Macrolide Antibiotics Flashcards Preview

Pharmacology Test #2 > Macrolide Antibiotics > Flashcards

Flashcards in Macrolide Antibiotics Deck (36)
Loading flashcards...

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

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


What happens to the empty tRNA?

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


How do macrolides inhibit bacterial protein synthesis?

by binding reversibly to the P site of the bacterial ribosome


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

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


Macrolide binding mainly involves what?

the bacterial 23S RNA and not the protein


Where do macrolides tend to accumulate?

within leukocytes


What is significant about macrolide accumulation inside leukocytes?

They are therefore actually transported into the site of infection


Four basic mechanisms of macrolide resistance:

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


What do efflux pumps do?

ejects drugs from the cell by an active transport process


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

reduce the use of macrolide antibiotics


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

Pseudomonas spp. and Enterobacter spp.


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

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



6-OCH3 derivative


Describe Azithromycin

acid stable with reliable absorption
N-methylated methyleneamino moiety replaces the C-9 ketone (ketal formation is no longer possible)


main route of erythromycin metabolism

demethylation in the liver


main route of erythromycin elimination

in the bile, and a small portion in the urine


Erythromycin and clarithromycin can bind and inhibit?

CYP3A and related P450 isozymes


Drug interactions with dirithromycin?

has reduced capacity to inhibit P450 isozymes


Drug interactions with azithromycin?

no reported cases of significant drug interactions


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

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


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

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


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

Stevens-Johnson syndrome and toxic epidermal necrolysis


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

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


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.

pyloric stenosis


Describe cholestatic jaundice

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


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

the drug should be replaced by a nonmacrolide antibiotic


When is erythromycin estolate contraindicated?

in patients with preexisting liver disease or dysfunction


What is erythromycin estolate used to treat?

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)


How is erythromycin ethyl succinate be used?

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


C-6 methyl ether of erythromycin