30)Aminoglycosides

Question 1

Aminoglycosides

Answer 1

These inhibit protein synthesis

These are broad spec antibiotics

Effective against many G^-ve + SOME G⁺ MOs

Includes:

• Streptomycin
• Gentamycin
• Kanamycin
• Amikacin
• Tobramycin
• Netilmicin
• Neomycin - topically
• Paromomycin - orally - effective against some protozoa

Question 2

Mechanism of action

Answer 2

• Bactericidal
• Bind irreversibly to 30s Ribosomal subunit ⇢ Inhibits bacterial protein synthesis
• Passively diffuses into bacteria via porin channels of outer membrane
• Moves across cytoplasmic membrane via ⇢ oxygen-dependant AT
• Resistance ⇢ develops due to enzymatic degradation

Question 3

Pharmacokinetics

Answer 3

• NOT absorbed orally
• Parental administration ⇢ IM or IV
• Distributed in ECF ⇢ < 30% protein bound
• Not metabolised
• Excreted UNCHANGED in urine
• ½ life = 2-3 hours
• DOES NOT penetrate BBB
• DOES cross placenta

Question 4

Adverse effects

Answer 4

• Nephrotoxic ⇢ May damage proximal tubule ⇢ Gentamycin + Tobramycin are most nephrotoxic
• Combining use of Amphotericin B may ⇡ RENAL toxicity

Question 4

Adverse effects

Answer 4

• Nephrotoxic ⇢ May damage proximal tubule ⇢ Gentamycin + Tobramycin are most nephrotoxic
• Combining use of Amphotericin B may ⇡ RENAL toxicity
• Ototoxicity ⇢ auditory/vestibular damage may occur with any aminoglycoside + may be irreversible ⇢ Neomycin + Kanamycin
• Allergic skin reaction ⇢ Neomycin
• Bronchoconstriction
• Neuromuscular paralysis ⇢ inhibit release of ACh in post-synaptic cleft

Question 5

Clinical use

Answer 5

Gentamycin, Tobramycin + Amikacin ⇢ Useful against G^-ve bacteria

• E.coli
• Enterobacter
• Klebsiella
• Proteus
• Pseudomonas
• Serratia
• Bacterial endocarditis
• Tularaemia
• Tuberculosis ⇢ Streptomycin
• Pulmonary infections in patients w/cystic fibrosis ⇢ Tobramycin

Question 6

Drug interactions

Answer 6

• Ototoxic effect ⇡ when OTHER ototoxic drugs are administered at same time
• Risk of nephrotoxicity ⇡ when combined w/amphotericin B

Answer 7