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Infectious Disease > Aminoglycosides > Flashcards

Aminoglycosides Flashcards

1
Q

Name the Aminoglycosides?

5

A 
Gentamicin 
Tobramycin 
Amikacin 
Streptomycin
Neomycin
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2
Q

Mechanism of action for Aminoglycosides?2

A
  1. Crosses outer bacterial membrane by passive diffusion via porin channels,
  2. then binds to 30s ribosomal subunit and thus inhibits protein synthesis
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3
Q

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

A
  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
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4
Q

Are aminoglycosides bactericidal or bacteriostatic?

A

bactericidal

leaks content too = lysis

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5
Q

Whats the main mechanism of resistance for aminoglycides?

Describe two other ways bacteria can become resistant?

A

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
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6
Q 
Describe the pharmacokinetics:
Vd?
Protein bound?
Metabolism?
Excretion?
Who is dose adjustments required for?
A

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

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7
Q

Spectrum of activity?
5 examples

What is it synergistically used with and what for? 3

A 
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)
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8
Q

HOw do we treat Enterococcus faecalis endocarditis?

4

A

bacteriocidal combo (ampicillin or penicillin + gentamicin or streptomycin)

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9
Q

Staphylococcus aureus endocarditis?

2

A

quicker killing (naficillin + gentamicin)

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10
Q

WHat kind of bacteria is aminoglycosides?

A

Negligible anaerobic coverage

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11
Q

What is bacteria death dependant on in amicoglycosides?

A

Concentration-Dependent Killing (Dose-Dependent Killing)

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

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12
Q

Aminoglycosides have a postantibiotic effect. What is it?

2

A
  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
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13
Q

Aminoglycoside clinical uses?

7

A
  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
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14
Q

What are Parenteral aminoglycosides used for?

A

mycobacterial infections

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15
Q

What is the most widely used aminoglycoside?

A

Gentamicin (Garamycin)

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16
Q

What are gentamicin’s dosage forms?

4

A

IV, IM
Topical
Ophthalmic

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17
Q

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

It comes in an inhalation form to treat what?

A

better Pseudomonas coverage
More expensive

CF

18
Q

What is Amikacin used for?

A

Used for resistant bacteria

IV, IM

19
Q

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

A
  1. 2nd line TB
  2. Enterococcus faecalis endocarditis
  3. Viridans streptococcus endocarditis
20
Q

Neomycin (Mycifradin) use?

A

Limited to topical and oral use

21
Q

What is paromomycin (humanity) used for?

2

A

intestinal amebiasis
And hepatic coma/encephalopathy
PO

22
Q

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

A

Kanamycin (Kantrex)
IV, IM

Netilmicin (Netromycin) (not in US) IV IM

Spectinomycin (Trobicin) (Not in US) IM

23
Q

Aminoglycosides
Pregnancy?
Lactation?

A

D

Probably safe but safety unknown

24
Q

Aminoglycosides
Contraindications
2

A
  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)
25
Q

Aminoglycosides
Adverse Effects
What are the BBW?
4

A

NEPHROTOXICITY
OTOTOXICITY
NEUROTOXICITY
NEUROMUSCULAR BLOCKADE

26
Q

How do we monitor nephrotoxic levels when giving aminoglycosides?

Three other things we would monitor?

A

Elevated troughs

renal casts
urine output
SCr

27
Q

What are the most nephrotoxic aminoglycosides?
3

What helps prevent nephrotoxicity?

A

neomycin, tobramycin, gentamycin

a once daily dosing instead of more. Helps renal tubular cells decrease intracelluar levels

28
Q

What are the most ototoxic aminoglycosides?

3

A

Neomycin, kanamycin, amikacin

29
Q

Does it affect vestibular or cochlear?

A

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

30
Q

Is nephrotoxicity and otoxicity irreversible?

A

nephro- yes

Oto- no

31
Q

How do we measure ototoxic levels?

A

peak levels

32
Q

What causes Neuromuscular Blockade when giving aminoglycosides?2

How would we treat this?

A

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

calcium gluconate

33
Q

What are dosing levels of aminoglycosides based on?2

A

disease state & pt. specifics

34
Q

When should the peak be measured for aminoglycosides?

Trough levels should be measured when?

A

30 minutes after infusion

30 minutes before infusion

35
Q

Aminoglycosides
Drug Interactions?

5

A
  1. Chemotherapy agents Agalsidase Alfa/beta
  2. Loop Diuretics
  3. Neuromuscular-Blocking Agents
  4. Beta-lactam abx
  5. Vitamin K Antagonists (eg, warfarin)
36
Q

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

A

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

37
Q

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

A

aerobic gram-negative bacilli and certain gram-positive organisms

38
Q

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

A

certain mycobacterial infections.

39
Q

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

A

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

40
Q

Myasthenia gravis is an absolute contraindication to aminoglycoside use!

A

Statement!

Infectious Disease (29 decks)

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