Aminoglycosides Ch45 Pharm

Front 1

Question: What is the MOA of gentamicin, and other aminoglycosides?

Back 1

They are bactericidal inhibitors, by binding to 30S and inhibit the formation of the initiation complex while also causing mRNA misreading, and inhibit translocation.

Front 2

Aminoglycosides are dependent on what and therefore, are ineffective against what?

Back 2

They are dependent on oxygen for uptake into bacterial cell; therefore, they are ineffective against anaerobes.

Front 3

Gentamicin, tobramycin, and amikacin are important drugs against?

Back 3

Aerobic gram-negative bacteria (E. coli, Enterobacter, Kelbsiella, Proteus, Providencia, Pseudomonas, and Serratia.

Front 4

Streptomycin is used to treat?

Back 4

With combination of penicillin, os more effective in enterococcal carditis than other aminoglycosides. Tuberculosis, plaque, and tularemia.

Front 5

Due to neomycin toxicity, it is restricted to?

Back 5

Bowel surgery (kills bowel flora; therefore, reducing chance of infection) and topical use.

Front 6

What are the toxicity associated with aminoglycosides.

Back 6

1. Nephrotoxicity (especially with amphotericin BH, vancomycin, or cephalosporin)

2. ototoxicity (esp. with loop diuretic); and teratogen.
3. Rare curare-like effect (neuromusclar blockade--muscle paralysis and apnea)
4. Skin Rash
Always follow PT's BUN and creatinine levels.

Front 7

Question: A 70 kg PT with creatinine clearance of greater than 80 mL/min has a gram-negative infection. Amikacin is administered intramuscularly at a dose of 5 mg/kg every 8 hours, and the PT begins to respond. After 2 days, creatinine clearance declines to 30 mL/min. Assuming that no information is available about amikacin plasma levels, what would be the most reasonable approach to management of the PT at this point?

Back 7

Decrease the dosage to 120 mg every 8 hours. Because creatinine clearance is only one third of the starting value, a dose reduction should be made to one third of that given initially.

Front 8

Aminoglycosides are often used synergistically with what?

Back 8

Beta-lactams work synergistically with Aminoglycosides;

1. Gentamicin with ampicillin or vancomycin to treat enterococcal endocarditis.

2. Aminoglycosides with cephalosporins to treat life-threatening bacterial infections.

Front 9

What is a correct statement about bacterial resistance to aminoglycosides?

Back 9

Clinical resistance mainly occurs through plasmid mediated formation of group transferase enzymes.

Front 10

Which antibiotic is the most effective agent in the treatment of an infection due to enterococci if used in combination with penicillin G?

Out of: amikacin, gentamicin, neomycin, neomycin, spectinomycin, streptomycin

Back 10

Streptomycin. About 15% of enterococcal isolates that are resistant to gentamicin and other systemic aminoglycosides remain susceptible to streptomycin.

Front 11

Why does gentamicin have antibacterial action beyond administration?

Back 11

Antibacterial action of aminoglycosides is concentration-dependent rather than time-dependent. When the plasma level of gentamicin falls below the minimal inhibitory concentration, the drug continues to exert antibacterial effects for several hours--a postantibiotic effect.

Note: this explains the administration of a single large does instead of multiple smaller doses.

Front 12

An adult PT weights 70 kg, has bacteremia, suspected from a gram-negative rod. Tobramycin is administered once a day, and the loading dose must be calculated to achieve a peak plasma level of 20 mg/L. Assume normal renal function. Vd = 20 L; T 1/2 = 3 h; CL = 80 mL/min. What loading dose should be given?

Back 12

400 mg. LD = plasma concentration x volume distribution.

Front 13

What drug is most likely to be effective against multi-drug-resistant strains of M. tuberculosis, including those resistant to streptomycin.

Back 13

Amikacin. Treatment of TB, amikacin or streptomycin are always used in combination with other antitubercular agents.

Front 14

A 67 yo man is seen complaining of pain in and behind the right hear. There is edema of external otic canal with purulent exudate and weakness of the muscles on the right side of face. Pt is diabetic. Gram stain of exudate shows polymorphonucleocytes and gram-negative rods. Diagnosis is external otitis. What is the appropriate plan?

Back 14

The PT should be hospitalized and treatment started with gentamicin plus ticarcillin.

Likely pathogens include E. coli and Pseudomonas aeruginosa, and coverage must include other gram-negative rods. Combination of aminoglycoside plus a wider spectrum penicillin is must suitable for pseudomonas strains.

Front 15

Regarding the toxicity of gentamicin, what is correct?

Back 15

More nephrotoxic effects than ototoxicity. Ototoxicity is irreversible, which increases by loop diuretics.

Front 16

What is true about neomycin?

Back 16

Used in hepatic coma, to decrease protein intake and suppress coliform bacteria; therefore, reducing ammonia intoxication.

Also, used for sterilization prior to bowel surgery.

Front 17

Streptomycin is the DOC for?

Back 17

Plaque, tularemia, adjunctive value in TB.

Front 18

This drug has pharmacodynamic and pharmacokinetic properties almost identical to those of gentamicin, but has poor activity in combination with penicillin against enterococci.

Back 18

Tobramycin, and must less effective than either gentamicin or streptomycin when used in combination with penicillin or vancomycin for enterococcal endocarditis.

