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Foundations- Antibiotics > Cell Wall Synthesis Inhibitors and Protein Synthesis Inhibitors > Flashcards

Cell Wall Synthesis Inhibitors and Protein Synthesis Inhibitors Flashcards

1
Q

describe the tiers of beta lactam antibiotics

A

penicillin and aminopenicillins: first line/tier 1

cephalosporins
1st and 2nd gen: first line/tier 1
3rd gen: tier 2
4th and 5th gen: restricted

carbapenems: restricted

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2
Q

give the mechanism of action of ALL beta lactams

A

inhibit cell wall synthesis by binding to penicillin-binding proteins (transpeptidases), preventing formation of NAG-NAM cross linkages, causing the THICK cell wall netting to become progressively porous, allowing fluid to diffuse across cell membrane and cell to swell and explode

-this class is most effective against actively dividing bacteria!

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3
Q

describe the prototypes/others of beta lactam penicillins

A
  1. PENICILLIN G: benzylpenicillin
    -formulations:
    –potassium-PenG
    –sodium PenG
    –Procrain PenG: absorption slower than elimination
  2. aminopenicillins: amoxicillin, ampicillin
  3. extended spectrum penicillins (anti-pseudomonal)
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4
Q

describe the spectrum of activity of beta lactam penicillins

A
  1. time dependent! (T>MIC)
  2. narrow: gram + and anaerobes
  3. bactericidal
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5
Q

describe route of administration of beta lactam penicillins

A
  1. IV, IM, SQ: need to give every 6 hours (IV very common)
  2. IM: PROCAINE PenG: slower absorption so less frequent admin
    -NEVER give IV in horses! can cause a hyperexcitable reaction that can result in trauma or death, always aspirate!
  3. oral: amoxicillin
  4. intrasynovial: potassium or sodium PenG
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6
Q

describe disposition of beta lactam penicillins

A
  1. polar
  2. water soluble
  3. excreted unchanged in urine with some active renal tubular secretion; so if significant renal tubular secretion, be careful with dose and timing!
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7
Q

describe toxicity of beta lactam penicillins

A
  1. GI upset: more common in LA
  2. anaphylactic/allergic
  3. hypersensitivity reactions (IMHA, IMTP)
  4. PROCAINE reaction!!!
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8
Q

describe specific indications and contraindications of beta lactam penicillins

A

indication:
1. gram + infections and ANAEROBES
2. streptococcal infections
3. select atypical bacteria: leptospira, borrelia, listeria

contraindications:
1. animals with known hypersensitivity
2. NEVER give PROCAINE PenG IV
3. watch for development of staph resistance

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9
Q

what is the main mode of resistance to beta lactam penicillins? how do we fight this?

A

bacterial production of beta lactamase enzymes to chop up beta lactam ring to prevent beta lactam from binding to PBPs

we counteract with beta-lactamase inhibitors! potentiating agents that extend the spectrum of activity
-clavamox is the only veterinary labeled potentiated beta lactam drug

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10
Q

describe the prototype and others of beta lactam cephalosporins

A

1st gen: pha or fa
3rd gen: all the rest
4th gen: 2 to recall

1st gen: cephalexin, cefazolin

3rd gen: cefpodoxomine, ceftiofur, cefovecin

4th gen: cefepime, cefquinome

there is a 5th gen

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11
Q

describe the spectrum of activity of beta lactam cephalosporins

A
  1. bacteridical; time above the MIC for the pathogen

1st gen: (like PenG) gram + and anaerobes

3rd gen: gram +, gram -, and some anaerobes

4th gen: gran - and gram +

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12
Q

describe the routes of administration of beta lactam cephalosporins

A

ORAL: cephalexin (1st gen), cefpodoxime (3rd gen), proxetil, cefepime and cefquinome (4th gen)

PARENTERAL (SQ, IV, IM): cefazolin (1st gen), ceftiofur cefovecin and cefotaxime (3rd gen)

