Antimicrobial use in Lung Infection 1 Flashcards
what are the modes of action of antimicrobial compounds
- DNA replication
- RNA synthesis
- protein synthesis
- cell wall synthesis
- antimetabolites
what are short acting tetracyclines
tetracylcine
chlortetracylcine
oxytetracycline
what are long acting tetracyclines
doxycycline
minocycline
what is the mode of action of tetracyclines
- bacteria uptake –> diffuse across outer cell membrane, active carrier mediated process through inner cell membrane
- bind reversibly to bacterial ribosomes
- inhibit bacterial protein synthesis
how are tetracyclines classified
bacteriostatic broad-spectrum antimicrobials
how do tetracyclines cause adverse effects
may bind to mammalian ribosomes
what is the mechanism of action of tetracycline
tetracycline binds to ribosome –> A site of 30S (small one) where mRNA template is found –> competes with protein translation and causes the polypeptide chain to not grow anymore
list 5 pharmacokinetics of tetracycline
- oral absorption is low (except Dox and Min) –> given IM or IV
- oral absorption is further lowered by food (tetracyclines chelate metal ions Ca, Mg, Fe, Al)
- enter most tissues and body fluids (min and dox are best)
- generally don’t get into brain
- cross placenta and secreted in milk
how are chlor-, oxy- and tetracycline metabolized and excreted
metabolism: minimal –> excreted unchanged in urine (and to lesser extent bile)
undergo some enterohepatic recirculation (increases half life to 6-10h)
glomerular filtration: urinary excretion and impaired renal function will increase half life
long acting formulations persist at injection site (often in oily vehicle)
list 2 pharmacokinetics of minocycline and doxycycline
semi synthetic derivatives of tetracyclines –> more lipid soluble
- better penetration into brain, ocular tissue and broncial secretions
- good absorption after oral admin
what is the metabolism and excretion of minocycline and doxycycline
mino: some metabolism and excreted in bile and feces (used in GI infections)
doxy: no renal excretion (may be good for animals with renal impairment)
enter intestine via bile and direct diffusion (may cause probelms in horses)
list 7 signs of tetracycline toxicity
- broad spectrum suppression of intestinal flora can lead to super-infection with resistant pathogens in horses (oral admin)
- idiosyncratic liver damage in some animals if there is renal impairement
- renal tubular damage (storage)
- irritant (long acting esp.)
- anaphylaxis when IV (give slow)
- deposited at active sites of ossification and in teeth
- photosensitivity
why is tetracycline widely used
widely used because broad spectrum activity (aerobic/anaerobic, gram - and gram +, local/systemic), low cost, ease of admin and difficulties in practice in ID of causative microorganism
when are tetracyclines particularly useful
mixed bacterial infections
dox and min also have anti-inflammatory properties
what are indications of tetracycline use in cattle (6)
- resp infections in calves
- bovine pneumonia (feedlots, feed)
- anaplasmosis
- infectious keratoconjunctivitis
- parenteral admin for serious udder infection
what are indications of tetracyclines in sheep
- Q fever
- enzootic abortion (chlamydophilla abortus)
- prevent pasteurella hemolitica pneumonia
- foot rot
- with streptomycin for brucella ovis
what are indications of tetracycline use in pigs
- atrophic rhinitis
- lower resp disease
- eradicate leptospira
what are the indications of tetracycline use in horses
limited spectrum
what are indications of tetracycline use in cat and dogs (6)
- urinary tract infections
- Echlirchia canis, Rickettsia rickettsii
- otitis externa
- chlamydial infection in cats
- upper resp tract
- conjunctiva
what are the indications of tetracycline use in poultry
- enteric and resp infection
largely administered in feed
what is the spectrum of macrolides
mainly gram +
some gram - (Pasteurella spp)
mycoplasmas
some rickettsiae
moderate activity against anaerobes
what are macrolides
bacteriostatic
what are some examples of macrolides
erthyromycin
tilmicosin
tylosin
spiramcyin
tulathromycin
what is the the structure of erythromcyin
macrocyclic lactone nucleus with one or more deoxy-sugars
what is the mechanism of action of macrolides
- bind to P site on 50S subunit
- stop the translocation of amino acid onto the growing polypeptide chain
don’t bind to mammalian ribosomes
what is the distribution of macrolides
broad distribution in tissues
do macrolides cross BBB and synovial fluid
no
how do macrolides have a broad distribution
non-polar
highly lipid soluble
high intracellular concentrations
where do macrolides enter in the cell
concentrated in phagocytes –> get to site of infection
what is a side effect of macrolides
decrease mucus production –> reduces environment for bacteria
what do macrolides enhance
host’s immunomodulary response
anti-inflammatory actions (inhibit pro-inflammatory cytokines)
list 5 pharmacokinetics of erythromycin
- weak base (ion trapped in acidic fluids)
- available orally as base, sterate or phosphate salts or thiocyanate (for chronic resp disease in chickens)
- high lipid solubility –> well distributed in tissues (but CSF and prostate levels low)
- well absorbed orally but base is unstable in gastric acid –> food lowers oral absorption
- partly inactivated by hepatic metabolism (excreted in bile, lost in feces) –> urinary excretion low (<5%)
what are the toxic effects of erythromycin (5)
- oral irritant (thrombophlebitis, periphlebitis)
- IM severe pain
- intramammary –> inflammatory rxn
- GI disturbances common (sm. stimulation)
- serious in horses because of bile excretion
one of safest antimicrobials
what is tylosin
macrolide
better activity then erythromycine against mycoplasmas
what are the issues with spiramycin
concentrates greatly in tissue (milk, lacrimal fluid, resp secretions)
very long half life but persistent drug residues
what is tilmicosin
concentrates in tissues like lung
Micotil causes rapid depletion of Ca and heart problems and can be fatal IM pigs, horses, goats, man
what are the clinical uses of macrolides
alt. to penicillin in sensitive animals
what are the clinical indications of erythromycin
campylobacter jejuni and mycoplasma infections
resp diseases in pigs, cattle, poultry (micotil, pulmotil, tylan 200)
what are the clinical indications of spiramicin
with metronidazole for peridontal infection in dogs and cats (stomorgyl)
dysentry, pneumonia in pigs, calves, poultry
what are advanced generations of macrolides
- azithromycin (zitrhomax)
- clarithromycin
- roxithryomcyin
- tulathromycin
what are the benefits of advanced generation of macrolides (4)
- higher bioavailability following oral admin
- broader spectrum of activity
- longer half lives
- higher tissue concentrations allowing infrequent dosage
what is DRAXXIN
tulathromcyin
what is tulathromycin (draxxin) used for
bovine and procine resp disease
what are the the pharmacokinetics of tulathromycin
SC in cattle
IM pigs
- high distribution within 30 min with slow elimination
- half life 90h (above MIC for 9-15 days)
- bioavailability > 85%
what are the advantages of tulathromcyin
- improved gram - spectrum
- high concentration in lung tissue, in neutrophils and alveolar macrophages (lung elimination time in cattle and swine is 6-7 days)
what are the withdrawal times of tulathryomycin
22 days cattle
13 pigs
16 sheep
