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Pharmacology > Vancomycin and Macrolides > Flashcards

Vancomycin and Macrolides Flashcards

1
Q

vancomycin and teicoplanin

A

glycopeptides

-both in clinical use

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2
Q

what does vancomycin do?

A

inhibitor of G(+) cell wall biosynthesis

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3
Q

MOA of vancomycin

A

binding to the peptidyl side chain D-alanyl-D-alanyl terminus in the peptidoglycan precursor -> process of cross-linking
-transpeptidase reaction that is required for cross-linking is inhibited by high affinity binding of vancomycin to the substrate.

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4
Q

how have bacteria become resistant to vancomycin?

A

mutation of the peptidoglycan cell wall precursor from D-A-D-A to D-A-D-Lactate
-vancomycin does not inhibit transpeptidase with this mutation because has 1000 less affinity

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5
Q

what are some rare complications from vancomycin?

A

nephrotoxicity and ototoxicity-> associated with high concentrations of drugs
-red skin rash and potential anaphylaxis

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6
Q

erythromycin

A

mcrocyclic lactones

-14 membered lactone ring

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7
Q

what is essential to macrolide antibiotics?

A

deoxyhexose sugars

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8
Q

why is the pKa of erythromycin important?

A

pKa= 8.8

allows to form stable salts that are more soluble

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9
Q

MOA of macrolides

A

inhibit bacterial protein synthesis by binding reversibly to the P site of the bacterial ribosome-> inhibit translocation of peptidyl-tRNA from A site to P site

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10
Q

what ribosome to macrolides bind to?

A

23S RNA

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11
Q

macrolide action is mainly

A

bacteriostatic

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12
Q

how are macrolides transported to site of infection?

A

accumulate in leukocytes, there transported directly to infection

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13
Q

resistance: lactone ester hydrolase

A

is induced to degrade the macrolides by hydrolysis of the macrocycle.

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14
Q

resistance: drug induced production of?

A

RNA methylase

-methylates an adenine base on the 23 S RNA of the 50S ribosomal subunit-> inhibits binding of macrolides to 50S subunit

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15
Q

resistance: mutation of which base?

A

adenine to guanine at specific A2058 site

-10,000 fold reduction in binding of erythromycin and clarithromycin to 23 S ribosomal RNA

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16
Q

resistance: evolved way to get ride of drugs?

A

efflux pump ejects drugs from the cell by an active transport process

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17
Q

how can erythromycin be inactivated?

A

under acidic conditions by a process involving the 6-OH group
-intramolecular acit-catalyzed ketal-formation

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18
Q

the ketal-formation is active or inactive?

A

inactive

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19
Q

how is erythromycin orally administered?

A

enteric coated tablets or more stable salts or esters

20
Q

how can acid stability be achieved?

A

with a 6-OCH3 derivative-> enhances oral absorption

21
Q

what does the 6-OCH3 do to erythromycin stability?

A

blocks ketal formation at low pH

22
Q

what is the name of the antibiotic with a 6-OCH3?

A

clarithromycin

23
Q

what antibiotic is the amine analog that is more acid stable?

A

azithromycin

  • reliable absorption
  • N-methylated methyleneamino moiety replaces C-9 ketone-> no ketal formation
24
Q

how is erythromycin degraded?

A

demethylation in liver

-elimination route in bile ( small % in urine)

25
Q

erythromycin half life

A

1.5 hours

26
Q

what do erythromycin and clarithromycin both do?

A

bind and inhibit CYP3A and related P450 enzymes

-can increase activities of certain drugs due to inhibition of their metabolism

27
Q

what two drugs reduce the activity of erythromycin?

A

rifampicin and rifabutin

28
Q

what is the common side effects with 14-membered macrolides?

A

stimulate GI motor activity: V, gastric cramps, abdominal pain

29
Q

what are rare but serious side effects of macrolides?

A

steven’s johnson syndrome and toxic epidermal necrolysis

30
Q

how does erythromycin cause jaundice?

A

long term use (10-20 days) can induce reversible cholestatic hepatitis which manifests as jaundice with cramping/ nausea and fever
-relieved upon termination of drug therapy

31
Q

what is a side effect of a pregnant women or while nursing who take erythromycin?

A

increased probability of pyloric stenosis in child

32
Q

prodrug of erythromycin?

A

erythromycin estolate

propionyl ester, lauryl sulfate

33
Q

what does the propionyl ester do for erythromycin estolate?

A

makes it more lipophilic than erythromycin itself-> increases oral absorption and blood levels of erythromycin after oral administration

34
Q

what can be a complication from erythromycin estolate?

A

cholestatic jaundice

-bile becomes granular impede bile duct flow> backed up bile salts get into circulation

35
Q

erythromycin estolate is contraindicated in?

A

people with liver disease or dysfunction

36
Q

what is erythromycin estolate used to treat?

A

GABH strep
syphilis
amebic dysentery
prophylactically prior to surgery to prevent: endocarditis from alpha-hemolytic strep (viridans group)

37
Q

erythromycin ethyl succinate

A
  • also makes more lipophilic and increases absorption

- used as flavored oral suspension for pediatric use to mask bitter taste, or as coated tablet

38
Q

clarithromycin

A

ketal formation blocked by C-6 methyl ether

39
Q

what has better antibiotic activity that clarithromycin itself?

A

its metabolite-> 14-R-hydroxy

-especially against H. influenza

40
Q

why is clarithromycin better to use than erythromycin?

A

better oral absorption
high blood levels
produces less GI upset b/c of blocked ketal formation

41
Q

how is azithromycin different from erythromycin and clarithromycin?

A

15 membered lactone ring-> N-CH3 been inserted between C 9 and 10, carbonyl oxygen removed
-prevents cyclic ketal formation

42
Q

is azithromycin stable in acidic conditions?

A

yes

43
Q

what is azithromycin half life?

A

terminal half life of 68 hours

-concentration of azithromycin in tissues can be 50 times higher than in plasma

44
Q

why shouldn’t antacids be taken with azithromycin?

A

Mg and Al can form coordination complexes with azithromycin and prevent absorption

45
Q

how is azithromycin predominantly excreted?

A

biliary excretion

46
Q

what bacteria does azithromycin target?

A

gram negative

47
Q

most common side effects of azithromycin?

A

diarrhea, azithromycin N&V, and abdominal pain

Pharmacology (14 decks)

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