Brainscape's Knowledge GenomeTM

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


See full index

PHARM/MHD EXAM - 3 > L8 Pharm: Clindamycin, Macrolides, Streptogramins (Synercid) > Flashcards

L8 Pharm: Clindamycin, Macrolides, Streptogramins (Synercid) Flashcards

1
Q

What class of drugs are used mainly for ATYPICAL pneumonia, STI,s gram positive cocci and B. pertussis?

What 3 bacteria show atypical pneumonia?

What does the pneumonic MACRO clue you in on?

A
  1. MACROLIDES
    - for STI (chlamydia)
    - gram positive cocci (streptococcal infections in pts. allergic to PCN)
    - B. Pertussis

a) Mycoplasma
b) Legionella
c) Chlamydia

MACRO is the toxicity related to using macrocodes

M - motility issues
A - Arrhythmia due to prolonged QT!
C - Cholestatic Hepatitis
R - Rash
O - eOsonophilia

Increases serum concentrations of theophylline, oral antigoaluants.

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

Which two macrolides inhibit C450?

Why not the third?

A

Clarithromycin & Erythromycin

  • NOT AZYTHROMYCIN - eliminated in Bile not in the liver like C & E
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which drug is mainly used for ANAEROBIC infections ABOVE the diaphragm?

Which treats them BELOW the diaphragm? (previous lecture)

A
  1. Clindamycin

(bacteroides/ Clostridium)

Also effective for Group A strep (pneumonia)

  1. METRONIDAZOLE (anaerobic infections below the diaphragm)

TOXICITY: pseudomembranous colitis (C. DIff) + fever + diarrhea

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

State the following for Clindamycin:

  1. Spectrum of Activity
  2. Indication/Clinical use
A
  1. Gram positive Aerobes
    + ANAEROBES 9above diaphragm; metronidazole is for below the diaphragm)
  2. Anaerobic infections excluding CNS
    - Skin & soft tissue infection (PCN allergic, CA-MRSA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

State the following for Clindamycin:

  1. Mechanism of Action
  2. Adverse Effects (main 1, plus 3 rare)
A
  1. Inhibits protein synthesis by binding to 50s subunit (bacteriostatic)
  2. ADVERSE:
    - Nausea, vomiting, diarrhea, WORST INDUCER OF C. DIFF!!! (treat with Vanc or Metronidazole)

RARE:

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

State the following for Macrolides (Erythromycin, Clarithromycin, Azithromycin):

  1. Spectrum of Activity (main 1 is listed 1st)
  2. Indication/Clinical use
A
  1. ATYPICALS**
    (chlamydia, mycoplasma, legionella)
    + pertussis + Strep Infections in people allergic to PCN

Gram positive aerobes

  • Gram negative aerobes **(clindamycin doesn’t have activity against this)
    2. INDICATIONS/ CLINICAL USE:
  • Respiratory Tract infections (atypicals)
  • Uncomplicated skin infections
  • STDs
  • MAC***
  • Alternative for PCN allergic patients
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

State the following for Macrolides:

  1. Mechanism of Action
  2. Adverse Effects (main 1, plus 3 rare)
A
  1. Inhibit protein synthesis by binding to 50s subunit
    - Bacteriostatic
  2. Most common: GI side effects (nausea, vomiting, diarrhea)
MACRO
M- motility issues
A - arrhythmia caused by prolonged QT interval
C - Cholestatic Hepatitis
R - rash
O - eOsinophiluria

RARE:

  1. allergic reacction
  2. cholestatic hepatitis
  3. thrombophlebitis
  4. Prolonged Qt
  5. Transiet/reversible TINNITUS
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

State the following for Streptogramin (Quinupristin/Daltopristin)

  1. Spectrum of Activity
  2. Indication/Clinical use (1 main one)
A
  1. GRAM POSITIVE BACTERIA
    ( MSSA, MRSA, coag negative Staph, PRSP, Enterococcus FAECIUM - including VRE)
    Clostridium
  2. Indication/Clinical use:
    VRE BACTEREMIA!!!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

State the following for Streptogramin (Quinupristin/Daltopristin):

  1. Mechanism of Action
  2. Adverse Effects (main 1, plus 3 rare)
A
  1. Inhibits protein synthesis by binding to 50s subunit
    - bacteriostatic
  2. Most common:
    - venous irritation
    - Nausea, vom, diarrhea (GI irritation)

RARE:

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

What is the MOA of Clindamycin?

