Topic 15-Macrolides. Ketolides.

Question 1

What is the mechanism action for macrolides

Answer 1

Inhibition of protein synthesis by irreversibly binding to a site on the 50 S ribosome

Question 2

Spectrum for macrolides?

Answer 2

similar to penicillin spectrum
1.)Gram positive and gram negative cocci
neisseria, bordetella pertusis, campylobacter gastroenteritis, trepenoma pallidum, H. influenze (50% resistant), Staph, cornybacterium, mycobacterium avium and kansisii, listeria+H pylori+oral anaerobes (weak effect) and 2.)community acquired pneumonia
-streptococci
-pneumococci (40% resistant)
-legionella
-mycoplasma
3.)Intracellular pathogens
Mycoplasma pneumoniae, Leionella, Ureplasma urealyticum, chlamydia ureithritis, lymes disease
Chlamydia
-ocular
-pneumonia
-genital
4.)Antiprotazoal
Toxoplasmosis in pregnancy

Question 3

What does the Macrolide spectrum not cover

Answer 3

Enteric gram negative rods
enterococci, strep dificile, bacteriods fragilis
UTI

Question 4

Marcolides Pharmacokinetics
Bactericidal or bacteriostatic
Administration (special capsule?)
Metabolism
Distribution
Length of treatment

Answer 4

Bacteriostatic unless bacteria is highly susceptible, then bacteriocidal
Administration is oral and needs enteric coated tables since it is gastric acid sensitive
Metabolized in liver
Good distribution, 100x more concentrated intracellularly via active transport
3 day treatment since it takes 2 days to take effect

Question 5

Which Macrolide makes an active metabolite? Which bacteria does it treat?

Answer 5

Clarithromycin forms an active metabolite to treat H. influenzae and H. pylori

Question 6

Which Macrolide accumulates in the macrophages and granulocytes

Answer 6

Azithromycin

Question 7

Therapeutic indications of macrolides?

Answer 7

1. )atypical and upper respiratory infections
2. )Penicillin allergy
3. )Stomach ulcer, skin infection, periodontal infection
4. )toxoplasmosis in pregnancy (spiramycin)
5. )Toxic shock syndrome for strept with penicillin
6. )STDs, Diptheria, pertussis, listeriosis

Question 8

Resistance to Macrolides is called? Methods of resistance?

Answer 8

MLS resistance (3 abx that all bind to the same site on 50s ribosome)
Macrolides, LIncosamides (Clindamycin) and Streptogramin B (Quinupristine)
1.)hysteresis, enzyme degrades macrolides
2.)efflux pump and decreased permeability

Question 9

Adverse effects in Macrolides?

Answer 9

1. ) GI symptoms- motilin like metabolite, stimulates gut to increase motility (nausea and diarrhea)
2. ) Enzyme inhibitor, inhibition of P450 system
3. ) Hepatotoxic, prolongued QT intervals
4. ) Similar in structure to penicillin, might have allergy if they have penicillin allergy

Question 10

Natural Macrolide compounds?

Answer 10

Erythromycin
Josamycin
Spiramycin

Question 11

Semisynthetic Macrolide compounds?

Answer 11

Clarithromycin
Roxithromycin
Azithromycin

Question 12

What is Erythromycin used for?

Answer 12

Equal Gram positive and negative activity
Gram positive upper respiratory tract infection, skin infection, intracellular pathogens, penicillin allergy.
Strong GI adverse effects

Question 13

What is Roxithromycin used for?

Answer 13

Same as Erythromycin, less GI effects

Question 14

What is Clarithromycin used for?

Answer 14

More potent against Gram positive bacteria
Effective against gram positive cocci, gram negative bacteria
Metabolite treats H. influenzae, H. pylori, and Mycobacterium avium
Used in respiratory tract infection, gastric ulcer and gastritis

Question 15

How is Clarithromycin administered

Answer 15

IV or per os

Question 16

What are the adverse effects of Clarithromycin?

Answer 16

GI effects and acute cholestatic hepatitis

Question 17

What are the interactions of Macrolides

Answer 17

inhibits CYP450 causing anti-histamines to not get degraded leading to building up and arrhythmia

Question 18

Which Macrolide doesn’t inhibit the CYP450

Answer 18

Azithromycin

Question 19

What is Azithromycin effective against

Answer 19

Most potent against gram negative bacteria
Effective against gram-positive cocci (respiratory tract infection), gram-negative cocci (H. influenzae), borrelia burgdorferi (lymes)
Accumulates highly intracellular and less GI effects and no interactions

Question 20

What is Spiramycin effective against?

Answer 20

First choice drug, active against toxoplasma, especially during pregnancy
Second choice drug is tetracycline then fluoroquinolones

Question 21

What is the Ketolide drug name?

Answer 21

Telithromycin

Question 22

Where does Telithromycin originate

Answer 22

Part of the macrolide group but probably structurally different

Question 23

What is the pharmacokinetics of Telithromycin
Bactericidal or bacteriostatic
Absorption
Time or concentration dependent
Elimination

Answer 23

Bactericidal
Good GI absorption, given once daily
Concentration dependent effect
Metabolized in liver and removed in bile (70%) and kidney (30%)

Question 24

Spectrum of effect for Telithromycin

Answer 24

Similar spectrum to macrolides plus gram neg. cocci, rods (in repsiratory infection, only used in noscomial acquired pneumonia), and effective in macrolide resistant strains

Question 25

Adverse effects of Telithromycin

Answer 25

Nausea, vomiting, diarrhea
Hepatitis
Inhibits CYP3A4