Inhibitors Of Protein Synthesis I And Ii

Front 1

What 4 inhibitors of protein synthesis act at 30S subunit?

Back 1

-tetracyclines
-tigecycline
-aminoglycoside
-spectinomycin

Front 2

What 5 inhibitors of protein synthesis act at 50S subunit?

Back 2

-macrolide ab
-chloramphenicol
-streptogramins
-oxazolidinones
-lincosamides

Front 3

What protein synthesis inhibitor doesn't bind ribosomal subunits at all

Back 3

mupirocin - acts at tRNA synthetase

Front 4

Three general characteristics of protein synthesis inhibitors an exception examples

Back 4

-bacteriostatic (aminoglycoside are cidal)
-given orally (tigecycline)
-broad spectrum (several examples)

Front 5

Tetracyclines:
MOA
mode for selective toxicity
spectrum

Back 5

-reversible binding to 30S subunit (blocks aatRNA)
-will only affect 70S mitochondrial ribosomes, not cytoplasmic ribosomes
-very broad - can cause superinfections, more active against G+, static

Front 6

Three mechanisms for bacterial resistance to tetracyclines

Back 6

-decreased intracellular levels (decreased influx, increased efflux)
-enzymatic inactivation of drug
-expression of proteins taht protect ribosomes from drug

Front 7

Three things that affect absorption of tetracyclines

Back 7

-oral administration = varies absorption
-divalent and trivalent cations (dairy, iron, antacids)
-elevated gastric pH (pt on antacid or H2 blocker)

Front 8

Distribution of tetracycline:
-accumulates where
-CNS penetration
-placenta

Back 8

-wide accumulation in liver, spleen, bone marrow, bone, dentine, enamel of unerupted teeth
-good penetration into CNS
-crosses placenta

Front 9

Excretion of tetracycline:
-where
-2 exceptions

Back 9

most cleared through kidneys, some reabsorbed in small intestine
-doxycycline - eliminated as inactive chelate in feces
-minocycline - metabolized by liver, passed in feces

Front 10

What is tetracycline the drug of choice for

Back 10

-rickettsial diseases, chlamydia, mycoplasma pneumonia, yersinia pestis, vibrio cholera, lyme disease

Front 11

5 adverse effects of tetracycline

Back 11

GI irritation/superinfections --> pseudomembranous colitis
-photosensitivity
-hepatotoxicity
-renal toxicity
-discoloration of teeth

Front 12

Drug interactions of tetracyclines

Back 12

-may compromise efficacy of bactericidal antibiotics
-can alter pharm activity of other drugs like warfarin

Front 13

How does tigecycline MOA differ from tetracycline

Back 13

-binds with higher affinity
-is static against MRSA
-effective against strains that are tet-resistant

Front 14

aminoglycosides (mycins)
-MOA
-cidal/static

Back 14

-bind irreversibly to 30s and inhibits protein synthesis in several ways
-cidal**
-concentration dependent killing with signification PAE

Front 15

aminoglycoside
-spectrum
-tx for staph a and staph e

Back 15

-extended spectrum, primarily gm - aerobic bacilli
-combo w/penicillin or vancomycin for syn to tx staph

Front 16

aminoglycoside:
absorption
distribution
clearance

Back 16

-poorly absorbed from GI tract, usually IM/IV
-not well distributed to cells, eyes, CNS; but high in inner ear adn renal cortex --> toxicity
-renal

Front 17

three adverse effects of aminoglycosides

Back 17

-ototoxicity, vestibular toxicity, renal toxicity

Front 18

Spectinomycin:
MOA
spectrum
uses
absorption

Back 18

-binds 30s ribosomal subunit, static
-mostly G- but some G+
-used against MRSA and gonorrhea
-IM, rapid absorption

Front 19

macrolide ab:
MOA

Back 19

-bind reversibly to 50s subunit, block tRNA/peptide from A to P site
-static

Front 20

What rx's cannot be combined with macrolide ab and why

Back 20

-streptogramins, clindamycin, chloramphenicol
-competitively inhibit ribosomal binding of these drugs, becomes antagonism

