Macrolides

Question 1

Macrolides include

Answer 1

erythromycin, clarithromycin, azithromycin

Question 2

Clarithromycin and azithromycin are

Answer 2

semi-synthetic derivatives of erythromycin

Question 3

Macrolides contain ____ in their structure

Answer 3

lactone ring attached to several sugars

Question 4

Erythromycin and clarithromycin are ____ membered rings

Answer 4

14

Question 5

Azithromycin is a ___ membered ring

Answer 5

15

Question 6

Minor structural modifications between the 3 drugs contribute to

Answer 6

improved acid stability
tissue penetration
broadened spectrum of activity

Question 7

Macrolides MOA

Answer 7

reversibly bind to domain V of 23S ribosomal RNA of the 50s subunit of the ribosome

Question 8

The result of macrocodes binding to 23S rRNA

Answer 8

blocks transpeptidation and indirectly interferes with translocation step

Question 9

Macrolides are bactericidal/bacteriostatic

Answer 9

bacteriostatic

Question 10

Macrolides spectrum coverage gram +

Answer 10

most active in vitro against gram + cocci and bacilli

Gram +: s. pneumoniae, streptococcus, staphylococci including MSSA, corynebacterium, listeria monocytogenes

Question 11

Gram + activity: order of which drug works the best to the least

Answer 11

Clarithromycin> erythromycin> azithromycin

Question 12

Macrolides spectrum coverage gram -

Answer 12

modest gram - activity
h. influenzae, Neisseria, pasteurella multocida, bordetella pertussis, c. jejuni, mortadella catarrhalis, h. pylori, bartonella, rickettsia

Question 13

Gram - activity: order of which drug worst the best to least

Answer 13

Azithromycin> clarithromycin> erythromycin

Question 14

Macrolides atypicals coverage

Answer 14

mycoplasma pneuomoniae, chlamydia (pneumoniae and trachomatis), mycobacterium, legionella, spirochetes (syphilis), protozoa

Question 15

Macrolides cover most

Answer 15

respiratory pathogens

Question 16

Macrolides do not cover

Answer 16

MRSA
enterococci
enterobacteriaceae
pseudomonas aerugingsa and other non-lactose fermenting gram -

Question 17

Macrolide resistance mechanisms in which organisms

Answer 17

strep and staph

Question 18

Alteration of the drug binding site on the ribosome is caused by ____; this is ___ level resistance

Answer 18

methylation/erm gene; high

Question 19

Drug efflux is caused by ___ in staph and ____ in strep; this is ___ level resistance

Answer 19

msr, mef; low

Question 20

What other 2 resistance mechanisms can staph and strip have against macrolides?

Answer 20

drug modification through enzymes and target mutation (altered binding to ribosome)

Question 21

Erythromycin formulations

Answer 21

oral, IV, topical (ophthalmic)

Question 22

Erythromycin base is ___ by stomach acid and requires ___

Answer 22

destroyed; enteric coating

Question 23

Erythromycin ____ are better absorbed and more acid resistant

Answer 23

esters

Question 24

Erythromycin ester examples

Answer 24

erythromycin stearate, erythromycin estolate, erythromycin ethylsuccinste

Question 25

Which erythromycin formulation is best for oral use?

Answer 25

erythromycin estolate

Question 26

Erythromycin base in incompletely absorbed from the

Answer 26

upper small intestine

Question 27

Where do enteric coated tablets dissolve?

Answer 27

duodenum

Question 28

Food should/should not be taken with erythromycin base, stearate, or ethylsuccinate

Answer 28

should NOT

Question 29

Food should/should not be taken with erythromycin estolate

Answer 29

should

Question 30

Erythromycin distribution to CSF

Answer 30

poor, inflamed meninges only 7-25%

Question 31

Erythromycin is ___ protein bound

Answer 31

highly

Question 32

Erythromycin is mostly eliminated in

Answer 32

bile/feces

Question 33

Erythromycin does/does not require renal adjustment

Answer 33

does not

Question 34

1/2 life of Erythromycin may be prolonged in patients with

Answer 34

anuria

Question 35

Can Erythromycin be removed by hemodialysis?

Answer 35

no

Question 36

Does Erythromycin cross placenta?

Answer 36

yes

Question 37

Erythromycin cross into breast milk?