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13
Q

describe the disposition of beta lactam cephalosporins

A
  1. 1st gen similar to PenG
  2. as increase in generations, becomes more lipophilic (but most are still polar in this class)
  3. excreted unchanged in urine with some active renal tubular excretion (like penicillins)

NOTE: ceftiofur is metabolized in the plasma to the active metabolite defuroylceftiofur)

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14
Q

describe the toxicity of beta lactam cephalosporins

A
  1. anaphylactic
  2. hypersensitivity reactions (IMHA, IMTP)
  3. GI upset in horses
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15
Q

describe the specific indications and contraindications of beta lactam cephalosporins

A

indications:
1. skin infections
2. urinary tract infections
3. respiratory infections

contraindications:
1. animals with known hypersensitivity

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16
Q

give one known and clinically relevant fact about cefovecin, a 3rd gen beta lactam cephalosporin

A

increases free concentrations of carprofen, furosemide, doxycycline, and ketoconazole due to competitive protein binding

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17
Q

describe the elimination of beta lactam cephalosporins and what this means about extra-label use

A

LONG elimination: half life is 5.5 days so it takes 65 days to eliminate 97% of the drug

extra-label use for off-label indications in cattle, swine, and poultry is OKAY as long as all other labeled directions (dose, route, duration, frequency, species) are follow but

NO EL USE for prevention and NO ELA USE of human cephalosporins

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18
Q

describe beta lactam carbapenems

A

BIG GUNS only use with specific indications and when backed up by culture and sensitivity!!!

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19
Q

describe the prototype and others of beta lactam carbapenems

A
  1. imipenem
  2. meropenem
  3. dorapenem
  4. ertapenem
  5. potentiated carbapenem (imipenem with beta lactamase inhibitor cilastatin)

if reaching for these you MUST HAVE A REASON

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20
Q

describe the spectrum of activity of beta lactam carbapenems

A
  1. broad
  2. bactericidal
  3. time dependent
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21
Q

describe route of administration of beta lactam carbapenems

A

IV, IM, intrasynovial

POOR oral bioavailability

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22
Q

describe the disposition of beta lactam carbapenems

A

metabolized to inactive form in renal tubules (these drugs have low efficacy against UTIs)

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23
Q

describe the toxicity of beta lactam carbapenems

A
  1. imipenem: CNS toxicity in dogs and cats
  2. GI upset
  3. anaphylactic
  4. hypersensitivity reactions (IMHA and IMTP)
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24
Q

describe specific indications and contraindications of beta lactam carbapenems

A

indications: treatment of infection resistant to first and second tier beta lactams IF you think it will help for real

contraindications: due to CNS toxicity of imipenem
1. meningitis
2. head trauma or seizure disorder

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25
Q

describe antimicrobial stewardship as it related to beta lactam carbapenems

A

this class is typically reserved for treatment of HUMANS with resistant infection or severe systemic illness due to the emergence of carbapenemase producing enterobactericeae

26
Q

describe the tiers of aminoglycoside antibiotics

A

first line/tier 1 EQUINE

tier 2 in small animals!!

RESTRICTED in food producing animals

27
Q

describe the mechanism of action of aminoglycoside antibiotics

A

inhibit protein synthesis via 30S ribosomal subunit but OXYGEN DEPENDENT (NO anaerobic action!!)

28
Q

describe the prototype and others of aminoglycosides

A

systemic activity, IV, IM, SQ: amikacin, gentamicin

not systemic and topical only: neomycin, kanamycin, tobramycin, streptomycin

29
Q

describe the spectrum of activity of aminoglycosides

A

CONCENTRATION DEPENDENT; uniquely bactericidal!!!

narrow spectrum: GRAM - AEROBES!!
(some SELECT gram + cocci, mycoplasma)

30
Q

describe route of administration of aminoglycosides

A

IV, IM, SQ, intrasynovial or topically (ophthalmic/otic)

NO oral bioavailability: must catheterize or stick muscle! can’t send these home!

