Antimicrobials: Protein Synthesis Inhibitors and DNA Distruptors Flashcards
List 5 types of antimicrobials that are proteins synthesis inhibitors
phenicols
macrolides
lincosamides
aminoglycosides
tetracyclines
What is the mechanism of action of tetracycline
uptake by bacteria via an energy dependent mechanism that animal cells don’t do
they bind ribosome (30S) and interfere with tRNA binding
reversible binding to ribosome
Preferential for bacterial ribosomes
What are the general characteristics of tetracycline drugs
bacteriostatic
time dependent
named after the number of carbon rings
What are 3 mechanisms bacteria have developed to build resistance to teracycline drugs
efflux pumps
alter targets (30S structure)
develop enzymes to degrade the antibiotic
How are tetracycline drugs administered
IM
IV
PO
depends on the drug
What are the pharmacokinetics for tetracycline drugs
varied absorption
- lipophilic
doxycycline is more lipophilic vs oxytetracycline
varied protein binding and excretion
doxycycline = GI excrete
oxytetracycline = renal excretion
What bacteria are tetracyclines effective against
gram (+) aerobes
gram (-) aerobes (not pseudomonas)
- more effective against resp than enteric
good against (+) and (-) anaerobes
= broad spectrum
also ricketts/mycoplasma/erlichia
What are the adverse effects of tetracyclines
teeth discolouration
reduced bone growth in young
fever = cat
hepatotoxic = rare
Nephrotoxic at high doses
will cross placenta and enter milk
- can alter neonate development
hypotension and collapse if you give it IV too fast
- give slowly
- reduced Ca in heart
What is oxytetracycline used for mainly
large animals
pneumonia
metritis
footrot
potomac horse fever
tendon contracture in neonates
keratoconjunctivitis (moraxella bovis)
chlamydia abortus (sheep)
What causes potomac horse fever? What are the clinical signs
ingestion of snails infected with neorickettsia risticii
causes diarrhea, fever, laminitis
How is potomac horse fever treated
IV oxytetracycline diluted in saline
What causes tendon contracture in neonates and how is it rectified?
shortening of the check ligament
treat with a splint and oxytetracycline (give slowly and diluted SID for 1-3d)
- makes tendon more pliable
What are 4 adverse effects of oxytetracycline when treating tendon conracture
nephrotoxicity - ensure well hydrated
rhabdomyolyisis - can impact mitochondria
tooth discolouration
impact growth and healing
What class drug is oxytetracycline
class 3
- resistance is common
How does ocytetracycline compare to macrolides
macrolides: long lasting but higher risk of multidrug resistance
- class 1 drug
oxytetracycline: shorter acting but can repeat treatment if needed
- lots of resistance exists
How is doxycycline administered? What is it mainly used for?
PO or IV in small animals
- NEVER IV to horse
tx
vector borne diseases
- erlichia canis
- borrelia burgdorferi
- rickettsia
- mycoplasma haemofelis
myoplasma
chlamydia
kill heartworm
anti-inflammatory
- chronic rhinitis in cats
What are the pharmacokinetic sof doxycyline
feces excretion
- cannot treat UTI but also doesn’t impact renal failure
more lipophilic vs ocytetracycline
What is an adverse effect of doxycycline given PO
can cause esophageal strictures in cats
ensure you are giving with lots of water or food
How does doxycycline treat heartworm
Heartworm has a symbiotic bacteria (wolbachia)
kills wolbachia = kill heartworm
How does doxycycline have anti-inflammatory effects
inhibits
- matrix metalloproteinase
- neutrophil activation
- t cell proliferation
What is the mechanism of aminoglycosides
premature termination of proteins chains via irreversible binding to 30S ribosome
enters gram (-) via porins and are actively transported through the inner membrane (need O2)
displaces Ca and Mg in biofilm and disrupts polysaccharide crosslinks
What are the general characteristics of aminoglycoside drugs
bactericidal
concentration dependent
oxygen dependent
inactivated by
- low pH
- organic debris
- combination with other drugs
What bacteria are aminoglycosides effective against
good against gram (-) aerobes
good in combination with penicillin
What are the pharmacokinetic properties of aminoglycosides
not absorbed in GI and dont cross tissue barriers
- do not enter BBB or prostate
- large and ionized
not protein bound
accumulate in the renal cortex
- excreted via glomerulus
- resorbed in the proximal tubule
- can cause violative residues 1 year post administration
What animicrobials can you not give to production animals
aminoglycosides
- long renal residues
chloramphenicols
- aplastic anemia
metronidazole
- carcinogenic and teratogenic
What are the adverse effects of aminoglycosides
nephrogenic (accumulate in cortex and destroy proximal tubules)
otogenic
- accumulate in inner ear
- dogs = auditory dysfxn
- cats = vistibular
- may be irreversible
List 3 types of aminoglycosides
