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Pharmacology > Exam 3: Antimicrobial Families > Flashcards

Exam 3: Antimicrobial Families Flashcards

1
Q

What are the adverse effects associated with aminoglycosides?

A

Nephrotoxicity
Ototoxicity
Neuromuscular blockade

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2
Q

What are the common adverse effects associated with macrolides?

A

Inject site tissue reaction

Hyperthermia due to anhidrosis may occur in foal receiving macrolides for Rhodococcus pneumonia

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3
Q

What are the adverse effects associated with erytromycin (macrolide)?

A

GI disturbances are common

IM causes severe tissue reaction

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4
Q

What are the adverse effects associated with tylosin (macrolide)?

A

Injectable product
Severe tissue reaction
—May cause colic and death in horses

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5
Q

What are the adverse effects associated with tilmicosin (macrolide)?

A

Some SC tissue irritation in cattle

Cardiotoxic to ducks, goats, horses, pigs, and man

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6
Q

What are the adverse effects associated with tildipirosin (macrolide)?

A

Toxic in swine

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7
Q

What are the adverse effects associated with azithromycin (macrolide)?

A

Foals might be at risk of hyperthermia due to anydrosis

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8
Q

What are the adverse effects associated with clarithromycin (macrolide)?

A

Foals might be at risk of hyperthermia due to anydrosis

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9
Q

What are the adverse effects associated with lincoasmides?

A

Neuromuscular blockade has been reported, but seems to be of minimal clinical significance
Most adverse reactions relate to GI tract:
In man, related to pseudomembranous colitis due to suppression of endogenous flora allowing overgrowth of Clostridium difficle
GI problems have been reported following:
—Oral used of lincosamides in ruminants
—Any lincosamide use in horses, rabbits, hamsters, and guinea pigs

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10
Q

What are the adverse effects associated with tetracyclines?

A

Potential teratogen in 1st trimester
Staining of teeth from in utero exposure of exposure prior to eruption of adult teeth
Photosensitivity (demeclocycline)
—White areas get sunburn with exposure to sun
GI floral disruption
Sudden collapse following rapid IV administration
Tissue necrosis and pain at IM, SQ, injection site
Tablets (doxycycline) cause esophageal ulcers in cats

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11
Q

What are the adverse effects associated with sulfonamides?

A

Type A:
Crystalluria
Prone to drug interactions due to high protein binding
For sulfaquinoxaline, a hemorrhagic syndrome has been reported due to inhibition of intestinal vitamin K production

Type B:
KCS
Polyarthropathy
Hepatotoxicity
Cutaneous drug eruptions
Hypothyroidism
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12
Q

What are the side effects associated with diaminopyrimidines/benzylpyrimidine?

A

Due to sulfonamide content
Type A:
Crystalluria due to sulfonamide is not a concern

Type B:
KCS
Polyarthropathy
Hepatoxicity 
Cutaneous drug eruptions
Hypothyroidism

Due to diaminopyrimidine content
Type A:
Diaminopyrimidine inhibition on mammalian DHFR can lead to:
Bone marrow suppression
Teratogenesis
Supplementation of folinic acid serves as an antidote to the above toxicities

Type B:
Simultaneous injections of detomidine has caused death in horses

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13
Q

What are the adverse effects associated with phenicols?

A

Chloramphenicol (also believed to be applicable to florfenicol)
1. Chloramphenicol is not well tolerated in cats —> anorexia and depression
2. Prone to drug interactions due to its inhibition of the P450 enzyme system
3. Use cautiously in:
a. Cats
b. Pregnancy
c. Neonates
Florfenicol causes some injection site reaction in cattle
Florfenicol is contraindicated in horses and causes severe diarrhea and colitis
Peripheral neuropathy manifesting as muscle weakness in dogs
Long-term use can cause a dose-dependent bone marrow suppression with chloramphenicol and probably florfenicol
In primates, chloramphenicol can be lead to fatal aplastic anemia
—Does not occur with florfenicol

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14
Q

What are the adverse effects associated with fluoroquinolones?