31
Q

describe the disposition of aminoglycosides

A
  1. highly polar: no good cell penetrating availability, use water channels to penetrate bacteria
  2. inactivated in purulent material
  3. renal excretion: accumulation in proximal renal tubular epithelial cells
32
Q

describe the toxicity of aminoglycosides (NON

A
  1. nephrotoxicity
  2. ototoxicity
  3. neurotoxicity

therapeutic drug monitoring is key!

33
Q

describe specific indications and contraindications of aminoglycosides

A

indications:
1. susceptible gram - infections: enterobacteriaceae
2. polymicrobial coverage: combination therapy with beta lactam
3. achieve high concentrations in the URINE

contraindications:
1. dehydration/hypovolemia
2. renal injury/insufficiency
3. during general anesthesia
4. voluntary ban in food producing animals: 18 months meat withdrawal

34
Q

describe synergism of beta lactam and aminoglycoside antibiotics

A

for polymicrobial infections and critically ill sepsis (take care with kidneys!)

synergy: disruption of gram + cell wall enhances aminoglycoside penetration into the cell

35
Q

describe tiers of tetracycline antibiotics

A

tetracyclines: first line/tier 1 in small animals and food producing animals

doxycycline/minocycline: tier 2 in small animal dermatitis and equine

36
Q

describe the mechanism of action of tetracyclines

A

inhibit protein synthesis of protein synthesis via 30s ribosomal subunit but does not require oxygen like aminoglycosides!!

37
Q

describe the prototype and others of tetracyclines

A

feed additives: tetracycline, oxytetracycline, chlortetracycline

companion and equine: doxycycline, minocycline

38
Q

describe the spectrum of activity of tetracyclines

A
  1. TIME DEPENDENT (maybe some AUC:MIC)
  2. bacterioSTATIC
  3. broad spectrum! Gram - and +, some anaerobes (beware resistance) AND
    -atypical bacteria:
    rickettsia, mycoplasma, leptospira, chlamydophila
39
Q

describe route of administration of tetracyclines

A

IV, SQ: oxytetracycline
Oral: doxycycline and minocycline
-bioavailability is 50-60% in dogs but lower in farm and equine
ophthalimic, topical

40
Q

describe the disposition of tetracyclines

A
  1. moderately lipophilic
  2. amphoteric- always ionized = active
  3. chelates: cations
    4 high protein binding (esp doxycycline)
  4. MIXED:
    -renal excretion: active drug in urine (oxytet) and
    -liver: enterohepatic circulation, hepatic metabolism (doxycycline, minocycline)
41
Q

describe the toxicity of tetracyclines

A
  1. nephrotoxicity
  2. GI:
    -esophageal structure due to oral doxycycline
    -GI upset
    -enamel hypoplasia (discolored teeth)
  3. FATAL:
    -IV doxycycline in horses
    -collapse with rapid admin of IV oxytetracycline
42
Q

give specific indications and contraindication of tetracyclines

A

specific indications:
1. for fairly broad spectrum coverage
2. atypical or INTRACELLULAR bacterial infections
-mycoplasma, ricketsia, ehrlichia, anaplasma, leptospira, borrelia
3. TICK BORNE DISEASE: treatment of choice
4. potomac horse fever (neorickettsia risticii)
5. wolbachia in dogs with heartworm infections

contraindications:
1. hypovolemia/dehydration
2. renal injury/insufficiency

43
Q

describe the tiers of macrolide, lincosamides, and fenicol antibiotics as well as mechanism of action

A

lincosamides: first line/tier 1 for all

florfenicol: tier 1 for food animal

macrolides and fenicols: tier 2

all are protein synthesis inhibitors via the 50S ribosome subunit; macrolides and lincosamides bind at the same site, but chlorampehnicols bind at a different site

