Macrolide Antibiotics Flashcards Preview

KG - Pharmacology > Macrolide Antibiotics > Flashcards

Flashcards in Macrolide Antibiotics Deck (56):
1

What part of bacteria do macrolides target?

protein synthesis - 50s
G+ most susceptible

2

prototype macrolide?

Erythromycin - oral, IV
targets 50s

3

top 3 macrolides?

Erythromycin - oral, IV
Clarithromycin - oral
Azithromycin - oral, IV

4

which drug is most similar to erythromycin?

clarithromycin

5

do macrolides bind reversibly or irreversibly to 50s ribosomal subunits?

reversibly

6

are macrolides bacteriostatic are bactericidal?

- bacteriostatic
- concentration/organism dependent - cidal activity

7

macrolide absorption/excretion/elimination?

oral absorption
biliary excretion
fecal elimination

8

macrolide antibacterial spectrum?

- similar to penicillin G
- majority of G- organisms are resistant to erythromycin (can't penetrate the membrane)
- some S. aureus becoming resistant

9

what is an alternative therapy for H. pylori?

- clarithromycin + omeprazole (+ ampicillin)

10

Resistance of macrolides? (erythromycin, clarithromycin, azithromycin)

- efflux pumps
- methylation of drug binding site (ribosome)

11

toxicity of macrolides? (erythromycin, clarithromycin, azithromycin)

- headache, GI, nausea, vomiting, diarrhea, anal burning
- mild allergic rxns, urticaria, rashes may occur
- IV erythro - ototoxicity
- hepatic changes (jaundice, cholestatic hepatitis, hyperbilirubinemia, abnormal liver function tests)

12

which macrolide has worst GI side effects? (erythromycin, clarithromycin, azithromycin)

erythromycin

13

which macrolide has least GI side effects? (erythromycin, clarithromycin, azithromycin)

clarithromycin

14

with what drugs do macrolides have drug interactions? what are they?

w/ drugs that require CYP3A4
- can inhibit hepatic metabolism of other drugs that require CYP3A4, increasing serum concentrations and potentially causing toxicity

15

which drug is a potent inhibitor of CYP3A4?
(and similar? and least?)

- most potent = erythromycin
- similar = clarithromycin
- azithromycin = more favorable

16

what problems were reported w/ macrolide drug interactions?

- serious QT prolongation
- cardiac arrhythmias when erythromycin was coadministered w/ cisapride or pimozide, sparfloxacin or grepafloxacin

17

macrolide GI side effects (worse to least)

erythromycin --> azithromycin --> clarithromycin

18

macrolide drug interaction (worse to least)

erythromycin/clarithromycin --> azithromycin

19

Which bacteria are better treated with clarithromycin compared to erythromycin? (increased activity?)

- G+ cocci = S. aureus, S. pyogenes, S. pneum
- G- bacilli = moraxella catarrhalis
- G-bacilli (other) = LEGIONELLA PNEUMOPHILA, H. flu
- chlamydia = chlamydia trachomatis

20

Which bacteria are better treated with azithromycin compared to erythromycin? (increased activity?)

- G- bacilli = moraxella catarrhalis
- G-bacilli (other) = H. flu
- chlamydia = CHLAMYDIA TRACHOMATIS
- mycoplasma = mycoplasma pneumonia

21

Which bacteria has decreased activity with azithromycin compared to erythromycin? (decreased activity)

- G+ cocci = S. aureus, S. pyogenes, S. pneum

22

"Azithromycin is an alternative to _____ in treating uncomplicated urethral, endocervical, rectal, or epididymal infections due to Chlamydia."

"Azithromycin is an alternative to TETRACYCLINE in treating uncomplicated urethral, endocervical, rectal, or epididymal infections due to Chlamydia."

23

"_________ is the drug of choice for urogenital infections due to Chlamydia occurring during pregnancy."

"ERYTHROMYCIN is the drug of choice for urogenital infections due to Chlamydia occurring during pregnancy."

24

What is used to treat mycoplasmal pneumonia?

Erythromycin or tetracycline

25

What is used to treat syphilis in patients who are allergic to penicillin G?

erythromycin

26

What is used to treat the carrier state of corynebacterium diphtheria?

erythromycin or penicillin

27

what is used to treat legionairres' disease?

azithromycin

28

what part of bacteria do ketolides target?

- block bacterial protein synthesis
- bind to TWO sites on 50s ribosomal RNA
- more affinity w/ macrolides
- inhibits translation, inhibits prolongation

29

characteristics of Telithromycin (Ketek)?

- BROAD SPECTRUM, first in new family ketolides
- bacteriostatic
- resembles macrolides, but more antibacterial activity than macrolides
- telithromycin binds to a site on bacterial 23S ribosomal RNA of 50S SUBUNIT

30

spectrum of activity of telithromycin?

- good against respiratory pathogens including erythromycin and penicillin resistant pneumococci
- great activity against intracellular and atypical bacteria

31

dosing of telithromycin?

