EXAM 1 Antimicrobials II Flashcards
what makes up the 70S ribosome complex?
30 S subunit + 50 S subunit
what makes up the 80S ribosome complex?
40S subunit + 60S subunit
describe the 3 ribosomal binding sites for tRNA
- A site
- holds AA to be added
- P site
- holds growing polypeptide chain
- E site
- exit site for tRNA
once the initiation complex is in place, the ___ assembles onto the ___ and the initiate proteins disassociate.
- large ribosomal subunit
- small subunit
after the large ribosomal subunit assembles onto the small ribosomal subunit and the initiation proteins disassociate, what happens?
the ribosome is now ready to begin translation
prokaryotic translation occurs on ___ ribosomes
70S
eukaryotic translation occurs on ___ ribosomes
80S
describe the main steps of translation after the initiation complex is in place and the large and small ribosomal subunits are assembled
- codon recognition
- peptide bond formation
- translocation
- ribosome is ready for the next aminoacyl tRNA
what are the 4 functional targets of antimicrobial PSIs?
- chloramphenicol
- erythromycin (macrolides)
- tetracyclines
- streptomycin (aminoglycoside)
___ binds to the 50S ribosomal subunit portion and inhibits formation of the peptide bond
chloramphenicol
___ binds to the 50S ribosomal subunit portion, preventing translocation/movement of the ribosome along mRNA
erythromycin (macrolide)
___ interfere with attachment of tRNA to the mRNA-ribosome complex
tetracyclines
___ changes shape to the 30S ribosomal subunit portion, causing the code on mRNA to be read incorrectly
streptomycin (aminoglycoside)
what are the 5 aminoglycosides?
- gentamycin
- amikacin
- tobramycin
- streptomycin
- neomycin
what class of antimicrobials has the following mechanism of action?
binds to the 30S ribosomal subunit changing its shape, which can have the following three consequences: (1) blocked initiation of mRNA translation, (2) premature termination of mRNA translation, and (3) misreading of the mRNA and incorporation of incorrect amino acids
aminoglycosides
describe streptomycin
- aminoglycoside drug
- IM, IV administration
- oldes of the family
- high level of bacterial resistance
describe gentramycin
- aminoglycoside drug
- IV preffered administration
- most commonly prescribed aminoglycoside
- used in combination with penicillins
describe amikacin
- aminoglycoside drug
- IM, IV administration
- broadest spectrum of all aminoglycosides
- used for hospital acquired infections
describe tobramycin
- aminoglycoside drug
- IM, IV administration
- excellent activity against pseudomonas aeruginosa
describe neomycin
- aminoglycoside drug
- topical administration only
- used primarily as topical for skin infections
- neomycin enema
what is a neomycin enema?
to flush and detoxify the colon and lower bowel before bowel surgery
aminoglycosides are used primarily to treat infections caused by what class of bacteria?
aerobic gram negative
the utility of aminoglycosides is limited by the occurrence of ___
serious toxicities
describe the bactericidal effect of aminoglycosides
- concentration-dependent killing (type 1)
- mild post-antibiotic effect (PAE)
- once-daily dosing
- effective, reduces risk of toxicity
describe the exceptions to daily dosing of aminoglycosides
- administered every 8 hours for:
- pregnancy
- neonatal infections
- bacterial endocarditis
- monitor creatinine clearance and BUN
aminoglycosides are generally given via IV or IM. the exception is neomycin, which is given topically. why?
due to nephrotoxicity
in anuric patients, the 1/2 life of aminoglycosides can increase by how much?
