Inhibitors Of Protein Synthesis

Front 1

Examples of Aminoglycosides
-structure

Back 1

streptomycin, gentamicin, tobramycin, amikacin
-2 amino sugar joined by glycosidic linkage

Front 2

MOA of Aminoglycosides

Back 2

-diffuse through porins in outer membrane of G- organisms to periplasmic space (blocked by Mg+, Ca2+, acidic pH); need O2 to get into cell (never active against anaerobes)
-irreversibley bind to 30S and 50S initiation complexes
to inhibit protein synthesis (long PAE)
-killing (cidal) is directly proportional to concentration/MIC

Front 3

AG
1. Pk
2. what effects elimination?

Back 3

1. excluded from certain body compartments (eye cns); high concentration in renal cortex, urine, perilymph and endolymph of inner ear (nephro and ototoxicity); small VOD b/c charged
2. renal fxn, age (less renal bld flow), fever, weight, ob pts, burn pts, pediatric pts, ascites increases Vd, dialysis

Front 4

AG activity

Back 4

Enterbacter, Klebsiella, Proteus, Pseudomonas, Serratia
-G+: enterococcus (w/ another drug)
-long PAE effect; better to give a single daily dose)
-serious G- infections (used in combo with other meds for sepsis)

Front 5

AG Toxicities

Back 5

1. Ototoxicity: cochlear (high pitched tinnitus, high tone loss then conversational tone loss), vestibular (upright vertigo, ataxia)
2. Nephrotoxicity
3. Neuromuscular blockade (treat with calcium, AChE)

Front 6

Quinupristin/dalfopristin
1. what are they?
2.MOA
3. Spectrum
4. SE

Back 6

1. streptogramins
2. act synergistically on bacterial ribosome; form stable drug-ribosome comp.ex which disallows extrusion of proteins
3. Enterococcus faecium (not faecalis), MRSA, MSSA, MRSE and MSSE, G- cocci (N. meninitidis. M. catarrhalis), G+ bacilli (Legionella, M. pneumoniae, C. perfringens), CDJK....don't use for anything but VREFaecium
4. IV infusion site (pain, edema; central line preferred), arthralgias, myalgias, inc conjugated bilirubin, CYP3A4 inhibitor

Front 7

Oxazolidones: linezolid
1. MOA
2. static vs. cidal
3. Spectrum
4. Pk

Back 7

1. binds 50S ribosome at step involving binding of mRNA to ribosome at initiation of translation (binds 50s near interface w/ 30S ribosome, preventing formation of 70S initiation comples
2. static in general, may be cidal for S. pneumoniae, B. fragilis, C. perfringens)
3. G+ (MS and MR S. aureus, coag negative staph aureus, enterococci faecalis and faecium); less active against G- (M. catarrhalis, H. influenzae, Legionella, N. gonorrhoeae); some anaerobe (G+>G-), mycoplasma, and chlamydia activity; active in >60% of CDJK
3. hemodialysis pts may need supplement; cleared renally and non-renally (may not need dose reduction)

Front 8

Oxazolidinones: linezolid
1. Side Effects
2. Uses

Back 8

1. GI, HA, skin rash, weak MAO inhibitors (inc effect of cold meds), BM suppression (leukopenia, pancytopenia)- need to do weekly CBCs, myalgias and arthralgias (dose-limiting toxicity)
2. drug resistance infections; VR E. faecium and faecalis (static), nosocomial and CAP, skin structure infections

Front 9

Tetrocyclines
1. MOA
2. static vs. cidal
3. Spectrum
4. SE
5. uses
6. interactions

Back 9

1. reversibly bind 30S ribosome preventing access of tRNA to mRNA-ribosome complex
2. static
3. G+ cocci (staph, strep, pneumococcus)
4. GI, phototoxicity (bad sunburn), tooth discoloration, hypoplastic enamel (contraindicated w/ PG), hypersensitivity, dark sclera, prophylaxis for meningococcal carrier state
5. atypical (mycoplasma, ureaplasma, tularemia, rickettsia), acne, SIADH (demeclocycline), rosaciae
5. Fe, Ca, increased gastric pH (antacids) all impair absorption

