Macrolides (Anti-Biotics)

Question 1

Name the 3 Macrolides and 1 Ketolide

Answer 1

Macrolides are Azithromycin, Erythromycin and Clarithromycin, the Ketolide is Telithromycin. ECAT mnemonic, Erythro clarithro azithro telithro.

Question 2

How are they administered and which also has IV administration?

Answer 2

All oral, however erythro and Azithro can come via IV.

Question 3

Acidity and macrolides?

Answer 3

Erythro is acid labile while the others are acid stable.

Question 4

Vd including CSF and crossing through the placenta?

Answer 4

Widely distributed, high levels found in liver, pulmonary tissues, middle ear and phagocytic cells. Doesn’t cross BBB into the CSF, crosses the placenta.

Question 5

Why is erythromycin of inferior chemistry?

Answer 5

Because the other 3 have better oral absorption, improved half lives, and better tissue and intracellular penetration than erythro

Question 6

CYP interactions of everything except azithro?

Answer 6

Clarithro, Erythro and Telithro are all 3A4 substrates and STRONG inhibitors of 3A4 and PGP. Azithro is excreted unchanged in bile, no cyp involvement.

Question 7

Which has the shortest half life and which have the longest?

Answer 7

Erythro has the shortest (1.5 hrs, which is why clarithro and azithro were made), azithro has a 40-68 hr halflife, telithro has a 10 hr half life but hangs out in the macrophages for 24+ hrs.

Question 8

What is the MOA of macrolides?

Answer 8

Site of action is the 50S subunit, where they block the transpeptidation step of protein synthesis by preventing the tRNA with the AA’s from moving from the A site to the P site. Macrolides can also have other MOAs that I guess isn’t understood yet.

Question 9

General activity of macrolides?

Answer 9

Good activity vs gram +, good activity against M. catarrhalis and B. pertussis both gram neg and both cause pulmonary infections. Decent activity against H. influenza (azithro most), N. meningitidis it has meh activity. bad activity against enteric gram neg bacteria.

Question 10

Activity against enteric gram neg bacteria?

Answer 10

Negligable to none.

Question 11

Activity against H. influenza?

Answer 11

Azithro has the most but its moderate activity.

Question 12

Activity against atypical organisms?

Answer 12

Good activity in general.

Question 13

What do atypical organisms tend to cause?

Answer 13

Respiratory infections.

Question 14

Clarithro and Azithro specifically has good activity against what?

Answer 14

Against gram +, M. catarrhalis, Borellia, H. pylori, atypicals, M. avium intracellulaire (MAC) and some protozoa. Clarithro can be used for M. Leprae as well.

Question 15

When would we want to use telithromycin?

Answer 15

Macrolide resistant S. Pneumoniae, and other respiratory pathogens. Thus, limited application.

Question 16

What organisms are intrinsically resistant to macrolides?

Answer 16

Enterococci, most enterobactericiae, Pseudomonas, C. diff, B. Fragilis, the reason being that macrolides poorly penetrate the outer membrane of the gram neg bacilli.

Question 17

What is an acquired mode of resistance between active efflux of the drug?

Answer 17

Methylase binding of the ribosomes that modify the binding site of macrolides and prevent them from binding. S. pyogenis, S. pneumoniae, S. aureas are known to do this.

Question 18

Describe the cross resistance with macrolides?

Answer 18

MLS B, refering to macrolides, Lincosamides and Streptogramin B are all cross resistant. Due to the erm gene.

Question 19

Why are enterobactericiae resistant to macrolides in general?

Answer 19

They have esterases that degrade the drug.

Question 20

Activity against penicillin resistant strep pneumoniae and MRSA and macrolides?

Answer 20

These organisms are generally resistant.

Question 21

C. trachomata infections and canchroids?

Answer 21

Azithro has good activity against these.

Question 22

What can telithro be used for?

Answer 22

S. pneumoniae (community acquired) and the ones that are susceptable, H. influenzae, M. catarrhasis, M. and C. pneumoniae.

Question 23

What is one of the main reasons why erythromycin has GI toxicities (other macrolides have GI tox too)

Answer 23

Erithro stimulates the motilin receptors which exacerbates the diarrhea, also have cramps nausea and vomitting.

Question 24

Which macrolide is associated with hepatotox?

Answer 24

Erythro estolate especially but other macrolides too.

Question 25

Class CV effects of macrolides?

Answer 25

QT prolongation leading to arrythmias such as torsades, which leads to v fib.

Question 26

List the 5 main class AE’s of macrolides

Answer 26

CV problems such as QT prolongation leading to torsades and v fib, GI tox including cramps nausea vomitting and diarrhea, hepatotox esp with erythro estolate, HS reactions and injection site reactions.

Question 27

What is the black box warning of telithro?

Answer 27

Myasthenia gravis exacerbation that can lead to respiratory failure.

Question 28

Besides the black box warning what are the other AE’s associated with telithro?

Answer 28

Severe liver injury, loss of consciousness, visual disturbances, QT prolongation.

Question 29

Preggo and macrolides?

Answer 29

Cat B for erithro and azithro, C for clarithro and telithro.

Question 30

Which macrolides are approved for children to use?

Answer 30

Everything except telithro.

Question 31

DDI’s with macrolides?

Answer 31

Drugs that act near the 50S subunit, warfarin, and other drugs that extend the QT intervals. Anything that needs 3A4 and PGP, since these drugs are a potent inhibitor of those.

Question 32

Name some specific drugs that are effected because of the 3A4 and pgp inhibition.

Answer 32

Corticosteroids, cyclosporin, lovastatin, simvastatin, atorvastatin, theophaline, triazolam (benzadiazapine), carbamazepine, valproate (both anti-convulsants), ergot alkaloids, and digoxin.