A

Enrofloxacin causes muscle irritation
—High dose can cause seizures
Arthropathy is dose-dependent and species dependent
Blindness due to retinal injury in cats with enrofloxacin and orbifloxacin
Pradofloxacin can cause bone marrow suppression in dogs

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15
Q

What are the adverse effects associated with spectinomycin?

A

May cause neuromuscular blockade

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16
Q

What are the adverse effects associated with metronidazole?

A 
Neurologic disturbances
Anorexia, vomiting
Bone marrow suppression
Reddish brown urine
May interfere with olfaction
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17
Q

What are the adverse effects associated with rifampin?

A

Dogs: elevated liver enzyme leading to rifampin-induced hepatitis
Discoloration of urine and tears

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18
Q

What are the adverse effects associated with nitrofurans?

A

Mutagenic and procarcinogenic, resulting in the band of ELDU in food animals including topically
Furazolidone is a MAOI and must be used cautiously with drugs metabolized by this enzyme

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19
Q

What are the adverse effects associated with oxazolidones (linezolid)?

A

A monoamine oxidase inhibitor
Use cautiously with other drugs impacting serotonin and/or catecholamines
Bone marrow suppression, peripheral neuropathy, and lactic acidosis

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20
Q

What are the toxicities associated with aminoglycosides?

A

Nephrotoxicity
Ototoxicity
Neuromusclar blockade

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21
Q

What are the strategies to minimize nephrotoxicity cause by aminoglycosides?

A 
Use q24 h dosing interval
Keep patient well hydrated
Limit other nephrotoxic drugs
Perform TDM to optimize efficacy while minimizing toxicity
IV calcium gluconate
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22
Q

What is the toxicity associated with tilmicosin (macrolide)?

A

Cardiotoxic to ducks, goats, horses, pigs, and man

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23
Q

What is the toxicity associated with toldipirosin (macrolide)?

A

Toxic in swine

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24
Q

What are the toxicities associated with tetracycline?

A

Hepatotoxicity associated with used during pregnancy in women and the bitch
Nephrotoxic in high doses

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25
Q

What is the toxicity associated with sulfonamides?

A

Hepatotoxicity

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26
Q

What is the toxicity associated with diaminopyrimidines/benzylpyrimidine?

A

Hepatotoxicity

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27
Q

What is the toxicity associated with ionophores?

A

Toxicity is seen as severe muscle damage, including cardiac muscle

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28
Q

What is the toxicity associated with isoniazid?

A

Toxicity mostly in CNS and GI

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29
Q

What is the toxicity associated with bacitracin?

A

Nephrotoxic

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30
Q

What are the toxicities associated with polymyxin B?

A

Nephrotoxic

Neurotoxic

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31
Q

What are the toxicities associated with vancomycin?

A

Potentially nephrotoxic and ototoxic

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32
Q

What is the public health concern for sulfonamides?

A

Sulfonamides in lactating dairy cattle are not allowed because we don’t want it in milk for children

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33
Q

What is the public health concern for chloramphenicol?

A

Causes aplastic anemia in humans

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34
Q

What is the public health concern for fluoroquinolones?

A

Peripheral neuropathy
Tendonitis and tendon rupture
Changes in levels of resistance to fluoroquinolones over time by Campylobacter and Salmonella species are being monitored
Sarafloxacin label was withdrawn in 2000
Enrofloxacin for poultry was withdrawn in 2005

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35
Q

What is the public health concern for nitroimidazoles?

A

A carcinogenic effect observed in lab animals

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36
Q

What is the public health concern for nitrofurans?

A

Mutagenic and procarcinogenic

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37
Q

What is the public health concern for virginiamycin?

A

Possible cross-resistance with Synercid

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38
Q

Are aminoglycosides bacteriostatic or bactericidal? What are the known pharmacodynamic characteristics?

A

Bactericidal

Concentration-dependent killing

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39
Q

Are macrolides bacteriostatic or bactericidal? What are the known pharmacodynamic characteristics?

