Clindamycin and Tetracycline Antibiotics Flashcards
MOA of clindamycin?
inhibits protein synthesis by binding mainly to the 23S RNA part of the 50S ribosomal subunit (binds to the same site as erythromycin)
Clindamycin is most effective against:
- Aerobic gram (+) cocci - some members of the Staphylococcus and Streptococcus genera
- Anaerobic gram (-) bacilli - some members of the Bacteroides and Fusobacterium genera
Clindamycin may be used systemically to treat
bone infections with Staphylococcus aureus, or topically to treat severe acne
available as a vaginal cream for treatment of bacterial vaginosis
Clindamycin has replaced penicillin for treatment of what?
lung abscesses and anaerobic lung and pleural space infections - also used to treat MRSA
Clindamycin is administered IV with pyrimethamine and leucovorin to treat what?
AIDS patients with encephalitis caused by Toxoplasma gondii
What limits the use of clindamycin to treat infections in which it is clearly the superior agent?
the relatively high incidence of pseudomembranous colitis and diarrhea
What is clindamycin metabolized by?
cytochrome P450 in the liver
Clindamycin penetrates the CNS in high enough concentrations to be useful in the treatment of what?
cerebral toxoplasmosis in HIV patients
How are clindamycin and its metabolites mainly excreted?
in urine and bile
Accumulation of clindamycin can occur in which patients?
patients with hepatic failure
Adverse effects of clindamycin?
diarrhea, pseudomembranous colitis, nausea, vomiting, abdominal cramps and rash, contact dermatitis (topical)
Potentially lethal condition commonly associated with clindamycin
pseudomembranous colitis
What do you treat C. diff/pseudomembranous colitis with?
metronidazole or vancomycin
What kind of foods should tetracyclines not be administered with?
foods rich in calcium because the insoluble calcium chelates are not absorbed from the GI tract
What other medications should tetracyclines not be administered with?
antacids that contain multivalent metals (ex TUMS) or with hematinics containing iron
What happens if you administer tetracyclines to children when they are forming their permanent teeth?
permanently brown or gray teeth because tetracyclines chelate calcium during formation of teeth
To minimize the pain on injection of tetracycline, what has been added to injectable formulations?
EDTA, which chelates the calcium (buffered to acidic pH where chelation is suppressed)
What should you do with discolored, old tetracycline samples?
throw them out
What are the problems with 4-epianhydrotetracycline?
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
Fanconi-like syndrome
failure of the reabsorption mechanism in the proximal convoluted tubule
Commercial samples of tetracycline are closely monitored for what?
4-epianhydrotetracycline
Tetracycline MOA?
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
Specifically, what do tetracyclines inhibit?
they are inhibitors of the codon-anticodon interaction
Do the tetracycline binding sites overlap with the erythromycin binding site?
No.
Why are tetracyclines not likely to inhibit protein synthesis in the host?
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
Most common use of tetracyclines
treatment of acne
Tetracyclines are the treatment of choice for what kind of infections?
infections caused by chlamydia, Rickettsia, brucellosis, and spirochetal infections
also used to treat anthrax, plague, tularemia, and Legionnaires’ disease
Tetracycline is produced by the fermentation of what?
Streptomyces aureofaciens
What side effects does minocycline have that are not shared with other tetracyclines?
vestibular toxicities (vertigo, ataxia, and nausea)
Why is doxycycline considered the tetracycline of choice by many physicians?
it has no potential for 4-epianhydrotetracycline-mediated toxicity and produced fewer GI symptoms
When is chloramphenicol mainly used in the West?
used as an alternative drug in situations where the benefits clearly outweigh the toxicity risks
Why is chloramphenicol used more prevalently in third-world countries?
because it is inexpensive
MOA of chloramphenicol
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)
What does chloramphenicol inhibit?
inhibits the peptidyl transferase activity of the ribosome and thus blocks peptide bond formation between the P site and the A site
Main therapeutic use of chloramphenicol.
used in ointment or in eye drops to treat bacterial conjunctivitis
When is chloramphenicol sodium succinate (IV or IM administration) specifically indicated?
for bacterial meningitis, typhoid fever, rickettsial infections, intraocular infections and other serious infections where bacteriological evidence or clinical judgment indicates chloramphenicol is appropriate
Resistance to chloramphenicol results from:
- reduced membrane permeability
- mutation of the 50S ribosomal subunit
- 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
Most serious toxicity of chloramphenicol.
aplastic anemia - rare but generally fatal
Bone marrow suppression is common with which drug?
chloramphenicol
Increased risk of what in children with chloramphenicol?
increased risk of childhood leukemia (risk increases with length of treatment)
Some side effects of chloramphenicol occasionally in adults but rarely in children?
nausea, vomiting and diarrhea
when do you reduce the dose of chloramphenicol?
if hepatic function is impaired
Why should you never give chloramphenicol to a baby?
neonates cannot metabolize chloramphenicol
