Aminoglycosides

Question 0

What are the 5 aminoglycosides?

Answer 0

1. streptomycin
2. tobramycin
3. gentamicin
4. amikacin
5. neomycin

Question 1

What do aminoglycosides do?

Answer 1

Aminoglycosides inhibit protein synthesis by binding to the 30s ribosomal subunit

Question 2

What is the mode of administration for streptomycin and what does it treat?

Answer 2

IV/IM

second line TB drug

Question 3

what is the mode of administration for gentamicin?

Answer 3

IV/IM/Topical

Question 4

what is the mode of administration for Tobramycin?

Answer 4

IV/IM/topical

Question 5

what is the mode of administration for amikacin?

Answer 5

IV/IM

Question 6

what is the mode of administration for neomycin?

Answer 6

topical/PO

Question 7

Describe the structure of aminoglycosides and how this affects their pharmacokinetics?

Answer 7

Aminoglycosides are amino sugars in glycosidic linkage. They are polycations. Their polarity affects their absorption and distribution (it explains why they must be taken in combination with inhibitors of cell wall synthesis)

Question 8

What do aminoglycosides do to the 30s ribosomal subunit?

Answer 8

They irreversibly bind to the 30s ribosomal subunit and block its activity. Because this binding is irreversible, aminoglycosides are bacteriocidal!

Question 9

What requirements must be met for aminoglycosides to be functional?

Answer 9

Aminoglycosides must be actively transported into the bacterial cells which involves the use of O2. Therefore, aminoglycosides are only useful against aerobic and not anaerobic bacteria

Question 10

In general, when are aminoglycosides used?

Answer 10

They are used to specifically treat aerobic G- enteric (rods) bacteria. They are also used when sepsis or endocarditis is suspected.

Question 11

Streptomycin uses:

Answer 11

1. tularemia
2. bubonic plague
3. TB
4. endocarditis (part of combination therapy)

Question 12

which aminoglycosides are effective against P. aeruginosa?

Answer 12

gentamicin, tobramycin, amikacin

Question 13

Neomycin and gentamicin uses:

Answer 13

topical application of wounds and burns caused by aerobic G- bacteria

gentamicin is also active against P. aeruginosa

Question 14

What is the DOC for enterococcus species?

Answer 14

penicillin + aminoglycosides

Question 15

Explain resistance and synergism when it comes to aminoglycosides and ICWS:

Answer 15

Aminoglycosides are too large and polar to enter the cells on their own. They are unable to cross the membrane. ICWS have a hard time completely breaking down the walls of G- bacteria but they are able to weaken it. ICWS weaken the cell walls of G- bacteria enough to allow the aminoglycosides to enter the cells and bind to the 30s ribosomal subunit irreversibly, where the inhibit protein synthesis and cause the cell to die.

Question 16

What is the DOC for P. aeruginosa?

Answer 16

antipseudomonal penicillin + aminoglycosides

Question 17

Do aminoglycosides fall under concentration dependent killing or time dependent killing?

Answer 17

Aminoglycosides are concentration dependent killing antibiotics. Increasing the concentration of aminoglycosides increases the number of susceptible bacteria they are able to kill and the rate at which they kill the bacteria

Question 18

Explain the post antibiotic effect (PAE) of aminoglycosides:

Answer 18

Aminoglycosides exhibit a PAE. That is, antibacterial activity persists even when you can no longer detect the antibiotics. This means that a single large dose is more effective than multiple small doses which allows for decreased toxicity b/c toxicity is based on number of repeat exposure and total time the drug is detectable in the body

Question 19

Aminoglycoside toxicity:

Answer 19

1. Ototoxicity and Nephrotoxicity
2. GI (N/V)
3. Superinfections
4. Allergies

Question 20

which types of drugs should not be administered with aminoglycosides and why?

Answer 20

1. loop diuretics should not be administered with aminoglycosides b/c it increases the risk of ototoxicity (synergism)
2. cephalosporins, vancomycin, cisplatin, and cidofovir should not be given with aminoglycosides bc they act synergistically and cause nephrotoxicity

Question 21

Aminoglycosides pharmacokinetics:

Answer 21

1. IV/IM/Topical (PO neomycin - 3% absorption)
2. renal excretion
3. poor CNS penetration

Question 22

Resistance and aminoglycosides:

Answer 22

If a bacteria develops resistance to one aminoglycoside it might be resistant to other aminoglycosides. This phenomenon is known as cross resistance.
Bacteria can develop resistance to aminoglycosides a few ways:
1. deficiency of ribosomal receptor
2. lack of permeability to drug
3. enzymatic modification of aminoglycoside

Question 23

What are the three broad spectrum antibiotics?

