Brainscape's Knowledge GenomeTM

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


See full index

Pharm test #3 > Protein synthesis inhibitors > Flashcards

Protein synthesis inhibitors Flashcards

1
Q

Clindamycin mechanism of action

A

Inhibits protein synthesis by binding exclusively to the 50S ribosomal subunit

Binds in close proximity to macrolides and Quinupristin/Daltopristin (Synercid®)– may cause competitive inhibition

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

clindamycin binding site

A

50S ribosomal subunit

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

is clindaycin bactericidal or bacteriostatic

A

bacteriostatic typically but bactericidal at high concentrations

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

Clindamycins main mechanism of resistance

A

Altered target sites – encoded by the erm gene, which alters 50S ribosomal binding site; confers high level resistance to macrolides, clindamycin and Synercid® (MLSb resistance)

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

erm gene

A

alters 50S ribosomal binding site; confers high level resistance to macrolides, clindamycin and Synercid® (MLSb resistance)

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

mef gene

A

encodes for an efflux pump that pumps macrolides out of the cell but NOT clindamycin

Confers low level resistance to macrolides, but clindamycin still remains active

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

clindamycin’s spectrum of activity

A

gram + aerobes (MSSA, some MRSA and Streps not PRSP )

anaerobes: including peptostreptococcus, clostridium (except C. diff)

and a few others

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

clindamycin absorption

A

good bioavailability both IV and PO

Rapidly and completely absorbed (90%); food has minimal effect on absorption

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

clindamycin’s distribution

A

Good serum concentrations with both formulations

Good tissue penetration including bone; minimal CSF penetration

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

Clindamcin’s elmination

A

Clindamycin primarily metabolized by the liver (85%); enterohepatic cycling

Half-life is 2.5 to 3 hours (dosed 6 to 8 hrs)

Clindamycin is NOT removed during hemodialysis (no renal adjustments)

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

clindamycin clinical uses

A

Anaerobic Infections OUTSIDE of the CNS
Pulmonary, intraabdominal, pelvic, diabetic foot and decubitus ulcer infections

Skin & Soft Tissue Infections (good gram+ but pcn might be better)
PCN-allergic patients
Patients with infections due to CA-MRSA

Alternative therapy
C. perfringens, PCP, Toxoplasmosis, malaria, bacterial vaginosis

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

clindamycin’s adverse effects on the GI system

A

Gastrointestinal – 3 to 4% (especially with oral formulation)
Nausea, vomiting, diarrhea, dyspepsia

Clostridium difficile colitis (0.01-10%)– one of worst inducers
Ranges from mild - severe diarrhea
Requires treatment with metronidazole or oral vancomycin

GI side effects occur more commonly with oral administration

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

clindamycin adverse effects

A

GI

Hepatotoxicity - rare
Elevated transaminases

Allergy – rare (rash)

Hematological abnormalities-neutropenia and thrombocytopenia (rare)

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

Macrolides that are used clinically

A

erythromycin, clarithromycin, and azithromycin

erythromycin is the least commonly used due to adverse effects

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

Macrolide’s mechanism of action

A

Inhibit protein synthesis by reversibly binding to the 50S ribosomal subunit

Results in suppression of protein synthesis and bacterial growth is halted

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

are Macrolides bacteriostatic or bactericidal?

A

bacteriostatic except in high concentrations

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

Do macrolides have time or concentration depended effects

A

erythromycin and clarithromycin display time dependent activity

azithromycin is concentration dependent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

2 mechanisms of resistance to macrolides

A
  1. Active efflux (accounts for 70-80% in US) – mef gene encodes for an efflux pump that pumps the macrolide out of the cell away from the ribosome; confers low level resistance to macrolides
  2. Altered target sites (primary resistance mechanism in Europe) – encoded by the erm gene which alters the macrolide binding site on the ribosome; confers high level resistance to all macrolides, clindamycin, and Synercid®

Cross-resistance occurs between all macrolides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

macrolides spectrum of activity compared to clindamycin

A

similar gram positive but macrolides also have activity against bacillus and cornynebacterium spp.

clinda has no gram negative aerobe activity but macrolides have some (NOT Enterobacteriaceae)

macrolides have anaerobe and atypical bacteria activity

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

which macrolide has the best gram positive activity

A

clarithro > Erythro > Azithro

21
Q

which gram negative spp. do macrolides have activity against?

