Aminoglycosides Flashcards
Name the Aminoglycosides?
5
Gentamicin Tobramycin Amikacin Streptomycin Neomycin
Mechanism of action for Aminoglycosides?2
- Crosses outer bacterial membrane by passive diffusion via porin channels,
- then binds to 30s ribosomal subunit and thus inhibits protein synthesis
The binding of aminoglycosides to the bacteria prevents what?
Causes what?
Increases what?
- Prevent the formation of an initiation complex of peptide formation
- Cause misreading of the messenger RNA message, leading to the production of nonsense peptides
- Increase membrane leakage
Are aminoglycosides bactericidal or bacteriostatic?
bactericidal
leaks content too = lysis
Whats the main mechanism of resistance for aminoglycides?
Describe two other ways bacteria can become resistant?
Transferase enzyme inactivates aminoglycoside
- Impaired entry of aminoglycoside into the cell (genotypic or phenotypic)
- Receptor protein on 30S ribosomal subunit may be deleted or altered
Describe the pharmacokinetics: Vd? Protein bound? Metabolism? Excretion? Who is dose adjustments required for?
Vd- poorly distributed(increased in patients with ascites, burns, pregnancy, and other conditions (such as cystic fibrosis))
poorly protein bound
No metabolism
Excreted through the urine
dosing adjustments for renal pts and not hepatic disease
Spectrum of activity?
5 examples
What is it synergistically used with and what for? 3
aerobic gram-negative bacilli including Pseudomonas, Enterobacter, Serratia, Acinetobacter, and Klebsiella.
- beta-lactams to treat gram postive bacteria
- protozoa (paromomycin)
- mycobacterial infections (tobramycin, streptomycin, and amikacin)
HOw do we treat Enterococcus faecalis endocarditis?
4
bacteriocidal combo (ampicillin or penicillin + gentamicin or streptomycin)
Staphylococcus aureus endocarditis?
2
quicker killing (naficillin + gentamicin)
WHat kind of bacteria is aminoglycosides?
Negligible anaerobic coverage
What is bacteria death dependant on in amicoglycosides?
Concentration-Dependent Killing (Dose-Dependent Killing)
–Increasing concentrations kill an increasing proportion of bacteria and a more rapid rate
Aminoglycosides have a postantibiotic effect. What is it?
2
- Antibacterial activity persists despite unmeasurable drug concentrations - because the half life is so long
- May last for several hours, and varies with type of bacteria
Aminoglycoside clinical uses?
7
- Serious, life-threatening gram-negative infection
- Complicated skin, bone or soft tissue infection
- Complicated urinary tract infection (only thing it was sensitive to was an aminoglycoside)
- Sepsis
- Osteomyelitis
- Endocarditis
- complicated intraabdominal infections
What are Parenteral aminoglycosides used for?
mycobacterial infections
What is the most widely used aminoglycoside?
Gentamicin (Garamycin)
What are gentamicin’s dosage forms?
4
IV, IM
Topical
Ophthalmic
Tobramycin (Nebcin) has basically the same coverage as gentmycin except for what?
It comes in an inhalation form to treat what?
better Pseudomonas coverage
More expensive
CF
What is Amikacin used for?
Used for resistant bacteria
IV, IM
Streptomycin used in combination for with beta-lactams for what?
3
- 2nd line TB
- Enterococcus faecalis endocarditis
- Viridans streptococcus endocarditis
Neomycin (Mycifradin) use?
Limited to topical and oral use
What is paromomycin (humanity) used for?
2
intestinal amebiasis
And hepatic coma/encephalopathy
PO
What are three other aminoglycosides that were mentioned in the talk?
Kanamycin (Kantrex)
IV, IM
Netilmicin (Netromycin) (not in US) IV IM
Spectinomycin (Trobicin) (Not in US) IM
Aminoglycosides
Pregnancy?
Lactation?
D
Probably safe but safety unknown
Aminoglycosides
Contraindications
2
- Previous allergy or hypersensitivity reaction to aminoglycosides
- Myasthenia gravis- neuromuscular blockade risk too high (already have a problem with ACH so you cant blcok it even more)
Aminoglycosides
Adverse Effects
What are the BBW?
4
NEPHROTOXICITY
OTOTOXICITY
NEUROTOXICITY
NEUROMUSCULAR BLOCKADE
How do we monitor nephrotoxic levels when giving aminoglycosides?
Three other things we would monitor?
Elevated troughs
renal casts
urine output
SCr
What are the most nephrotoxic aminoglycosides?
3
What helps prevent nephrotoxicity?
neomycin, tobramycin, gentamycin
a once daily dosing instead of more. Helps renal tubular cells decrease intracelluar levels
What are the most ototoxic aminoglycosides?
3
Neomycin, kanamycin, amikacin
Does it affect vestibular or cochlear?
Both
Vestibular: 2/3 of ototoxicity; manifests as vertigo, ataxia, loss of balance, tinnitus
Cochlear: 1/3 of ototoxicty; manifests as high frequency hearing loss, deafness is unusual
Is nephrotoxicity and otoxicity irreversible?
nephro- yes
Oto- no
How do we measure ototoxic levels?
peak levels
What causes Neuromuscular Blockade when giving aminoglycosides?2
How would we treat this?
neuromuscular blockade at very 1. high doses given
2. too fast resulting
in respiratory paralysis
calcium gluconate
What are dosing levels of aminoglycosides based on?2
disease state & pt. specifics
When should the peak be measured for aminoglycosides?
Trough levels should be measured when?
30 minutes after infusion
30 minutes before infusion
Aminoglycosides
Drug Interactions?
5
- Chemotherapy agents Agalsidase Alfa/beta
- Loop Diuretics
- Neuromuscular-Blocking Agents
- Beta-lactam abx
- Vitamin K Antagonists (eg, warfarin)
Despite the relatively broad spectrum of activity, widespread clinical use is generally limited because ?
the availability of less toxic agents with comparable efficacy and without the need for serum drug concentration monitoring.
Aminoglycosides remain important as a second agent in treatment of serious infections due to?2
aerobic gram-negative bacilli and certain gram-positive organisms
Also important as part of a multi-drug regimen for?
certain mycobacterial infections.
There are rare instances in which monotherapy with aminoglycosides is adequate treatment.
What are they?
3
Tularemia
Plague
Uncomplicated urinary tract infections caused by drug-resistant gram-negative organisms.
Myasthenia gravis is an absolute contraindication to aminoglycoside use!
Statement!