- oral
- one dose daily is as effective as clarithromycin, trovafloxacin, amoxicillin for some infections

32

how is telithromycin metabolized? half life?

- metabolized by hepatic cytochrome P450 isoenzymes (mostly CYP3A4
- half life = 9-10 hrs

33

side effects telithromycin?

- DIARRHEA, nausea/vomiting, dizziness

34

contraindication of telithromycin?

- contraindicated in pts with myasthenia gravis

35

what happened during clinical trials/post-marketing with telithromycin?

- reports of serious hepatotoxicity
- clinical trials in children stopped
- use for treatment of UTIs
- remains on market for pneumonia (not DOC, use as macrolide)

36

characteristics of clindamycin?

- reversibly binds to 50S ribosomal subunits
- inhibits protein synthesis
- active against wide range of G+ cocci, several anaerobic G- & G+ organisms (G- & enterococci are resistant)

37

is clindamycin bactericidal or bacteriostatic?

can be either bacteriostatic or bactericidal depending on:
- its concentration at site of action &
- on specific susceptibility of organism

38

dosing of clindamycin?

- oral, parenteral, topical

39

how is clindamycin metabolized?

- metabolized by liver, minimally excreted by kidneys

40

use of clindamycin?

- many species of streptococci (except enterococci), staphylococci are extremely susceptible (MRSA)
- toxic shock syndrome (use with vancomycin)
- osteomyelitis - obtains high concentration in bones
- toxoplasma encephalitis - CSF concentrations are poor, not indicated for treatment of meningitis, however, useful in treating toxoplasma encephalitis

41

toxicity of clindamycin?

- skin rashes, GI disturbances, abdominal pain, nausea, vomiting, diarrhea
- WELL-KNOWN CAUSE OF PSEUDOMEMBRANOUS COLITIS, overgrowth of Clostridium dificile
- crosses placenta, distributed into breast milk

42

characteristics of Dalfopristin & Quinupristin?

- individually bacteriostatic, together synergistic & bactericidal
- STREPTOGRAMINS
- INHIBITS PROTEIN SYNTHESIS by blocking ribosome function
- dalfopristin binds to 50S ribosomal particle and inhibits early phase of protein synthesis
- quinupristin binds to 50S subunit and inhibits late phase of protein synthesis

43

how is dose of Dalfopristin & Quinupristin administered?

IV infusion - combo synergistic and bactericidal

44

what is of Dalfopristin & Quinupristin used for?

- vancomycin-resistant Enterococcus faecium bacteremia
- complicated skin/skin structure infections due to S. aureus (MRSA/MSSA)
- pencillin resistant S. pneum, MDR streptococci

45

pharmokinetics of Dalfopristin & Quinupristin?

synercid administered by IV infusion

46

adverse reactions of Dalfopristin & Quinupristin?

- hepatotoxicity, nausea/vomiting, pain, pruritis, rash
- inhibit P450 drug metabolizing system (CYP3A4), many metabolic interactions (warfarin, diazepam)

47

contraindications of Dalfopristin & Quinupristin?

- breast feeding
- children
- hepatic disease
- pregnancy
- streptogramin hypersensitivity

48

characteristics of oxazolidinones (LINEZOLID)?

- new class of synthetic antibiotics known as fluorinated OXAZOLIDINONES
- activity against AEROBIC G+ ORGANISMS

49

mechanism of action of linezolid?

- inhibits protein synthesis
- binds to site on bacterial 23S ribosomal RNA of 50S subunit
- prevents formation of functional 70S initiation complex
- bacteriostatic, except for streptococci it is bactericidal
- REVERSIBLE, NON-SELECTIVE INHIBITOR OF MONOAMINE OXIDASE (MAO)

50

when to use linezolid?

- G+ infections (bacterial pneum, skin/skin infections, vancomyin resistant enterococcal infections, methicillin resistant staphylococci (MRSA))
- should be reserved as alternative agent for treatment of infections caused by MDR strains
- overuse will hasten selection of resistant strains and lead to loss of this agent

51

pharmokinetics of linezolid?

- IV infusion or oral, oral bioavailablity = 100%
- metabolized via oxidation but oxidative metabolism of linezolid is non-enzymatic and does not involve hepatic microsomal oxidative system

52

adverse reactions linezolid?

- diarrhea 8.3%, headache 6.5%, nausea/vomiting
- insomnia, constipation, rash, dizziness, fever
- usual side effects and interaction as MAO inhibitors
- superinfection can occur

53

contraindication of linezolid?

- hypersensitivity
- pheochromocytoma

54

drug interactions of linezolid?

- beta blockers (IMPORTANT!)
- general anesthesia
- local anesthesia (epinephrine)
- sympathomimetics
- MAO inhibitors
- (anything that would increase neurotransmitters)

Also:
- heterocyclic antidepressants (amoxapin, maprotiline, mirtazapine, trazadone, tricyclic antidepressants, SSRIs)

55

main drug of ketolides?

telithromycin (ketek)

56

main drug of oxazolidinones?

linezolid (zyvox)