A

Bacteriostatic

Believed to have time-dependent inhibition

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40
Q

Are lincosamides bacteriostatic or bactericidal? What are the known pharmacodynamic characteristics?

A

Bacteriostatic

Efficacy dependent on time above MIC

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41
Q

Are tetracyclines bacteriostatic or bactericidal? What are the known pharmacodynamic characteristics?

A

Bacteriostatic

Time-dependent
AUC/MIC is perhaps the better target

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42
Q

Are sulfonamides bacteriostatic or bactericidal? What are the known pharmacodynamic characteristics?

A

Bacteriostatic

Efficacy dependent on time above MIC

43
Q

Are diaminopyrimidine/benzylpyrimidine bacteriostatic or bactericidal? What are the known pharmacodynamic characteristics?

A

Bactericidal
Time-dependent and concentration-dependent
—Most of the data supports time-dependent

44
Q

Are phenicols bacteriostatic or bactericidal? What are the known pharmacodynamic characteristics?

A

Bacteriostatic

Efficacy dependent on time above MIC

45
Q

Are fluoroquinolones bacteriostatic or bactericidal? What are the known pharmacodynamic characteristics?

A

Bactericidal
AUC/MIC ratio
—Concentration-dependent killing

46
Q

Is spectinomycin bacteriostatic or bactericidal?

A

Bacteriostatic

47
Q

Is rifampin bacteriostatic or bactericidal?

A

Bactericidal

48
Q

What is the mechanism of action for aminoglycosides?

A

Cidal action by protein synthesis inhibition at 30s ribosomal subunit

49
Q

What is the mechanism of action for macrolides?

A

Inhibition of protein synthesis at the 50S ribosomal subunit

50
Q

What is the mechanism of action for lincosamides?

A

Inhibition of protein synthesis at the 50S ribosomal subunit

51
Q

What is the mechanism of action for tetracyclines?

A

Bacterial penetration mechanisms:
Gram-negative
—Passive diffusion through hydrophilic channels in outer membrane
—Energy dependent active transport through inner cytoplasmic membrane
Gram-positive
—Requires energy dependent system

Protein synthesis inhibition:
—Tetracyclines bind to the 30S ribosomal subunit, preventing access of transfer RNA to the ribosome-messenger RNA complex

52
Q

What is the mechanism of action for sulfonamides?

A

Sulfas compete with Para Amino Benzoic Acid for incorporation into the scheme for folic acid synthesis, which is used for purine synthesis. This biological antagonism leads to decreased RNA, inhibiting protein synthesis
Disrupts DNA

53
Q

What is the mechanism of action for diaminopyrimidine/benzylpyrimidine?

A

Inhibition of dihydrofolate reductase thereby interfering with purine and pyrimidine synthesis

54
Q

What is the mechanism of action for phenicols?

A

Protein synthesis inhibition at the 50S subunit of bacterial ribosomes

55
Q

What is the mechanism of action for fluoroquinolones?

A

Inhibition of bacterial DNA gyrase or topoisomerase IV thereby preventing DNA supercoiling and replication

56
Q

What is the mechanism of action for ionophores?

A

Complexes with cell-wall sodium, causing export of potassium and import of hydrogen into the bacterial cell

57
Q

What is the mechanism of action for spectinomycin?

A

Static action by binding to the 30S ribosomal subunit, inhibiting protein synthesis

58
Q

What is the mechanism of action for avilamycin?

A

Works at 50s ribosome against gram-positive bacteria

59
Q

What is the mechanism of action for nitromidazole?

A

Reduction of the nitro group in anaerobic bacteria produces unstable metabolites, which breaks DNA strands and inhibits repair enzymes

60
Q

How are aminoglycosides eliminated?

A

Renal elimination

61
Q

How are macrolides eliminated?

A

Hepatic elimination

62
Q

How are lincosamides eliminated?

A

Hepatic elimination

63
Q

How are tetracyclines eliminated?

A

Renal elimination, except for doxycycline which is hepatic

64
Q

How are sulfonamides eliminated?

