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Module 9 > Antimicrobial use in Lung Infection 1 > Flashcards

Antimicrobial use in Lung Infection 1 Flashcards

1
Q

what are the modes of action of antimicrobial compounds

A
  1. DNA replication
  2. RNA synthesis
  3. protein synthesis
  4. cell wall synthesis
  5. antimetabolites
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2
Q

what are short acting tetracyclines

A

tetracylcine

chlortetracylcine

oxytetracycline

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3
Q

what are long acting tetracyclines

A

doxycycline

minocycline

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4
Q

what is the mode of action of tetracyclines

A
  1. bacteria uptake –> diffuse across outer cell membrane, active carrier mediated process through inner cell membrane
  2. bind reversibly to bacterial ribosomes
  3. inhibit bacterial protein synthesis
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5
Q

how are tetracyclines classified

A

bacteriostatic broad-spectrum antimicrobials

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6
Q

how do tetracyclines cause adverse effects

A

may bind to mammalian ribosomes

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7
Q

what is the mechanism of action of tetracycline

A

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

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8
Q

list 5 pharmacokinetics of tetracycline

A
  1. oral absorption is low (except Dox and Min) –> given IM or IV
  2. oral absorption is further lowered by food (tetracyclines chelate metal ions Ca, Mg, Fe, Al)
  3. enter most tissues and body fluids (min and dox are best)
  4. generally don’t get into brain
  5. cross placenta and secreted in milk
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9
Q

how are chlor-, oxy- and tetracycline metabolized and excreted

A

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)

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10
Q

list 2 pharmacokinetics of minocycline and doxycycline

A

semi synthetic derivatives of tetracyclines –> more lipid soluble

  1. better penetration into brain, ocular tissue and broncial secretions
  2. good absorption after oral admin
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11
Q

what is the metabolism and excretion of minocycline and doxycycline

A

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)

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12
Q

list 7 signs of tetracycline toxicity

A
  1. broad spectrum suppression of intestinal flora can lead to super-infection with resistant pathogens in horses (oral admin)
  2. idiosyncratic liver damage in some animals if there is renal impairement
  3. renal tubular damage (storage)
  4. irritant (long acting esp.)
  5. anaphylaxis when IV (give slow)
  6. deposited at active sites of ossification and in teeth
  7. photosensitivity
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13
Q

why is tetracycline widely used

A

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

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14
Q

when are tetracyclines particularly useful

A

mixed bacterial infections

dox and min also have anti-inflammatory properties

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15
Q

what are indications of tetracycline use in cattle (6)

A
  1. resp infections in calves
  2. bovine pneumonia (feedlots, feed)
  3. anaplasmosis
  4. infectious keratoconjunctivitis
  5. parenteral admin for serious udder infection
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16
Q

what are indications of tetracyclines in sheep

A
  1. Q fever
  2. enzootic abortion (chlamydophilla abortus)
  3. prevent pasteurella hemolitica pneumonia
  4. foot rot
  5. with streptomycin for brucella ovis
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17
Q

what are indications of tetracycline use in pigs

A
  1. atrophic rhinitis
  2. lower resp disease
  3. eradicate leptospira
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18
Q

what are the indications of tetracycline use in horses

A

limited spectrum

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19
Q

what are indications of tetracycline use in cat and dogs (6)

A
  1. urinary tract infections
  2. Echlirchia canis, Rickettsia rickettsii
  3. otitis externa
  4. chlamydial infection in cats
  5. upper resp tract
  6. conjunctiva
20
Q

what are the indications of tetracycline use in poultry

A
  1. enteric and resp infection

largely administered in feed

21
Q

what is the spectrum of macrolides

A

mainly gram +

some gram - (Pasteurella spp)