A

H. influenzae (not erythro), M. catarrhalis, Neisseria spp.

22
Q

which macrolides have the best gram negative activity

A

Azithro > Clarithro > Erythro

23
Q

Macrolides are mainly used for treatment of

A

atypical bacteria:
Legionella pneumophila – DOC*
Chlamydophila (psittacosis) and Chlamydia spp.
Mycoplasma spp.

all macrolides have excellent activity against them

others: Mycobacterium avium complex (can be used for treatment or prophylaxis

24
Q

bioavailability of macrolides

A

Clarithro > azithro > erythro

25
Q

ways to increase the absorption of Erythromycin

A

variable absorption (15 to 45%); food may decrease the absorption

Base: destroyed by gastric acid; enteric coated

Esters and ester salts: more acid stable

26
Q

absorption of which macrolide is affected by the presence of food in the stomach

A

erythromycin

27
Q

macrolide distribution

A

Extensive tissue and cellular distribution – clarithromycin and azithromycin with higher tissue concentrations
Minimal CSF penetration

28
Q

do macrolides enter the CSF

A

Not really

29
Q

macrolide elimination

A

Erythromycin is excreted in bile and metabolized by CYP450

Clarithromycin is metabolized and also partially eliminated by the kidney (18% of parent and all metabolites)

30
Q

clinical uses for Macrolides

A

Respiratory Tract Infections
Pharyngitis/ Tonsillitis – PCN-allergic patients

Sinusitis,COPD exacerbation, Otitis Media (azithro best if H. influenzae suspected)

Community-acquired pneumonia

Uncomplicated Skin Infections

STDs – Single 1 gram dose of azithro

MAC

Alternative for PCN-Allergic Patients:

31
Q

macrolide use in pneumonia

A

Community-acquired pneumonia – monotherapy in outpatients;

with ceftriaxone for inpatients

32
Q

Macrolide use for Mycobacterium avium complex (MAC)

A

Azithromycin for prophylaxis;

Clarithromycin/ Azithromycin combination for treatment

33
Q

Macrolide use as an Alternative for PCN-Allergic Patients

A

Group A Strep upper respiratory infections
Prophylaxis of bacterial endocarditis
Syphilis and gonorrhea
Rheumatic fever prophylaxis

34
Q

GI adverse effects of macrolides

A

up to 33%
Nausea, vomiting, diarrhea, dyspepsia
Most common with erythro; less with clarithromycin and azithromycin (10%)

more common that cindamycin but less chance of sever complications from C. diff

35
Q

side effects of Macrolides

A

Gastrointestinal

Cholestatic hepatitis - rare
> 1 to 2 weeks of erythromycin estolate

Thrombophlebitis – IV Erythro and Azithro
Dilution of dose; slow administration

Allergic reactions

  • Prolonged QTc; aggravated by concomitant drugs that also prolong QTc (e.g. anti‐arrhythmics)

Transient /reversible tinnitus or deafness (with long term use)

Drug‐drug: e.g., Colchicine: potentially fatal interaction

36
Q

which protein inhibitors inhibit p450

A

macrolides: Erythromycin and clarithromycin

Quinupristin/Daltopristin (Synercid®)

potentially more drug interactions

37
Q

Streptogramins what is the clinically used drug

A

Quinupristin/Daltopristin (Synercid®)

38
Q

what was the target for Quinupristin/Daltopristin (Synercid®)

A

Developed in response to the need for antibiotics with activity against resistant gram-positive bacteria, namely VRE

39
Q

Quinupristin/Daltopristin (Synercid®) mechanism of action

A

Each agent acts individually on 50S ribosomal subunits to inhibit early and late stages of protein synthesis

Binds on the 50S ribosome near where the macrolides and clindamycin binding site

Bacteriostatic (may be bactericidal against some bacteria)

40
Q

Quinupristin/Daltopristin (Synercid®) mechanism of resistance

A

Alterations in ribosomal binding sites (erm)

Enzymatic inactivation

41
Q

Quinupristin/Daltopristin (Synercid®) spectrum of activity

A

mainly used for gram positives

includes MRSA, PRSP, and VRE

42
Q

which protein inhibitor show a post-antibiotic effect

A

Quinupristin/Daltopristin (Synercid®)

43
Q

how is Quinupristin/Daltopristin (Synercid®) administered

A

only IV

44
Q

Quinupristin/Daltopristin (Synercid®) distribution

A

penetrates into extravascular tissue, lung, skin/soft tissue

not CSF

45
Q

Quinupristin/Daltopristin (Synercid®) elmination

A

both agents are hepatically and biliary excreted

46
Q

Quinupristin/Daltopristin (Synercid®) common clinical uses

A

VRE (faecium) bacteremia

Complicated skin and soft tissue infections due to MSSA or Streptococcus pyogenes

Limited data in treatment of catheter-related bacteremia, infections due to MRSA, and community-acquired pneumonia

47
Q

Quinupristin/Daltopristin (Synercid®) adverse effects

A

Venous irritation 
(66%) – especially when administered through a peripheral vein

Gastrointestinal – nausea, vomiting, diarrhea

Myalgias, arthralgias – 2%

Rash-2.5%

48
Q

which classes of drugs inhibit protein synethsis by binding to the 50S subunit of the ribosome

A

Lincosamides (clindamycin)

Macrolides

Streptogramins (Quinupristin/Daltopristin (Synercid®))

Pharm test #3 (17 decks)

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