Immunity And Infection Antibiotics Targeting Protein Synthesis

Front 1

What do the majority of Bacterial protein synthesis inhibits target? Which do not?

Back 1

Most target 50S ribosome except tetracyclines

Front 2

What are the broad, immediate, and narrow spectrum bacterial protein synthesis inhibitors?

Back 2

Broad = Chloramphenicol, Tetracyclines
Intermediate = Macrolides, Ketolides
Narrow spectrum = Lincosamides, Streptogramins, Linezolid

Front 3

What mode of action do tetracyclines have?

Back 3

Reversible binding to 30S ribosome subunit blocks amnoacyl-tRNA access to acceptor site.

Front 4

Would you use a Beta lactam for treating mycoplasma?

Back 4

NO, do not have PG so ineffective

Front 5

What organisms are susceptible to protein synthesis targeting antibacterials?

Back 5

Many G+ and G- bacteria including Anaerobes, rickettsiae, chlamydiae, mycoplasmae

Front 6

What protein synthesis drug will act against protozoa?

Back 6

Doxycycline is effective against Entamoeba and Plasmodium falciparum

Front 7

How do protein synthesis inhibitors get into bacteria?

Back 7

Both active and passive transport

Front 8

What are the methods in which Resistance to tetracyclines occurs?

Back 8

1) Upregulaton of efflux pump
Resistance depends on whether pump binds drug
Pseudomaonas and Proteus (resistant to all tetracyclines)
Staph. aureus efflux pump doesn't bind doxycycline and minocycline

2)Production of proteins interfering with ribosomal binding.

3) Can sometimes find impaired uptake via active process and enzymatic inactivation of the drug.

Front 9

What is the normal functon of the 50s ribosome?

Back 9

Transpeptidation

Front 10

How are Tetracyclines given?

Back 10

Orally except for Tigecycline that must be given i.v.

Front 11

What can interfere with the absorption of tetracyclins?

Back 11

Food uptake, divalent cations (Ca++, Mg++), antancids, dairy products.

Front 12

What percentage of tetracyclins in the blood are bound to plasma proteins?

Back 12

40-80%

Front 13

Where does tetracyclin diffuse in the body?

Back 13

Enters all body fluids well except CSF.

Front 14

How is Tetracyclin excreted?

Back 14

In bile and then into feces
Also urine (except doxycycline and tigecycline)

Front 15

What are the concerns about using tetracyclin in pregnant women?

Back 15

Crosses placenta and enters breast milk

Front 16

Why should tetracyclins not be used in growing children?

Back 16

Chelate with calcium and cause binding to growing bones and teeth which caues damage.

Front 17

What color are teeth that have deposits of tetracyclin?

Back 17

Yellowish or brownish grey. Discoloration becomes more brownish after exposure to light.

Front 18

Do the tetracyclins enter the CSF?

Back 18

NO

Front 19

What are the adverse reactions of tetracyclins?

Back 19

Irritation of GI tract (diarrhea, vomiting, nausea)
GI effects due to microbial flora change
Teeth/bone effects
Liver toxicity
High doses cause vestibular toxicity
Significant urinary excrretion of most drugs means higher toxicity in those with impaired kidney function.
Hypersensitivity is uncommon

Front 20

What is the spectrum of Tigecycline? What is it not effective against?

Back 20

Very broad spectrum
Not effective against Pseudomonas or Proteus where the efflux pump is effective causing intrinsic resistance.

Front 21

How is Tigecycline adminstered and excreted? What side effects does it have in addition to other normal tetracycline side effects?

Back 21

Administered I.V. (very poorly absorbed orally)
Excreted mainly via bile like doxycyclin (no renal adjustment)
Has nausea in addition to most tetracycline class side effects

Front 22

What function do macrolides block?

Back 22

Transpeptidation of the 50s ribosome.

Front 23

What organisms are susceptible to macrolides?

Back 23

G+ and G- organisms including Neisseria
Some mycobactria
Intracellular bacteria, spirochetes (Treponema), mycoplasmae, legionella, Listeria, Helicobacter

Front 24

How is Erythromycin resistance found in bacteria? How does it occur?

