Macrolide Antibiotics

Question 1

During peptide bond formation, the polypetide attached to the tRNA in the P site of the ribosome is transferred where?

Answer 1

transferred to the amino group of the aminoacyl-tRNA in the A site (transpeptidation) - ribosome then moves to the next codon

Question 2

What happens to the empty tRNA?

Answer 2

ejected and the peptidyl-tRNA is shifted from the A site to the P site (translocaiton) - new aminoacyl-tRNA then binds to the A site

Question 3

How do macrolides inhibit bacterial protein synthesis?

Answer 3

by binding reversibly to the P site of the bacterial ribosome

Question 4

What does reversibly binding to the P site of the bacterial ribosome do?

Answer 4

inhibits translocation of peptidyl-tRNA from the A site to the P site

Question 5

Macrolide binding mainly involves what?

Answer 5

the bacterial 23S RNA and not the protein

Question 6

Where do macrolides tend to accumulate?

Answer 6

within leukocytes

Question 7

What is significant about macrolide accumulation inside leukocytes?

Answer 7

They are therefore actually transported into the site of infection

Question 8

Four basic mechanisms of macrolide resistance:

Answer 8

1. lactone ester hydrolase induced
2. drug-induced production of an RNA methylase
3. mutation of adenine to guanine at the specific site A2058
4. An efflux pump ejects drugs from the cell by an active transport process

Question 9

What do efflux pumps do?

Answer 9

ejects drugs from the cell by an active transport process

Question 10

How can you reduce the incidence of resistant S. pneumoniae strains?

Answer 10

reduce the use of macrolide antibiotics

Question 11

What organisms exhibit intrinsic resistance by not allowing entry of macrolide antiobiotics?

Answer 11

Pseudomonas spp. and Enterobacter spp.

Question 12

Why is oral erythromycin administered as enteric coated tablets or as more stable salts or esters?

Answer 12

under acidic conditions, macrolide antibiotics undergo intramolecular acid-catalyzed ketal formation and the ketal reaction product is inactive

Question 13

Clarithromycin

Answer 13

6-OCH3 derivative

Question 14

Describe Azithromycin

Answer 14

acid stable with reliable absorption

N-methylated methyleneamino moiety replaces the C-9 ketone (ketal formation is no longer possible)

Question 15

main route of erythromycin metabolism

Answer 15

demethylation in the liver

Question 16

main route of erythromycin elimination

Answer 16

in the bile, and a small portion in the urine

Question 17

Erythromycin and clarithromycin can bind and inhibit?

Answer 17

CYP3A and related P450 isozymes

Question 18

Drug interactions with dirithromycin?

Answer 18

has reduced capacity to inhibit P450 isozymes

Question 19

Drug interactions with azithromycin?

Answer 19

no reported cases of significant drug interactions

Question 20

Potential drug interactions can be expected with macrolides (ex. Azithromycin) and which drugs that are also metabolized by P450 enzymes?

Answer 20

carbamazepine, cyclosporin, disopyramide, midazolam, quinidine, rifampicin, rifabutin, theophylline, triazolam, zidovudine

Question 21

What do the 14-membered macrolides strongly stimulate which induces a side effect?

Answer 21

strongly stimulates gastrointestinal motor activity and can cause vomiting, gastric cramps and abdominal pain

Question 22

Serious side effects that may occur but are rare with macrolides.

Answer 22

Stevens-Johnson syndrome and toxic epidermal necrolysis

Question 23

What can long term (10-20 days) use of macrolide antibiotics induce?

Answer 23

reversible cholestatic hepatitis which will manifest as a jaundice with cramping/nausea/fever - relieved upon termination of drug therapy

Question 24

Erythromycin has been shown to increase the probability of what in children whose mothers took the drug during the late stages of pregnancy or while nursing.

Answer 24

pyloric stenosis

Question 25

Describe cholestatic jaundice

Answer 25

bile becomes granular in the bile duct impeding bile flow, so bile salts back up into the circulation

Question 26

What should you do when cholestatic jaundice occurs with erythromycin estolate use?

Answer 26

the drug should be replaced by a nonmacrolide antibiotic

Question 27

When is erythromycin estolate contraindicated?

Answer 27

in patients with preexisting liver disease or dysfunction

Question 28

What is erythromycin estolate used to treat?

Answer 28

group A beta-hemolytic streptococcal infections, primary synphilis, amebic dysentery, and prophylactically prior to surgery to prevent endocarditis caused by alpha-hemolytic streptococci (viridans group)

Question 29

How is erythromycin ethyl succinate be used?

Answer 29

used as a flavored oral suspension for pediatric use to mask the bitter taste, or as coated tablets

Question 30

C-6 methyl ether of erythromycin

Answer 30

clarithromycin

Question 31

How is clarithromycin better than erythromycin?

Answer 31

it has better oral absorption and produces higher blood levels - also, less gastric upset

Question 32

Why is azithromycin an advantage in patients who comply poorly?

Answer 32

azithromycin has a longer half-life than erythromycin, allowing once-a-day dosage

Question 33

What can form coordination complexes with azithromycin and prevent absorption?

Answer 33

magnesium and aluminum present in some antacids

Question 34

Major route of elimination of azithromycin?

Answer 34

biliary excretion of azithromycin, predominately unchanged

Question 35

Azithromycin has greater activity against?

Answer 35

gram (-) bacteria

Question 36

Common side effects of azithromycin?

Answer 36

diarrhea, nausea, abdominal pain, and vomiting - allergic reactions extremely rare