1 and translocates to P site

Answer 6

prokaryotic translation

Question 7

generally narrow spectrum with bactericidal effect, uptake is oxygen dependent only working on aerobic organisms, used in combination with B-lactam antibiotics to treat serious gram - infections and are not absorbed well from the gut, binds to 30s and perhaps 50s ribisomes blocking formation of initiation complex disrupting mRNA and 30s binding which would occur prior to step 1 of prokaryotic translation, causes nephortoxicity by renal tubular necrosis and ototoxicity

Answer 7

amingoglycosides/ streptomycin, gentamicin, kanamycin, amikacin, tobramycin, neomycin

Question 8

aminoglycosides, gram + and gram - aerobic organisms, primarily used for gram - aerobic organisms, used also in pneumonia and UTI, resistance by expression of enzymes altering chemical structure of the drug, adminstered intramuscularly, subq, or topic, poor absorption from the GI tract, eliminated through urine as a parent compound, kidney function affects half life

Answer 8

streptomycin, gentamycin, kanamycin, amikacin, tobramycin, and neomycin

Question 9

macrocyclic lactone ring structure including natural compounds and semisynthetics, covers mostly gram + and some gram -, overall narrow in spectrum of activity, concentrates in lungs, tonsils, and cervix, spectrum increases as A>C>E, binds to 50s and impairs translocation to the P site, causes stomach cramps, nausea, vomiting, diarrhea due to motilin activity, prolongs QT interval, skin hypersensitivity reactions

Answer 9

erythromycin, clarithomycin, azithromycin

Question 10

macrolide, narrow spectrum but broadest of all macolides, used in pneumonia, pharyngitis, sinusitis, tonsillitis, STDs, resistance by drug efflux, changes in drug binding to 50s ribosomes, oral and IV administration, concetrations in many tissues like the lungs, tonsils, and cervix, long half life up to 68 hours

Answer 10

azithromycin

Question 11

macrolide, narrow spectrum but broader than erythromycin, pneumonia, pharyngitis, sinusitis, STDs, resistance by drug efflux and changes in drug binding to the 50s ribosome, oral administration

Answer 11

clarithromycin

Question 12

macrolides, narrowest spectrum, pneumonia, pharyngitis, tonsillitis, STDs, resistance by drug efflux or changes in drug binding to 50S ribosome, oral adminstration, eliminated by liver metabolism thus hepatic dosing considerations - not renal

Answer 12

erythromycin

Question 13

four ring structure, broad spectrum with bacteriostatic effect, binds 30S subunit of ribosome and prevents binding of new aminoacyl-tRNA, causes nutrient interactions with calcium which results in disrupted growth of calcified tissue (bone, teeth) particularly during growth with discoloration of the teeth, disrupts normal flora, causes nausea, vomiting, diarrhrea, skin hypersensitivity and photosensitivity, also acts as a chelator preventing absorption of divalent cations

Answer 13

tetracyclines

Question 14

tetracycline, broad spectrum, used in patients with pencillin allergy, STDS, acne, resistance by drug efflux, adminstered orally, eliminated by the kidney so renal considerations, binds to di and tri valent cations such as calcium and aluminum so food delays absorption

Answer 14

tetracycline

Question 15

tetracycline, broad spectrum, used in patients with pencillin allergy, STDS, acne, resistance by drug efflux, adminstered orally, IV and topically, eliminated hepatically and renally so impairment considerations, binds di and trivalent cations such as calcium and aluminum so food delays absorption

Answer 15

minocycline

Question 16

tetracycline, broad spectrum, used in patients with pencillin allergy, STDS, acne, resistance by drug efflux, adminstered IV, severe hepatic insufficiency requires dose adjustements, binds di and trivalent cations such as calcium and aluminum, food delays absorption

Answer 16

tigecycline

Question 17

tetracycline, broad spectrum, used in patients with pencillin allergy, STDS, acne, resistance by drug efflux, adminstered orally and IV, no hepatic metabolism so there are no hepatic or renal considerations, can bind di and trivalent cations such as calcium and aluminum, however no food restrictions

Answer 17

doxycycline

Question 18

relatively narrow spectrum, commonly used in treatment of soft tissue infections caused by strep and staph, also used when treating community acquired MRSA of the skin and soft tissue, binds to 50S subunit of the ribosome and prevents formation of initiation complexes and also blocks translocation step, causes nausea, vomiting, diarrhea, and c.diff infection, also causes skin rashes

Answer 18

clindamycin

Question 19

broad spectrum antibiotic exerting bacteriostatic effect, rarely used except for serious infections such as typhys and rocky mountain spotted fever, also used to treat eye infections, binds to 50S subunit of the ribosome and prevents transpeptidation or peptidyl bone formation, causes suppression of red blood cell production, gray baby syndrome due to lack of glucuonic acid production, nausea, vomiting, diarrhea, and superinfection of oral and vaginal candidiasis

Answer 19

chloramphenicol

Question 20

effective against most gram + organisms but not very effective for most gram -, effective against penicillin/methicillin/vancomycine resistant strains, inhibits protein synthesis by binding to the P site of the 50S ribosome and inhibits the formation of the ribosomal fMet-tRNA complex blocking first tRNA amino acid binding, causes myelosuppression resulting in anemia, leukopenia, pancytopenia, and thrombocytopenia, inhibits monoamine oxidase so affects these drugs

