Aminoglycosides

Question 1

MoA

Answer 1

Irreversibly bind to bacterial ribosomes.
Active against gram negative aerobe (pseudomonas aeruginosa)
Broad spectrum
Bactericidal

Question 2

Uses

Answer 2

Severe sepsis
Pyelonephritis
Complicated UTI
Endocarditis

Question 3

Administration

Answer 3

Parenteral injection
Not absorbed by gut

Question 4

Different types of aminoglycosides

Answer 4

Gentamicin - choice; active against pseudomonas aerguinoa
Tobramycin - via inhaler for pseudomonal infection in cystic fibrosis
Streptomycin - active against mycobacteria; reserved for TB
Neomycin - parenterally toxic; use in bowel sterilisation
Amikacin - gentamicin resistant gram negative bacilli

Question 5

Gentamicin

Answer 5

Choice drug in UK
Active against pseudomonas aeruginosa
Blind therapy in serious infection in combination with pencillin/metronidazole

Question 6

Gentamicin - therapeutic index

Answer 6

Narrow T.I
Monitor Cp
MUST monitor Cp in:
- parenteral aminoglycosides
- elderly
- obesity
- cystic fibrosis
- high doses
- RENAL impairment

Question 7

ONCE daily regimen

Answer 7

Avoid in:
- Renal impairment (<20 ml/min)
- HACEK or Gram+ endocarditis
- Burns covering >20% of body
Consult local guidelines for serum monitoring.

Question 8

Multiple dose regimens

Answer 8

Monitor after 3 or 4 doses AND after a dose change.
Renal impairment = more frequent + earlier monitoring

Question 9

Post-dose (peak) level after 1 hour is too HIGH

Answer 9

Reduce dose to 5-10mg/ml (3-5 mg/ml for endocarditis)

Question 10

Pre-dose (trough) level before next dose is too HIGH

Answer 10

Increase interval <2mg/ml (<1mg/ml for endocarditis)

Question 11

Renal impairment

Answer 11

Increase interval

Question 12

Severe renal impairment

Answer 12

<30 ml/min
Reduce dose

Question 13

Pregnancy

Answer 13

Can give - AVOID unless essential
Monitor Cp

Question 14

Side effects

Answer 14

Dose related - do not exceed 7 days
Common in elderly and renal failure (renally cleared)

Question 15

Nephorotoxicity

Answer 15

Aminoglycosides are excreted by kidneys
Assess renal function before treatment
Correct any dehydration
Signs:
- Low urine output/CrCl
- High serum creatinine/urea

Question 16

Interactions - increased risk of nephrotoxicity

Answer 16

Ciclosporin
Tacrolimus
Vancomycin
AVOID concomitant nephrotoxic drugs (DAMN)

Question 17

Reversible ototoxicity

Answer 17

Monitor auditory and vestibular function before treatment
Counsel pt to report:
- Hearing loss
- Tinnitus
- Vertigo

Question 18

Interactions - increased risk of ototoxicity

Answer 18

Loop diuretics
- If giving concomitant ototoxic loop diuretics, separate by as long a period as possible
Cisplatin
AVOID concomitant ototoxic drugs

Question 19

Other Side effects

Answer 19

Peripheral neuropathy
Impaired neuromuscular transmission
- C/I in myasthenia gravis
Electrolytes:
HYPO K, Ca + Mg

Question 20

MHRA: Potential histamine related adverse drug effects

Answer 20

Some batches may contain histamine residue from manufacturing process.
Monitor for signs of histamine-related reactions.
Caution in concomitant drugs known to cause histamine release, in children + severe renal impairment

Question 21

MHRA: increased risk of deafness in patients with mitochondrial mutations

Answer 21

Increased risk of deafness in patients with mitochondrial mutations (particularly the m.1555A>G mutation), including cases where the patient’s aminoglycoside serum levels were within the recommended range.