aminoglycosides

Question 1

ACtivity
bactericidal or static?
mechanism
what is the aim in the dose and what happens after?

Answer 1

Bactericidal, accumulated intracellulary in microorganism via an oxygen dependent uptake-> anerobs are innately reistant!

Binds irreversibly to the 30s ribosomal subunit.

Efficacy is dose dependent-
i.e. the drug aim is about 8times the MIC and shows a bacterial supression even after the dose is reduced (Post antibiotic effect)- larger dose–> larger PAE.
Usually given as one dose orally, short infusion or intramusculary.

RAther a toxic drug

Question 2

Mention drugs related to the aminoglycosides!

Answer 2

Gentamicines
GENTAMICIN, NETILMICIN, SISOMICIN

Kanamycines
KANAMYCINE, TOBRAMYCIN, AMIKACIN

Others
STREPTOMYCIN, NEOMYCIN,
SPECTINOMYCIN

Question 3

Spectrum of the drug

Answer 3

Only Gram - and gram Positive AEROBS!!!
DOES NOT WORK ON ANEROBS YOU IDIOT!!

aerobic Gram+ bacteria
Staphylococcus,
Streptococcus infections

aerobic Gram- bacteria
Neisseria, Haemophilus influenzae, Escherichia coli Klebsiella, , Proteus mirabilis, Pseudomanas, Serratias Acinetobacter
hospital infections
Enterobacter

ineffective against
anaerob bacteria,
atypical pathogens,
intracellular pathogens

Question 4

resistance to aminoglycosides

Answer 4

Inactivation by chemical rxns- acetylation/ phosphorylation etc.
Impaired entry to the cell or S30 is altered.

Question 5

Kinetics
Admin?
Half life
Tissue distribution?.
Excretion?

Answer 5

Pharmacokinetics:
IM / IV are also applied.
Are polar compounds which are not absorbed orally or widely distributed into tissues.
IM / IV prefered due to low absorption from oral route.
Low half life (2-3 hours).
Do not enter CNS

Renal elimination proportional to GFR, and major dose reduction needed in renal dysfunction.

Question 6

Once-daily dosing of aminoglycosides

Answer 6

antibacterial effect depend mainly on peak drug leve (rather than time) and continue with blood levels < mic a postantibiotic effect-

Toxicity depend both on blood level and the time that such levels are >than a specific threshold (i.e. total dose).

Question 7

combo drugs

Answer 7

combinations:
aminoglycoside antibiotics can be added in combination with other antibiotics acting on cell wall synthesis such as
β-lactam antibiotics,
glycoprotein antibiotics

Question 8

adverse effects

Answer 8

1) nephrotoxic- revesible, can lead to ATN.
2) ototoxicity- irreversible deafness (accumulation in the organ of corti). reversible vestibular dysfunction.
3) neruomuscular blockade (under anesthesia).
4) allergic reaction- contact dermititis is a common reaction to topically applied neomycim.

Question 9

Clinical use:

Answer 9

G+ bacteria, G- bacteria infections
in combination with β-lactam antibiotics to extend G+ and G- antibacterial spectrum

in monotherapy
urinary infections