Front 21

macrolide ab spectra:
G+/-
-vs. penicillin
-vs. erythromycin

Back 21

-accumulate to a greater extent in Gm+
-braoder than penicillin (but generally narrow)
-more effective than erythromycin against anaerobes

Front 22

**KNOW**
how does bacterial resistance develop in macrolide ab

Back 22

-chromosomal mutation altering ribosome's ability to bind drug
-develops rapidly
-cross-resistance common w/other 50s inhibitors

Front 23

What are three mechanisms of induced resistance to macrolide antibiotics

Back 23

-efflux pump
-methylase (modifies ribosome so drug can't bind)
-hydrolysis of macrolides by esterases

Front 24

macrolide:
administration
distribution
excretion

Back 24

-acid stable except erythromycin (coated for oral use)
-poor CNS penetration, erythro will penetrate abscess
-erythro - in bile; clarithro - met by liver, secrete by kidney

Front 25

**KNOW**
therapeutic uses for macrolide ab

Back 25

-alternative to penicillins in allergic pts
-used for common bacterial infections but resistance develops rapidly

Front 26

macrolide ab adverse effects (2)

Back 26

-GI disturbances w/oral erythro
-hepatotoxicity (reversible cholestatic hepatitis)

Front 27

drug interactions with macrolide ab

Back 27

-inhibit CYP3A4 which then potentiates effects of other drugs (warfarin)
**azithromycin will NOT do this

Front 28

Chloramphenicol MOA

Back 28

binds reversibly to 50S at peptidyltransferase site
-near site for clindamycin and macrolides

Front 29

chloramphenicol:
activity
spectrum
resistance

Back 29

-static
-broad spectrum, most anaerobes, most Gm - bacilli
-resistance due to acetyltransferases that modify drug

Front 30

chloramphenicol:
administration
fetal
CNS
metabolized/excretion

Back 30

-oral or parenteral
-crosses placenta
-penetrates CNS
-liver, urine

Front 31

Uses and adverse effects of chloramphenicol

Back 31

-infections not treatable with less toxic drugs
-tetracycline backup
-hematological toxicities, aplastic anemia, hypersensitive skin, gray baby syndrome

Front 32

chloramphenicol drug interactions

Back 32

-inhibits P450 enzymes so prolongs half-life of drugs metabolized by CYPs

Front 33

streptogramins (quinupristin/dalfopristin):
MOA
activity

Back 33

-q binds 50S, D binds nearby so it synergistically enhances q binding
-combined they are cidal, individually static

Front 34

streptogramins
therapeutic uses
adverse effects

Back 34

-VRSA
-pain, phlebitis, deregulation of levels of drugs that are metabolized by CYPs

Front 35

Oxazolidinones
MOA
activity
used to tx

Back 35

-50S binding (like chloramphenicol, but no inhibition of peptidyl transferase)
-static
-MRSA and other resistant bact (reserved for unresponsive infections)

Front 36

Lincosamides - clindamycin
MOA
spectrum

Back 36

-exclusive to 50S of bacterial
-most Gm+, better than macrolides against anaerobes, no activity against Gm- aerobes

Front 37

Clindamycin resistance

Back 37

-ribosomal methylase modifies the target
-NOT induced by clindamycin

Front 38

Clindamycin:
administration
distribution
excretion

Back 38

-oral/parenteral
-wide (active in bone); low in CNS
-metabolized by liver, excreted in urine (impaired in hepatic failure pts)

Front 39

4 common uses for clindamycin

Back 39

-respiratory tract infections caused by anaerobes
-abscesses
-group A strep
-osteomyelitis

Front 40

clindamycin adverse effects

Back 40

-diarrhea, pseudo col
-skin rash, SJS, anaphylaxis

Front 41

What is mupirocin used for and why

Back 41

MRSA, inhibits tRNA synthetase, rapidly metabolized, TOPICAL only