Bacteriostatic or Cidal?

A
  1. 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
  2. Clindamycin typically displays bacteriostatic activity, but may be bactericidal when present at high concentrations against very susceptible organisms

All protein synthesis inhibitors (except Aminoglycosides) are BACTERIOSTATIC

Remember this from the PCN lecture:

CONCENTRATION DEPENDENT:

  1. metronidazole
  2. aminoglycosides
  3. fluoroquinolones
  4. AZITHROMYCIN (only macrolide that is conc. dep)
  5. Daptomycin (lipopeptide)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the 5 drugs that are concentration dependent?

A
  1. Metronidazole
  2. Fluoroquinolones
  3. Aminoglycosides
  4. Daptomycin
  5. AZITHROMYCIN (only macrolide)

Conc. dep = extended PAE

(the only exception to this is time dependent SYNERCID)

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

What is the main MOR for Clindamycin, Synercid, & Macrolides?

Which gene (mer or erm) encodes for this?

The second MOR is ACTIVE efflux encoded by ____ gene. Which drug does not get pumped out by this?

A
  1. Altered Target site
    - erm gene alters 50s binding site
  • confers high level resistance to macrolides, clindamycin and Synercid (MLSb resistance)
    2. Active efflux - mef gene!
  • pumps MACROLIDES out of the cell but NOT clindamycin!!!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the gram positive aerobes targeted by Clindamycin? (3)

A
  1. Methicillin-susceptible Staphylococcus aureus*, and some CA-MRSA
  2. Streptococcus pneumoniae (only PSSP) – resistance is developing
  3. Group and viridans streptococci

BUT REMEMBER THAT IT IS MOSTLY USED FOR ANAEROBES

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

What are the ANAEROBES targeted by Clindamycin? (8)

What are 3 other bacteria?

A
  1. Clostridium (EXCEPT C. DIFF)
  3. Peptostreptococcus
  4. Actinomyces
  5. Propionibacterium
  6. Clostridium
  7. some Bacteroides**
  8. Prevotella
  9. Fusobacterium
  10. Pneumocystis Carinii
  11. Toxoplasmosis Gondii
  12. Malaria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

CLindamycin:

  1. Absorption:
    - available in what forms?
    - Does food have an effect?
  2. Distribution
    - serum conc. good?
    - describe the tissue penetration
    - minimal ____ penetration
  3. Elimination
    - how is it eliminated?
    - is it removed during HD?
A
  1. IV AND PO!
    - rapid/complete absorption
    - food has minimal effect
  2. Distribution
    - Good serum concentrations with both formulations
    - Good tissue penetration including bone;

**minimal CSF penetration
(common theme for protein synthesis inhibitors- minimal CSF penetration)

  1. Elimination
    - Clindamycin primarily metabolized by the LIVER (85%); enterohepatic cycling
    - Half-life is 2.5 to 3 hours
    - Clindamycin is NOT removed during hemodialysis (SINCE LIVER METABOLIZES!)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the 3 main uses of Clindamycin?

