4. Aminoglycosides

Question 1

Aminoglycosides:

-structure

Answer 1

• Neomycin
• Gentamycin: contains 6-amino groups
• NH2 is positively charged and when it binds to something negatively charged it accumulates, eg in kidney and primary sensory cell(ear).
• It can therefore destroy the kidney or the hearing: ototoxic, nephrotoxic
• Spectinomycin - aminocyclitol
• is not glycoside but aminoglycitol

Question 2

Aminoglycosides:

• mechanism of action

Answer 2

• uptake with acitive transport (O2) - potentiation
• Anaerobic bacteria can therefore not be killed (because of the O2)
• Aminoglycosides will produce inappropriate proteins
• Tetracyclines stop synthesis
• Cell membrane toxicity
• RNA-structure damage

Question 3

Aminoglycosides:

• mode of action

Answer 3

• Bactericidal
• concentration dependent
• PAE
• acts on 30S, changes the protein synthesis

Question 4

Aminoglycosides:

• Antibacterial spectrum

Answer 4

• Aminoglycosides can not kill anaerobic bacteria or Streptococci
• slight differences
• gram - aerobic + staphylococcus spp

Question 5

Aminoglycosides:

• Resistance

Answer 5

• Ab Ovo: except for anaerobic
• Plasmids: eg E.coli resistance is spreading
• Eltering enzymes (periplasmic space –> acetylation, adenylation)
• reduced permeability: bc energy is needed for transport and uptake
• Cross resistance: One way

Question 6

Aminoglycosides:

• pharmacokinetics

Answer 6

• Absorption:
• PO <-> parenteral
• intramammal, intrauterine, abscess (cats are very sensitive, so it can be absorbed through the absess and lead to toxicosis)
• only 1-2%
• eg Neomycin is very hydrophilic, only 1-2% will be absorbed, therefore it can be used if you have many bacteria in the stomach. Otherwise its very toxic.
• Escept Aramycin, F= 0.3 in swine
• Distribution (very hydrophilic, not so good), Accumulation (good, ear+kidney)
• metabolism: no liver, only kidney
• Excretion: kidney, active form

Question 7

Aminoglycosides:

• toxicity

Answer 7

proportional with the number of functional groups (N-groups)

• Streptomycin:
• LD50 = 450mg/kg
• Neomycin:
• LD50 = 200 mg/kg
• More functional groups, more toxic!
• Spectinomycin:
• LD50 = 200 mg/kg
• 1. Adsorption and accumulation in the cells - membrane damage
• 2. pinocytosis in the cell (lipid peroxidation)
• Lysosomal destruction (membrane)
• Damage of mitochondria (membrane)
• Predisposing factors: kidney, hydrationstate, operation
• long term application (7-10days)
• Amicacin: 2 weeks
• Spectinomycin: 3 weeks
• preferring SID in high doses!
• Neuromuscular blocade:
• dont combine them with muscle relaxant because they will inhibit ACh-release, eg combination with Diazepam can lead to suffucation

Question 8

Aminoglycosides:

• Indications

Answer 8

• Respiratory infections
• Gastrointestinal infections
• UTI
• Mastitis
• dermatitis
• Topical administration
• septicaemia (combination)

Question 9

Streptomycin/dihidrostreptomycin

Answer 9

• Not alone:
• not effective against strept.
• combination with penicillins (TTG)
• effective against strept.
• IM, SC, duration 3 days

Question 10

Neomycin

Answer 10

• Alone
• against GI infection and mastitis
• Cobination: usually no combination with penicillin
• only in life threatening disease
• Per os, parenteral (not often), topical admin.

Question 11

Gentamicin

Answer 11

• Aone:
• mastitis, UTI
• ear drops, eye drops
• Combination with penicillins
• Only if life threatening
• per os, parenteral, topical admin.

Question 12

Spectinomycin

Answer 12

• Bacteristatic, mycoplasma spp.
• also alone and combination with lincomycin
• per os, parenteral

Question 13

Apramycin

Answer 13

• bioavailability is better orally
• Swine = 0.3
• Per os –> respiratory, GI

Question 14

Tobramycin

Answer 14

• most active
• toxic
• topical (ear drops, eyedrops), parenteral

Question 15

Amikacin

Answer 15

• one of the most active
• slightly toxic
• parenteral
• good against MRSA, MRSP
• Pseudomonas: Amikasin, tobramycin, Gentamycin