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Pharmacology II > LEC 18, 19 - Inhibitors of Protein Synthesis > Flashcards

LEC 18, 19 - Inhibitors of Protein Synthesis Flashcards

1
Q

What are the adverse effects of tetracyclines?

A

Nephrotoxic

Staining of unerupted teeth

Superinfections

GI upset

Anti-anabolic

Photosensitivity

Hepatotoxicty

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2
Q

What animals is gentamycin used in?

A

Pigs, but no other food animals

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3
Q

Tetracyclines (5)

A

Doxycycline

Minocycline

Tetracycline

Oxytetracycline

Chlortetracycline

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4
Q

How do ionophores work?

A

Complex with Na+ in cell membrane

Produce passive extracellular transport of K+

Intracellular influx of H+

Kills bacteria + coccidian by lowering intracellular pH

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5
Q

Why is there sometimes an anti-anabolic effect with the use of tetracyclines?

A

high doses cause binding to mitochondrial ribosomes

Elevated BUN with pre-existing renal disease

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6
Q

How is linezolid metabolized?

A

Oxidation but it is non-enzymatic and does not involve hepatic microzome system

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7
Q

how is neomycin used?

A

Orally for enteric infections (food animal)

Topically for skin + ear + eye infections

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8
Q

What are tetracyclines used for in small animals medicine?

A

Respiratory + Urinary tract infections

Psittacosis in birds

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9
Q

How does linezolid work?

A

Inhibits bacterial protein synthesis by interfering with translation

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10
Q

Why is the use of lincosamides contraindicated in some animals?

A

Produce severe, often fatal diarrhea due to altered GI flora involving C. Diff

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11
Q

What animals is most sensitive to ionophore toxicity?

A

Horses

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12
Q

What is the basic structure of the aminoglycosides?

A

Contain amino sugars in glycosidic linkage

Polycations

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13
Q

How is chloramphenicol absorbed?

A

From GI tract and distributed to all tisuses including CNS and eye

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14
Q

What type of CNS infection is clindamycin used for?

A

Toxoplasma encephalitis

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15
Q

How are lincosamides adminstered?

A

PO + Paraenterally + Topically

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16
Q

What are the four major uses for linezolid?

A

Bacterial pneumonia

Skin/suture infections

VRE infections

MRSA infections

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17
Q

What are the regulations when it comes to the use of oxyteracyclines in food animals?

A

Cattle =

Extralabel Withdrawl time = 28 days for intrauterine treatment Test milk after intrauterine treatment

Sheep/goats =

Extralabel withdrawl time = 28 days IM/SC treatment

Milk withdrawl time = 96 hours

Swine =

Withdrawal time = 14 days

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18
Q

What impairs absorption of tetracylcines?

A

Divalent or trivalent cations

Avoid milk, antacids, or iron salts for three hours before and after administration

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19
Q

What are the ionophores derived from?

A

polyther from Streptomyces

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20
Q

What is the distribution pattern of florfenicol?

A

Widely distributed, including CNS

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21
Q

What does it mean when something has concentration dependent killing?

A

Increasing concentrations kill an increasing population of bacteria

More rapid

Adverse effect are time dependent

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22
Q

How is tylosine adminstered?

A

IM or PO, BID or SID - Swine + Calves + Lambs + Dogs + Cats

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23
Q

What situations are aminoglycosides most often used?

A

Gram-negative enteric bacteria

Suspicion of sepsis or endocarditis

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24
Q

What are the three ways that aminoglycosides interact with the 30s subunit causing the block of protein synthesis?

A

Block initiration of protein synthesis

Block further translation and elicit premature termination

Incorporation of incorrect amino acid

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25
Q

What is gentamicin and amikacin used against specifically?

A

Pseudomonas

Proteus

Staphylococcus

Corynebacterium

(Wider spectrum of activity)

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26
Q

What are the restrictions to absorption of erythromycin?

A

Gastric acids destroy base

need to modify formula for oral admin

Enteric coated or film-coated

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27
Q

What is pirlimycin used for?

A

Bovine mastitis

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28
Q

What is the mechanism of action for tetracyclines?

A

Inhibition of bacterial protein synthesis

Bind reversibly to 30S ribosomes + prevent access of aminacyl tRNA to receptor site on mRNA-ribosome complex

Prevents addition of AA to growing peptide chain

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29
Q

How is resistance developed against eryhtromycin?