mycoplasmas

some rickettsiae

moderate activity against anaerobes

22
Q

what are macrolides

A

bacteriostatic

23
Q

what are some examples of macrolides

A

erthyromycin

tilmicosin

tylosin

spiramcyin

tulathromycin

24
Q

what is the the structure of erythromcyin

A

macrocyclic lactone nucleus with one or more deoxy-sugars

25
Q

what is the mechanism of action of macrolides

A
  1. bind to P site on 50S subunit
  2. stop the translocation of amino acid onto the growing polypeptide chain

don’t bind to mammalian ribosomes

26
Q

what is the distribution of macrolides

A

broad distribution in tissues

27
Q

do macrolides cross BBB and synovial fluid

A

no

28
Q

how do macrolides have a broad distribution

A

non-polar

highly lipid soluble

high intracellular concentrations

29
Q

where do macrolides enter in the cell

A

concentrated in phagocytes –> get to site of infection

30
Q

what is a side effect of macrolides

A

decrease mucus production –> reduces environment for bacteria

31
Q

what do macrolides enhance

A

host’s immunomodulary response

anti-inflammatory actions (inhibit pro-inflammatory cytokines)

32
Q

list 5 pharmacokinetics of erythromycin

A
  1. weak base (ion trapped in acidic fluids)
  2. available orally as base, sterate or phosphate salts or thiocyanate (for chronic resp disease in chickens)
  3. high lipid solubility –> well distributed in tissues (but CSF and prostate levels low)
  4. well absorbed orally but base is unstable in gastric acid –> food lowers oral absorption
  5. partly inactivated by hepatic metabolism (excreted in bile, lost in feces) –> urinary excretion low (<5%)
33
Q

what are the toxic effects of erythromycin (5)

A
  1. oral irritant (thrombophlebitis, periphlebitis)
  2. IM severe pain
  3. intramammary –> inflammatory rxn
  4. GI disturbances common (sm. stimulation)
  5. serious in horses because of bile excretion

one of safest antimicrobials

34
Q

what is tylosin

A

macrolide

better activity then erythromycine against mycoplasmas

35
Q

what are the issues with spiramycin

A

concentrates greatly in tissue (milk, lacrimal fluid, resp secretions)

very long half life but persistent drug residues

36
Q

what is tilmicosin

A

concentrates in tissues like lung

Micotil causes rapid depletion of Ca and heart problems and can be fatal IM pigs, horses, goats, man

37
Q

what are the clinical uses of macrolides

A

alt. to penicillin in sensitive animals

38
Q

what are the clinical indications of erythromycin

A

campylobacter jejuni and mycoplasma infections

resp diseases in pigs, cattle, poultry (micotil, pulmotil, tylan 200)

39
Q

what are the clinical indications of spiramicin

A

with metronidazole for peridontal infection in dogs and cats (stomorgyl)

dysentry, pneumonia in pigs, calves, poultry

40
Q

what are advanced generations of macrolides

A
  1. azithromycin (zitrhomax)
  2. clarithromycin
  3. roxithryomcyin
  4. tulathromycin
41
Q

what are the benefits of advanced generation of macrolides (4)

A
  1. higher bioavailability following oral admin
  2. broader spectrum of activity
  3. longer half lives
  4. higher tissue concentrations allowing infrequent dosage
42
Q

what is DRAXXIN

A

tulathromcyin

43
Q

what is tulathromycin (draxxin) used for

A

bovine and procine resp disease

44
Q

what are the the pharmacokinetics of tulathromycin

A

SC in cattle

IM pigs

  1. high distribution within 30 min with slow elimination
  2. half life 90h (above MIC for 9-15 days)
  3. bioavailability > 85%
45
Q

what are the advantages of tulathromcyin

A
  1. improved gram - spectrum
  2. high concentration in lung tissue, in neutrophils and alveolar macrophages (lung elimination time in cattle and swine is 6-7 days)
46
Q

what are the withdrawal times of tulathryomycin

A

22 days cattle

13 pigs

16 sheep

Module 9 (43 decks)

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