Antibiotics 4 - Aminoglycosides

Question 1

Core structures of Aminoglycoside (three ex.)

Answer 1

1,3 diaminocyclitol structures

• Streptidine
• 2-deoxystreptamine
• Spectinamine

Question 2

7 Clinically important Aminoglycosides

Answer 2

• Tobra
• Strepto
• Spectino
• Kana-A
• Amikacin A
• Neo-B
• Genta-C2

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TSS-KANG

Question 3

Aminoglycoside MOA (general and specific)

Answer 3

Bind 30S subunit - inhibit protein synthesis

Bind to the 16S rRNA forming the A site = interferes with formation of the initiation complex, blocks translation, and elicits premature termination

Question 4

Aminoglycosides also cause impairment of ______

Answer 4

proofreading functions of the ribosome

(resulting in nonsense protein)

**nonsense proteins affect cell wall function

Question 5

What effect do the “nonsense” proteins have on the cell?

Answer 5

They impair the function of the cell wall

(causes membrane destabilization, allowing more Aminoglycoside to enter the cell and completely halt protein synthesis)

Question 6

Ultimately, Aminoglycosides cause _______ and ______ resulting in cell death

Answer 6

leakage of ions and disruption of the cell membrane

Question 7

How does the Aminoglycoside get into the cell

Answer 7

Displacement of Mg⁺⁺ and Ca_⁺⁺ ions that form salt bridges with Phosphate groups (on phospholipids) makes the membrane more permeable.

Question 8

Passage of Aminoglycosides through the cytoplasmic membrane occurs…

Answer 8

via active transport

Question 9

How do bacteria inactivate Aminoglycosides?

Answer 9

acetylation

adenylation

phosphorylation

Question 10

The genes responsible for enzymatic metabolism of Aminoglycosides can be…

Many of these enzymes…

Answer 10

…transferred to other bacteria

Many enzymes have cross-resistance specificity

Question 11

Aminoglycosides are not metabolized by…

Answer 11

humans

They are largely excreted unchanged via the urine.

Question 12

Three mechanisms for Aminoglycoside resistance in bacteria

Answer 12

1. Metabolism (acylation, adenylation, and phosphorylation)
2. Altered ribisomes (16S altered by point mutations)
3. Altered Aminoglycoside uptake (reverts after drug removal)

Question 13

All Aminoglycosides are ____ and _____

Answer 13

ototoxic (irrev.) and nephrotoxic (rev.)

Question 14

3 Risk factors for ototoxicity of Aminoglycoside use

Answer 14

1. Other ototoxic drugs (loop diuretics, vancomycin)
2. Compromised renal function
3. Genetic vulnerability

Question 15

Aminoglycoside + loop diuretics =

Answer 15

potentiated nephortoxicity of both.

Monitor creatinine clearance, discontinue if evidence of ototoxicity appears (dizzy, vertigo, tinnitus)

Question 16

Less common Aminoglycoside effect

Answer 16

Curare-like effects

(requires high dose)

Question 17

Respiratory paralysis can be reversed by ___ or ____

Answer 17

Neostigmine or calcium gluconate

Question 18

Aminoglycoside toxicity is more likely if Tx involves… (4)

Answer 18

• > than 5 days duration
• elderly
• renal impairment
• high dose

Question 19

Spectrum and use of Aminoglycoside

Answer 19

broad spec (+/-)

but mainly used for Gram -

Question 20

Aminoglycosides are often used in combo with ____

Answer 20

Penicillins

but must be administered in different compartments to avoid rxn!

Question 21

Penicillin/Aminoglycoside combo used to treat…

Answer 21

Bacterial endocarditis

Question 22

Streptomycin used to treat…

Answer 22

TB

Question 23

Gentamicin is used for….(4)

Answer 23

UTI

Burns

Some PNAs

Joint/bone infections (caused by susceptible Gram-)

Question 24

Aminoglycoside-resistant bacteria common in…

Answer 24

hospitals.

Question 25

Amikacin has retained activity against ____.

It’s used to treat ____.

Answer 25

Aminoglycoside-resistant strains in hospital.

Nosocomial infections.

Question 26

Most aminoglycosides are based on _______

Answer 26

2-deoxstreptamine structure

Question 27

High risk patients should be assed by ______ during aminoglycoside course

Answer 27

serial audiograms