C15+16

Question 1

Macrolides

3

Answer 1

• Clarithromycin
• Azithromycin
• Roxithromycin

Question 2

Ketolides

Answer 2

Telithromycin

Question 3

Macrolides MOA

Answer 3

• bacterioSTATIC inhibitors of protein synth. (50s)

- block transpeptidation

Question 4

macrolide structure?

Answer 4

• cyclic lactone ring with sugars attatched

Question 5

Clarithromycin Pharmacokinetics

Answer 5

• administration : oral !
• Bioavailability: good oral bioavailability
• distribution: most body tissues
• metabolism: hepatic
• elimination: urinary excretion

Question 6

Azithromycin pharmacokinetics

Answer 6

• absorption: impeded by food (not good oral availability)
• administration: I.V
• distribution: levels in tissues & phagocytes > plasma
• clearance: Hepatic

Question 7

Antimicrobial activity of Azithromycin and Clarithromycin

Answer 7

• CAP
• Corynebacteria
• Chlamydial infection
• Pertussis
  (CCCP)
• G+ cocci,
• some G- organisms

Question 8

G+ resistance mechanisms?

Answer 8

• efflux pump

- production of a methylase –> adds a methyl to the ribosomal binding site

Question 9

what is special indications of Azithromycin?

Answer 9

given IV

• effective in gonorrhea (alternative to ceftriaxone)
• effective in syphilis (alternative to penicillin G)

Question 10

Macrolides clinical uses?

Answer 10

• CAP (Chlamydophila pneumoniae, Legionella pneumophila, M. pneumoniae)
• cornyebacteria
• chlamydia
• pertussis
• G+ cocci (except PRSP)

Question 11

special clinical uses of Azithromycin?

[ H&M ;) ]

Answer 11

• H influenzae
• Neisseria
• Moraxella catarrhalis

also:
UGIs by: C.Trachomatis
(long 1/2 life –> single dose is given)

also:
CAP (4-d course)

Question 12

special clinical uses of Clarithromycin

Answer 12

• Prophylaxis treatment of Mycobacterium avium complex

- component of drug regimens for ulcers (by H pylori)

Question 13

Macrolides Toxicity in general?

Answer 13

• G.I. irritation (motolin rec. Stim)
• Hepatic dysfunction
• QT prolongation
• CYP450 inhibition (NOT azithromycin)
• skin rashes
• eosinophilia

Question 14

Clarithromycin toxicity?

Answer 14

• inhibits several cyt.P450 –> increase the plasma levels of other drugs
  (ex. anticoagulants, carbamazepine, digoxin, theophylline)

Question 15

Azithromycin Toxicity?

Answer 15

• drug interactions are uncommon (does not inhibit hepatic cyt.P450)

Question 16

about Telithromycin?

Answer 16

ketolide structurally related to macrolides

Question 17

Telithromycin MOA and spectrum

Answer 17

similar to Macrolides but narrower spectrum\

bind 50s subunit > inhibit protein syn
bacterioSTATIC

Question 18

why we use Telithromycin?

Answer 18

• some macrolide-resistant strains are susceptible to Telithro
• because it binds more tightly to ribosomes and is a TOO LARGE substrate for efflux pumps

Question 19

Telithromycin clinical uses?

Answer 19

• used in CAP (including MDRs)

Question 20

Telithromycin pharmacokinetix

Answer 20

oral!

eliminated in the bile and the urine

Question 21

Telithromycin Toxicity?

Answer 21

• hepatic dysfunction
• QTc interval prolongation
• inhibitor of the CYP3A4

Question 22

Clindamycin MOA

Answer 22

• binds 50S ribosome> inhibits bacterial protein synth.
• block transpeptidation

bacteriostatic

Question 23

Resistance to Clindamycin ?

Answer 23

• binding site methylation on 50S
• enzymatic inactivation
• Clinda has poor penetration through the outer membrane of G- Aerobes!

Question 24

Clindamycin Pharmacokinetix

Answer 24

oral, IV

• distribution: Good tissue penetration after oral abs
• clearance: hepatic
• Elimination: biliary & renal excretion (both intact drug + metabolites)

Question 25

Clindamycin uses?

Answer 25

* skin, soft tissue infections * ANaerobic infection (ex. Bacteroides -severe-) - backup against G+ cocci (ex. MRSA) - prophylaxis of endocarditis in valvular disease (allergix to penicillin) - against P.jirovecii

Question 26

Clindamycin Toxicity?

Answer 26

- G.I. upset - C.difficile colitis - skin rashes - NEUTROpenia - hepatic dysfunction

Question 27

Streptogramins?

Answer 27

Quinupristin-dalfopristin bactericidal!!

Question 28

Quinupristin-dalfopristin MOA?

Answer 28

- Bactericidal - 50S ribosomal subunit --> constricting the exit channel on the ribosome --> nascent polypeptides are extruded. - tRNA synthetase activity is inhibited --> decrease in free tRNA within the cell

Question 29

Quinupristin-dalfopristin activity?

Answer 29

* staphylococci | * VRE. faecium

Question 30

Quinupristin-dalfopristin Spectrum?

Answer 30

- PRSP - MRSA - VRSA - VRE.Faecium

Question 31

Quinupristin-dalfopristin administration?

Answer 31

I.V.

Question 32

Quinupristin-dalfopristin Toxicity?

Answer 32

- pain - infusion related arthralgia-myalgia syndrome inhibitors of CYP3A4 --> increase plasma levels of drugs (cyclosporine, diazepam, NNRTI, warfarin)

Question 33

Oxazolidinones?

Answer 33

Linezolid

Question 34

Linezolid MOA?

Answer 34

- bacterioSTATIC | - 50S --> Block tRNA-ribosome-mRNA ternary complex formation --> inhibit initiation

Question 35

Linezolid Spectrum?

Answer 35

- against drug-resistant G+ cocci, including strains resistant to penicillins 1. MRSA (skin &soft tissue infections) 2. PRSP 3. vancomycin (eg, VRE) - against L. monocytogenes and corynebacteria indications kinda similar to streptogramins (quinapristin/dalfopristin )

Question 36

can linezolid be resisted?

Answer 36

RARE

Question 37

Linezolid formulation?

Answer 37

both Oral and I.V

Question 38

Linezolid Pharmacokinetix?

Answer 38

-oral, I.V - metabolism: hepatic - elimination half-life: 4–6 h

Question 39

Linezolid Toxicity?

Answer 39

* dose-related ANEMIA * optic Neuropathy * in immunocompromised: Thrombocytopenia * Neutropenia