Protein Synthesis Inhibitors Flashcards
What are the protein synthesis inhibitors?
AT CELLS
Aminoglycosides
Tetracyclines
Chloramphenicol
Erythromycin
Lincosamines
Linozelid
Streptogramins
what are the aminoglycosides?
GNATS KN
Gentamycin
Neomycin
Amikacin
Tobramycin
Streptomycin
Kanamycin
Netilmycin
how do aminoglycosides work?
bind to 30s subunit and block the initiation complex and cause misreading of mRNA
what is the mechanism of resistance needed to evade aminoglycosides?
- Impaired penetration into the cell through porin channels: Strep and Enterococci
- Altered receptor in subunit 30s
- production of transferace enzyme by bacteria
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?
parentally (IV or IM)
concentration killing, it kill more bacteria using 1 large dose
it targets gram neg. aerobic bacteria
what drug combination do you use for enteroccocal infections?
and for P. aeruginosa infection?
AG + Penicillin G / ampicillin
AG + extended spectrum penicillin/cephalosporin
what aminoglycosides are used topically?
amikacin, tobramycin, Gentamicin
what do you use for hepatic coma?
why?
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.
what is the least preferred aminoglycosides to prescribe?
why?
streptomycin
because it is highly nephrotoxic
what side effects can we see with aminoglycosides?
- Nephrotoxicity: Proteinuria, hypokalemia, acidosi
- Ototoxicity: causes cochlear deafness or vestibular damage (look for nausea, vertigo, dizzyness)
- Neuromuscular blockade: can cause respiratory paralysis
- Contact dermatitis: with neomycin
Neuromuscular blockade with aminoglycosides is reversible when admnistered what?
calcium and neostigmine.
what are the Tetracyclines?
Doxycycline, Chlortetracycline, Oxytetracycline, Demeclocycline, Minocycline
how do tetracyclines work?
Bind to 30S subunit, interfere with the attachment of aminoacyl tRNA to acceptor site, prevents addition of amino acids to the growing peptide
how do bacteria develop resistance to tetracyclines?
Development of efflux pumps.
what can cause tetracyclines dose to decrease?
which is the only tetracycline that has an exception to the previous question? why?
in renal dysfunction
doxycycline; eliminated by liver
tetracyclines can bind to what strucutres?
what can decrease absorption of tetracyclines?
which tetracycline has the Best CSF penetration?
when are tetracyclines contraindicated?
teeth or bones
Calcium, Magnesium, Iron
Minocycline
pregnancy, children, renal insufficiency
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?
G. Positive: Clostridium, Listeria, Corynebacterium, Bacilus Antracis
G. Negative: Y. pestis, H. pylori
Spirochetes: T. pallidum, Borrelia
Atypical: Rickettsia (DOC), Chlamydia, Mycoplasma
what are the side effects of tetracyclines?
- Teeth: permanent brown discoloration & ill-formed teeth
- Stunted bone growth
- Phototoxicity on exposure to UV light- demeclocycline, doxycycline (seen in long term and exposure and in those sensitive to UV rays)
- In Super infections will cause Diarrhea, Candida
- Nephrotoxicity- doxycycline safe
- Fanconi’s syndrome: A form of renal tubular acidosis is attributed to use of outdated tetracyclines
how does Chloramphenicol work?
what effect does it have on CYP 450?
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
in which bacteria will chloramphenicol be highly active?
for what Anaerobic infections will you use tetracycline?
- Salmonella, H. influenza, N. meningitides
- bacteroides fragilis
what side effects will chloramphenicol have?
- In Superinfections can cause candidiasis
- Bone marrow suppression - dose dependent- leads to aplastic anemia
- Grey baby syndrome- occurs in neonates- due to deficient hepatic glucuronosyltransferase- lack of effective glucuronic acid conjugation degradation of chloramphenicol
- C/F: vomiting, abdominal distension, cyanosis, refusal to feed, CV collapse, death
what are the Macrolides drugs?
- Erythromycin
- Clarithromycin
- Azithromycin
- Roxithromycin, Telithromycin
how do macrolides work?
Bind to 50S subunit, prevent the translocation of peptidyl tRNA from A site to P site and blocks the formation of initiation complexes.
how can bacteria develop resistance to macrolides?
- Gram positive: efflux pump, production of methylase enzyme (enzyme will inactivate drug)
- Enterobacteriacease: formation of drug metabolizing esterases
- Aquired resistance: specific mutation of ribosomal RNA of the 50S subunit
erythromycin is acid liable or acid stable?
is erythromycin cyp 450 inhibitor or inducer? this happens when? this may lead to what?
acid liable
cyp450 inhibitor, when used with Terfenadine/Astemizole/Cisapride; can cause prolongation of QT
when is erythromycin used?
atypical pneumonia caused by mycoplasma
whooping cough
strep infection when pt is allergic to penicillin
legionaire’s pneumonia
erythromycin can cause what side effects?
diarrhea by stimulating motilin receptors
when is clarithromycin used?
Upper and lower respiratory tract infection
H. pylori recurrent peptic ulcer
Leprosy
is Azithromycin acid liable or acid stable?
what half life does it have?
can it be used in pregnancy?
when is Azithromycin used?
acid stable
long half life
yes
Legionnaire’s pneumonia, Chlamydia infection of urogenital tract
when is Roxithromycin, Telithromycin used?
Macrolide resistant Strep. pneumoniae
how do lincosamides work?
Bind to 50S subunit, prevent the translocation of peptidyl tRNA from A site to P site and blocks the formation of initiation complexes.
name a Lincosamide
when is lincosamide used?
what is an important side effect that lincosamides cause?
Clindamycin
Bacteroides fragilis, Pneumocystis jiroveci, Toxoplasma gondii, pneumocystis jiroveci pneumonia
First known drug to cause pseudomembranous enterocolitis
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?
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
how do Linezolids work?
what happens if used with other protein synthesis inhibitors?
when is it used?
what is a side effect they cause?
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