Answer 20

linezolid

Question 21

narrow spectrum with gram + coverage, used in skin and soft tissue infections including CA-MRSA, cross resistance with macrolides because of similar mechanism of action, administered IV IM and topically, eliminated primarily hepatically, good tissue penetration particularly in abscesses, but no good CSF penetration

Answer 21

clindamycin

Question 22

broad spectrum, good against anaerobic bacteria, resistance by expression of inactivating enzymes, administered oral, IV, and topically, eliminated by the liver and excreted by the kidneys, well absorbed orally and widely distributed, penetrates CSF

Answer 22

choramphenicol

Question 23

mostly gram + coverage, has some resistant organisms, adminstered orally and IV, no dosage adjustments necessary, 100% bio-availability after oral administration so oral and IV dose are the same

Answer 23

linezolid

Question 24

sulfur containing compounds, broad spectrum covering gram + and gram - bacteria, not frequently used as a single agent, do not effect mammalian cells because they depend upon exogenous folate and do not synthesize folate, resistance in bacteria can occur if excess PABA is produced, sulfonamide uptake is altered, or sulfonamide binding to dihydropteroate synthase is altered, works by competing with PABA for dihydropteroate synthase and blocks dihydrofolic acid synthesis and this DNA synthase, causes skin hypersensitivity, photosensitivity, steven-johnson syndrome presenting as serious/fatal skin and mucous membrane eruption, also nausea, vomiting, diarrhea, and urine preciptates causing crystalluria, hematuria, and obstruction

Answer 24

sulfonamides - sulfadiazine/sulfamethoxazole/sulfamethizole

Question 25

pyrimidine compunds including trimethoprim and pyrimethamine, covers gram - bacteria, resistance in bacteria may occur if there is change in drug uptake or reduced reductase binding, inhibitor of bacterial dihydrofolate reductase in impaired DNA synthesis, causes bone marrow suppression, megaloblastic anemia, leukopenia, and granulocytopenia, also nausea, vomiting, and diarrhea

Answer 25

trimethoprim/pyrimethamine - antifolates

Question 26

combination, commonly used to treat urinary tract infection and prostatitis, in addition at lower doses used prophylactially to treat recurrent urinary tract infection, in addition is effective in treating pneumonia, shigellosis, and systemic salmonella infections, works by synergistic effect of combining trimethoprim-sulfamethoxazole, causes same adverse effect of each of the individual agents

Answer 26

trimethoprim sulfamethoxazole - TMP/SMX

Question 27

synthetic flourinated compounds, broad spectrum antibiotics covering gram + and gram - bacteria, used in the treatment of urinary, gastrointestinal and respiratory infections as well as some sexually transmitted diseases like gonorrhea, effective against anthrax, works by disrupting the winding of DNA and the separation of DNA strands during transcription and replication specifically inhibiting topoisomerase II (DNA gyrase) and topoisomerase IV, causes nausea, vomiting, diarrhea, drug-nutrient interactions by binding divalent cations and preventing absorption, prolongs QT interval, causes rash, itching, photosensitivity, also causes tendinopathy in adults and arthropathy due to growing cartilage

Answer 27

fluoroquinolones/ ciprofloxacin and levofloxacin

Question 28

least active fluoroquinolone

Answer 28

norfloxacin

Question 29

fluoroquinolone working well against gram - with some activity against gram +

Answer 29

ciprofloxacin, levofloxacin, ofloxacin

Question 30

best activity against gram +

Answer 30

gatifloxacin, gemifloxacin, moxifloxacin

Question 31

unknown mechanism of action which is antibacterial and antiprotozoal, coverage limited to anaerobic bacteria, good tissue penetration and distribution, used in the treatment of abdominal infections, vaginitis, c. diff colitis, and brain abscess, works as a prodrug inactive until taken up by the organism and undergoes chemical reduction, reaction metabolites bind to DNA and disrupt function and cause damage, causes nausea, vomiting, diarrhea, affects metabolism with disulfiram effect so avoid alcohol, also causes neuropathy

Answer 31

metronidazole - DNA damaging agent

Question 32

antifolate with broad spectrum coverage, used for UTI, resistance by changes in folate synthesis pathway or drug uptake, adminstered orally, renal impairment increases half life so renal considerations necessary, although renal clearance decreases, can still be used to treat kidney infection,

Answer 32

sulfamethoxazole

Question 33

antifolate with gram - coverage, used in UTI, resistance by changes in folate synthesis pathway or drug uptake, administered orally, half life increases with renal impairment

Answer 33

trimethoprim

Question 34

fluoroquinolone with broad spectrum activity, used in UTI, abdominal, respiratory, skin and soft tissue infections, and anthrax, resistance is by changes in drug targets or drug efflux pumps, administered orally or IV, no hepatic elimination adjustments necesssary, but minor change to half life with renal impairment, is absorbed well and avoids first pass metabolism

Answer 34

ciprofloxacin

Question 35

covers anaerobic organisms and c. diff infection, resistance is by mutations in the rdxA gene, adminstered orally, IV and topically, no elimination dose adjustments necessary

Answer 35

metronidazole