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Flashcards in More 50S inhibitors Deck (28):
1

Clindamycin: MoA? - Static or cidal?

Bind and inhibit 50S subunit. - Static (cidal at high conc.) Binds in close proximity to macrolides and Quinupristin/Daltopristin (Synercid)– may cause competitive inhibition

2

Clindamycin: mech of resistance?

- 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) - Active efflux – mef gene encodes for an efflux pump that pumps antibiotic out of the cell - Drug inactivation

3

Describe the spectrum of activity of clindamycin.

Gram positive aerobes: - *MSSA and some CA-MRSA - PSSP: PCN-susc. strep pneumo - Group + viridians strep Anaerobes: * Some bacteriodes spp. - Peptostreptococcus, actinomyces, prevotella spp, propionibacterium, fusobacterium, clostridium spp. (not C. difficile) Other bacteria: - Pneumocystis carinii, Toxoplasmosis gondii, Malaria

4

How is clindamycin administrated? What is the % absorption?

IV, PO (90% absorption, can switch b/w IV and PO)

5

Does clindamycin penetrate the CSF?

Not really

6

Clindamycin primarily metabolized by the ___________. - Does it need adjustments during renal failure? - Is it removed during hemodialysis?

- Liver - Doesn't need adjustments during renal failure - No

7

What are the clinical uses of clindamycin?

- Anaerobic Infections OUTSIDE of the CNS: Pulmonary, intraabdominal, pelvic, diabetic foot and decubitus ulcer infections - Skin & Soft Tissue Infections: Good option for PCN-allergic patients and infections due to CA-MRSA - Alternative therapy: C. perfringens, PCP, Toxoplasmosis, malaria, bacterial vaginosis

8

What are the 2 main side-effects for clindamycin?

- GI - *C-diff colitis (one of the main inducers)

9

What category of drug does clindamycin belong?

Lincosamide

10

What are the 3 macrolides we should know?

- Azithromycin - Clarithromycin - Erythromycin

11

Which 2 macrolides are derivatives of the other?

Azithromycin and clarithromycin derivatives of erythromycin

12

How do azithro and clarithromycin improve upon erythromycin?

- Broader spectrum of activity - Improved PK properties: better bioavailability, better tissue penetration, prolonged half-lives - Improved tolerability

13

Macrolides: MoA? - Cidal or static?

- Reversibly binding to the 50S ribosomal subunit - Static (cidal at high conc)

14

Which of the macrolides and time-dependent, and which are conc.-dependent?

- Erythromycin and clarithromycin are time-dependent - Azithromycin is conc-dependent

15

Macrolides: mech of resistance?

- Active efflux pump (mef gene) - Altered target sites (erm gene)

16

What is the spectrum of activity for macrolides? (groups are targets)

- Gram-pos aerobes (*MSSA) - Gram-neg aerobes - Anaerobes (esp. upper airway) - Atypical bacteria (*Legionella, DOC) - Other bacteria

17

What bacterium do macrolides importantly NOT have activity against?

Enterobacteriacea (gram-neg aerobe class)

18

What are the relative levels of activity for the 3 macrolides against gram-positive aerobes?

CEA Clarithro > Erythro > Azithro (ACE for gram-neg)

19

What are the relative levels of activity for the 3 macrolides against gram-negative aerobes?

ACE Azithro > Clarithro > Erythro (CEA for gram-pos)

20

Discuss the bioavailabilities of each of the of the 3 macrolides. - Which are acid stable?

- Erythromycin: variable absorption (15 to 45%) - Clarithromycin: well-absorbed (55%) - Azithromycin: 37% bioavail. regardless of food Acid stable: Clarithromycin and azithromycin

21

Do macrolides penetrate the CSF?

Not really

22

Describe the elimination routes of each of the 3 macrolides. * Which are metabolized by CYP450 enzymes?

- Erythromycin: excreted in bile, metabolized by *CYP450 - Clarithromycin: also metabolized (*CYP450) and partially eliminated by the kidney - Azithromycin: liver, NO CYP450

23

Name the clinical uses of macrolides.

Respiratory Tract Infections - Pharyngitis/ Tonsillitis: PCN-allergic pts - Sinusitis, COPD exacerbation, OM - CA-PNA: monotherapy in outpatients; with ceftriaxone for inpatients Uncomplicated Skin Infections STDs MAC Alternative for PCN-Allergic pts: - Group A Strep upper respiratory infections - Prophylaxis of bacterial endocarditis - Syphilis and gonorrhea - RF prophylaxis

24

Which macrolide is best when H. influenzae is suspected?

Azithromycin

25

Which macrolide is best for STDs?

Azithromycin

26

How are macrolides used to treat MAC (mycobacterium avium complex)? I hope to god this doesn't come up

- Azithromycin for prophylaxis - Clarithromycin/ Azithromycin for tx

27

What are the adverse effects of macrolides? (there is 1 common group and the others are rare)

- GI (only ones that are common) - Cholestatic hepatitis (rare) - Thrombophlebitis - Prolonged QTc - Ototoxicity (tinnitus/deafness)

28

*Erythromycin and clarithromycin– are inhibitors of cytochrome p450 system in the liver and may increase concentrations of: (just read)

Theophylline Digoxin, Disopyramide Carbamazepine Valproic acid Cyclosporine Terfenadine, Astemizole Phenytoin Cisapride Warfarin Ergot alkaloids