Aminoglycosides & Broad Spectrum Antibiotics Flashcards Preview

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Flashcards in Aminoglycosides & Broad Spectrum Antibiotics Deck (48):
1

mechanism of aminoglycosides?

- targets protein synthesis (targets 30S) - irreversibly inhibits protein synthesis of susceptible microorganisms by inhibiting functioning of 30S subunit
- blocks initiation of translation and causes the misreading of mRNA

2

"All aminoglycosides are usually used ________"

"All amino glycosides are usually used IN COMBINATION."

3

list of aminoglycosides

- streptomycin - TB second line agent (now more first line), IV/IM
- gentamycin - G-, combo - IV/IM, topical
- tobramycin - G-, combo - IV/IM, topical
- amikacin - G-, combo - IV/IM
- neomycin - oral, topical

4

characteristics of aminoglycosides

- contain amino sugars in glycosidic linkage
- polycations
- POLARITY RESPONSIBLE FOR PHARMOKINETIC PROPERTIES
- BACTERICIDAL (used in combo w/ PCN)
- to be effective must be transported into susceptible bacteria (req O2) and bind to 30S subunit to produce non-functional 30S initiation complex
- under aerobic conditions = BACTERICIDAL
- not effective in anaerobes

5

when are aminoglycosides used?

to treat infection caused by susceptible AEROBIC G- ENTERIC BACTERIA (rods) (usu combined w/ beta-lactam antibiotics), or when suspicion of SEPSIS or ENDOCARDITIS

6

when is streptomycin used?

- tularemia (francisella tularensis)
- bubonic plague (yersinia pestis)
- TB
- endocarditis when w/ other agents in combo therapy

7

when is gentamycin/tobramycin/emikacin used?

against P. aeruginosa

8

when is neomycin/gentamycin used?

topical application of wounds & burns caused by gram neg organisms

9

What is the recommendation for infections due to Enterococci?

- two synergistic antibiotics
- rec therapy = gentamycin or streptomycin + vancomycin or a b-lactam (such as PCN)

10

DOC for Gram + cocci (enterococci species)?

aminoglycoside + PCN

11

DOC for tularemia? (rabbit fever)

gentamycin

12

DOC for pseudomonas aeruginosa?

aminoglycoside + antipseudomonal PCN
(tobramycin + piperacillin/ticarcillin)

13

amino glycosides are CONCENTRATION DEPENDENT KILLING. what does this mean?

increasing concentrations kill an increasing population of bacteria and at a more rapid rate

14

aminoglycosides have a significant POST-ANTIBIOTIC EFFECT - explain

- antibacterial activity persists beyond time that antibiotic is measurable
- single large dose has better efficacy than multiple smaller doses - reduces toxic side effects

15

toxicity of aminoglycosides

- OTOTOXICITY
- NEPHROTOXICITY
- overgrowth of non-susceptible organism
- GI upset
- neuromuscular weakness
- nausea, vomiting
- allergy
- diarrhea

16

toxicity of loop diuretics (ethacrynic acid, furosemide)? (usu given at same time as aminoglycoside)

- OTOTOXICITY

17

toxicity of vancomycin, cephalosporins, cisplatin, cidofovir?

- NEPHROTOXICITY

18

pharmokinetics of aminoglycosides

- IM or IV or topical
- none absorbed adequately after oral admin (not absorbed through GI tract; 3% for neomycin)
- none penetrates CSF readily
- normal kidney rapidly excretes all

19

mechanism of action chloramphenicol

reversibly binds to 50S subunit of bacterial 70S ribosomes and prevents attachment of amino acid containing end of aminoacyl-tRNA to acceptor sire on ribosome
- inhibits protein synthesis
- BACTERIOSTATIC
- can be bactericidal against H.flu, Neisseria mening, strep pneu at therapeutic concentrations
- can INHIBIT MITOCHONDRIAL PROTEIN SYNTHESIS IN MAMMALIAN CELLS

19

resistance of aminoglycosides?

- deficiency of ribosomal receptors (if it can't bind, can't have effect)
- lack of permeability of drug molecule into bacteria
- enzymatic modification by bacteria

*** aminoglycosides usu used in COMBO w/ other antibiotics

20

3 classes of BROAD SPECTRUM ANTIBIOTICS?

