Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHRM 865 EXAM2 > Erdman Macrolides & ketolides > Flashcards

Erdman Macrolides & ketolides Flashcards

1
Q

chemical difference between erythromycin and clarithromycin

A

clarithromycin is a derivative of erythromycin that substitutes a methoxy group for the C-6 hydroxyl group

  • improves bioavailability (increases acid stability), enhances antibacterial activity, enhances tissue penetration and prolongs half life
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

chemical difference between erythromycin and azithromycin

A

azithromycin is a derivative of erythromycin that has an amino group inserted into the ring at position 9a. 15 membered ring - technically an “azalide”

  • improves bioavailabilty, antibacterial activity (especially against H. influenzae), tissue penetration and increased half life
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

MOA of macrolides

A

interfere with microbial protein synthesis (translocation step)

reversibly bind to 50s ribosomal subunit so that protein synthesis is supressed and growth is inhibited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

T/F: macrolides display bactericidal activity

A

False: they typically display bacteriostatic activity

at very susceptible organisms and at high concentrations they MAY have some bactericidal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the MOR for macrolides

A

Active efflux

Alteration in the binding site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do bacteria develop the active efflux machanism of resistance

A

mef gene encodes for pumps - confers LOW-LEVEL resistance to macrolides

macrolides may still be used

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do bacteria develop the alteration in binding site mechanism of resistance

A

erm gene causes a methylation of the macrolide 50S binding site leading to low affinity binding - confers HIGH-LEVEL resistance to ALL macrolides and other Abx that bind to 50S (clinda & synercid)

Sucks - common in Europe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

T/F: cross resistance is NOT usually observed

A

False

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

When bactericidal, macrolides display _______ activity

A

time-dependent

azithromycin may display concentration-dependent in “some cases”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Gram (+) aerobe bacteria covered?

A

S. pneumoniae (65-70% of strains, primarily PSSP)

MSSA (mild-moderate only)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which macrolide has the best gram (+) aerobe coverage

A

Clarithromycin

Clarithromycin > Erythromycin > Azithromycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which macrolide has the best gram (-) aerobe coverage

A

Azithromycin

Azithromycin > Clarithromycin > Erythromycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Gram (-) aerobes covered

A

NOT THE ENTEROBACTERIACEAE

H. influenzae (not erythromycin)
M. catarrhalis
Neisseria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Atypical coverage?

A

Legionella pneumophila – a DOC*
Chlamydophila and Chlamydia spp.
Mycoplasma pneumoniae
Ureaplasma urealyticum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Absorption characteristics of erythromycin

A

variable bioavailability (15-45%)

  • base is acid labile and subject to destruction in stomach
  • ester and salt derivatives more stable in acid
  • food delays absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Absorption characteristics of clarithromycin

A

acid stable and well absorbed fro stomach regardless of food (F= 52-55%)
- peak concentration at about 3 hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Absorption characteristics of azithromycin

A

acid stable, F= 37%

  • peak at 2-3 hours
  • food does not affect absorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

distribution of macrolides

A
  • all distribute well into all tissues (EXCEPT CSF) and cells
  • obtain high tissue concentrations but minimal serum concentrations
    - may be ineffective against bacteremia*****
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which macrolide must be adjusted for renal insufficiency

A

Clarithromycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How is erythromycin eliminated

A

biliary and hepatic (CYP450 enzymes)

21
Q

How is clarithromycin eliminated

A

extensively by hepatic (CYP450) and renal

dose adjust in CrCl <30

22
Q

How is azithromycin eliminated

A

biliary excretion

23
Q

Half lives of macrolides

A

Azithromycin (68 hrs) > Clarithromycin (3-7 hrs) > Erythromycin (1.4 hrs)

24
Q

T/F macrolides are removed during dialysis

A

False: NONE are removed

25
Q

Used in the treatment of __________ in penicillin allergic patients

A 
Group A strep Upper respiratory infections
prophylaxis of bacterial endocarditis
syphilis and gonorrhea
superficial minor staph infections
rheumatic fever prophylaxis
26
Q

Used in the treatment of….

A

RTI
uncomplicated skin and soft tissue infections
STD
mycobacterium avium complex infections (MAC)

27
Q

What is the treatment of nongonococcal urethritis or cervicitis due to CHLAMYDIA TRACHOMATIS

A

a single 1-gram dose of azithromycin

28
Q

T/F - clarithromycin and azithromycin have small volume of distributions

A

FALSE: very large Vds

29
Q

Other bacterial coverage by macrolides?

A

Mycobacterium avium complex (MAC – only A and C)

30
Q

macrolide treatment of CAP?

A

monotherapy in outpatients and in combination with ceftriaxone for inpatients

especially for atypical coverage

31
Q

macrolide tx of MAC

A

azithromycin for prophylaxis

clarithromycin for treatment

32
Q

ADE with macrolide use

A

gastronintestinal, thrombophlebitis/infusion site irritation, QT prolongation

33
Q

when is gastrointestinal SE most common and how can it be minimized

A

oral administration of erythromycin - give with food if possible

34
Q

How to partially avoid thrombophlebitis

A

dilute the dose (at least 250mL), infuse slowly, and give into a large vein

35
Q

Ototoxicity is seen…?

A

rarely - in patients with renal insufficiency and receiving high doses of erythromycin IV

36
Q

Drug interactions of E & C

A

both inhibitors of CYP450
theophylline, carbamazepine, valproate, cyclosporin, digoxin, phenytoin, warfarin

may increase serum concentrations & risk of toxicity

37
Q

Drug interactions for azithromycin

A

not an inhibitor of CYP450 - no drug-drug interactions however monitor PT/INR on patients stable on warfarin due to cases of hypoprothrombinemia

38
Q

Only approved ketolide is

A

telithromycin

39
Q

difference in MOA between macrolides and ketolide

A

ketolide binds to 2 different sites (domain II and V) on the ribosome
10 times tighter binding to domain II -> provides activity against macrolide resistant strains

40
Q

MOR of ketolide

A

alteration in binding site

41
Q

ketolides display ______ activity

A

bacteriostatic

**concentration-dependent cidal activity against some organisms*

42
Q

Spectrum of activity of ketolide

A

same as macrolides (A&C) except

  • covers macrolide-resistant S. pnuemoniae
  • potentially less active against M. catarrhallis & H. influenzae
  • 10x better against borrelia burgdorferi
43
Q

T/F: telithromycin is available only IV

A

false: only oral

44
Q

Pharmacollogy of ketolide

A

A - F=57%, Tmax in 1-2 hours and NOT affected by food
D - penetrates tissues well
E - metabolized by CYP450 and feces - No dosage adjustment for renal insufficiency

45
Q

ADE for telithromycin

A

hepatotoxicity & diarrhea, QTc prolongation (exacerbation of myasthenia), decreased visual acuity and blurred vision

46
Q

Drug interactions of ketolides

A

CYP450 drugs (similar to C & E macrolides)

47
Q

Only FDA approved use of ketolide

A

CAP

48
Q

Telithromycin dose for tx of CAP

A

800 mg QD x7-10 days

49
Q

T/F: telithromycin is approved for the tx of sinusitis and brochitis

A

FALSE - no longer approved due to adverse effect profile

PHRM 865 EXAM2 (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions