Macrolides, clindamycin, and chloramphenicol Lecture 19 Flashcards Preview

Exam 2 > Macrolides, clindamycin, and chloramphenicol Lecture 19 > Flashcards

Flashcards in Macrolides, clindamycin, and chloramphenicol Lecture 19 Deck (20):
1

Structure and chemistry of erythromycin, clarithromycin, and azithromycin

clarithromycin is a 6 methoxy erythromycin

azithrymycin has a nitrogen group added to the 14 member macrolide ring

2

MoA of erythromycin, clarithromycin, and azithromycin

reversibly binds to the 50s ribosomal subunit of bacteria to decrease protein synthesis

bacteriostatic

3

absorption of erythromycin, clarithromycin, and azithromycin

Erythromycin: base, stearate, and ethylsuccinate are more completly absorbed in the fasting state. Erythromycin estolate is not affected by food.

4

Distribution erythromycin, clarithromycin, and azithromycin

distributes in tissues longer than in blood

hgh concentrations in alveolar macrophages and leukocytes compared to those in extracellular fluid

azithromycin tissue concentrations exceeds serub by 10-100 fold: allows for 5 day course of therapy

5

Metabolism/excretion erythromycin, clarithromycin, and azithromycin

erythromycin/clarithromycin: hepatic metabolism. 1.4 h half life

clarithromycin: metabolized in the liver by oxidation and hydrolysis. 20-30% of drug excreted into the urine unchanged.

azithrymycin: major route of elimination in feces via biliary excretion. 68 hr half life, consistent witha slow release of drug from tissues. Aids in allowing 5 day regimen

6

AE: erythromycin,

Erythromycin: Gi abdominal crambs, N/V/D, stimulates the motolin receptor in the gut and hormone that stimulates gastric motility.

Thromophelbitis (IV).

Allergic reactions.

Cholestatic hepatitis (rare) Estolate prep; chiefly in adults and pregnant paitnets (avoid estolate form in pregnancy).

N/V, abdominal pain followed by jaundice, fever, LFT changes, Hypsersensitivity reaction to the structure of the estolate compound

generally clears up within days to a few weeks of d/c

7

AE: clarithromycin, and azithromycin

Gi- not as severe as erythromycin

HA, Dizziness

allergic reactions

8

Drug interactions erythromycin, clarithromycin, and azithromycin

erythromycin/clarithromycin: Erythromycin: generally by interfering with cytochorme p450 enzymes. Metabolites form inactive complexes with p450. Decreased matbaolism of theophylline, warfarin, carbamazepine, cyclosporine

azithrymycin: does not inactivate p450

9

SoA: erythromycin, clarithromycin, and azithromycin

G+, Atypicals (all three)

H. Flu, M.Cat (clarithro, azithro)

clarithro: h pylori

10

uses: erythromycin, clarithromycin, and azithromycin

penicillin allergic patients

mycoplasma pneumoniae

legionnaire's disease

chlamydia trachomatis nongonococcal urethrtisis and cervicities: single i gm dose of azithromycin= 7 days of doxycycline

C. trachomatis during pregnancy (but not the estolate form)

11

Clindamycin Chemistry

derived from lincymycin

chemical modification allowed clindamycin more potency and absorption

12

MoA clinda

Binding of 50 S ribosome resulting in inhibition of protein synthesis

13

pharmacokinetics Clinda

Bioavailability= 90%; food delays absorption but does not affect extent

good tissue penetration

metabolized by the liver

14

SoA: Clinda

G+ and anaerobic coverage.

Strep, Staph (limited bactericidal rate compared to b lactams), anaerobes: bacteroids, including B fragilis, clostridium perfringens, peptostreptococci, peptococci, toxoplasmosis (allergic to sulfonamides)

15

AE: clinda

allergic reactions

diarrhea: 20% of patients; more common with oral form

clostridium difficile (pseudomembranous colitis)- big culprit

hepatotoxicitiy (mild to severe)

16

MoA Chloramphenicol

reversibly binds to the larger 50 S subunit of the 70 S ribosome

17

pharmacokinetics: Chloramphenicol

suspension: must be hydrolyzed in the intestines for active chloramphenicol

IV form has incomplete hydrolysis; therefore, serum concentrations after IV therapy are only about 70% of those after oral administration

excellent CSF concentrations, 30-50% without inflamed meninges

metabolism via glucuronidation in the liver

wide variations in metabolism and excretion in children: must monitor serum levels

18

SoA: Chloramphenicol

wide variety of G+, G-, aerobic and anaerobic organisms.

Rickettsia, chlamydia

19

AE: Chloramphenicol

Hematologic: reversible bone marrow depression due to direct pharacologic effect on inhibition of mitochondrial protein synthesis. Anemia, leukopenia, thrombocytopenia.

Idiosyncratic aplastic anemia: majority of cases occur weeks to months after completion of therapy and is not necessairly dose related

childhood leukemia: increased incidence

Gray baby syndrome: abdominal distention, vomiting, cyanosis, circulatory collapse. DIminished ability of neonates to conjugate chloramphenicol and to excrete the active form in the urine. Generally associated with concentrations > 50mcg/ml

20

Uses: chloramphenicol

bacterial meningitis (h. flu, strep pneumo, neiseria meningitidis). Penicillin/cephalosporin allergic. Oral alternative when IV cannot be used.

Rickettsial infections.