2: Clindamycin + Tetracyclines + Chloramphenicol Flashcards Preview

Pharm > 2: Clindamycin + Tetracyclines + Chloramphenicol > Flashcards

Flashcards in 2: Clindamycin + Tetracyclines + Chloramphenicol Deck (44):
1

where does clindamycin come from?

lincomycin treated with chlorine + triphenylphosphine in acetonitrile

2

clindamycin MOA

-same as macrolides
-inhibits protein synthesis - binds 23S RNA at same site as erythro

*antagonism/cross resistance b/w clinda and erythro

3

clindamycin uses

-aerobic G(+) cocci (staph, strep)
-anaerobic G(-) bacilli (bacteroides, fusobacterium)

-bone infections w/ S. aureus
-severe acne
-bacterial vaginosis
-replaced penicillin for lung abscesses, anaerobic lung and pleural space infections
-MRSA
-IV w/ pyrimethamine + lucovorin for AIDS toxoplasma encephalitis

4

clindamycin admin

-capsules, oral suspension
-IV: clindamycin phosphate
-topical: clindamycin HCl/ clindamycin phosphate

5

clindamycin metabolism

CYPs in liver -> inactive sulfoxide + N-demethylated derivative

6

clindamycin PK:
-% absorbed?
-where it goes?
-excretion?
-half life?

-90% absorbed from GI
-penetrates CNS (tx of cerebral toxoplasmosis in HIV)
-excreted in urine/bile
-t1/2 = 1.5-5h

7

what happens to clindamycin in hepatic failure?

accumulates

8

clindamycin AE

-diarrhea
-pseudomembranous colitis (C. diff inherently resistant, treat w/ metronidazole or vancomycin)
-nausea
-vomit
-abdominal cramping
-rash (hypersensitivity)

9

where do tetracyclines come from?

broad spec from streptomyces (mummy bones)

10

tetracycline contraindications

form stable chelates w/ polyvalent metal ions (Ca2+, Al3+, Cu2+, Mg2+) -> insoluble:
-don't give w/ foods rich in Ca, antacids, hematinics w/ Fe
-give metals 1h before or 2h after tetracycline
-chelates Ca during tooth formation -> permanently gray/brown that worsens w/ time due to photo-oxidation rxn (don't give to kids)
-pain on injection due to formation of insoluble Ca complexes so now inject w/ EDTA to chelate Ca

11

describe epimerization of tetracyclines

deprotonation -> followed by reprotonation, but in opposite orientation, rendering it inactive

12

describe dehydration of tetracyclines

-tertiary benzylic -OH at C6 is antiperiplanar w/ proton at C5a -> set up for dehydration
-results in 4-epianhydrotetracycline (inactive, toxic)

13

describe toxicity of 4-epianhydrotetracycline

produces Fanconi-like syndrome: failrue of reabsorption mechanism in PCT
-electrolytes not reabsorbed -> water follows electrolytes -> increased urine output, dehydration, electrolyte imbalances

14

what two tetracyclines do not form the toxic intermediate? why?

minocycline, doxycycline
-do not have -OH at C6 position

15

what happens to tetracyclines in basic solution?

cleavage -> forms a lactone product that is inactive

16

tetracycline MOA

-binds 30S subunit, blocks anticodon-codon interaction in A site, resulting in termination of peptide growth
*does not overlap with erythromycin binding site
*can inhibit human protein synthesis, but eukaryotes don't have a tetracycline uptake mechanism, so usually not a problem
-binds in 6 different spots; Tet1 has highest occupancy

17

tetracyclines uses

-acne
-chlamydia (trachoma, psittacosis, salpingitis, urethritis, LGV)
-Rickettsia (typhus, RMSF)
-brucellosis
-spirochetes (borreliosis, syphilis, Lyme disease)

18

tetracyclines structures

study cheat sheet

19

tetracycline: contraindications

decrease oral absorption 50% if taken with food or milk

20

tetracycline: original organism

strep aureofaciens

21

demeclocycline: contraindications

decrease oral absorption 50% if taken with food or milk

22

demeclocycline: why slower dehydration than tetracycline?

2nd -OH at C6 -> secondary cation intermediate is less stable and has higher energy barrier to overcome

23

demeclocycline: original organism

strep aureofaciens

24

minocycline: contraindications

decrease oral absorption 20% if taken with food or milk

25

minocycline: bioavailability

90-100% orally

26

minocycline: why no toxic intermediate?

no -OH at C6

27

minocycline: original organism

from demeclocycline

28

minocycline: AE

vestibular toxicities

29

oxytetracycline: contraindications

decrease oral absorption 50% if taken with food or milk

30

oxytetracycline: bioavailability

60%, orally (not great therapeutically), but most hydrophilic tetracycline

31

oxytetracycline: original organism

strep rimosis

32

doxycycline: contraindications

decrease oral absorption 20% if taken with food or milk

33

doxycycline: bioavailability

90-100%, orally

34

doxycycline: why no toxic intermediate?

no -OH on C6

35

doxycycline: why is it the preferred tetracycline?

-good bioavailability
-lesser degree of absorption reduction w/ food/milk
-less GI sx
-no toxic intermediate
-t1/2 = 18-22h (once a day dosing)

36

where does chloramphenicol come from?

strep venezuelae

37

chloramphenicol MOA

-binds reversibly to 50@ at a site near the site for erythro/clinda (competitive binding interactions among these drugs)
-inhibits peptidyl transferase -> blocks peptide bond formation b/w P and A sites

38

chloramphenicol uses

-ointment/eye drops: bacterial conjunctivitis
-chloramphenicol Na succinate = prodrug for IV/IM admin:
-hydrolyzed to chloramphenicol in liver
-bacterial meningitis
-typhoid fever
-Rickettsial infections
-intraocular infections

39

why is it important that chloramphenicol is lipid soluble?

remains relatively unbound to plasma proteins -> penetrates into all tissues, including brain

40

chloramphenicol resistance: 3 mechanisms

1. decrease membrane permeability
2. mutation of 50S subunit
3. elaboration of chloramphenicol acetyltransferase (don't bind 50S)

41

chloramphenicol toxicity, worst one

aplastic anemia:
-rare, but generally fatal
-weeks to months post treatment
-highest risk w/ oral suspension
-lowest risk w/ eye drops
-keep blood levels

42

chloramphenicol toxicity, common ones

-bone marrow suppression due to impairment of mitochondrial fxn once you reach a cumulative dose of 20g (completely reversible)
-increased risk of childhood leukemia + risk increases with length of treatment
-adults: nausea, vomit, diarrhea (rare in kids)

43

chloramphenicol metabolism

turned into its glururonide in liver (inactive) -> excreted by kidneys
-therefore must decrease dose if decreased hepatic fxn

44

why should you never give neonates chloramphenicol?

they can't metabolize it