A

Renal excretion

65
Q

How are diaminopyrimidines elimiated?

A

Hepatic elimation
Pyremetamine: hepatic
Trimethoprim: renal

66
Q

How are phenicols elimiated?

A

Hepatic elimiation

67
Q

How are fluoroquinolones eliminated?

A

Renal elimination, though the liver does contribute

68
Q

What drugs have an intracellular (all tissue including CNS) tissue distribution pattern?

A

Tetracyclines
—Doxycycline and minocycline cross most barriers but do not treat meningitis
Sulfadiazine is the exception for sulfonamides Diaminopyrimidines/Benzylpyrimidine
Chloramphenicol
Florfenicol
Fluoroquinolones

69
Q

What drugs have an intracellular, but do not cross the BBB without inflammation tissue distribution pattern?

A

Macrolides
Tetracyclines
—chlortetracycline, tetracycline HCl, and oxytetracycline
Lincosamides

70
Q

What drugs have an extracellular tissue distribution pattern?

A

Aminoglycosides
Sulfonamides
Spectinomycin

71
Q

What drugs are more active in an alkaline environment?

A

Aminoglycosides
Macrolides
Fluoroquinolones

72
Q

What drugs lose activity in purulent debris?

A

Aminoglycosides

Rifampin

73
Q

What drugs require oxygen in the environment?

A

Aminoglycosides

74
Q

What are the 3 toxicities associted with parenteral amingolycoside use?

A

Nephrotoxic
Ototoxic
Neuromuscular blockade

75
Q

What part of the kidney is damaged by aminoglycosides?

A

Proximal renal tubules

76
Q

How does amikacin differ from gentamicin relative to probability of susceptibility of most pathogens?

A

Gram negative % susceptibility is in the high 90s for amikacin
Gram negative % susceptibility is in the low 90s for gentamicin

77
Q

How does amikacin differ from gentamicin relative to the risk of nephrotoxicity?

A

Amikacin is less nephrotoxic than gentamicin

78
Q

Know how to monitor aminoglycoside therapy to minimize the risk of nephrotoxicity. Especially note the relative value of monitoring the BUN, serum creatinine, serial urinalysis, urine GGT:urine creatinine ratio.

A

Increase in serum BUN or creatinine occur too late to be helpful
Perform serial urinalyses and watch for:
—Increasing tubular casts
—Increasing protein
—Possible decreasing specific gravity and increasing glucose
Perform serial urine GGT:Creatinine ratios
—Increase more than 3x baseline may indicate imminent toxicity —> check UA

79
Q

How do the newer macrolides differ in their activity versus older macrolides against gram‐negative nonenteric pathogens?

A

With newer macrolides, as the MIC rises the percentage of isolates decreases
With older macrolides, as the MIC rises the percentage of isolate increases
—It hits a peak at a MIC of 2 before decreasing again
Newer macrolides are more effective

80
Q

Which drugs are contraindicated in horses?

A 
Lincosamides
Ionophores
Florfenicol
Tilmicosin in its injectable forms
Tylosin
81
Q

Which drugs are contraindicated in guinea pigs, rabbits, and hamsters?

A

Lincosamides

82
Q

Which drugs are not well tolerated by cats?

A

Doxycycline tablets
Fluoroquinolone
Oral sulfonamides
Chloramphenicol

83
Q

Tetracyclines remain the drug of choice in treating chlamydial infections in veterinary medicine. What other antimicrobial is has shown activity against chlamydia and is sometimes used in human medicine for this purpose?

A

Doxycycline

84
Q

Azithromycin has been found useful to treat what diseases in dogs or cats due to an effect other than its antimicrobial activity?

A

Cytauxzoonosis in cats
Canine Babesia gibsoni
May be helpful in oral papillomatosis in dogs

85
Q

Which drugs are enzyme inducers?

86
Q

Which drugs are enzyme inhibitors?