A
  1. Anaerobic Infections OUTSIDE of the CNS
    - Pulmonary, intra-abdominal, pelvic, diabetic foot and decubitus ulcer infections
  2. Skin & Soft Tissue Infections
    - PCN-allergic patients
    - Patients with infections due to CA-MRSA
  3. Alternative therapy
    - C. perfringens,
    - PCP,
    - Toxoplasmosis,
    - malaria,
    - bacterial vaginosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

State the adverse affects of Clindamycin on the following:

  1. GI
  2. Worst inducer of _____
    (treat with 2 drugs)
  3. Hepatotoxicity (marked by)
  4. Allergy (1)
  5. Hematologic abnormalities (2)
A
  1. Gastrointestinal
    – 3 to 4% (especially with oral formulation)
    Nausea, vomiting, diarrhea, dyspepsia
2. Clostridium difficile colitis – one of worst inducers** 
Ranges from mild - severe diarrhea
Requires treatment with 
a). metronidazole
b)  oral vancomycin
  1. Hepatotoxicity - rare
    Elevated transaminases*
  2. Allergy –
    rare (rash)
  3. Hematological abnormalities-
    a) neutropenia and
    b) thrombocytopenia (rare)
18
Q

Macrolides:

Name the 3

A

Macrolides in clinical use today include

  • erythromycin,
  • clarithromycin,
  • and azithromycin

Erythromycin is a naturally-occurring macrolide derived from Streptomyces erythreus

Structural derivatives include clarithromycin and azithromycin:

  • Broader spectrum of activity
  • Improved PK properties – better bioavailability, better tissue penetration, - prolonged half-lives
    Improved tolerability
19
Q
  1. What is the MOA of Macrolides?
  2. Bacteriostatic or cidal?
  3. Which 2 have time dependent activity?
  4. Which is concentration dependent?
A
  1. Inhibit protein synthesis by reversibly binding to the 50S ribosomal subunit
    - Results in suppression of protein synthesis and bacterial growth is halted
  2. Macrolides typically display BACTERIOSTATIC activity, but may be bactericidal when present at high concentrations against susceptible organisms
  3. Erythromycin and clarithromycin display time-dependent activity;
  4. AZITHROMYCIN is concentration-dependent !!!

5 conc. dependent drugs:

  1. fluroquinolones
  2. aminoglycosides
  3. metronidazole
  4. daptomycin
  5. AZITHROMYCIN (can give 1 dose)

Conc dep = peak

Time = time spent above the MIC

20
Q

What are the 2 MOR for Macrolides?

Which genes?

Does cross-resistance for macrocodes exist?

A
  1. Active efflux

– 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 (not clindamycin)

  1. Altered target sites

– encoded by the ERM gene which alters the macrolide binding site on the ribosome;

– confers high level resistance to all macrolides, clindamycin, and Synercid®

  1. Cross-resistance occurs between all macrolides
21
Q

What is the macrolide spectrum of activity for GRAM POSITIVE AEROBES?

(5 total - only 2 more that Clindamycin didn’t have)

Which is most affective (clarity, azithro, erythro?)

A

Clarithro>Erythro>Azithro

  1. Methicillin-susceptible Staphylococcus aureus (MSSA)*
  2. Streptococcus pneumoniae (only PSSP) – resistance is developing
  3. Group and viridans streptococci
  4. Bacillus spp.,
  5. Corynebacterium spp.
    (clindamycin did NOT have this activity!)
22
Q

What is the gram negative coverage of Macrolides? (3)

How is this different from Clindamycin?

Which macrolide is most affective? Least?

No activity against any _______.

A

Gram-Negative Aerobes: clinda had NO gram negative coverage!
Azithro>Clarithro>Erythro

  1. H. influenzae (not erythro),
  2. M. catarrhalis,
  3. Neisseria spp
  4. Do NOT have activity against any Enterobacteriaceae (large amount of resistance within this family)
23
Q

Macrolide’s are used mainly for treating what type of bacteria?
(3 total: it is the DOC for what bacteria?)

What are other bacteria it targets? (1) - which drugs from macrolide class?

A

A) Atypical Bacteria!!!!

– all macrolides have excellent activity against atypical bacteria including:

  1. Legionella pneumophila – DOC*
  2. Chlamydophila (psittacosis) and Chlamydia spp.
  3. Mycoplasma spp

B) Mycobacterium Avium Complex (MAC)
- only Azithromycin & CLarithromycin

M. chelonae,
 H.pylori combination tx,  (clarithromycin) 
Bordetella, 
Brucella, 
Pasteurella (ELLA)

Anaerobes – activity against upper airway anaerobes
(but rely on clindamycin for anaerobes!)

