Macrolides Flashcards
Macrolides include
erythromycin, clarithromycin, azithromycin
Clarithromycin and azithromycin are
semi-synthetic derivatives of erythromycin
Macrolides contain ____ in their structure
lactone ring attached to several sugars
Erythromycin and clarithromycin are ____ membered rings
14
Azithromycin is a ___ membered ring
15
Minor structural modifications between the 3 drugs contribute to
improved acid stability
tissue penetration
broadened spectrum of activity
Macrolides MOA
reversibly bind to domain V of 23S ribosomal RNA of the 50s subunit of the ribosome
The result of macrocodes binding to 23S rRNA
blocks transpeptidation and indirectly interferes with translocation step
Macrolides are bactericidal/bacteriostatic
bacteriostatic
Macrolides spectrum coverage gram +
most active in vitro against gram + cocci and bacilli
Gram +: s. pneumoniae, streptococcus, staphylococci including MSSA, corynebacterium, listeria monocytogenes
Gram + activity: order of which drug works the best to the least
Clarithromycin> erythromycin> azithromycin
Macrolides spectrum coverage gram -
modest gram - activity
h. influenzae, Neisseria, pasteurella multocida, bordetella pertussis, c. jejuni, mortadella catarrhalis, h. pylori, bartonella, rickettsia
Gram - activity: order of which drug worst the best to least
Azithromycin> clarithromycin> erythromycin
Macrolides atypicals coverage
mycoplasma pneuomoniae, chlamydia (pneumoniae and trachomatis), mycobacterium, legionella, spirochetes (syphilis), protozoa
Macrolides cover most
respiratory pathogens
Macrolides do not cover
MRSA
enterococci
enterobacteriaceae
pseudomonas aerugingsa and other non-lactose fermenting gram -
Macrolide resistance mechanisms in which organisms
strep and staph
Alteration of the drug binding site on the ribosome is caused by ____; this is ___ level resistance
methylation/erm gene; high
Drug efflux is caused by ___ in staph and ____ in strep; this is ___ level resistance
msr, mef; low
What other 2 resistance mechanisms can staph and strip have against macrolides?
drug modification through enzymes and target mutation (altered binding to ribosome)
Erythromycin formulations
oral, IV, topical (ophthalmic)
Erythromycin base is ___ by stomach acid and requires ___
destroyed; enteric coating
Erythromycin ____ are better absorbed and more acid resistant
esters
Erythromycin ester examples
erythromycin stearate, erythromycin estolate, erythromycin ethylsuccinste
Which erythromycin formulation is best for oral use?
erythromycin estolate
Erythromycin base in incompletely absorbed from the
upper small intestine
Where do enteric coated tablets dissolve?
duodenum
Food should/should not be taken with erythromycin base, stearate, or ethylsuccinate
should NOT
Food should/should not be taken with erythromycin estolate
should
Erythromycin distribution to CSF
poor, inflamed meninges only 7-25%
Erythromycin is ___ protein bound
highly
Erythromycin is mostly eliminated in
bile/feces
Erythromycin does/does not require renal adjustment
does not
1/2 life of Erythromycin may be prolonged in patients with
anuria
Can Erythromycin be removed by hemodialysis?
no
Does Erythromycin cross placenta?
yes
Erythromycin cross into breast milk?
yes
Erythromycin indications
respiratory tract infections SSTI Chlamydia in infants diphtheria pertussis gastroparesis
Erythromycin is used to treat chlamydia in
infants
Erythromycin is the only FDA approved macrolide to treat
diphtheria
Erythromycin is used in gastoparesis as off label
pro kinetic agent
Erythromycin adverse effects
GI toxicity
cardiac toxicity (QT prolongation, tachycardia)
hepatotoxicity
Hepatotoxicity with Erythromycin is associated with
long use (10-20 days after start)
Hepatotoxicity symptoms with Erythromycin will resolve
when drug is discontinued
Hepatotoxicity is greatest with which macrolide?
Erythromycin
Clarithromycin formulations
oral tablets, ER tablets, oral powder for suspension
Clarithromycin is absorbed ___ from GI tract
readily
Clarithromycin has a large amount of ____ that decreases bioavailability by 50-55%
first pass metabolism
Clarithromycin should be given
with or without food
Clarithromycin ER should be given with food to
improve bioavailability
Clarithromycin parent drug and ____ achieve high intracellular concentrations in the body
active metabolite
Clarithromycin is metabolized by
liver
Clarithromycin metabolism is ____ and results in higher doses with ____
saturable; longer 1/2 lives
Clarithromycin has ____ kinetics
non linear
Clarithromycin has 40-70%
protein binding
Clarithromycin tissue penetration is
good
How much Clarithromycin is excreted in urine?
20-40%
Clarithromycin needs dosage adjustments in patients with
CrCl < 30 ml/min
Clarithromycin needs/does not need adjustment in hepatic impairment
does not
Clarithromycin adverse effects
GI distress but to lesser degree than erythromycin
less risk of cardio toxicity compared to erythromycin
less hepatotoxicity compared to erythromycin
Clarithromycin can interact with
concomitant anti arrhythmic drugs or drugs that prolong QT
Clarithromycin indications
respiratory tract infections
h. pylori in combo with omeprazole and amoxicillin
mycobacterial infections
Azithromycin formulations
oral (ZPAK and Tri-Pak)
oral powder
IV
ophthalmic
Azithromycin oral absorption
PO absorbed rapidly but incompletely; 30-40%
Azithromycin distributed ___ throughout body
widely; extensive tissue distribution
Azithromycin can achieve ___ concentrations within cells (including phagocytes)
high
Azithromycin major excretion
biliary
Only ___ % is excreted in the urine
12
Azithromycin has a ___1/2 life due to extensive tissue sequestration and binding
long
Azithromycin adverse effects
GI distress lesser degree than erythromycin
less cardio toxicity than erythromycin
less hepatotoxicity than erythromycin
Drug that Azithromycin can interact with
concomitant anti arrhythmic and QT prolonging
Azithromycin indications
respiratory tract infections
chlamydia
pertussis
mycobacteria infections
Azithromycin is favored in treating respiratory tract infections because
broader spectrum, ease of dosing, better tolerability
Which macrolide has the longest 1/2 life?
azithromycin
Which macrolide has the created bioavailability?
clarithromycin
ZPAK dosing
500mg po on day 1 then 250mg po on days 2-5
eryhthromycin and clarithromycin strongly inhibit
CYP3A4
Azithromycin is ___ to be involved in drug interactions
much less likely
Which macrolide has the greatest potential to cause side effects?
erythromycin