A 
Chloramphenicol
---Inhibits P450 enzme
Fluoroquinolones
Nitrofurans
---Monoamine oxidase inhibitor (MAOI)
Oxazolidones: Linezolid
---MAOI
Pleuromutilins (Tiamulin)
87
Q

What are the formulation differences for oxytetracycline and how does it impact use?

A

50 mg/ml in propylene glycol (Terramycin)
100 mg/ml in propylene glycol (Liquimycin)
200 mg/ml in PVP (LA200)
300 mg/ml in glycerol formal and PEG (Tetadure)

The 50 and 100 mg/ml formulations only last at best 24 hours. The 200 mg/ml and 300 mg/ml products are designed as repository (long-lasting) formulations lasting 2-3 days and 7-8 days, respectively.

88
Q

What is the non-antimicrobial effect of tetracyclines?

A

Inhibit collagenase to some degree
May have anti-inflammatory or immunomodulating effects
Oxytetracycline in a single high dose is reported to help relax contracted tendons in foal and calves
—Evidence supporting this is relatively weak

89
Q

What is the non-antimicrobial effect of gentamicin?

A

Destroys the ciliary body when injected into the eye

A palliative treatment for glaucoma when sight has already been lost and owner refuses surgical enucleation

90
Q

What is the non-antimicrobial effect of Polymyxin B?

A

Can bind endotoxin in plasma

91
Q

What fluoroquinolones have a high probability of activity against Pseudomonas?

A

Ciprofloxacin and marbofloxacin are more active

92
Q

What is the order of susceptibility for each species to fluoroquinolone arthropathy?

A

Cattle/cats: least susceptible
Dogs: second most susceptible
Horses: most susceptible

93
Q

What substance can be administered that will counteract the bone marrow suppression seen with diaminopyrimidines such as trimethoprim?

A

Folinic acid

94
Q

Why is potentiated sulfonamide use in cattle viewed skeptically? (Based on bioavailability of the two drugs.)

A

The half-life of trimethoprim is extremely short in cattle, such that sc dosing often results in undetectable concentrations
Diaminopyrimidines are not well absorbed in ruminants

95
Q

All diaminopyrimidines (benzylpyrimidine) work on the same enzyme. Rank the three drugs as to their relative affinity for the bacterial, protozoal, and mammalian forms of the affected enzyme.

A

Trimethoprim and Ormethoprim:

  1. Bacterial
  2. Protozoal
  3. Mammalian

Pyrimethamine

  1. Protozoal
  2. Mammalian
  3. Bacterial
96
Q

What drugs can be used orally in horses?

A

Erythromycin when combined with rifampin to treat Potomac Horse Fever
Doxycycline
Minocycline
Chloramphenicol is well absorbed orally in all non-ruminants
Fluoroquinolones vary in oral bioavailability
—Enrofloxacin, marbofloxacin, and orbifloxacin are adequately absorbed
—Ciprofloxacin is not absorbed

97
Q

What drugs can be used orally in cattle?

A 
Sulfonamides: Sulfadiazine
Chlortetracycline
Oxytetracyline
Macrolides (tylosin and tilmicosin)
Ionophores
Bacitracin
Virginiamycin
98
Q

What drugs can be used to treat Potomac Horse Fever?

A

Erythromycin combined with rifampin
Oxytetracycline
Doxycycline

99
Q

Which neonatal species is born with near adult hepatic metabolism and how does this relate to chloramphenicol use?

A

Foals
You can use chloramphenicol in foals because the glucuronyl transferase reaches adult level in one week. In other neonatal species, elimination of chloramphenicol is much slower

100
Q

What is the effect of urine pH on activity with methenamine?

A

Requires urine acidification

101
Q

What is the efficacy in treating a cystitis versus a pyelonephritis with metheamine?

A

Will not treat a pyelonephritis

102
Q

Rank the major species regarding the susceptibility to ionophore toxicity

A

Cattle and poultry are relatively resistant
Swine and small animals are intermediate
Horses are most sensitive

103
Q

Study the drugs and what they have activity against

A

Study the drugs and what they have activity against

Pharmacology (17 decks)

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