24
Q

Absorption:

Food may decrease absorption of which macrolide?

Which drug is acid stable & well absorbed?

Which is acid stable with bioavailability of 37%?

A
  1. Erythromycin
  • variable absorption (15 to 45%);
    Food may decrease the absorption !!!

Base: destroyed by gastric acid; enteric coated
Esters and ester salts: more acid stable

  1. Clarithromycin – acid stable and well-absorbed (55%) regardless of presence of food
  2. Azithromycin –acid stable; bioavailability = 37% regardless of presence of food
25
Q

Macrolide Distribution:

  1. Which 2 drugs have higher tissue concentrations?
    - Do they penetrate CSF?
  2. How is erythromycin excreted & metabolized?
  3. How is Clarithromycin?
A

Extensive tissue and cellular distribution

  1. clarithromycin and azithromycin with higher tissue concentrations
    - Minimal CSF penetration * (similar to clindamycin)
  2. Erythromycin is excreted in BILE and metabolized by CYP450
  3. Clarithromycin is metabolized and also partially eliminated by the kidney (18% of parent and all metabolites)
26
Q

What are the 3 clinical uses of Macrolides for Respiratory Tract infections?

A

Respiratory Tract Infections

  1. Pharyngitis/ Tonsillitis – PCN-allergic patients
  2. Sinusitis,COPD exacerbation, Otitis Media (azithro best if H. influenzae suspected)
  3. Community-acquired pneumonia
    – monotherapy in outpatients;
    - with ceftriaxone for inpatients
27
Q

What drug is used for:

  1. Uncomplicated skin infections
  2. STDs (1 gram dose of ___)
  3. MAC (____ for prophylaxis, 2 for treatment)
A
  1. Uncomplicated Skin Infections (not usually used for this)
  2. STDs – Single 1 gram dose of azithro
  3. MAC –
    Azithromycin for prophylaxis;

Clarithromycin/ Azithromycin for treatment

28
Q

Macrolides main use is for what? what 4 instances?

A

Alternative for PCN allergic patients!

  1. Group A Strep upper respiratory infections
  2. Prophylaxis of bacterial endocarditis
  3. Syphilis and gonorrhea
  4. Rheumatic fever prophylaxis
29
Q

What are 7 adverse effects of Macrolides?

Erythromycin is the most common cause of what?

A
  1. Gastrointestinal – up to 33% (more than clindamycin)
    Nausea, vomiting, diarrhea, dyspepsia

Most common with ERYTHROMYCIN; less with clarithromycin and azithromycin (10%)

  1. Cholestatic hepatitis - rare
    > 1 to 2 weeks of erythromycin estolate
  2. Thrombophlebitis – IV Erythro and Azithro*
    Dilution of dose; slow administration
  3. Allergic reactions
  4. Prolonged Qtc
  5. Reversible TINNITIS (deafness)
  6. Drug Drug interaction with COLCHICINE
30
Q

_____ and ______ ONLY– are inhibitors of cytochrome p450 system in the liver and may increase concentrations of:

Theophylline	           Digoxin, 
Disopyramide	
Carbamazepine
Valproic acid
Cyclosporine	            Terfenadine, Astemizole
Phenytoin		Cisapride
Warfarin		
Ergot alkaloids
A
  1. Erythromycin

2. Clarithromycin

31
Q

What is the first available streptogramin?

Why was it developed?

A

Quinupristin/Daltopristin (Synercid®) is the first available streptogramin,

  1. needed antibiotics with activity against resistant gram-positive bacteria, namely VRE!!!
  • Synercid® is a combination of two semi-synthetic pristinamycin derivatives in a 30:70 w/w ratio:
    Quinupristin(30):Dalfopristin (70)
32
Q

What is the MOA of synercid?