Back 24

Plasmid encoded
Reduces intracellular concentration (reducing permeability or increasing efflux)
Hydrolysis by esterases
Methylation of the binding site in the 50s ribosome
Methylation can be induced by the presence of a macrolide

Front 25

What will methylation of the binding site in 50s ribosome result in resistance to? How about MLSb resistance?

Back 25

methylation = All macrolides and clindamycin and streptogramin B.

MLSb resistance = macrolide, licosamide and streptogramin B

Front 26

What are the macrolides with a lactone ring with deoxy sugars attached?

Back 26

Erythromycin
Clarithromycin
Azithromycin
Kelotides

Front 27

How is erythromycin absorbed and excreted?

Back 27

Given orally but must use enteric coating as is acid sensitive.

Esters and salts can also provide acid resistance.

Food interferes with its uptake.

I.V. preparations also used

Majority excreted in bile

Front 28

What is Erythromycin used to treat?

Back 28

Corynebacterium (erythrasma and diptheria as well)
Chlamydial infections
Community acquired pneumonia (gets both Strep. Pneumoniae and Legionella)
Used for susceptible Staph and Strep infections with penicillin allergic persons

Front 29

What are the adverse reactions of Erythromycin?

Back 29

Nausea, anorexia, diarrhea
Gi intolerance causing increased gut motility
Liver toxicity
Allergy

Front 30

What drug/enzyme interactions does erythromycin have?

Back 30

Increases bioavailibilty of oral digoxin and inhibits cytochrome P450 enzymes.

Front 31

What are the additional organisms that clarithromycin is effective against?

Back 31

Corynebacterium
Chlamydia
Strep. Pneumo
Legionella
Staph and Strep
All like erythromycin

Also Works on Mycobacterium avium, M. leprae, Toxoplasma gondii

Front 32

What organisms is azithromycin effective against? How is it different from the other macrolides and what is it used for mostly in particular?

Back 32

Used for
Corynebacterium
Strep. pneumo
Legionella
Staph and Strep infections in penicillin allergic
Mycobacterium avium, M. leprae, Toxoplasma gondii
Very active against Chlamydia
Penetrates tissues to high concentration with slow release
Very useful for STDs

Does NOT interact with P450s

Front 33

What organisms are ketolides (telithromycin used for)?

Back 33

Used for macrolide resistant strains where efflux pumps give resistance.
doesnt work with resistance due to to methylated target in ribosome
Useful for community acquired pneumonias (mycoplasma, chlamydia, Legionella, Strep. pneumonia)
DOES interact with P450 3A4

Front 34

What type of drug is Clindamycin? What is its mechanism of action? What is its major target?
What is the major danger with its use?
What is it mostly used to treat?

Back 34

It is a lincosamide and it acts on Ribosomoal 50s.
Enterococci and gram- aerobes are resistant
Most anaerobes are susceptible

High risk of inducing C. diff colitis

Mainly used for treating acne and in a combination for treating and preventing mixed anaerobe infections (abdominal wounds, dental procedures, pelvic abscess and septic abortion)

Front 35

How does chloramphenicol work?

Back 35

binds 50s subunit and blocks transpeptidation

Front 36

How is chloramphenicol delivered?

Back 36

Orally or with succinate salt for i.v.

Front 37

Where does chlorampheincol distribute to?

Back 37

CNS and all body fluids

Front 38

Where is chloramphenicol inactivated?

Back 38

Liver

Front 39

How is chlormapheiincol excreted?

Back 39

Urine

Front 40

What organisms are chormphenicol effective against?

Back 40

Aerobic and anaerobic G+ and G- bacteria, Rickettsiae

NOT chlamydiae

Front 41

What is chloramphenicol resistance due to?

Back 41

Plasmid encoded acetyltranferase which inactivates the drug.

Front 42

Where is chloramphenicol metabolised? What considerations must one take due to this?

Back 42

Metabolised in the liver via conjugation with glucuronic acid and exceted in the urine.

Dose must be reduced if liver dysfunciton.

