Tetracyclines, Chloramphenicol, Aminoglycosides

Question 1

MOA for tetracyclines, chloramphenicol, and aminoglycosides

Answer 1

Bind to ribosomal subunits and inhibit formation of polypeptide chains and block protein synthesis

Question 2

Tetracycline action

Answer 2

First broad-spectrum antibiotics
Gram + and Gram - bacteria
Mycoplasma
some mycobacteria
Anaplasma, Rickettsia
Protozoan and filarial parasites
First line drugs in food animals, aquaculture, exotic animals, honeybees

Question 2

Tetracycline MOA

Answer 2

Inhibits tRNAs from binding to the docking site on the ribosome and mRNA codon to block peptide synthesis
Some anti-inflammatory action

Question 3

Are tetracyclines bacteriostatic or bactericidal

Answer 3

Most statis
Some time-dependent bactericidal activity for doxycycline

Question 4

Tetracyclines Resistance

Answer 4

Main 2:
Energy dependent efflux systems
Ribosomal protection proteins that remove drug from binding site

Question 5

Tetracycline PK

Answer 5

Poor oral bioavailability
Wide tissue distribution: osteotropic (deposit in teeth and bone)
Excreted by glomerular filtration

Question 6

Tetracycline Toxicities

Answer 6

Irritants: vomiting and tissue damage at injection site
Enterocolitis
Doxycycline tablets cause esophageal stricture in cats!!!!!
Administration to growing animals causes yellow discoloration of teeth

Question 7

What is the drug of choice for rickettsial infections in small animals?

Answer 7

Doxycycline

Question 8

When do we use tetracyclines?

Answer 8

Respiratory disease complexes in pigs and cows
Plague, tularemia, listeriosis
Chlamidophila felis -cats

Question 9

Chloramphenicol MOA

Answer 9

Binds irreversibly to the 50S subunit of bacterial ribosome
Also inhibits mitochondrial protein synthesis in mammalian bone marrow cells: dose-dependent
Generally bacteriostatic

Question 10

Chloramphenicol uses

Answer 10

Broad-spectrum
Gram + and - aerobes and anaerobes

Question 11

Chloramphenicol Resistance

Answer 11

Enzymatic inactivation by acetylation of the drug
Efflux of drug from bacterial cells by transporters

Question 12

Chloramphenicol PK

Answer 12

Rapidly absorbed orally and parenterally
Wide distribution including CNS and eye
Hepatic metabolism (glucuronidation)

Question 13

Chloramphenicol Toxicity

Answer 13

Inhibits cytochrome P450 -must be careful when given with phenobarbital (barbituate overdose)
Bone marrow suppression (dose-dependent)
Banned for use in food animals (aplastic anemia in people)

Question 14

Uses of chloramphenicol

Answer 14

Serious ocular infections, prostatitis, otitis media/interna and salmonellosis in horses dogs and cats

Question 15

Aminoglycosides MOA

Answer 15

Bactericidal -concentration dependent
Bind to 30S ribosomal subunit and cause misreading of genetic code aka makes bad proteins
Pumped into cell with O2 dependent mechanism so do not work with anaerobes

Question 16

Aminoglycosides spectrum of activity

Answer 16

Primarily aerobic gram - bacteria
Some gram +
No anaerobes or aerobes in anaerobic environ

Question 17

Aminoglycoside resistance

Answer 17

Acetylation from plasma-mediated enzymes prevents binding to ribosomal subunit

Question 18

Aminoglycoside PK

Answer 18

Poorly absorbed orally
Small vol of distribution
Renal elimination

Question 19

Aminoglycosides Tox

Answer 19

Ototoxic and nephrotoxic
Acute tubular necrosis is most common adverse effect (related to duration of therapy, elevated troughs)

Question 20

How do we reduce aminoglycoside toxicity?

Answer 20

Ca supplementation
High protein/high Ca diet
Once daily admin at higher doses, allows trough conc to drop below critical level before next dose

Question 21

Examples of aminoglycosides

Answer 21

Gentamicin
Neomycin
amikacin
streptomycin