Bind near where?

Static or Cidal?

A
  1. Each agent acts individually on 50S ribosomal subunits to inhibit early and late stages of protein synthesis
  2. Binds on the 50S ribosome near where the macrolides and clindamycin binding site
  3. Bacteriostatic (may be bactericidal against some bacteria)

TIME DEPENDENT!

33
Q

What are the 2 MOR of synercid?

A

Mechanisms of Resistance

  1. Alterations in ribosomal binding sites (erm)
  2. Enzymatic inactivation
34
Q

What bacteria does SYnercid target?

WHICH WAS THE MAIN BACTERIA???

A
  1. Methicillin-Susceptible and Methicillin-Resistant Staph aureus
  2. coagulase-negative staphylococci*
  3. Streptococcus pneumoniae (including PRSP*)
  4. viridans streptococcus, 5. Group streptococcus (same for MACROLIDES & CLINDAMYCIN)
  5. Enterococcus faecium (including VRE)
    WHY SYNERCID WAS INITIATED!!
 Corynebacterium, 
Bacillus.
 Listeria, 
Actinomyces
Clostridium spp. (except C. difficile),
 Peptococcus, Peptostreptococcus
35
Q

T/F: Synercid is used for gram negative aerobes.

What atypical bacteria does it target? (2)

A

Gram-Negative Aerobes (not used here)
Limited activity against Neisseria sp. and Moraxella

Atypical Bacteria (in vitro activity)
Mycoplasma, Legionella
36
Q

Synercid shows time or concentration dependent activity?

Cidal or Static?

What is unique about this drug?

What is the only form of Synercid (iv or PO?)

How is it distributed?

How is it eliminated?

A
  1. TIME DEPENDENT!
  2. Bacteriostatic
  3. Shows PAE for Gram positive bacteria (usually time dependent bacteria do not have PAE)
  • 2-8 hours for S. Aureus
  • 8 hrs for VSE, 3 for VRE
  1. IV!! (parenteral)
  2. Distribution –
    penetrates into extravascular tissue, lung, skin/soft tissue; minimal CSF penetration (same as clinda/macrolide)
  3. both agents are hepatically and biliary excreted
37
Q

What drug is used for VRE bacteremia?

A

Synercid

  • 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

38
Q

What drug is a cytochrome p450 3A4 inhibitor?

A

SYNERCID

  • can lead to increased concentrations (and thus drug drug interactions)
39
Q

What are the 4 main Adverse Effects of SYnercid?

A
  1. Venous irritation (66%) – especially when administered through a peripheral vein
  2. Gastrointestinal – nausea, vomiting, diarrhea
  3. Myalgias, arthralgias – 2%
  4. Rash-2.5%
40
Q

Which one of the following statements regarding Clindamycin is true?
A. Clindamycin is readily removed by either hemodialysis or peritoneal dialysis
B. Clindamycin is ineffective in the treatment of CNS infections
C. Clindamycin levels in serum are non-existent after oral administration
D. Clindamycin’s activity is limited to Gram-positive anaerobes
E. Clindamycin has never been associated with causing C. difficile colitis

A

B. Clindamycin is ineffective in the treatment of CNS infections

41
Q

Which one of the following drugs does NOT interact with Cytochrome P-450 enzymes?

A. Erythromycin
B. Azithromycin
C. Clarithromycin
D. Telithromycin
E. Quinupristin-Dalfopristin
A

B ) Azithromycin

42
Q

Which one of the following represents the primary mechanism of resistance to Clarithromycin in the US?

A. Mutations in Topoisomerase IV
B. Decreased affinity of clarithromycin binding proteins present in the bacterial cell wall
C. Increased activity of an antibiotic efflux pump
D. Enzymatic inactivation (other protein synthesis inhibitors)
E. Alterations in the binding site on the 30S Ribosomal subunit

A

C) Increased activity of an antibiotic efflux pump*

PHARM/MHD EXAM - 3 (21 decks)

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