Lecture 22: Inhibitors of Protein Synthesis II

Question 1

what is the mechanism of action of tetracyclines

Answer 1

Inhibition of protein synthesis by inhibiting 50s ribosomes and prevent access of aminoacyl TNRA to receptor site on mRNA-ribosome complex

Question 2

Are tetracyclines bacteriostatic or bacteriocidal

Answer 2

Bacteriostatic

Question 3

Are tetracyclines narrow or broad spectrum

Answer 3

Broad

Question 4

Tetracycline have antimicrobial activity against what organisms

Answer 4

Gram positive and negative aerobes, anaerobes, Ricketssia (such as Anaplasma, Haemobartonella), spirochetes, mycoplasma clamydiae and some protozoans

Question 5

Uptake of tetracyclines is ___dependent so they poorly penetrate ___

Answer 5

Oxygen, anaerobes

Question 6

What are some uses for tetracyclines/ which ones in large animals

Answer 6

Tetracycline, chlortetracycline and oxytetracycline are used in treatment of local and systemic bacterial, chamydial, rickettsial and protozol infections in cattle, swine and sheep and as feed additives/ growth promoters in cattle, swine and poultry

Question 7

What are some uses for tetracyclines in small animals/which ones

Answer 7

Doxycycline, minocycline, and tetracycline used for respiratory and urinary tract infections in dogs and cats, specific therapy for Boreilla (Lyme), brucella, haemobartonella, adn Ehrlicha

Also tx coccidiosis in birds

Question 8

What tetracyclines have shown to be effective in abscesses in cats that don’t respond to B-lactams

Answer 8

Doxycycline and minocycline

Question 9

Tetracyclines treat what special condition in foals and what is MOA

Answer 9

Contracted tendons in foals, inhibit the collagen based contraction in myofibroblasts

Question 10

What is the drug of choice in treating tick borne diseases in animals

Answer 10

Doxycycline

Question 11

What tick borne diseases does doxycycline tx in cats

Answer 11

Mycoplasma and chlamydophilia Felis

Question 12

What tick borne diseases does doxycycline tx in dogs

Answer 12

Ehrlichia canis

Question 13

What drug is often added to heart worm tx against Wolbachia

Answer 13

Doxycycline

Question 14

Oral and parentally administered tetracyclines should be avoided in ___ due to danger in disrupting ___ or __ microflora

Answer 14

Horses, ruminal or colonic

Question 15

Divalent and trivalent cations impair absoprtion of tetracyclines therefore ___, ___ and ___, should be avoided 3hrs before and after oral adminsitration

Answer 15

Milk, antacids, iron salts

Question 16

What tetracyclines are more lipid soluble and distribute to CNS, eyes, and prostate

Answer 16

Doxycycline and minocycline

Question 17

Which tetracycline is extensively metabolized by the liver

Answer 17

Minocycline

Question 18

What is the route of elimination for doxycycline

Answer 18

Intestinal excretion

Question 19

How long is the withdrawal period after intrauterine administration of oxytetracycline in cattle. What do they also recommend

Answer 19

28 days
Also recommends milk testing

Question 20

What is the withdrawal period of IM or SQ administration of oxytetracycline in goats or sheep. And what is milk withdrawal time

Answer 20

28 days
Milk withdrawal 96 hrs

Question 21

What is the withdrawal time for swine receiving oxytetracycline in feed or water

Answer 21

14 days

Question 22

What are some adverse effects of tetracyclines

Answer 22

1. Nephrotoxicity
2. Permanent staining of unerupted teeth due to tetracycline calcium-phosphate complex
3. Superinfections
4. GI effects in cats
5. Anti-anabolic at high doses—> elevated BUN

Question 23

Oral tetracyclines should not be used long term in herbivores because of ___

Answer 23

Serious effects on ruminal digestion

Question 24

What tetracyclines don’t cause Nephrotoxicity and why

Answer 24

1. Doxycycline- intestinal excretion
2. Minocycline- metabolized by liver

Question 25

What is the mechanism of action of chloramphenicol and florfenicol

Answer 25

Binds 50S subunit and inhibits protein synthesis

Question 26

Is chloramphenciol bacteriostatic or bacteriocidal

Answer 26

Bacteriostatic, but can be bacteriocidal against certain meningeal pathogens such as H. Influenza, N. Meningitis, and Streptococcus pneumonias

Question 27

Why can chloramphenicol have negative effects on humans (MOA) and what are they

Answer 27

Mammalian mitochondria contain 70S ribosomes and chloramphenicol binds 50s subunit of bacterial 70s ribosomes, so chloramphenicol can cause dose-dependent bone marrow depression and gray syndrome due to inhibition of protein synthesis in host mitochondria

Question 28

What drug is illegal to use in food producing animals due to residue induced toxicity in hormones, aplastic anemia is fatal result

Answer 28

Chloramphenicol

Question 29

What is chloramphenicol used for

Answer 29

Used in dogs, cats, birds and horses for local and systemic infections inducing CNS, respiratory and ocular infections caused by anaerobes and Salmonella spp.