44
Q

describe the prototype and others of macrolides

A

for foals and small animals: erythromycin, clarithromycin, tylosin, azithromycin

for ruminants and pigs: tulathromycin, tildipirosin, gamithromycin, tilcomisin

45
Q

describe the spectrum of activity of macrolides

A
  1. time DEPENDENT
  2. bacterioSTATIC
  3. narrow spectrum: gram + AErobes and select anaerobes
    -SOME gram - pathogens: BRD/SRD
  4. unique: effective against mycoplasma
46
Q

describe route of administration of macrolides

A

oral OR SQ, IM, IV

47
Q

describe disposition of macrolide antibiotics

A
  1. highly lipophilic
  2. high concentration in leukocytes
  3. significant post-antibiotic effect
48
Q

describe toxicity of macrolides

A
  1. FATAL COLITIS in hindgut fermentors (adult horses, bunny, guinea pig)
  2. tilcomisin: cardiotoxicity in people and goats
  3. erythromycin: hyperthermia in foals due to partial anhidrosis/inabiltiy to sweat appropriately (reversible)
49
Q

describe specific indications and contraindications of macrolides

A

specific indications:
1. rhodococcus equi (with rifampin)
2. bovine respiratory disease complex (BRDC; including mycoplasma)
3. swine respiratory disease complex (SRD)

contraindications:
oral admin to hindgut fermentors

50
Q

what are 2 other effects of macrolides?

A
  1. anti-inflammatory
    -reduce airway mucous secondary to effects on interleukin and neutrophil influx
    -tylosin: companion animal treatment for anti-inflam bowel disease
  2. prokinetic:
    -erythromycin effect on motilin Rc in horses with ileus and ruminants with abomasal atony to increase motility but have to give IV and just a small amount so for antimicrobial stewardship purposes we don’t do that anymore
51
Q

describe the prototype and others for lincosamides

A

for cats: clindamycin

for swine: lincomycin

intramammary for ruminants with mastitis: pirlimycin

52
Q

describe the spectrum of activity for lincosamides

A
  1. time DEPENDENT
  2. bacterioSTATIC
  3. narrow spectrum: gram + aerobes and anaerobes similar to macrolides
    -NO GRAM - COVERAGE!!: intrinsic resistance of pasteurellaceae and enterobacteraceae
53
Q

describe routes of administration for lincosamides

A

clindamycin: oral suspension causes profuse salivation in cats

these are mostly oral with the exception of pirlimycin (intramammary)

54
Q

describe disposition of lincosamides

A

highly lipophilic

55
Q

describe toxicity of lincosamides

A
  1. FATAL COLITIS in hindgut fermentors (macrolides too)
  2. diarrhea in nursing puppies and kittens
56
Q

describe specific indications and contraindications of lincosamides

A

specific indications:
1. staphylococcal infections
2. oral abscess: dogs and cats
3. osteomyelitis/dental disease

contraindications:
1. oral admin to hindgut fermentors; DONT
2. oral admin to cattle

57
Q

describe prototype and others of chloramphenicol antibiotics

A

chloramphenicol and florfenicol

58
Q

describe the spectrum of activity of chloramphenicols

A
  1. time DEPENDENT
  2. chloramphenicol: bacterioSTATIC
  3. florfenicol: bacteriCIDAL against select pathogens
  4. BROAD activity: gram +, -, and anaerobes
59
Q

describe route of administration of chloramphenicols

A

oral, SQ, IM

60
Q

describe disposition of chloramphenicols

A
  1. highly lipophilic
  2. BBB and BPB cross
  3. hepatic metabolism/some renal clearance
61
Q

describe toxicity of chloramphenicols

A

chloramphenicol:
-people: fatal aplastic anemia
-dose dependent bone marrow suppression

florfenicol:
-GI upset
-injection site pain: RESTRAIN bc it STINGS
-colitis in horses

62
Q

describe specific indications and contraindications of chloramphenicols

A

specific indications:
1. chronic therapy for abscess, osteomyelitis
2. florfenicol: foot rot, BRD, SRD

contraindications:
1. hepatic/renal disease
2. dogs on phenobarbital: will increase phenobarb levels
3. CHLORAMPHENICOL BANNED IN FOOD ANIMALS because fatal aplastic anemia in people
4. don’t give florfenicol to horses: colitis

Foundations- Antibiotics (3 decks)

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