20-40x
with aminoglycosides, since the risk of nephrotoxicity and ototoxicity is concentration-dependent, it is crucial to do what?
reduce dosages, especially in patients with impaired renal function
aminoglycosides synergize with ___ or ___
beta-lactams or vancomycin (when used in combination)
all aminoglycosides have the potential to produce ___ toxicity
vestibular/cochlear and renal toxicity
(major limitation to the clinical utility of aminoglycosides)
ototoxicity caused by aminoglycosides may become irreversible rapidly. the toxicity correlates with what?
the number of destroyed hair cells
the frequent monitoring of what is essential during nephrotoxicity caused by aminoglycosides?
plasma concentration
ex. BUN and serum creatinine levels
name the 4 major adverse effects of aminoglycosides
- ototoxicity
- nephrotoxicity
- neuromuscular paralysis
- contact dermatitis
- accumulation in fetal plasma and amniotic fluid in utero (teratogenic)
what 4 groups are most at risk for aminoglycoside adverse effects?
- elderly
- impaired renal function
- septic patients
- must adjust dose
- previous exposure to aminoglycosides
- “functional accumulation”
name the 4 types of tetracyclines
- tetracycline
- doxycycline
- minocycline
- tigecycline
describe the spectrum of tetracyclines
- broad spectrum against gram positive and negative, and atypical intracellular organisms
which class of antimicrobials has the following mechanism of action?
binds reversibly to 30S subunit of bacterial ribosome blocking access of the amino acyl-tRNA to the mRNA-ribosome complex’s acceptor site
tetracyclines
the mechanism of action of tetracyclines inhibits the ___ subunit to prevent attachment of the ___
- 30S
- aminoacyl-tRNA
tetracyclines have a ___ action
bacteriostatic
___ is often used for the treatment of acne vulgaris
tetracycline
describe the cross-resistance of tetracyclines, and the exception
- if resistant to one TTC (tetracycline), then resistant to all TTCs
- exception: tigecycline
the oral absorption of tetracyclines is altered by what 3 things?
- dairy
- iron supplements
- antacids
where in the body does tetracycline tend to concentrate?
- Caclium-hydroxyapatite teeth/bones, or tumore with high calcium content
what are the 11 main adverse effects of tetracyclines?
- GI upset
- disulfuram-like effect (avoid alcohol)
- hepatotoxicity
- headache
- metallic taste
- phototoxicity
- vestibular problems
- benign intracranial hypertension
- itching in anal and genital areas
- superinfections
- don’t give to pregnant patients
describe superinfections as an adverse effect of tetracyclines
- candida
- pseudomonas colitis
- diarrhea due to overgrowth of c. difficile
what are the two main oral adverse effects of tetracyclines?
- hairy tongue
- deposition in bone and primary dentition
what are the contraindications for tetracyclines?
- pregnant patients
- breastfeeding patients
- children <8 yrs
- inpatients with liver and renal disease
describe the spectrum of bacteria tigecycline acts against
- same as doxycyline and other TTCs plus activity against:
- MRSA
- multidrug resistant s. pneumoniae
- vancomycin resistant enterococci
- some anaerobes
___ was developed to overcome TTC-resistance in complicated skin, soft tissue, and intra-abdominal infections
tigecycline
how is tigecycline administered?
IV
what are the adverse effects of tigecycline?
similar to other TTCs, including teeth and bones
what are the 3 macrolides?
erythromycin, clarithromycin, azithromycin
which antimicrobials has the following mechanism of action?
binds irreversibly to 50S subunit of bacterial ribosome to inhibit the translocation step of protein synthesis
macrolides (ketolides)
describe the spectrum of action of macrolides
gram positive and negative, and atypical bacteria (cross resistance within class)
what are considered the safest antimicrobials?
macrolides
the following clinical uses describe what antimicrobial?
2nd line agents for skin and soft tissue infections not due to MRSA; frequently used for URIs and community acquired pneumonia
macrolides
which macrolide is often used in patients allergic to penicillin?
erythromycin
erythromycin has largely been replaced by ___ and ___ for community acquired penumonia
clarithromycin and azithromycin
describe the clinical uses of azythromycin
- “z-pak”
- azithromycin is preferred therapy for urethritis caused by chlamydia
which of the macrolides has the longest 1/2 life and volume of distribution in its class?
azithromycin
