Protein Synthesis Inhibitors

Question 1

What are the protein synthesis inhibitors?

Answer 1

AT CELLS

Aminoglycosides

Tetracyclines

Chloramphenicol

Erythromycin

Lincosamines

Linozelid

Streptogramins

Question 2

what are the aminoglycosides?

Answer 2

GNATS KN

Gentamycin

Neomycin

Amikacin

Tobramycin

Streptomycin

Kanamycin

Netilmycin

Question 3

how do aminoglycosides work?

Answer 3

bind to 30s subunit and block the initiation complex and cause misreading of mRNA

Question 4

what is the mechanism of resistance needed to evade aminoglycosides?

Answer 4

1. Impaired penetration into the cell through porin channels: Strep and Enterococci
2. Altered receptor in subunit 30s
3. production of transferace enzyme by bacteria

Question 5

how are aminoglycosides administered?

is it better to adminster aminoglycosides in little doses or a lot in 1 dose?

Does it target aerobic, anaerobic or both type of bacteria?

Answer 5

parentally (IV or IM)

concentration killing, it kill more bacteria using 1 large dose

it targets gram neg. aerobic bacteria

Question 6

what drug combination do you use for enteroccocal infections?

and for P. aeruginosa infection?

Answer 6

AG + Penicillin G / ampicillin

AG + extended spectrum penicillin/cephalosporin

Question 7

what aminoglycosides are used topically?

Answer 7

amikacin, tobramycin, Gentamicin

Question 8

what do you use for hepatic coma?

why?

Answer 8

Neomycin

to decrease the coliform flora, causing a decrease in the production of ammonia that causes the levels of free nitrogen to decrease in the bloodstream.

Question 9

what is the least preferred aminoglycosides to prescribe?

why?

Answer 9

streptomycin

because it is highly nephrotoxic

Question 10

what side effects can we see with aminoglycosides?

Answer 10

1. Nephrotoxicity: Proteinuria, hypokalemia, acidosi
2. Ototoxicity: causes cochlear deafness or vestibular damage (look for nausea, vertigo, dizzyness)
3. Neuromuscular blockade: can cause respiratory paralysis
4. Contact dermatitis: with neomycin

Question 11

Neuromuscular blockade with aminoglycosides is reversible when admnistered what?

Answer 11

calcium and neostigmine.

Question 12

what are the Tetracyclines?

Answer 12

Doxycycline, Chlortetracycline, Oxytetracycline, Demeclocycline, Minocycline

Question 13

how do tetracyclines work?

Answer 13

Bind to 30S subunit, interfere with the attachment of aminoacyl tRNA to acceptor site, prevents addition of amino acids to the growing peptide

Question 14

how do bacteria develop resistance to tetracyclines?

Answer 14

Development of efflux pumps.

Question 15

what can cause tetracyclines dose to decrease?

which is the only tetracycline that has an exception to the previous question? why?

Answer 15

in renal dysfunction

doxycycline; eliminated by liver

Question 16

tetracyclines can bind to what strucutres?

what can decrease absorption of tetracyclines?

which tetracycline has the Best CSF penetration?

when are tetracyclines contraindicated?

Answer 16

teeth or bones

Calcium, Magnesium, Iron

Minocycline

pregnancy, children, renal insufficiency

Question 17

in what gram positive bacteria are tetracyclines used?

in what gram negative bacteria are tetracyclines used?

in what spirochete bacteria are tetracyclines used?

in what Atypical bacteria are tetracyclines used?

In the previous question, in which bacteris is a tetracycline the drug of choice?

Answer 17

G. Positive: Clostridium, Listeria, Corynebacterium, Bacilus Antracis

G. Negative: Y. pestis, H. pylori

Spirochetes: T. pallidum, Borrelia

Atypical: Rickettsia (DOC), Chlamydia, Mycoplasma

Question 18

what are the side effects of tetracyclines?

Answer 18

1. Teeth: permanent brown discoloration & ill-formed teeth
2. Stunted bone growth
3. Phototoxicity on exposure to UV light- demeclocycline, doxycycline (seen in long term and exposure and in those sensitive to UV rays)
4. In Super infections will cause Diarrhea, Candida
5. Nephrotoxicity- doxycycline safe
6. Fanconi’s syndrome: A form of renal tubular acidosis is attributed to use of outdated tetracyclines

Question 19

how does Chloramphenicol work?

what effect does it have on CYP 450?