Answer 23

1. chloramphenicol
2. tetracyclines
3. glycylcyclines

Question 24

What side effects is chloramphenicol associated with?

Answer 24

It is associated with fetal aplastic anemia and other fatal side effects.

Question 25

Describe the mechanism of action for chloramphenicol:

Answer 25

1. chloramphenicol reversibly binds the 50s subunit. 2. it is bacteriostatic. 3. it inhibits protein synthesis

Question 26

Chloramphenicol and mitochondrial ribosomes:

Answer 26

Mitochondrial ribosomes are slightly more similar to prokaryotic ribosomes and chloramphenicol is able to take advantage of this and inhibit mitochondrial protein synthesis in humans. This can have many adverse side effects a. dose dependent bone marrow depression b. gray baby syndrome

Question 27

Spectrum of Chloramphenicol vs. use:

Answer 27

Chloramphenicol is active against G+/G-, anaerobes, aerobes and atypicals. However it is only used for life threatening conditions: 1. Typhoid Fever 2. Meningitis 3. Rickettsia, Brucellosis, Rocky Mountain Spotted Fever, and Meliodosis 4. Bacterial Conjunctivitis (topical)

Question 28

Chloramphenicol pharmacokinetics:

Answer 28

1. Oral administration: complete absorption, no longer used (aplastic anemia) 2. parenteral administration 3. good tissue penetration (including eyes) 4. good CNS penetration 5. 90% metabolized in the liver. conjugated with glucuronic acid 6. metabolite excreted renally

Question 29

chloramphenicol resistance development:

Answer 29

1. inactivation by acetyl transferase 2. modify the binding site 3. efflux pumps

Question 30

What are the three tetracyclines and their modes of administration?

Answer 30

1. tetracycline: PO/topical 2. doxycycline: oral 3. minocycline: oral

Question 31

Tetracycline mechanism of action:

Answer 31

bind reversibly to 30s ribosomal subunit. bacteriostatic prevent protein synthesis

Question 32

Tetracycline spectrum:

Answer 32

G+/G- anaerobes/aerobes atypicals

Question 33

List the organisms that are resistant to tetracyclines:

Answer 33

1. B. fragilis 2. proteus 2. pseudomonas

Question 34

Therapeutic use for tetracyclines:

Answer 34

``` H. pylori infection cholera mycoplasma pneumonia chlamydia Rickettsia (rocky mountain spotted fever) amebiasis, acne, gonorrhea (acute) brucellosis Early Lyme disease plague vibrio species ```

Question 35

Tetracyclines are the DOC for what types of infections:

Answer 35

1. cholera 2. Rocky Mountain spotted fever 3. Early Lyme Disease 4. Mycoplasma Pneumonia 5. Chlamydia

Question 36

How do bacteria develop resistance to tetracyclines?

Answer 36

1. efflux pumps | 2. doxycycline and minocycline may still be effective b/c they are poor substrates for the efflux pumps

Question 37

Tetracycline pharmacokinetics

Answer 37

1. PO 2. chelation with Ca, Fe, and Al 3. all tissues except CNS and joints 4. deposit themselves in bone 5. liver metabolism 6. renal excretion 7. doxycycline is not metabolized by the liver and it is excreted in the feces 8. long acting tetracyclines are slowly excreted, longer t1/2 and less frequent dosing

Question 38

Tetracycline toxicity:

Answer 38

1. normal flora changes 2. prevents growth of long bones 3. teeth discoloration ** do not give to pregnant woman or children under 8 yo

Question 39

What is a glycylcycline?

Answer 39

1. synthetic minocycline derivative 2. IV administration only 3. complicated skin/skin-structure and complicated intra-abdominal infections 4. bind 30s ribosomal subunit - bacteriostatic 5. similar to tetracyclines but also has activity against tetracycline resistant organisms 6. 2/3 fecal elimination and 1/3 renal elimination 7. side effects similar to tetracycline 8. MRSA, MRSE, PRSP and VRE