Inhibitors of Microbial Protein Synthesis II

Question 1

Tetracycline Adverse Reactions

Answer 1

nausia, diarrhea, superinfections, enamel dysplasia and abnormal bone growth in fetus, hepatic disease in pregnancy, photosensativity, vestibulotoxicity

Question 2

Primary use of tetracyclines

Answer 2

mycoplasma pneumonia, Chlamydia, and Rickettsiae

Question 3

Newest Tetracycline

Answer 3

Tigecycline is a glycylcycline approved for MRSA and complicated intra-abdominal and skin infections, only injections once daily; gram negative bacteria with efflux pump and tetracycline resistant strains are susceptible

Question 4

Macrolides

Answer 4

Erythromycin, azithromycin, and clarithromycin

Question 5

Macrolides Mechanism of Action

Answer 5

bind 50s and block translocation of peptidyl-tRNA from acceptor to donor site, also blocks formation of initiation complex

Question 6

Macrolide Resistance

Answer 6

Across the class, three mechanisms: reduced permeability of cell membrane efflux, enterobacteria esterases metabolize drug, modified binding site (methylase adds methyl to site, also resistance to lincosamides and streptogramin B)

Question 7

Macrolide Adverse Reactions

Answer 7

GI irritation, rashes, eosinophilia, hypersensativity cholestatic hepatitis, pregnant hepatitis

Question 8

Tetracycline Interactions

Answer 8

Polyvalent cations and cholestyramine/cholestipol cholesterol lowering resins that bind tetracyclines

Question 9

Macrolide Clinical Uses

Answer 9

moderate spectrum bacteriostatic only for rapidly multiplying organisms, mycoplasma pneumoniae, Chlamydia, H. Pylori, prophylaxis, corynebacterial infections

Question 10

Ketolides

Answer 10

Synthetic macrolides for community pneumonia, bacterial sinusitis and chronic bronchitis but associated with liver failure and exacerbbation of myasthenia gravis

Question 11

Fidaxomicin

Answer 11

narrow spectrum macrolide that inhibits bacterial RNA polymerase and has no systemic absorption

Question 12

Linosamide (Clindamycin) Mechanism of Action

Answer 12

blocks translocation of peptidyl tRNA from acceptor site to donor site so charged tRNA cannot access receptor site (similar to macrolides)

Question 13

Linosamide Resistance

Answer 13

Methylation for 50s binding site and enzymatic inactivation, cross resistance with macrolides

Question 14

Lincosamides Adverse Reactions

Answer 14

GI irritation worsened by any peristalsis inhibitors, hepatic dysfunction, neutropenia, rash, thrombophlebitis at injection site, superinfections

Question 15

Lincosamides Interactions

Answer 15

Macrolides have same MOA so together each drug is less effective

Question 16

Primary clinical use for Lincosamides

Answer 16

Bacteriostatic used to treat severe anaerobic gram negative infections

Question 17

Treatments for Clostridium difficile

Answer 17

1. oral metronidazole for mild/moderate or oral vancomycin for severe, 2. fidaxomicin, 3. Investigating humanized neutralizing mAb against toxins A and B

Question 18

Qinupristin-dalfopristin

Answer 18

30:70 combination of streptogramin B (Q) and A (D) that has a longer duration than one drug alone

Question 19

Quinupristin-dalfopristin Mechanism of Action

Answer 19

bind 50s and constric exit channel on ribosome

Question 20

Quinupristin-dalfopristin Resistance

Answer 20

enzymatic inactivation of dalfopristin, modification of quinupristin binding site, binding interference, efflux interference

Question 21

Quinupristin-dalfopristin Adverse Reactions

Answer 21

pain at infusion site and arthralgia-myalgia

Question 22

Quinupristin-dalfopristin Interactions

Answer 22

Potent inhibitors of CYP34A so may increase plasma levels of many drugs

Question 23

Quinupristin-dalfopristin clinical uses

Answer 23

bactericidal reserved for treating resistant organisms: penicillin resistant pneumococci, VRSA, MRSA, vancomycin resistant Enterococcus faecium, methicillin caused skin infections

Question 24

Oxazolidinone (linezolid) mechanism of action

Answer 24

binds unique site, 23s of 50s, and blocks formation of tRNA-ribosome-mRNA complex

Question 25

Oxazolinfinones Resistance

Answer 25

Mutation of 23s ribosomal binding site, only enterococci so far

Question 26

What protein inhibitors are adjusted in Renal insufficiency and which are not?

Answer 26

tetracyclines except doxycycline, azithromycin, clarithromycin, licosamides, aminoglycosides, and cyclic lipopeptides must be adjusted

Question 27

Oxazolidinones Adverse Reactions

Answer 27

Thrombocytopenia, optic/peripheral neuropathy and lactic acidosis with prolonged use

Question 28

Oxazolindinones Interacitons

Answer 28

MAO inhibitor so enhances serotonergic drug effects, do not give oxazolindinone and serotonergic simultaneously

Question 29

Oxazolidinones clinical uses

Answer 29

bacteriostatic for enterococci and staphlococci, bactericidal for streptococci, active agains gram possitives resistant to beta lactams and vancomycin so reserved for treating resistant organisms and uses as last resort for multi-drug resistant strains

Question 30

Aminoglycosides

Answer 30

Amikacin, Gentomicin, Streptomycin, Tobramycin, Neomycin, Netilmicin, Paromomycin

Question 31

Aminoglycosides Resistance

Answer 31

Varying susceptibility to inactivating transferases, impaired cell entry, and changes in binding site

Question 32

Aminglycosides Adverse Reactions

Answer 32

Irreversible ototoxicity, auditory impairment from amikacin and kanamycin and vestibular impairment from gentamicin and streptomycin, reversible nephrotoxicity from gentomicin and tobramycin, neuromuscular blockade, and skin reactions

Question 33

Aminoglycosides Interactions

Answer 33

Other nephrotoxic drugs, loop diuretics increase ototoxicity, and synergy with beta lactam antibiotics

Question 34

Aminoglycoside Clinical Uses

Answer 34

bactericidal for aerobic gram negative bacteria

Question 35

Aminocyclitols (spectinomycin) Mechanism of Action

Answer 35

bind 30s but are not bactericidal and do not cause misreading

Question 36

Why are adverse reactions, interactions, and resistance rare for aminocyclitols?

Answer 36

Drug given as a single 2g IM injection dose

Question 37

Clinical uses of Aminocyclitols

Answer 37

Bacteriostatic against gram positive and negative but just used as alternative therapy for gonorrhea in patients allergic to other therapies, Aminocyclitos have no cross resistance with other gonorrheal antibiotics

Question 38

Cyclic lipopeptides (Daptomycin) Mechanism of Action

Answer 38

depolarize bacterial cell membrane causing loss of potential and potassium reflux leading to cell death.

Question 39

Cyclic Lipopetides Resistance/Interactions

Answer 39

None

Question 40

Cyclic Lipopeptides Adverse Reactions

Answer 40

Injection pain, GI, fever, CNS effects, elevated CPK which requires monitoring, decreased nerve conduction velocity, cardio-respiratory events, discontinue if muscle weakness, pain, or myopathy

Question 41

Cyclic Lipepeptides Clinical Uses

Answer 41

Bactericidal agains gram possitives including MRSA and vancomycin resistant Enterococcus faecalis, treatment for complicates skin and skin structure infections