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Pharm > 2: Clindamycin + Tetracyclines + Chloramphenicol > Flashcards

2: Clindamycin + Tetracyclines + Chloramphenicol Flashcards

1
Q

where does clindamycin come from?

A

lincomycin treated with chlorine + triphenylphosphine in acetonitrile

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2
Q

clindamycin MOA

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

*antagonism/cross resistance b/w clinda and erythro

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3
Q

clindamycin uses

A
  • 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
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4
Q

clindamycin admin

A
  • capsules, oral suspension
  • IV: clindamycin phosphate
  • topical: clindamycin HCl/ clindamycin phosphate
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5
Q

clindamycin metabolism

A

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

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6
Q

clindamycin PK:

  • % absorbed?
  • where it goes?
  • excretion?
  • half life?
A
  • 90% absorbed from GI
  • penetrates CNS (tx of cerebral toxoplasmosis in HIV)
  • excreted in urine/bile
  • t1/2 = 1.5-5h
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7
Q

what happens to clindamycin in hepatic failure?

A

accumulates

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8
Q

clindamycin AE

A
  • diarrhea
  • pseudomembranous colitis (C. diff inherently resistant, treat w/ metronidazole or vancomycin)
  • nausea
  • vomit
  • abdominal cramping
  • rash (hypersensitivity)
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9
Q

where do tetracyclines come from?

A

broad spec from streptomyces (mummy bones)

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10
Q

tetracycline contraindications

A

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
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11
Q

describe epimerization of tetracyclines

A

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

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12
Q

describe dehydration of tetracyclines

A
  • tertiary benzylic -OH at C6 is antiperiplanar w/ proton at C5a -> set up for dehydration
  • results in 4-epianhydrotetracycline (inactive, toxic)
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13
Q

describe toxicity of 4-epianhydrotetracycline

A

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

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14
Q

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

A

minocycline, doxycycline

-do not have -OH at C6 position

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15
Q

what happens to tetracyclines in basic solution?

A

cleavage -> forms a lactone product that is inactive

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16
Q

tetracycline MOA

A
  • 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
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17
Q

tetracyclines uses

A
  • acne
  • chlamydia (trachoma, psittacosis, salpingitis, urethritis, LGV)
  • Rickettsia (typhus, RMSF)
  • brucellosis
  • spirochetes (borreliosis, syphilis, Lyme disease)
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18
Q

tetracyclines structures

A

study cheat sheet

19
Q

tetracycline: contraindications

A

decrease oral absorption 50% if taken with food or milk

20
Q

tetracycline: original organism

A

strep aureofaciens

21
Q

demeclocycline: contraindications

A

decrease oral absorption 50% if taken with food or milk

22
Q

demeclocycline: why slower dehydration than tetracycline?

A

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

23
Q

demeclocycline: original organism

A

strep aureofaciens

24
Q

minocycline: contraindications

A

decrease oral absorption 20% if taken with food or milk

25
Q

minocycline: bioavailability

A

90-100% orally

26
Q

minocycline: why no toxic intermediate?

A

no -OH at C6

27
Q

minocycline: original organism

A

from demeclocycline

28
Q

minocycline: AE

A

vestibular toxicities

29
Q

oxytetracycline: contraindications

A

decrease oral absorption 50% if taken with food or milk

30
Q

oxytetracycline: bioavailability

A

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

31
Q

oxytetracycline: original organism

A

strep rimosis

32
Q

doxycycline: contraindications

A

decrease oral absorption 20% if taken with food or milk

33
Q

doxycycline: bioavailability

A

90-100%, orally

34
Q

doxycycline: why no toxic intermediate?

A

no -OH on C6

35
Q

doxycycline: why is it the preferred tetracycline?

A
  • 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
Q

where does chloramphenicol come from?

A

strep venezuelae

37
Q

chloramphenicol MOA

A
  • 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
Q

chloramphenicol uses

A
  • 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
Q

why is it important that chloramphenicol is lipid soluble?

A

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

40
Q

chloramphenicol resistance: 3 mechanisms

A
  1. decrease membrane permeability
  2. mutation of 50S subunit
  3. elaboration of chloramphenicol acetyltransferase (don’t bind 50S)
41
Q

chloramphenicol toxicity, worst one

A

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
Q

chloramphenicol toxicity, common ones

A
  • 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
Q

chloramphenicol metabolism

A

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

44
Q

why should you never give neonates chloramphenicol?

A

they can’t metabolize it

Pharm (19 decks)

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