Front 19

Your 23 year old female PT is pregnant and has gonorrhea. The medical history includes anaphylaxis following exposure to amoxicillin. Worried about compliance, you would like to treat this PT with a single dose, so you choose?

Back 19

Spectinomycin.

Avoid cephalosporins in PTs with history of hypersensitivity to penicillins; avoid fluoroquinolones in pregnancy.

Front 20

In the empiric treatment of severe bacterial infections of unidentified etiology, this drug, often used in combination with an aminoglycoside, provides coverage against many staphylococci.

Back 20

Nafcillin or cephalosporin.

Front 21

Which statement about "once-daily" dosing with aminoglycosides is accurate?

Back 21

Convenient for outpatient therapy; often less toxic; less nursing time and better for PTs with renal insufficiency.

Aminoglycosides are eliminated by the kidneys.

Front 22

Aminoglycosides must diffuse across the cell wall; therefore, they are often used with what that helps breaks down the wall to facilitate diffusion?

Back 22

Penicillin.

Front 23

What two bacteria are responsible for the "mycin" and "micin" nomenclature in most aminoglycosides?

Back 23

-mycin = streptomyces

- micin = micromonospora

Front 24

Owing to their polar nature, aminoglycosides are not?

Back 24

Absorbed after oral administration.

*except neomycin**

Front 25

Netilmycin is more likely to be effective than streptomycin in the treatment of?

Back 25

Hospital-acquired infection caused by Serratia marcescens.

Front 26

Because of what risk, streptomycin should not be used when other drugs will serve?

Back 26

Ototoxicity.

Front 27

Spectinomycin is used for?

Back 27

Its sole purpose is to be used as a backup drug, most commonly in those who are allergic to beta-lactams.

Front 28

What is amikacin derived from?

Back 28

Kanamycin

Front 29

Pseudomonas aeruginosa is a bug that often infects the immunocompromised or burn victims what is the T(x) of choice?

Back 29

tobramycin + peniccillin

Front 30

Francisella tularensis is a lymphoid disease associated with people who are around rabbits. What is the T(x) of choice?

Back 30

gentamicin

Front 31

Klebsiella is an aspiration pneumonia seen in alcoholics what is the T(x) of choice?

Back 31

aminoglycoside + penicillin

Front 32

What is the T(x) of choice for Yersinia pestis (bubonic plaque)

Back 32

Streptomycin + doxycycline

Front 33

What are some severe side effects of Streptomycin?

Back 33

vertigo, loss of balance

due to affect on vestibular app.

Front 34

Why are aminoglycosides advised not to be taken during pregnancy?

Back 34

The ototoxcity damages the fetus hearing in utero causing deafness.

Front 35

Neomycin is unique in the aminoglycoside family in that?

Back 35

1. can be taken orally (bowel prep)

2. can be used topically

3. cannot be given parenteral

4. severe nephrotoxicity

5. works against G(+)& G(-)

Front 36

Spectinomycin is an aminocylitol antibiotic used soley to treat what disease?

Back 36

gonorrhea

*not in us*

Front 37

Aminoglycosides are highly polar and therefore are not distributed where?

Back 37

CNS or fat

Front 38

Aminoglycosides MOA

Back 38

1. irreversible inhibitor of 30s subunit

2. disrupt innitiation

3. Misread RNA

4. break up polysomes

Front 39

Aminoglycosides resistance mechanisms of select bacteria?

Back 39

1. inactivation by adenylation, acetlyation, or phosphorylation

2. impaired entry

3. 30s subunit altered

Front 40

Why would you give an aminoglycoside?

Back 40

1. suspect G(-)

2. bug is drug resistant

3. suspicious of sepsis

Front 41

What heart bugs are associated with T(x) with an aminoglycoside?

Back 41

1. enterococcal endocarditis

2. viridians strep

3. staph endocarditis

Front 42

Main aminoglycosides listed for ototoxic effects (4)?

Back 42

1. Neomycin

2. kanamycin

3. amikacin

4. tobramycin

Front 43

Main aminoglycosides listed for ototoxic effects (2)?

Back 43

1. Streptomycin

2. gentamicin

Front 44

Main aminoglycosides listed for nephrotoxic effects (4)?

Back 44

1. neomycin

2. tobramycin

3. gentamicin

4. amikacin

Front 45

Aminoglycosides; bactericidal or basteriostatic

Back 45

Bactericidal

Front 46

What mechanisms of drug resistance occur in aminoglycosides?

Back 46

1. drug inactivation (transferase enzymes)

2. altered target (binding site)

3. reduced uptake across membrane

Front 47

Which aminoglycosides work best as antipseudomonal?

Back 47

tobramycin>> gentamicin

Front 48

Which aminoglycoside has antimycobacterial activity?

Back 48

streptomycin

Front 49

Which organisms do aminoglycosides not work against and why?

Back 49

Anaerobic bacteria ARE NOT SUSCEPTIBLE due to lack uptake through membrane

Front 50

Why can aminoglycosides be given once daily?

Back 50

Lasting post-antibiotic effect

Front 51

Why does aminoglycosides cause nephrotoxicity?

Back 51

disrupts calcium mediated transport process

can lead to acute tubular necrosis that is irreversible

Front 52

Large doses of aminoglycosides can cause neuromuscular paralysis was is the T(x) for reversal?

Back 52

calcium gluconate or

neostigmine