Answer 37

yes

Question 38

Erythromycin indications

Answer 38

``` respiratory tract infections SSTI Chlamydia in infants diphtheria pertussis gastroparesis ```

Question 39

Erythromycin is used to treat chlamydia in

Answer 39

infants

Question 40

Erythromycin is the only FDA approved macrolide to treat

Answer 40

diphtheria

Question 41

Erythromycin is used in gastoparesis as off label

Answer 41

pro kinetic agent

Question 42

Erythromycin adverse effects

Answer 42

GI toxicity cardiac toxicity (QT prolongation, tachycardia) hepatotoxicity

Question 43

Hepatotoxicity with Erythromycin is associated with

Answer 43

long use (10-20 days after start)

Question 44

Hepatotoxicity symptoms with Erythromycin will resolve

Answer 44

when drug is discontinued

Question 45

Hepatotoxicity is greatest with which macrolide?

Answer 45

Erythromycin

Question 46

Clarithromycin formulations

Answer 46

oral tablets, ER tablets, oral powder for suspension

Question 47

Clarithromycin is absorbed ___ from GI tract

Answer 47

readily

Question 48

Clarithromycin has a large amount of ____ that decreases bioavailability by 50-55%

Answer 48

first pass metabolism

Question 49

Clarithromycin should be given

Answer 49

with or without food

Question 50

Clarithromycin ER should be given with food to

Answer 50

improve bioavailability

Question 51

Clarithromycin parent drug and ____ achieve high intracellular concentrations in the body

Answer 51

active metabolite

Question 52

Clarithromycin is metabolized by

Answer 52

liver

Question 53

Clarithromycin metabolism is ____ and results in higher doses with ____

Answer 53

saturable; longer 1/2 lives

Question 54

Clarithromycin has ____ kinetics

Answer 54

non linear

Question 55

Clarithromycin has 40-70%

Answer 55

protein binding

Question 56

Clarithromycin tissue penetration is

Answer 56

good

Question 57

How much Clarithromycin is excreted in urine?

Answer 57

20-40%

Question 58

Clarithromycin needs dosage adjustments in patients with

Answer 58

CrCl < 30 ml/min

Question 59

Clarithromycin needs/does not need adjustment in hepatic impairment

Answer 59

does not

Question 60

Clarithromycin adverse effects

Answer 60

GI distress but to lesser degree than erythromycin less risk of cardio toxicity compared to erythromycin less hepatotoxicity compared to erythromycin

Question 61

Clarithromycin can interact with

Answer 61

concomitant anti arrhythmic drugs or drugs that prolong QT

Question 62

Clarithromycin indications

Answer 62

respiratory tract infections h. pylori in combo with omeprazole and amoxicillin mycobacterial infections

Question 63

Azithromycin formulations

Answer 63

oral (ZPAK and Tri-Pak) oral powder IV ophthalmic

Question 64

Azithromycin oral absorption

Answer 64

PO absorbed rapidly but incompletely; 30-40%

Question 65

Azithromycin distributed ___ throughout body

Answer 65

widely; extensive tissue distribution

Question 66

Azithromycin can achieve ___ concentrations within cells (including phagocytes)

Answer 66

high

Question 67

Azithromycin major excretion

Answer 67

biliary

Question 68

Only ___ % is excreted in the urine

Answer 68

12

Question 69

Azithromycin has a ___1/2 life due to extensive tissue sequestration and binding

Answer 69

long

Question 70

Azithromycin adverse effects

Answer 70

GI distress lesser degree than erythromycin less cardio toxicity than erythromycin less hepatotoxicity than erythromycin

Question 71

Drug that Azithromycin can interact with

Answer 71

concomitant anti arrhythmic and QT prolonging

Question 72

Azithromycin indications

Answer 72

respiratory tract infections chlamydia pertussis mycobacteria infections

Question 73

Azithromycin is favored in treating respiratory tract infections because

Answer 73

broader spectrum, ease of dosing, better tolerability

Question 74

Which macrolide has the longest 1/2 life?

Answer 74

azithromycin

Question 75

Which macrolide has the created bioavailability?

Answer 75

clarithromycin

Question 76

ZPAK dosing

Answer 76

500mg po on day 1 then 250mg po on days 2-5

Question 77

eryhthromycin and clarithromycin strongly inhibit

Answer 77

CYP3A4

Question 78

Azithromycin is ___ to be involved in drug interactions

Answer 78

much less likely

Question 79

Which macrolide has the greatest potential to cause side effects?

Answer 79

erythromycin