Answer 19

Bind to 50S subunit, inhibits the activity of peptidyltransferase and inhibits the transfer of the peptide chain from P site to acceptor site

CYP 450 inhibitor

Question 20

in which bacteria will chloramphenicol be highly active?

for what Anaerobic infections will you use tetracycline?

Answer 20

• Salmonella, H. influenza, N. meningitides
• bacteroides fragilis

Question 21

what side effects will chloramphenicol have?

Answer 21

1. In Superinfections can cause candidiasis
2. Bone marrow suppression - dose dependent- leads to aplastic anemia
3. Grey baby syndrome- occurs in neonates- due to deficient hepatic glucuronosyltransferase- lack of effective glucuronic acid conjugation degradation of chloramphenicol
4. C/F: vomiting, abdominal distension, cyanosis, refusal to feed, CV collapse, death

Question 22

what are the Macrolides drugs?

Answer 22

1. Erythromycin
2. Clarithromycin
3. Azithromycin
4. Roxithromycin, Telithromycin

Question 23

how do macrolides work?

Answer 23

Bind to 50S subunit, prevent the translocation of peptidyl tRNA from A site to P site and blocks the formation of initiation complexes.

Question 24

how can bacteria develop resistance to macrolides?

Answer 24

1. Gram positive: efflux pump, production of methylase enzyme (enzyme will inactivate drug)
2. Enterobacteriacease: formation of drug metabolizing esterases
3. Aquired resistance: specific mutation of ribosomal RNA of the 50S subunit

Question 25

erythromycin is acid liable or acid stable? is erythromycin cyp 450 inhibitor or inducer? this happens when? this may lead to what?

Answer 25

acid liable cyp450 inhibitor, when used with Terfenadine/Astemizole/Cisapride; can cause prolongation of QT

Question 26

when is erythromycin used?

Answer 26

atypical pneumonia caused by mycoplasma whooping cough strep infection when pt is allergic to penicillin legionaire's pneumonia

Question 27

erythromycin can cause what side effects?

Answer 27

diarrhea by stimulating motilin receptors

Question 28

when is clarithromycin used?

Answer 28

Upper and lower respiratory tract infection H. pylori recurrent peptic ulcer Leprosy

Question 29

**is Azithromycin acid liable or acid stable?** **what half life does it have?** **can it be used in pregnancy?** when is Azithromycin used?

Answer 29

**acid stable** **long half life** **yes** Legionnaire’s pneumonia, Chlamydia infection of urogenital tract

Question 30

when is Roxithromycin, Telithromycin used?

Answer 30

Macrolide resistant Strep. pneumoniae

Question 31

**how do lincosamides work?**

Answer 31

**Bind to 50S subunit, prevent the translocation of peptidyl tRNA from A site to P site and blocks the formation of initiation complexes.**

Question 32

**name a Lincosamide** when is lincosamide used? **what is an important side effect that lincosamides cause?**

Answer 32

**Clindamycin** Bacteroides fragilis, Pneumocystis jiroveci, Toxoplasma gondii, pneumocystis jiroveci pneumonia **First known drug to cause pseudomembranous enterocolitis**

Question 33

**name the 2 streptogramins** **how are they used?** **how do they work?** **are the CYP Inhibitors or Inducers?** **When are they used?** **when are streptogramins used?**

Answer 33

Quinupristin, Dalfopristine always given in combination Bind to **50S** ribosomes and **prevent** the **interaction** of _**aminoacyl** **t**-**RNA**_ with **_acceptor site_**, **decreases release of completed polypeptide** **Inhibitors** **(DOC) MRSA, VRSA, VRE** Arthralgia-Myalgia Syndrome: muscle pain, joint pain, fever

Question 34

how do Linezolids work? what happens if used with other protein synthesis inhibitors? when is it used? what is a side effect they cause?

Answer 34

Bind to **23S** ribosomal RNA of the **50S** ribosomes, **inhibits formation of initiation complex** No cross-resistance to other protein synthesis inhibitors so nothing VRSA, VRE, Drug resistant pneumococci Thrombocytopenia