Pharm - Macrolides + Lincosamides Flashcards
macrolides contain a macrocyclic lactone ring. this ring usually contains how many atoms?
what is attached to the ring?
14-16
deoxy sugars
name 4 macrolides
erythromycin
clarithromycin
azithromycin
telithromycin
differentiate between the structure of erythromycin vs clarithromycin
clarithromycin has a CH3 at R2 rather than an H
that’s the only difference
recap: fedaxomycin chemical class and brief MOA
also a macrolide!!
c diff RNA synthesis inhibitor
are macrolides static or cidal
static
is spectrum of macrolides (like erythromycin) narrow or broad
BROAD - many gram pos and neg
explain MOA of macrolides***
reversibly binds 50s subunit - specifically 23s rRNA
seems to inhibit the translocation step — peptide chain at the A site can’t move to P (donor) site
also, they may binds and cause a conformational change that stops protein synthesis by indirectly interfering with transpeptidation and translocation
true or false
macrolide antibiotics bind irreversibly to the 50s 23S rRNA subunit
false
reversibly (everything else right)
3 mechanisms of macrolide resistance
- reduce permeability or increased efflux
- production of esterases that hydrolyze macrolides
- (main) - modify the ribosomal binding site of rna by chromosomal mutation OR by macrolide-inducable methylase
what is
“MLS Type B resistance”
resistance mechanism in which the ribosomal binding site is altered by chromosomal mutation
MLS = macrolides, lincosamides, streptogramins
important consideration with MLS antibiotics
once there’s MLS resistance to one of the AB’s, cant use any others in MLS (CROSS RESISTANCE!!! COMMON AND COMPLETE)
also, don’t use the MLS antibiotics together bc they act at similar place
_____ and _______ are the most important resistance mechanisms in gram positive organisms against macrolides
efflux and methylase production
As mentioned, esterases can be produced to hydrolyze macrolides as a resistance mechanism
which bacteria in particular does this
enterobacteriaceae
how do macrolides come and why
as ENTERIC COATED tablets - bc they’re susceptible to acid - want to release in small intestine.
how are macrolides largely excreted
in the BILE (feces)
only 5% in urine!
do macrolides cross placenta?
what about brain and CSF?
cross placenta but NOT brain and CSF
______ delays absorption of macrolides
food
MAJOR clinical uses of macrolides
for resp tract infections (CAP)
and for pen allergic ppl with staph or strep infections
acne (good against anaerobes!)
2 main toxicities of macrolides
cardiac (arrythmia, QT prolongation)
hepatotoxicity (hepatitis)
also NVD - broad spectrum
macrolides are administered as salts
which of these salts is the most hepatotoxic
estolate salt
DDI concern with macrolides
they are metabolized by the CYP system in the liver. they are reversible inhibitors of CYPS (3A4, A12, 2C9)
this can increase the concentrations of some drugs - can be dangerous if they have narrow therapeutic index
advantage of clarithromycin over erythromycin
clar has improved acid stability and oral absorption
advantage of azithromycin over erythro and clar
NO DDI
because of its structure - doesnt really inhibit the CYPS
which macrolide is less susceptible to resistance, BUT can also exacerbate myasthenia gravis
telithromycin
indication telithromycin
CAP
azithromycin is better than erythromycin for _____ and less active than eryth and clar for _______
azi better than ery for H. influenzae
less active than eryth and clar for staph and strep
clindamycin is a _____-substituted derivative of ______
chlorine substituted derivative of lincomycin
true or false
clindamycin is not a macrolide
TRUE - it is a lincosamide
name 2 things that are resistant to clindamycin and what can be used instead
enterococci and gram negative aerobic
use aminoglycosides! very good against gram negative aerobic
clindamycin has the same mechanism as…..
macrolides!!
explain the spectrum of clindamycin
broad spectrum - both gram pos and neg
IS active against anaerobes (remember - can be used for acne)
enterobacter and gram negative aerobic are RESISTANT
true or false
clindamycin has the same binding site and mechanism as macrolides
TRUE
3 resistance mechanisms for clindamycin
- mutation of ribosomal receptor site
- modify receptor by constitutively expressed methylase (MLS-B)
- enzymatic inactivation of clindamycin
can clindamycin be used against community acquired MRSA
YES
name some clinical uses of clindamycin
SSTI caused by step and stap (covers gram +!)
community strains of MRSA
prevent endocarditis in pen allergies
clindamycin can be used in combo with a ____ or ____ to penetrate the wounds of the abdomen and gut, and for femal genital tract infections
cephalosporin or aminoglycoside
will cover gram (-) aerobe
clindamycin + ___________ is used for pneumocystis jiroveci pneumonia in AIDS patients
primaquine
clindamycin can be used in _______ as a secondary agent
malaria
clindamycin + ___________ can treat AIDS-related toxoplasmosis of the brain
pyrimethamine
common AE clindamycin
NVD
skin rash
serious and rare AE of clindamycin
neuromuscular block (in combo with neuromuscular drugs)
pseudomembranous colitis (inflammation of colon lining) that causes abdominal pain, mucus, blood in stool, impaired liver fx, etc
true or false
clindamycin is NOT effective against gram negative anaerobes
FALSE - it is
not active against gram negative aerobes