A

Active pump mechanism

Ribosomal protection by inducible or constitutive production of methylase enzymes = modification of ribosomal target

Macrolide hydrolysis by esterases

Chromosomal mutations that alter 50S ribosomal protein

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30
Q

What ionophores are used for prevention of coccidiosis in broilers?

A

Salinomycin

Narasin

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31
Q

Why does erythromycin react with chloramphenicol and clindamycin?

A

All these drugs bind to similar spots on the 50s subunit

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32
Q

What is the basic structure of macrolides?

A

Macrocylic lactone ring which sugars are attached

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33
Q

What are the regulations of chloramphenicol use in food animals? Why?

A

ILLEGAL

Due to residue0induced toxicity in humans

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34
Q

Why does iatrogenic endotoxicosis occur with phenicol adminstration?

A

Rapid killing of gram (-) bacteria

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35
Q

What is lincomycin used for?

A

Swine - control/txt of swin dysentery

Treatment of:

Staphlococcal

Streptococcal

Mycoplasmal

…infectiosn

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36
Q

Aminoglycosides (7)

A

Neomycin

Gentamicin

Amikacin

Apramicin

Tobramycin

Plazomicin

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37
Q

How is clarithromycin administered?

A

PO, BID - Dogs + Cats + Ferrets

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38
Q

Oxazolidinones

A

Linezolid

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39
Q

What are the restrictions for tildiprosin when using it with food animals?

A

Withdrawl time for meat - 21 days

Do not use in female cattle over 20 months

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40
Q

What drugs should not be used with linezolid?

A

MAO inhibitors

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41
Q

How does plazomicin differ from the other aminoglycocides?

A

Devoid of nephrotoxic + ototoxic effects

Not influenced by bacterial enzymes that modify/inactivate aminoglycosides

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42
Q

What are ways that resistance against aminoglycosides occurs?

A

Plasmid mediated chemical changes of enzymes that adenylate + phosphorylate + acetylate aminoglycoside drugs

Resistance may involve alteration of bacterial ribosomes which aminoglycosides attach

Cannot enter the cell

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43
Q

What is tildipirosin used for?

A

BRD - Mannheimia haemolytica + Pasteurella multocida + Histophilus somni

Control of BRD - MH + PM + HS

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44
Q

What side effects do you see in dogs, cats, cattle, and swine from the use of lincosamides?

A

Rare

Neuromuscular blockade at high doses or when used with anesthetics

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45
Q

What is used with clindamycin for preventative purposes? Why?

A

Metronidazole

Avoid C. diff-mediated pseudomembranous colitis associated with clindamycin in dogs

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46
Q

What is the mechanism of action for lincosamides?

A

Bind to 50S ribosomal subunits of bacteria = protein syntehsis inhibition

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47
Q

What are the three common tetracyclines used in small animals?

A

Doxycycline

Minocycline

Tetracycline

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48
Q

What is the mechanism of action for erythromycin?

A

Inhibition of protein synthesis of susceptible bacteria

Binds reversibly to 50S subunit to prevent translocation of AA

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49
Q

What is the major use of ionophores?

A

Poultry + swine feed efficiency + anticoccidial activity

50
Q

What is clindamycin used for?

A

Dogs/Cats = Peridontal disease + osteomyelitis + dermatitis + deep soft tissue infections caused by gram + infections + TOXOPLASMOSIS

Dogs = Neoporosis

51
Q

How is tilmicosin adminstered?

A

SC, every 72 hours - Cattle

52
Q

What does it mean to have post-antibiotic effect?

A

Antibacterial activity persists beyond the time that the antibiotic is measurable

53
Q

how does tobramycin compare to gentimycin?

A

More potent anti-pseudomonal activity + reduced nephrotoxicity

54
Q

How do tetracyclines aid in contracted tendons in foals?

A

Inhibit collagen-based contractions in myofibroblasts

55
Q

What do ionophores do within the rumen?

A

Select for Gram + bacteria, shifting the bacterial community to Gram (-)’s

This increases the production of propionic acid and decreases the production of acetic and butyric acids

56
Q

What are the adminstration requirements for gamithromycin in food animals?