- chloramphenicol
- tetracyclines
- glycylcyclines

20

characteristics CHLORAMPHENICOL (chloromycetin)

- broad spectrum
- first/prob only successful synthetic antibiotic
- associated w/ FATAL APLASTIC ANEMIA and other serious/fatal side effects (used when no other options available)

21

toxicities of chloramphenicol

- dose dependent (bone marrow suppression) - anemia, leukopenia, thrombocytopenia, reversible upon discontinuation of drug
- dose independent (fatal aplastic anemia = rare)
- GRAY BABY SYNDROME in infants - inadequate activity of glucoronyl transferase in newborn liver
- rash, angioedema, urticaria
- rarely anaphylactic rxns

21

chloramphenicol resistance

- acetyl transferase acetylates and inactivates chloramphenicol
- efflux pumps

22

when is chloramphenicol used? (for life threatening infections)

- typhoid fever
- meningitis (H.flu [bactericidal], N. meningitidis [PCN resistant], S. pnuem.)
- rickettsia, brucellosis, rocky mountain spotted fever, melioidosis
- bacterial conjunctivitis (topical)

22

pharmokinetics of chloramphenicol

- parenteral admin
- best CNS penetration
- metabolized in liver (90%), CONJUGATED w/ GLUCURONIC acid to form chloramphenicol glucoronate - inactive metabolite
- metabolite excreted in kidney

23

list of tetracyclines

- TETRACYCLINE (sumycin) - oral, topical
- doxycycline (vibramycin) - oral
- minocycline (minocin) - oral

24

mechanism of action of tetracyclines

- inhibition of bacterial protein synthesis
- bacteriostatic
- bind reversibly to 30S ribosomes, prevent access of aminoacyl tRNA to receptor site on mRNA complex
- this prevents acids to growing peptide chain

25

spectrum of tetracyclines

- G-
- G+
- anaerobes
- aerobes
- atypicals

26

organisms related to tetracyclines?

- B. fragilis
- proteus (most strains)
- pseudomonas (most strains)

27

treatment for H. pylori?

tetracyclines w/ metronidazol & bismuth

28

treatment for cholera?

DOC = tetracyclines (doxycycline)

29

treatment for mycoplasma pneumonia?

- DOC = tetracyclines
- erythromycin

30

treatment for infections w/ chlamydia?

- DOC = tetracyclines
- azithr/erythromcin

31

treatment for rickettsial infection/RMSF?

- DOC = tetracyclines
- doxycycline for RMSF

31

treatment for Vibrio species?

DOC = tetracyclines

32

treatment for brucellosis?

tetracyclines

32

treatment for lyme disease?

early - DOC = tetracyclines (doxycycline)

33

treatment for plague?

tetracyclines in combo w/ aminoglycosides

34

contraindications of tetracyclines?

- pregnant women
- children < 8 yo
- breastfeeding women

35

resistance to tetracyclines

- usu conferred by efflux pumps
- resistant strains may be susceptible to doxycycline, minocycline, tigecycline - all poor substrates for efflux pumps

36

pharmokinetics of tetracyclines

- absorption after ORAL use adequate but incomplete (D & M better)
- chelation w/ Ca++, Fe++, Al+++ (D & M better)
- distribution in all tissues except CNS & joints
- tetracyclines DEPOSIT THEMSELVES IN BONE/TEETH (chelate Ca2+
- metabolized by liver and excreted in urine & bile
- doxycycline not hepatic ally metabolized, major route excretion via FECES
-

37

adverse reactions to tetracyclines

- GI upset (from incomplete absorption)
- NORMAL FLORA CHANGES
- bone and teeth
- liver damage
- Fanconi syndrome
- photosensitivity
- hypersensitivity uncommon

38

contraindications of tetracyclines?

- pregnant women
- children < 8 yo
- breastfeeding women

39

characteristics of glycylcyclines (tigecycline/tigacil)

- synthetic derivative of minocycline
- IV admin only
- antibiotic for complicated skin/skin structure infections and intra-abdominal infections
- bind to 30S ribosomal subunit
- BACTERIOSTATIC
- spectrum of activity of tigecycline similar to tetracycline, doxycycline, and minocycline, but shows activity against tetracycline resistant organisms

40

when to use tigecycline?

- activity against MRSA, MRSE, PRSP, VRE

41

elimination of tigecycline?

- 2/3 dose via fecal matter, 1/3 by renal excretion

42

adverse effects tigecycline?

- similar to tetracyclines
- main effect = nausea/vomiting