Front 43

What are the serious reactions that can occur with chloramphenicol?

Back 43

Suprression of RBCs leading to aplastic anemia
Is bacteriostatics so may slow beta lactams
Inhibits liver metabolism of other drugs.

Front 44

What considerations must there b when giving a newborn chloramphenicol?

Back 44

Newborn infants have poor glucuronic acid conjugation and develop grey baby syndrome= gray color, flaccidity, hypothermia, shock

Front 45

What diseases is chloramphenicol used to treat?

Back 45

Serious rickettsial infections
Bacterial meningits when beta lactams cannot be used
And topical use in eye infections (not chlamydia)

Front 46

What is Quinupristin-dalfopristin?

Back 46

A combination of a streptogramin A with a streptogramin B.

Front 47

How does Quinupristin-dalfopristin work?

Back 47

Act on bacterial 50S ribosomal subunit to prevent protein formation (act on different sites)

Front 48

What is Quinupristin dalfoprisin used to treat?

Back 48

VRSA
MRSA
Vanocomycin resistant Enterococcus faecium

Front 49

What are the adverse reactions of Quinuprisitin-dalfopristin?

Back 49

Minor

Front 50

What is Linezolid used for?

Back 50

G+ including anaerobes
MRSA
VRSA
enterococci (both faecium and faecalis)

Front 51

How does linezolid work?

Back 51

Binds at 50s subuinit inhibiting protein synthesis

Front 52

What adverse effects does Linezolid cause?

Back 52

mild thrombocytopenia and bone marrow supression

Front 53

What are Aminoglycosides mainly used for?

Back 53

G- enteric bacteria (bacteremia and sepsis)
In combination with vancomycin or beta lactam (endocarditis)
Tuberculosis

Front 54

What are the broad spectrum aminoglycosides?

Back 54

Gentamicin
Amikacin
Tobramycin
Netilmicin

Front 55

What are the narrow spectrum aminoglycosides?

Back 55

Streptomycin
Neomycin
Kanamycin

Front 56

Do aminoglycosides cure disease?

Back 56

No! Do not work alone on serious infections by enterococci or streptococci but can increase antimicrobial activity of other drugs when used in combination.

Front 57

How does gentamicin work?

Back 57

Binds ribosomal 30s subunit, distorts it and causes misreading of codons.

Front 58

How do bacteria acquire resistance to aminoglycosides?

Back 58

Impair uptake of drug
Drug modification
-adenylation
-acetylation
-phosphorylation
Target modification/deletion
-30S ribosome

Front 59

What are some of the useful antibacterial features of aminoglycosides?

Back 59

Action independent of bacterial concentration (differs from most beta lactams) thus useful for intrabdominal infections with massive bacterial numbers
Persistent suppression of microbial growth after non lethal exposure

Front 60

How is Aminoglycoside absorbed/delivered? Excreted? Distribution?

Back 60

highly charged so not absorbed well. Must be given IV or IM.

Highly water soluble with little binding to plasma protiens
Plasma concentration = interstitial concentration
Concentration in bile
Poor penetration into CSF
Eliminated in urine but some readsorption in proximal tubule

Front 61

What is the peak dose for Aminoglycoside?

Back 61

12X MIC once a day.

Front 62

What is aminoglycoside toxicity dependent on?

Back 62

Amount of time the drug remains above a toxic concentration

Front 63

What are the adverse reactions of Aminoglycosides?

Back 63

Neuromoscular blockade (bind calcium in presynapse) (reversible)
Nephrotoxicity (Interfere with tubular function, increased toxicity in combination with vancomycin, amphotericin B, diuretics, others)
Ototoxicity (NOT reversible, accumulate in perilymph of inner ear and kill sensory cells in organ of Corti, hair cells) also vestibular damage. Loss of hearing at high frequencies

Front 64

Besides bacterial treatment what can aminoglycosides be used for?

Back 64

Treating genetic disease in humans caused by premature stop codon.
Alter ribosome and allow some normal read through.

Front 65

What is Spectomycin used to treat? What is its target?

Back 65

Treats Neisseria gonorrhoeae
Target is 30S ribosome