Aminoglycosides, Aminocyclitols, Fluoroquinolones

Neomycin

Aminoglycoside

Amikacin

Aminoglycoside

Gentamicin

Aminoglycoside

What are aminoglycoside pharmacodynamics dependent on?

Ratio of peak plasma concentration to pathogen MIC

How are renal and otic toxicity avoided with aminoglycosides?

Let the plasma concentration fall below standard through concentrations before the next dose

What is the mechanism of aminoglycoside mechanism?

A bactericidal protein synthesis inhibitor

Why are aminoglycosides ineffective against anaerobes?

They are oxygen dependent to get into the cell

Aminoglycoside administration

Parenterally

• Ophthalmic

• Otic

• Creams

• Ointments

What is the oral bioavailability of aminoglycosides?

3-5% (bad)

Aminoglycosides labeled for oral use are only effective where?

In the GI tract

What is the worst way to administer aminoglycosides?

CRI because it minimizes efficacy and maximized toxicity

What is the pharmacokinetics of aminoglycosides?

Highly hydrophilic

Low volume of distribution

Poor penetration into the CNS, eye, prostate

Short T1/2

Where are the highest tissue concentrations of aminoglycosides?

Renal cortex and cochlear tissue

Aminoglycoside excretion

Renal

T/F aminoglycosides experience significant binding to cellular debris at the site of infection?

True

What is the post antibiotic effect (PAE)?

Bacteria is put into an antibiotic-free culture medium and there is a lag time until growth starts again

What is the sub-MIC effect?

Suppression of bacterial growth even after concentration drops below the MIC

What do PAE and sub-MIC help with?

A longer stretch time between antibiotic administration

Aminoglycoside spectrum

Staph. aureus and pseudintermedius

Enterobacterales

Pasteurellaceae

Pseudomonas aeruginosa

Aminoglycoside adverse effects

Renal toxicity

Ototoxicity

Neuromuscular blockade

What aminoglycoside is less toxic than gentamicin?

Amikacin

T/F neomycin can be used systemically?

False

Describe the renal toxicity of aminoglycosides

Initial nonazotemic phase followed by a clinical azotemic phase

How can we prevent renal toxicity with aminoglycosides?

Monitor serum creatinine and if it doubles stop treatment

What are symptoms of ototoxicity of aminoglycosides?

Auditory or vestibular symptoms

Auditory symptoms of aminoglycosides are most frequent with what drugs?

Amikacin and neomycin

Vestibular symptoms of aminoglycoside ototoxicity are most frequent with what drug?

Gentamicin

Cats are more susceptible to what adverse effect of aminoglycoside?

Vestibular effects

Dogs are more susceptible to what aminoglycoside adverse effects?

Auditory effects

Why is it riskier to give aminoglycosides to a working dog?

You can mess up their hearing and make the working dog retire

What can increase the chance of a neuromuscular blockade due to aminoglycoside?

General anesthesia

What is the withdrawal time for extra-label use of aminoglycosides in food animals?

18 months

Spectinomycin

Aminocyclitol

Spectinomycin adminsitration

IV

IM

Sc

Water soluble

What are aminocyclitols?

Base molecule for aminoglycosides

Aminocyclitol toicity

Much less than aminoglycosides

Enrofloxacin

Second generation fluoroquinolone

Orbifloxacin

Second generation fluoroquinolone

Marbofloxacin

Second generation fluoroquinolone

Danofloxacin

Second generation fluoroquinolone

Pradofloxacin

Third generation fluoroquinolone

Criprofloxacin

Human-labeled second generation fluoroquinolone (poor bioavailability in dogs but some vets use it)

What is enrofloxacin metabolized to?

Ciprofloxacin

T/F the extralabel use of fluoroquinolones in food animals is legal?

Flase

Danofloxacin label in cattle

Bovine respiratory disease in cattle not intended for dairy production and not intended to be processed for veal

Enrofloxacin label in food animals

Swine respiratory disease

Control of colibacillosis

Bovine respiratory disease in dairy heifers under 20 months old

Food animal fluoroquinolone administration

Injectable

List of drugs that are illegal to use in any food animal?

Chloramphenicol

Nitroimidazoles

Nitrofurazones

Glycopeptides

Sulfonamide drugs in lactating dairy cattle

Second gen fluoroquinolone spectrum

Staph aureus and pseudintermedius

Enterococcus faecium and faecalis

Enterobacterales

Pasteurellaceae

Pseudomonas aeruginosa (marbofloxacin is best)

3rd gen Fluoroquinolone spectrum

Everything

What is the best veterinary 2nd gen fluoroquinolone for Pseudomonas?

Marbofloxacin

What is unique about the activity of fluoroquinolones?

They work at 2 sites of bacterial DNA

Fluoroquinolone pharmacokinetics

Good oral administration

Good injection absorption

High lipid solubility: penetrates eye, CNS, prostate

Fluoroquinolone excretion

Kidney

T/F the same dose of ciprofloxacin is equivalent to enrofloxacin?

False

Fluoroquinolone pharmacodynamics

Rapid bactericidal activity

Dependent on Cmax:MIC and AUC:MIC

When can cephalosporins be used for extralabel disease?

With a label regimen in major food animal species

T/F extralabel fluoroquinolones are allowed in food animals?

False

What influenza A drugs are prohibited to be used in chickens, turkeys, and ducks?

Adamantane

Neuraminidase inhibitors

Describe whats unique about Fluoroquinolone resistance?

Some pathogens can mutate one active site first resulting in low level resistance and other can develop resistance in one step

What is the MSW (mutant selection window)?

Space between plasma concentration between the MIC of the pathogen and 10x the MIC (term used in fluoroquinolons)

What is the goal with the MSW?

Spend as little time as possible there during dosing regiment

What are the adverse effects of fluoroquinolones?

Articular cartilage damage

Retinal degeneration (cats)

Neural effects (headaches, seizures)

Irritation

Tendon rupture

What animal is more susceptible to articular cartilage damage from fluoroquinolones?

Puppies

Concurrent therapy of lfuoroquinolones and what will increase plasma concentrations and toxicity?

Furosemide or cimetidine

What is a fluoroquinolone that does not cause retinal degeneration in cats?

Pradofloxacin

What fluoroquinolone is known for causing neural adverse effects?

Enrofloxacin

Adverse effect of pradofloxacin?

Bone marrow suppression in dogs. DO NOT USE

What is a disease that can be worsened by fluoroquinolones?

Myasthenia gravis

Why should you not use large animal injectable enrofloxacin in small animals?

It causes sterile abscesses