Front 10

Chloramphenicol
1. MOA
2. Pk
3. spectrum
4. Interactions

Back 10

1. reversibly binds 50s ribosomal subunit; prevents binding of tRNA to binding site
2. good CSF absorption
3. H. influenzae, S. pneumoniae, N. meningitidis (cidal); most aerobic and anaerobic organisms, chlamydia, mycoplasma, rickettsiae (static)
4. inhibits CYP450 (slower elimination of phenytoin, tolbutamide, chlorpropamide)

Front 11

Chloramphenicol Toxicities

Back 11

aplastic anemia (rarely given b/c of this), bone marrow suppression, inhibits mitochondrial protein synthesis reducing iron uptake, grey baby syndrome (cyanosis, abdominal distention, hypothermia-inadequate glucuronyl transferase activity; babies can't conjugate drug)

Front 12

Chloramphenicol Uses

Back 12

-typhoid fever (Salmonella)
-bacterial meningitis
-some anaerobic infections
-riskettsial diseases (rocky mt. spotted fever)

Front 13

Erythromycin (comes from Actinomycete Streptomyces Erthraeus)
1. MOA
2. static vs. cidal
2. Pk
3. Spectrum

Back 13

1. macrolide; binds 50S ribosomal subunit competing for attachment sites on the ribosome which prevents translocation of tRNA and its peptide chain
2. cidal or static depending on organism and concentration
3. degraded by acid; salts are used or enteric coating to increase absorption; enters prostatic fluid and macrophages; doesn't enter brain/CSF
3. G+ cocci (S. pyogenes, S. pneumoniae), mycoplasma,
legionella, campylobacter jejuni, chalmydia; not active vs G- (combine w/ AG or aztreonam for broad coverage)

Front 14

Erythromycin
1. Toxicities
2. Drug Interactions
3. Uses

Back 14

1. hepatitis (possibly allergic; associated with estolate salt), GI intolerance (cramping, motulin agonist)
2. (inhibits CYP) decreased metabolism of theophylline, carbamazepine, warfarin, cyclosporine; increased digoxin effect (QT prolong w/ rapid IV infusion)
3. strep infections in pcn allergic, outpt pneumonia, M. pneumoniae, Legionnaire's disease, S. pneumoniae

Front 15

Macrolides

Back 15

erythromycin, azithromycin (longest half life, dec GI effects, better G- and anaerobe activity), clarithromycin (dec GI effects, better Legionella, H. pylori, chlamydia, and M. catarrhallis activity)

Front 16

Ketolides

Back 16

telithromycin, clindamycin

Front 17

Telithromycin
1. what is it?
2. MOA
3. SE

Back 17

1. ketolide; derived from emycin
2. binds 50s ribosome to inhibit protein synthesis; resistant to drug-export pumps
3. severe hepatotoxicity (off market), visual disturbances, inhibits CYP3A4 (don't give w/ statins

Front 18

Clindamycin
1. what is it?
2. MOA
3. Pk
4.Spectrum
5. Toxicities
6. Uses

Back 18

1. ketolide
2. binds 50S ribosomal subunit to inhibit protein synthesis
3. C. palmitate prodrug is hydrolyzed to clindamycin
4. G+ similar to emycin (often S. aureus, but not MRSA), anaerobes (B. fragillis); NOT mycoplasma, G- bacilli, and enterococcus
5. C. difficile superinfection
6. anaerobic infections (lung abcess), sepsis in abdomen (w/ AG), PID, osteomyelitis, preventing glycocalyx formation

Front 19

Pentamidine Isethionate
1. MOA
2. uses
3. SE

Back 19

1. not clear; varies w/ parasite, kills replicating and nonreplicating cells
2. antitrypanosmal, pneumocystis carinii, leishmaniasis
3. very toxic; may cause coughing, hypoglycemia- DM may follow, hypotension/shock, inc Cr

Front 20

Metronidazole MOA

Back 20

1. inhibits hydrogen production by pyruvate phosphoroclastic rxn (anaerobes can't make H+ to survive); Nitro group- electron sink drawing electrons from reduced electron transfer protein

Front 21

Metronidazole
1. Spectrum
2. Uses
3. toxicities

Back 21

1. anaerobic protozoa (T. vaginalis, E. histolytica, G. lamblia), anaerobic bacteria (B. fragilis, B. melaninogenicus, Clostridium spp)
2. trichomonas vaginitis, CNS infections (anaerobic meningitis), anaerobic infections (B. fragilis), intraabdominal infections (+AG), not as effective as clindamycin for pleuropulmonary disease
3. disulfiram rxn (vomiting w/ alcohol)