tobramycin
gentamycin
amikacin
Compare gentamycin and amikacin
similar
amikacin has a wider spectrum of action (more gram (+) efficacy) and less resistance
gentamycin has less ability to cross cell membranes = lower volume of distribution
- not good intrauterine or PO
- can cause ciliary ablation in the eye = glaucoma tx
What is gentamycin and amikacin used for? How are they administered
IV IM SC
regional imb perfusion
interarticular
What is the mechanism of action of macrolides and lincosamides
bock polypeptide exiting 50S and prevent selongation
macrolides and lincosamides have the same mechanism of action and will compete against each other
What are the general characteristics of macrolides and lincosamides
bacteriostatic
time dependent
What bacteria are macrolides and lincosamides effective against
gram (+) and respiratory gram (-)
better efficacy at higher pH
accumulate in immune cells and at the site of infection
What adverse effects are associated with macrolides and lincosamides
few
dont bind mammal ribosomes
List 4 types of macrolides
tulathromycin
tilmicosin
azithromycin
clarithromycin
What species is tulathromycin and tilmicosin used for? What bacteria is it effective against
production animal
gram (-) and enteric/resp pathogens
some cytochrome P450 metabolism
prokinetic
What is one consideration to have in mind when working with tilmicosin
cardiotoxic to horses, sheep, goats, humans
- death
What is the relative efficacy of azithromycin and clarithromycin compared to tulathromycin and tilmicosin
they have more gram (+) than gram (-) activity
List 2 types of lincosamides
lincomycin
clindamycin
What animals are lincomycin and clindamycin used in? What bacteria is ti effective against?
SA and pigs
good against all EXCEPT gram (-) aerobe
What are 2 considerations to have when giving lincomycin and/or clindamycin
NOT for horses, ruminant, hamster, guinea pig
- fatal colitis
clindamycin tablets can cause esophageal injury
What is the mechanism of action of phenicols
bind 50S subunit
chloramphenic also inhibits mammal protein synthesis
- impacts the bone marrow
What are the general characteristics of phenicol drugs
bacteriostatic
time dependent
What bacteria are chloramphenicol effective against?
broad spectrum
effective against MRSA
NOT pseudomonas
What is the pharmacokinetics of chloramphenicols
good absorption and distribution
can give PO to horses
What is an adverse effect of phenicol drugs
cause fatal aplastic anemia
- can occur in humans = wear PPE
How does florphenicol compare to chloramphenicol
does not cause aplastic anemia but it has less efficacy
What bacteria is florphenicol effective against
gram (-) anaerobes
What is florphenicol used for
ruminant and swine respiratory disease
small animals
NOT horses = colitis
Name two nitroimidazole
metronidazole
fluoroquinolones
What is the mechanism of metronidazole
makes short lived intermediates and ROS in bacteria/protozoa
destroys DNA
What are the general characteristics of nitroimidazoles
concentration dependent
bacteriocidal
What is the efficacy of metronidazole
anaerobe
protozoa (giardia)
How is metronidazole administered
PO
tastes bad
What is metronidazole used for
dog/cat/people = giardia tx
antiinflammation in GI
What are the adverse effects of metronidazole administration
tastes bad
changes GI microbiome
causes neuropathy
reduces appetite
What is the mechanism of action of fluoroquiniolones
inhibit bacterial DNA gyrase (unwind DNA) = prevents DNA replication
- it iinhibits it at lower concentrations than it would like to inhibit mammal DNA gyrase
also inhibit topoisomerase 4 (separate daughter chromosomes)
What are fluoroquinolones effective against
good gram -
varied gram +
pseudomonas!
What are the characteristics of fluoroquinolones
bactericidal
concentration depndentt
higher risk of multidrug resistance - will predispose to itt
accumulates intracellularly
What category drug are fluoroquinolones
Category 1 (high human importance)
What are the pharmacokinetic characteeristics of fluoroquinolones
good PO absorption
- can be given topical
- giving IV is extra label: will precipitate in fluids (use separate lines and give slow)
will penetrate CNA/prostate and accumulates in the urine
What are the adverse effects of fluoroquinolones
no extralabel use in production animals
arthropathy (cartilage damage) in young animals
enters milk
cats = retinal toxicity = bliiind
- they are deficient in BRCP efflux protein in the retinal cells
seizure in predisposed animals
Give 1 example of fluoroquinolones
enrofloxacin (baytril)
What mechanisms of resistance are there against fluoroquinolones
change target enzyme
altere influx and efflux
plasmid mediated resistance allows fast resistance development and spread
What are 3 ways to mitigate AMR against fluoroquinolones
dont usee mass medication- metaphylaxis
use when supported by C/S
use on individual basis
