Macrolides

Question 0

What are the three Macrolides and their modes of administration?

Answer 0

1. Erythromycin: IV/PO
2. Clarithromycin: PO
3. Azithromycin: IV/PO

Question 1

Describe the differences between prokaryotic and eukaryotic ribosomes:

Answer 1

Prokaryotic ribosomes are 70s (50s and 30s subunits) while eukaryotes are 80s (60s and 40s subunits)

Question 2

In general, how do macrolides function?

Answer 2

Macrolides tend to target the 50s subunit of prokaryotic ribosomes and inhibit protein synthesis.

Question 3

Describe the characteristics of Macrolides:

Answer 3

1. macrolides inhibit protein synthesis by binding 50s subunit of ribosomes
2. they are mainly effective against G+ bacteria
3. tend to be bacteriostatic
4. PO
5. Biliary excretion
6. Fecal Elimination

Question 4

What is an alternative treatment for H. Pylori?

Answer 4

Clarithromycin + omeprazol

Question 5

What mechanisms do bacteria use to develop resistance against macrolides?

Answer 5

1. Efflux pumps

2. methylation of drug binding sites (50s ribosome)

Question 6

Macrolide toxicity:

Answer 6

1. headache
2. GI disturbances
3. Diarrhea
4. nausea/vomiting
5. anal burning
6. mild allergic reactions
7. IV erythromycin – ototoxicity
8. Liver changes - hyperbilirubinemia & abnormal liver function tests

Question 7

List the macrolides in order from most GI disturbances to least GI disturbances:

Answer 7

Erythromycin
Azithromycin
Clarithromycin

Question 8

What type of drug interactions are possible when you take a macrolide (erythromycin and clarithromycin more specifically):

Answer 8

They are potent inhibitors of CYP3A4. They inhibit liver metabolism of certain drugs which can lead to an accumulation of toxic levels.

These drugs include: carbamazepine, clozapine, cyclosporine, methadone, quinidine, and protease inhibitors

Question 9

Administration of Erythromycin with what other antibiotics can cause QT elongation and arrhythmias?

Answer 9

cisapride or pimozide

sparfloxacin or grepafloxacin

Question 10

What drug is in the Ketolide family and how do ketolides differ from macrolides in their mechanism of action?

Answer 10

Telithromycin. They bind to the 50s ribosomal subunit at 2 sites instead of just one. they are still bacteriostatic and prevent protein synthesis. They have greater antibacterial activity than macrolides.

Question 11

How does telithromycin work and what is its spectrum of activity:

Answer 11

It binds to the 23s site on the 50s rRNA subunit. It is used for respiratory pathogens including erythromycin and penicillin resistant pneumococci. it also has activity against atypical bacteria and intracellular bacteria.

Question 12

How is telithromycin administered and describe its elimination and side effects/contraindications?

Answer 12

PO once daily. metabolized by CYP3A4 with a half life of 9-10 hours. it causes diarrhea, nausea/vomiting and dizziness. it is contraindicated in patients with myasthenia gravis

Question 13

List the characteristics of Clindamycin:

Answer 13

1. PO/parenteral/topical
2. binds ribosomal 50s subunit; inhibits protein synthesis
3. G+ cocci, as well as G-/+ anaerobic bacteria
4. bacteriostatic or bactericidal
5. liver metabolism

Question 14

Discuss the uses of Clindamycin:

Answer 14

1. G+/- streptococci (not enterococci) and staphylococci are extremely susceptible (MRSA)
2. Used with vancomycin to treat TSS
3. Used to treat osteomyelitis bc it obtains high concentrations in the bones
4. Toxoplasmosis encephalitis (not meningitis b/c poor CNS penetration)

Question 15

Clindamycin Toxicity:

Answer 15

1. Rashes
2. GI disturbances
3. Abdominal Pain
4. Pseudomembranous colitis
5. crosses the placenta readily and distributed into breast milk: avoid use while pregnant

Question 16

what group of antibiotics does dalfopristin and quinpristin belong to?

Answer 16

streptogramins

Question 17

Describe the mechanism of action of quinupristin and dalfopristin

Answer 17

Dalfopristin: binds 50s ribosomal subunit and inhibits early phase of protein synthesis

Quinupristin: binds the 50s ribosomal subunit and inhibits late phase of proteins synthesis

they are delivered together via IV. this combination is bactericidal

Question 18

What do you treat with Dalfopristin and Quinupristin?

Answer 18

1. vancomycin resistant enterococcus
2. complicated skin infections (MSSA and MRSA)
3. penicillin resistant S. pneumo and MDR streptococci

Question 19

What adverse reactions are associate with quinupristin and dalfopristin?

Answer 19

1. hepatotoxicity
2. N/V
3. pruritis
4. inhibition of CYP3A4

Question 20

Under what circumstances are dalfopristin and quinupristin contraindicated?

Answer 20

1. breast feeding
2. children
3. hepatic disease
4. pregnancy
5. streptogramin hypersensitivity

Question 21

What drug is in the oxazolidinone family?

Answer 21

Linezolid

Question 22

what kind of bacteria is linezolid active against?

Answer 22

Aerobic Gram+

Question 23

Linezolid mechanism of action:

Answer 23

Protein synthesis inhibition. binds to 23s rRNA of 50s ribosomal subunit and prevents the formation of a functional 70s ribosome. Linezolid is bacteriostatic except for streptococci (bactericidal). It is a non selective inhibitor of MAO; therefore it prevents degradation of certain Neurotransmitters.

Question 24

Linezolid spectrum of activity

Answer 24

1. bacterial pneumonia
2. skin and skin structure infections
3. VRE
4. MRSA

Question 25

How is Linezolid administered and metabolized?

Answer 25

PO: 100% bioavailability

oxidative metabolism but does not involve the CYP450 system

Question 26

What adverse side effect is unique to Linezolid?

Answer 26

MAO inhibition

Question 27

What are the contraindications for Linezolid:

Answer 27

hypersensitivity and pheochromocytoma