Antibiotics 3 - Clindamycin and Tetracyclines Flashcards Preview

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Flashcards in Antibiotics 3 - Clindamycin and Tetracyclines Deck (42):
1

Clindamycin is synthesized from ______

How? What does this do?

Lincomycin

 

Tretment with Chlorine and tri-phenyl-phosphine in acetonitrile.

(This reaction inverts the configuration)

2

MOA of clindamycin

Inhibits protein synth.

Binds 23SrRNA of the 50S ribosomal subunit

 

3

Clindamycin binds to the same subunit as ________

erythromycin

4

Clindamycin is most effective against

Aerobic gram positive cocci (Staph/Strep)

Anaerobic gram negative bacilli (Bacteriodes/Fusobacerium)

5

Forms of clindamycin admistration

Systemic (bone infctns)

Topical  (acne)

Vaginal cream (bact. vaginosis)

6

Clinda has replaced Pen for _______ and ________

Treatment of lung abscesses and anaweobic lung and pleural space infections

7

How does clindamycin fit into treatment plan for Toxo encephalitis in AIDS patients?

Administered parenterally with pyrimethamine + leucovorin 

8

Metaboolism of Clindamycin:

  • Enzyme
  • Metabolites (and activity)
  •  

  • Metabolized by P450
  • to the sulfoxide and N-methylated derivative

(both are inactive)

9

Clinda IV form

Clinda Topical form

Clindamycin phosphate (IV)

Clindamycin phosphate or hydrochloride (Topical)

10

Clinda absorption? (where, how much)

90% of administered dose absorbed by GIT

11

Clindamycin excretion routes

Half life

Urine and bile

1.5 - 5 hours

12

In what case would you need to adjust the dose of clindamycin?

In cases of hepatic failure where accumulation occurs

13

Common sides of clinda

Diarrhea/pseudomembranous colitis, N/V, rash/dermatitis

14

Treatment of pseudomembranous colitis (c.diff)

Mzole or Vm

15

Tetracyclines have a base structure ring of ____

12 carbons

16

Tetracycline forms stable chelates with...

polyvalent metal ions

Ca++, Al+++, Cu++, Mg++

17

The chelates formed by Tetracyclines are _____

insoluble

18

Tetracycline should not be given with...

Calcium-rich foods or supplements

Hematinics containing Iron 

19

Tetracycline chelates calcium...

during the formation of teeth

20

Tooth discoloration by tetracycline is made worse as a result of...

photo-oxidation reaction

21

Why is inected Tetracycline painful?

Formation of Calcium chelates

Injectable formulations can contain EDTA to prevent this (it will chelate the calcium instead)

22

What is the reason for epimerization and enolization of Tetracycline?

because the H on the amine-bearing carbon is acidic 

 

**the epiTetracycline product can be formed in solution OR in solid state

23

EpiTetracycline product is...

pharmacologically inactive

 

formed most rapidly at pH 4.0 in solution

24

Tetracycline dehydration

The tertiary benzylic OH group at C6 has a ____ relationship with ______. What does this do?

 

The tertiary, benzylic hydroxyl group at C-6 has an antiperiplanar relationship with the proton at C-5a,

 

So it is "set up" for elimination

25

Why doesnt the C12 OH group get eliminated?

Its tertiary, but it is NOT next to an antiperiplanar H

 

(and it is also deactivated by being next to a carbonyl group --> stable)

26

Why shouldnt old tetracycline be used?

It is less active, and the 4-epianhydrotetracycline metabolite is toxic to kidneys

 

can produce a fatal Falconi-like syndrome

27

When does tetracycline undergo cleavage?

 

What does this form?

At pH 8.5 or above

 

an inactive lactone product

28

Tetracycline MOA

Tetracyclines bind to the 30S ribosomal subunit

=block the attachment of the aminoacyl-tRNA to the A site of the ribosome

 

= chain termination

29

Why doesnt tetracyline cause its effects in host cells?

eukaryotic cells do not have a tetracycline uptake mechanism

30

Tet binds to the ___ ribosomal subunit in ___ locations

small, 6

31

(tetracycline)

The site of highest occupancy

Tet1

located near where the aminoacyl tRNA binds to the A site

32

Most common use for tetracycline

 

It is DOC for _____ (4)

acne

 

Chlamydia, rickettsia, brucella, spirochete

33

Tet is also used to treat ____, ____, _____, and _____

anthrax

plague

tularemia

Legionnaires' disease

34

______ lowers tetracycline effetiveness by about 50%

food and milk

35

Demeclocycline structural difference

 

Demeclocycline _____ more slowly than tetracycline. Why?

has a secondary hydroxyl group at C-6 instead of the tertiary hydroxyl group

 

dehydrates more slowly because it forms secondary alcohol rather than tertiary alcohol as with tetracycline

36

Minocycline structural difference

 

What effect does this have?

Lacks the C6 hydroxyl group

 

Therefore does NOT undergo dehydration

= no potential for 4-epianhydrotetracycline-mediated toxicity

37

Minocycline BA

oral BA = 90-100%

38

Minocycline unique AE's

Vestubular toxicity

39

Most hydrophobic tetracycline

oxytetracycline

40

Oral BA of oxytetracycline

60%

41

Doxy contains what group at C6?

no group

No rxn = no 4-epianhydrotetracycline-mediated toxicity

42

Doxy half life

18-20 hours

allows DAILY admin