Question 30

What is florfenicol used for

Answer 30

Approved in cattle and swine for tx of respiratory diseases and foot rot in cattle Available as drinking medication in swine

Question 31

T or F: chloramphenicol is distributed to CNS and eyes

Answer 31

True

Question 32

What is the T1/2 life in dogs and cats for chloramphenicol and why is it different

Answer 32

Dogs: 1-1.5hrs Cats:4-5hrs Due to glucuronidation metabolism

Question 33

T or F: florfenicol is distributed to CNS

Answer 33

True

Question 34

What is the t 1/2 life of florfenicol in cattle

Answer 34

18 hours

Question 35

How is florfenicol excreted

Answer 35

2/3 is excreted in urine and 1/3 metabolized by liver

Question 36

What are some adverse effects of chloramphenicol

Answer 36

1. Anemia in humans and animals due to inhibition of iron uptake present in erythropoietic cells in bone marrow 2. Fatal aplastic anemia in humans 3. Iatrogenic endotoxicosis- rapid killing of gram negative bacteria

Question 37

Ionophores are antibiotics derived from ___ primarily used in poultry and swine for ___ and ___

Answer 37

Streptomyces, feed efficiency and anticoccidial activity

Question 38

What is the net effect of monesin/ MOA

Answer 38

Transmembrane exchange of sodium ions for protons—> elimination of membrane potential and active transport

Question 39

How do ionophores effect rumen/ what is their MOA there

Answer 39

Ionophores selectively affect gram + organisms, resulting in shift to gram - populations, increases production of propionic acid, decreases acetic and butryic acid production by rumen bacteria. This change in VFA increases feed efficiency by reducing bacterial energy losses to CO2 and methane, thereby increase energy content per unit of feed

Question 40

What are the uses for monesin, losalocid and laidlomycin

Answer 40

Administered as premixes or medicated feed for growth promotion, feed efficiency and control of coccidiosis in cattle and broiler chickens

Question 41

What are the uses for salinomycin and narasin

Answer 41

Administered as medicated feeds to broiler chickens to prevent coccidiosis

Question 42

What species are Ionophores particularly toxic in and why

Answer 42

Horses, absorption is more complete and metabolism is slower in monogastrics

Question 43

What are the signs of acute intoxication of ionophores in horses

Answer 43

Colic, sweating, incoordination, muscle weakness, elevated HR, dark urine, kidney failure, respiratory distress and going down

Question 44

What are the 3 important points in the veterinary feed directive

Answer 44

1. Limit antibiotic use for therapeutic uses instead of production purposes 2. Recommend drug manufactures voluntarily stop labeling drugs as “promoting animal growth” 3. Extra label use of antibiotics requires a VPCR before compounding

Question 45

What new class of synthetic antibiotics are known as flurinated oxazolidinones

Answer 45

Linezolid

Question 46

What do linezolids have activity against

Answer 46

Aerobic gram positive organisms

Question 47

What is the mechanism of action for linezolid

Answer 47

Inhibits bacterial protein synthesis by interfering with translation

Question 48

How is linezolid metabolized

Answer 48

Oxidation- spontaneously breakdowns

Question 49

What are some adverse effects of linezolid

Answer 49

Interaction with MAO inhibitors

Question 50

What are some uses for linezolid

Answer 50

1. Bacterial pneumonia 2. Skin infections 3. Vancomycin resistant enterococcal infections 4. Methicillin resistant staphylococci (MRSA)

Question 51

What are some drugs used to tx oropharyngeal anaerobic infections and lung abscess

Answer 51

1. Clindamycin 2. B-lactam/lactamase inhibitor 3. Metronidazole

Question 52

What are some drugs used to tx GI or female pelvic anaerobic infections (B. Fragillis often)

Answer 52

1. Metronidazole 2. Carbapenems 3. Moxifloxacin