A

SC in beef and non-lactating cattle only

Not for use in female dairy cows over 20months of age or calves that will be used for veal

57
Q

What specific bacteria do tetracyclines work against in small animal medicine?

A

Borrelia

Brucella

Haemobartonella

Ehrlichia

58
Q

How is azithromycin administered?

A

SID, PO - Dogs + Cats + Foals

59
Q

What are lincosamides active against?

A

Aerobic gram-positive cocci

Several anaerobic gram-negative/positive

60
Q

Why should PO and parenterally admin be avoided in horses?

A

Danger of disrupting ruminal or colonic microflora

61
Q

Which of the tetracyclines can pentrate the CNS, eyes, and prostate?

A

Doxycycline

Minocyline

62
Q

How do aminoglycosides get into the cell?

A

Oxygen dependent transport

63
Q

Why is it thought that tetracyclines work well with cat absecesses?

A

Contain L-form bacteria that lack cell walls and are sensitive to tetracyclines

64
Q

What are the three important characteristics of aminoglycosides when it comes to their pharmokinetics?

A

None is absorbed after oral administration

None pentrate CSF readily

Normal kidney rapidly excretes them all

65
Q

How do tetracyclines enter the bacterial cell?

A

Oxygen-dependent

66
Q

When are tetracyclines used for cat abscesses?

A

Those that do not respond to B-lactams

67
Q

What are the characteristics of distribution when it comes to erythromycin?

A

Passes through placeneta

Penetrates prostatic fluid

DOES NOT GO INTO CNS

68
Q

Phenicols (2)

A

Chloraphenicol

Florfenicol

69
Q

What is the protocol for Florfenicol in food animals?

A

Approved for use in cattle and swine

Respiratory disease + foot rot in cattle

70
Q

What is the mechanism of action for chloramphenicol?

A

Reversibly binds to 50S subunti

Prevents transpeptidation

71
Q

What are the five derivatives of erythromycin?

A

Tylosin

Tilmicosin

Tulathromycin

Azithromycin

Clarithromycin

72
Q

Macrolides (6)

A

Erthyromycin

Gamithromycin

Tildipirocin

Lincomycin

Clindamycin

Pirlimycin

73
Q

Why do tetracyclines tend to stain teeth?

A

Formation of tetracyclein-calcium phosphate complex in enamel and dentine

74
Q

What is the predominant activity of linezolid?

A

Aerobic gram-positive organism

75
Q

What are tetracyclines used for in large animals?

A

Local + systemic bacterial infections in sheep, cattle, horse, and swine

Feed additive/growth promoters in cattle and swine

76
Q

What are the six groups of drugs that act as inhibitors on protein synthesis?

A

Aminoglycosides

Macrolides

Tetracyclines

Phenicols

Ionophores

Oxazolidinones

77
Q

How is doxycycline secretion diifferent?

A

Intestinal excretion is major route of elimination

78
Q

Which of the tetracylcines are not nephrotoxic?

A

Doxycycline

Minocycline

79
Q

What is the veterinary feed directive?

A

Intends to limit antibiotic use for therapeutic needs instead of production

Recommends drug manufacturers VOLUNTARILY stop labeling drugs as “promoting animal growth”

80
Q

What is the difference between monogastric and ruminal animals when it comes to ionophore absorption?

A

More complete and metabolism is slower = increased toxicity

81
Q

What animals is lincosamides contraindicated in?

A

Horses

Rabbits

Hamsters

Guinea pigs

82
Q

What do aminoglycosides act on?

A

Inhibiting protein synthesis of susceptible organisms

Inhibit funciton of the 30S subunit of bacterial ribosomes

83
Q

What are the distribution characterisitics of clindamycin?

A

Crosses placenta

Gets into breast milk

Reaches high concentrations in teh bone

Does not get into the CNS

84
Q

How are ionophores excreted?

A

Bile

Elminated by feces

85
Q

What is a good way to get aminoglycocides to work against gram +’s?

A

Use with beta lactam

86
Q

Which of the phenicosl produces aplastic anemias?

A

Chloramphenicol

87
Q

What are the adverse effects of chloramphenicol?

A

Dose dependent

bone marrow depression

Gray syndrome

Due to inhibition of protein synthesis in host mitochondria

88
Q

How is florfenicol metabolized?

