Aminoglycosides

Question 1

Name the Aminoglycosides?

5

Answer 1

Gentamicin 
Tobramycin 
Amikacin 
Streptomycin
Neomycin

Question 2

Mechanism of action for Aminoglycosides?2

Answer 2

1. Crosses outer bacterial membrane by passive diffusion via porin channels,
2. then binds to 30s ribosomal subunit and thus inhibits protein synthesis

Question 3

The binding of aminoglycosides to the bacteria prevents what?
Causes what?
Increases what?

Answer 3

1. Prevent the formation of an initiation complex of peptide formation
2. Cause misreading of the messenger RNA message, leading to the production of nonsense peptides
3. Increase membrane leakage

Question 4

Are aminoglycosides bactericidal or bacteriostatic?

Answer 4

bactericidal

leaks content too = lysis

Question 5

Whats the main mechanism of resistance for aminoglycides?

Describe two other ways bacteria can become resistant?

Answer 5

Transferase enzyme inactivates aminoglycoside

1. Impaired entry of aminoglycoside into the cell (genotypic or phenotypic)
2. Receptor protein on 30S ribosomal subunit may be deleted or altered

Question 6

Describe the pharmacokinetics:
Vd?
Protein bound?
Metabolism?
Excretion?
Who is dose adjustments required for?

Answer 6

Vd- poorly distributed(increased in patients with ascites, burns, pregnancy, and other conditions (such as cystic fibrosis))

poorly protein bound

No metabolism

Excreted through the urine

dosing adjustments for renal pts and not hepatic disease

Question 7

Spectrum of activity?
5 examples

What is it synergistically used with and what for? 3

Answer 7

aerobic gram-negative bacilli including 
Pseudomonas, 
Enterobacter, 
Serratia, 
Acinetobacter, and 
Klebsiella. 

1. beta-lactams to treat gram postive bacteria
2. protozoa (paromomycin)
3. mycobacterial infections (tobramycin, streptomycin, and amikacin)

Question 8

HOw do we treat Enterococcus faecalis endocarditis?

4

Answer 8

bacteriocidal combo (ampicillin or penicillin + gentamicin or streptomycin)

Question 9

Staphylococcus aureus endocarditis?

2

Answer 9

quicker killing (naficillin + gentamicin)

Question 10

WHat kind of bacteria is aminoglycosides?

Answer 10

Negligible anaerobic coverage

Question 11

What is bacteria death dependant on in amicoglycosides?

Answer 11

Concentration-Dependent Killing (Dose-Dependent Killing)

–Increasing concentrations kill an increasing proportion of bacteria and a more rapid rate

Question 12

Aminoglycosides have a postantibiotic effect. What is it?

2

Answer 12

1. Antibacterial activity persists despite unmeasurable drug concentrations - because the half life is so long
2. May last for several hours, and varies with type of bacteria

Question 13

Aminoglycoside clinical uses?

7

Answer 13

1. Serious, life-threatening gram-negative infection
2. Complicated skin, bone or soft tissue infection
3. Complicated urinary tract infection (only thing it was sensitive to was an aminoglycoside)
4. Sepsis
5. Osteomyelitis
6. Endocarditis
7. complicated intraabdominal infections

Question 14

What are Parenteral aminoglycosides used for?

Answer 14

mycobacterial infections

Question 15

What is the most widely used aminoglycoside?

Answer 15

Gentamicin (Garamycin)

Question 16

What are gentamicin’s dosage forms?

4

Answer 16

IV, IM
Topical
Ophthalmic

Question 17

Tobramycin (Nebcin) has basically the same coverage as gentmycin except for what?

It comes in an inhalation form to treat what?

Answer 17

better Pseudomonas coverage
More expensive

CF

Question 18

What is Amikacin used for?

Answer 18

Used for resistant bacteria

IV, IM

Question 19

Streptomycin used in combination for with beta-lactams for what?
3

Answer 19

1. 2nd line TB
2. Enterococcus faecalis endocarditis
3. Viridans streptococcus endocarditis

Question 20

Neomycin (Mycifradin) use?

Answer 20

Limited to topical and oral use

Question 21

What is paromomycin (humanity) used for?

2

Answer 21

intestinal amebiasis
And hepatic coma/encephalopathy
PO

Question 22

What are three other aminoglycosides that were mentioned in the talk?

Answer 22

Kanamycin (Kantrex)
IV, IM

Netilmicin (Netromycin) (not in US) IV IM

Spectinomycin (Trobicin) (Not in US) IM

Question 23

Aminoglycosides
Pregnancy?
Lactation?

Answer 23

D

Probably safe but safety unknown

Question 24

Aminoglycosides
Contraindications
2

Answer 24

1. Previous allergy or hypersensitivity reaction to aminoglycosides
2. Myasthenia gravis- neuromuscular blockade risk too high (already have a problem with ACH so you cant blcok it even more)

Question 25

Aminoglycosides Adverse Effects What are the BBW? 4

Answer 25

NEPHROTOXICITY OTOTOXICITY NEUROTOXICITY NEUROMUSCULAR BLOCKADE

Question 26

How do we monitor nephrotoxic levels when giving aminoglycosides? Three other things we would monitor?

Answer 26

Elevated troughs renal casts urine output SCr

Question 27

What are the most nephrotoxic aminoglycosides? 3 What helps prevent nephrotoxicity?

Answer 27

neomycin, tobramycin, gentamycin a once daily dosing instead of more. Helps renal tubular cells decrease intracelluar levels

Question 28

What are the most ototoxic aminoglycosides? | 3

Answer 28

Neomycin, kanamycin, amikacin

Question 29

Does it affect vestibular or cochlear?

Answer 29

Both Vestibular: 2/3 of ototoxicity; manifests as vertigo, ataxia, loss of balance, tinnitus Cochlear: 1/3 of ototoxicty; manifests as high frequency hearing loss, deafness is unusual

Question 30

Is nephrotoxicity and otoxicity irreversible?

Answer 30

nephro- yes | Oto- no

Question 31

How do we measure ototoxic levels?

Answer 31

peak levels

Question 32

What causes Neuromuscular Blockade when giving aminoglycosides?2 How would we treat this?

Answer 32

neuromuscular blockade at very 1. high doses given 2. too fast resulting in respiratory paralysis calcium gluconate

Question 33

What are dosing levels of aminoglycosides based on?2

Answer 33

disease state & pt. specifics

Question 34

When should the peak be measured for aminoglycosides? Trough levels should be measured when?

Answer 34

30 minutes after infusion 30 minutes before infusion

Question 35

Aminoglycosides Drug Interactions? 5

Answer 35

1. Chemotherapy agents Agalsidase Alfa/beta 2. Loop Diuretics 3. Neuromuscular-Blocking Agents 4. Beta-lactam abx 5. Vitamin K Antagonists (eg, warfarin)

Question 36

Despite the relatively broad spectrum of activity, widespread clinical use is generally limited because ?

Answer 36

the availability of less toxic agents with comparable efficacy and without the need for serum drug concentration monitoring.

Question 37

Aminoglycosides remain important as a second agent in treatment of serious infections due to?2

Answer 37

aerobic gram-negative bacilli and certain gram-positive organisms

Question 38

Also important as part of a multi-drug regimen for?

Answer 38

certain mycobacterial infections.

Question 39

There are rare instances in which monotherapy with aminoglycosides is adequate treatment. What are they? 3

Answer 39

Tularemia Plague Uncomplicated urinary tract infections caused by drug-resistant gram-negative organisms.

Question 40

Myasthenia gravis is an absolute contraindication to aminoglycoside use!

Answer 40

Statement!