Clindamycin and Tetracycline Antibiotics

Question 1

MOA of clindamycin?

Answer 1

inhibits protein synthesis by binding mainly to the 23S RNA part of the 50S ribosomal subunit (binds to the same site as erythromycin)

Question 2

Clindamycin is most effective against:

Answer 2

1. Aerobic gram (+) cocci - some members of the Staphylococcus and Streptococcus genera
2. Anaerobic gram (-) bacilli - some members of the Bacteroides and Fusobacterium genera

Question 3

Clindamycin may be used systemically to treat

Answer 3

bone infections with Staphylococcus aureus, or topically to treat severe acne
available as a vaginal cream for treatment of bacterial vaginosis

Question 4

Clindamycin has replaced penicillin for treatment of what?

Answer 4

lung abscesses and anaerobic lung and pleural space infections - also used to treat MRSA

Question 5

Clindamycin is administered IV with pyrimethamine and leucovorin to treat what?

Answer 5

AIDS patients with encephalitis caused by Toxoplasma gondii

Question 6

What limits the use of clindamycin to treat infections in which it is clearly the superior agent?

Answer 6

the relatively high incidence of pseudomembranous colitis and diarrhea

Question 7

What is clindamycin metabolized by?

Answer 7

cytochrome P450 in the liver

Question 8

Clindamycin penetrates the CNS in high enough concentrations to be useful in the treatment of what?

Answer 8

cerebral toxoplasmosis in HIV patients

Question 9

How are clindamycin and its metabolites mainly excreted?

Answer 9

in urine and bile

Question 10

Accumulation of clindamycin can occur in which patients?

Answer 10

patients with hepatic failure

Question 11

Adverse effects of clindamycin?

Answer 11

diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal cramps and rash, contact dermatitis (topical)

Question 12

Potentially lethal condition commonly associated with clindamycin

Answer 12

pseudomembranous colitis

Question 13

What do you treat C. diff/pseudomembranous colitis with?

Answer 13

metronidazole or vancomycin

Question 14

What kind of foods should tetracyclines not be administered with?

Answer 14

foods rich in calcium because the insoluble calcium chelates are not absorbed from the GI tract

Question 15

What other medications should tetracyclines not be administered with?

Answer 15

antacids that contain multivalent metals (ex TUMS) or with hematinics containing iron

Question 16

What happens if you administer tetracyclines to children when they are forming their permanent teeth?

Answer 16

permanently brown or gray teeth because tetracyclines chelate calcium during formation of teeth

Question 17

To minimize the pain on injection of tetracycline, what has been added to injectable formulations?

Answer 17

EDTA, which chelates the calcium (buffered to acidic pH where chelation is suppressed)

Question 18

What should you do with discolored, old tetracycline samples?

Answer 18

throw them out

Question 19

What are the problems with 4-epianhydrotetracycline?

Answer 19

it’s not only inactive as an antibiotic, it is also toxic to the kidneys and can produce a Fanconi-like syndrome that can be fatal

Question 20

Fanconi-like syndrome

Answer 20

failure of the reabsorption mechanism in the proximal convoluted tubule

Question 21

Commercial samples of tetracycline are closely monitored for what?

Answer 21

4-epianhydrotetracycline

Question 22

Tetracycline MOA?

Answer 22

binds to the 30S ribosomal subunit and inhibits bacterial protein synthesis by blocking the attachment of the aminoacyl-tRNA to the A site of the ribosome, resulting in termination of peptide chain growth

Question 23

Specifically, what do tetracyclines inhibit?

Answer 23

they are inhibitors of the codon-anticodon interaction

Question 24

Do the tetracycline binding sites overlap with the erythromycin binding site?

Answer 24

No.

Question 25

Why are tetracyclines not likely to inhibit protein synthesis in the host?

Answer 25

they are less likely to reach the concentration required for toxicity because eukaryotic cells, in contrast to bacteria, do not have a tetracycline uptake mechanism

Question 26

Most common use of tetracyclines

Answer 26

treatment of acne

Question 27

Tetracyclines are the treatment of choice for what kind of infections?

Answer 27

infections caused by chlamydia, Rickettsia, brucellosis, and spirochetal infections also used to treat anthrax, plague, tularemia, and Legionnaires' disease

Question 28

Tetracycline is produced by the fermentation of what?

Answer 28

Streptomyces aureofaciens

Question 29

What side effects does minocycline have that are not shared with other tetracyclines?

Answer 29

vestibular toxicities (vertigo, ataxia, and nausea)

Question 30

Why is doxycycline considered the tetracycline of choice by many physicians?

Answer 30

it has no potential for 4-epianhydrotetracycline-mediated toxicity and produced fewer GI symptoms

Question 31

When is chloramphenicol mainly used in the West?

Answer 31

used as an alternative drug in situations where the benefits clearly outweigh the toxicity risks

Question 32

Why is chloramphenicol used more prevalently in third-world countries?

Answer 32

because it is inexpensive

Question 33

MOA of chloramphenicol

Answer 33

binds reversibly to the 50S ribosomal subunit at a site that is near the site for erythrymycin and clindamycin (competitive binding interactions occur among these drugs)

Question 34

What does chloramphenicol inhibit?

Answer 34

inhibits the peptidyl transferase activity of the ribosome and thus blocks peptide bond formation between the P site and the A site

Question 35

Main therapeutic use of chloramphenicol.

Answer 35

used in ointment or in eye drops to treat bacterial conjunctivitis

Question 36

When is chloramphenicol sodium succinate (IV or IM administration) specifically indicated?

Answer 36

for bacterial meningitis, typhoid fever, rickettsial infections, intraocular infections and other serious infections where bacteriological evidence or clinical judgment indicates chloramphenicol is appropriate

Question 37

Resistance to chloramphenicol results from:

Answer 37

1. reduced membrane permeability 2. mutation of the 50S ribosomal subunit 3. elaboration of chloramphenicol acetyltranferase, which acetylates one or both of the hydroxy groups to form metabolites that do not bind to the 50S ribosomal subunit

Question 38

Most serious toxicity of chloramphenicol.

Answer 38

aplastic anemia - rare but generally fatal

Question 39

Bone marrow suppression is common with which drug?

Answer 39

chloramphenicol

Question 40

Increased risk of what in children with chloramphenicol?

Answer 40

increased risk of childhood leukemia (risk increases with length of treatment)

Question 41

Some side effects of chloramphenicol occasionally in adults but rarely in children?

Answer 41

nausea, vomiting and diarrhea

Question 42

when do you reduce the dose of chloramphenicol?

Answer 42

if hepatic function is impaired

Question 43

Why should you never give chloramphenicol to a baby?

Answer 43

neonates cannot metabolize chloramphenicol