A

1/3 metabolized by the liver

2/3 of drug excreted as parent

89
Q

What is chloramphenicol used for in dogs, cats, horses, ad birds?

A

Local and systemic infections

Respiratory + CNS + Ocular

Due to Anaerobes + Salmonella

90
Q

What are the adverse reactions to erythromycin?

A

GI upset

Pyresis

Reversible jaundice

Elevated hepatic enzymes

Allergic reactions

QT prolongation

91
Q

How is florfenicol given to swine?

A

Drinking water

92
Q

What is the absorption rate of tetracyclines? What is the exception?

A

60 to 90%

Cholortetracycline - 35%

93
Q

When are macrolides effective?

A

Alternative agents to penicillin when patient is allergic and/or when in renal failure

94
Q

What are the adverse effects of the penicols?

A

Anemia

Aplastic anemia

Iatrogenic endotoxicosis

95
Q

How are tetracyclines excreted?

A

Glomerular filtration, with small amounts being excreted into the bile

96
Q

How is erythromycin administered?

A

PO or IM TID - Dogs + cats + foals

IM SID - Cattle + Sheep + Swine

97
Q

What does tetracycline work against?

A

Gram +/- aerobes/anaerobes

Rickettsiae

Spirochetes

Chlamydiae

Mycoplasma

Some protozoans

98
Q

How is linezolid adminstered?

A

IV or Oral

99
Q

What does plazomicin act against?

A

Klebsiella pneumoniae

Escherichia coliUse

100
Q

What is the major characteristic of aminoglycocides that give them their properties?

101
Q

How is erythromycin excreted?

A

Lost in feces in large amounts

5% excreted in urine

102
Q

What two drugs have contraindications with erythromycin?

A

Chloramphenicol

Clindamycin

103
Q

What is gamithromycin used for?

A

BRD - Manneimia haemolytica + Pasteurella multocide + Histophilus somni + Mycoplasma bovis

Control of BRD - M.H. and P.M.

104
Q

What are the characteristics of metabolism for tetracyclines? Which one differs and how?

A

Metabolism is very minimal in domestic animals

Exception = minocylcine, metabolized by the liver

105
Q

How is florfenicol given to cattle?

A

IM, one dose than another 48 hours later

Slow-release prep

106
Q

How is tulathromycin administerd?

A

one SC injection against cattle and swine respiratory infectiosn

107
Q

What are the gram negative rods that aminoglycocides are most effective against?

A

Enterbacteria

Proteus

Psudomonas

Serratia

108
Q

What ionophores are used in the feed for growth promotion and feed efficiency?

A

Monensin

Lasalocid

Laidlomycin

109
Q

What are the three lincosamides?

A

Lincomycin

Clindamycin

Pirilmycin

110
Q

What specific bacteria do tetracyclines kill in large animals?

A

Chlamydial

Rickettsial

Protozoal

111
Q

What drug are lincosamides mixed with to treat toxoplasmosis?

A

Pryimethamine

112
Q

When is chloramphenicol bacteriocidial?

A

Meningeal pathogens

H. Influenzae

Neisseria meningitidis

Streptococcos pneumoniae

113
Q

How does chloramphenicol cause aplastic anemia in humans?

A

Idiopathic

Why it is banned in food products

114
Q

What three tetracyclines are most commonly used in large animals?

A

Tetracycline

Chlortetracycline

Oxytetracycline

115
Q

Ionophores (5)

A

Monensin

Lasalocid

Laidlomycin

Salinomycin

Narasin

116
Q

When are aminoglycosides bactericidal?

A

Aerobic conditions, unknown why

117
Q

What two tetracyclines are used for cat abscesses?

A

Doxycycline

Minocycline

118
Q

Where do superinfections caused by tetracyclines tend to occur?

A

Gi tract

due to prolonged adminstration

119
Q

How is chloramphenicol metabolized?

A

Glucuronide conjugation

75% for cats

90% for dogs

120
Q

How should aminoglycosides be given since that have a large PAE?

A

Single, large dose will be the most efficective

121
Q

Why does chloramphenicol cause anemia?

A

Dose-related

Inhibits the uptake of iron in mitochondira present in erythropoeitic cells in bone marrow

Pharmacology II (20 decks)

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