Clindamycin is synthesized from ______
How? What does this do?
Tretment with Chlorine and tri-phenyl-phosphine in acetonitrile.
(This reaction inverts the configuration)
MOA of clindamycin
Inhibits protein synth.
Binds 23SrRNA of the 50S ribosomal subunit
Clindamycin binds to the same subunit as ________
Clindamycin is most effective against
Aerobic gram positive cocci (Staph/Strep)
Anaerobic gram negative bacilli (Bacteriodes/Fusobacerium)
Forms of clindamycin admistration
Systemic (bone infctns)
Vaginal cream (bact. vaginosis)
Clinda has replaced Pen for _______ and ________
Treatment of lung abscesses and anaweobic lung and pleural space infections
How does clindamycin fit into treatment plan for Toxo encephalitis in AIDS patients?
Administered parenterally with pyrimethamine + leucovorin
Metaboolism of Clindamycin:
- Metabolites (and activity)
- Metabolized by P450
- to the sulfoxide and N-methylated derivative
(both are inactive)
Clinda IV form
Clinda Topical form
Clindamycin phosphate (IV)
Clindamycin phosphate or hydrochloride (Topical)
Clinda absorption? (where, how much)
90% of administered dose absorbed by GIT
Clindamycin excretion routes
Urine and bile
1.5 - 5 hours
In what case would you need to adjust the dose of clindamycin?
In cases of hepatic failure where accumulation occurs
Common sides of clinda
Diarrhea/pseudomembranous colitis, N/V, rash/dermatitis
Treatment of pseudomembranous colitis (c.diff)
Mzole or Vm
Tetracyclines have a base structure ring of ____
Tetracycline forms stable chelates with...
polyvalent metal ions
Ca++, Al+++, Cu++, Mg++
The chelates formed by Tetracyclines are _____
Tetracycline should not be given with...
Calcium-rich foods or supplements
Hematinics containing Iron
Tetracycline chelates calcium...
during the formation of teeth
Tooth discoloration by tetracycline is made worse as a result of...
Why is inected Tetracycline painful?
Formation of Calcium chelates
Injectable formulations can contain EDTA to prevent this (it will chelate the calcium instead)
What is the reason for epimerization and enolization of Tetracycline?
because the H on the amine-bearing carbon is acidic
**the epiTetracycline product can be formed in solution OR in solid state
EpiTetracycline product is...
formed most rapidly at pH 4.0 in solution
The tertiary benzylic OH group at C6 has a ____ relationship with ______. What does this do?
The tertiary, benzylic hydroxyl group at C-6 has an antiperiplanar relationship with the proton at C-5a,
So it is "set up" for elimination
Why doesnt the C12 OH group get eliminated?
Its tertiary, but it is NOT next to an antiperiplanar H
(and it is also deactivated by being next to a carbonyl group --> stable)
Why shouldnt old tetracycline be used?
It is less active, and the 4-epianhydrotetracycline metabolite is toxic to kidneys
can produce a fatal Falconi-like syndrome
When does tetracycline undergo cleavage?
What does this form?
At pH 8.5 or above
an inactive lactone product
Tetracyclines bind to the 30S ribosomal subunit
=block the attachment of the aminoacyl-tRNA to the A site of the ribosome
= chain termination
Why doesnt tetracyline cause its effects in host cells?
eukaryotic cells do not have a tetracycline uptake mechanism
Tet binds to the ___ ribosomal subunit in ___ locations
The site of highest occupancy
located near where the aminoacyl tRNA binds to the A site
Most common use for tetracycline
It is DOC for _____ (4)
Chlamydia, rickettsia, brucella, spirochete
Tet is also used to treat ____, ____, _____, and _____
______ lowers tetracycline effetiveness by about 50%
food and milk
Demeclocycline structural difference
Demeclocycline _____ more slowly than tetracycline. Why?
has a secondary hydroxyl group at C-6 instead of the tertiary hydroxyl group
dehydrates more slowly because it forms secondary alcohol rather than tertiary alcohol as with tetracycline
Minocycline structural difference
What effect does this have?
Lacks the C6 hydroxyl group
Therefore does NOT undergo dehydration
= no potential for 4-epianhydrotetracycline-mediated toxicity
oral BA = 90-100%
Minocycline unique AE's
Most hydrophobic tetracycline
Oral BA of oxytetracycline
Doxy contains what group at C6?
No rxn = no 4-epianhydrotetracycline-mediated toxicity
Doxy half life
allows DAILY admin