Antibacterials - Clindamycin and Tetracycline Flashcards
Clindamycin is synthesized from …
the naturally occurring antibiotic lincomycin by treatment with chlorine and triphenylphosphine in acetonitrile
What is the mechanisms of action of clindamycin
Similar to that of macrolide antibiotics like erythromycin
inhibits protein synthesis by binding to the bacterial 50S ribosome
Antagonism and cross-reactivity between clindamycin and ____ have been reported
erythromycin
clindamycin is most effective against
- Aerobic gram+ cocci
- –strep
- –staph
- Anaerobic gram- bacilli
- –bacteroides
- –fusobacterium
Clindamycin can be used for …
- bone infections with s. aureus
- severe acne
- bacterial vaginosis
- lung abscesses and anaerobic lung and pleural space infections
- MRSA
Clindamycin is administered ____ with ___ and ___ to treat AIDS patients with ____
Clindamycin is administered IV with pyrimethamine and leucovorin to treat AIDS patients with Toxoplasma gondii
What do we see a lot with clindamycin treatment?
C. diff
Clindamycin knocks out all other organisms in colon except C. diff and then we get an overgrowth
C. diff is inherently resistant to clindamycin
Metabolism of clindamycin
- oxidative N-demethylation
- react with cytochrome P450 to oxide drug to sulfide
Both of these are inactive
Pharmacokinetics of clindamycin
Very readily absorbed from GI tract
Widely distributed among tissues - this is why it is useful for AIDS with CNS infection
Excreted in urine and bile
Elimination half life of 1.5-5 hours
Accumulation of clindamycin can occur in pts with …
hepatic failure … may need to adjust the dose
Tetracycline is a …
broad-spectrum antibiotic produced by streptomyces bacteria
Tetracyclines for stable …
consequences?
chelates with polyvalent metal ions such as Ca++, Al+++, Cu++, Mg++
consequences
1. should not be admin with calcium rich foods b/c insoluble chelates are not absorbed from GI tract; should not be admin with antacids that contain multivalent metals (TUMS)
- should not be admin to children when they are forming their permanent teeth, b/c chelate calcium during formation of teeth resulting in permanently brown or grey teeth
- pain on injection is caused by formation of insoluble calcium complexes (minimize pain by injection with EDTA which chelates the calcium)
WRT tetracycline, the hydrogen on the amine-bearing carbon atom is …, resulting in …
acidic, resulting in enolization and epimerization
this is an inactive product
Dehydration
tertiary, benzylic hydroxyl group at C6 has an antiperiplanar relationship with the proton at C5a and is set up for elimination
Epianhydrotetracycline is toxic to the … and can produce a ….. like syndrome, meaning
Toxic to the kidneys
Fanconi like syndrome
meaning that there is a failure of reabsorption in the renal tubules (PCT)
What forms of tetracycline are completely free of potential toxicity to the kidneys?
minocycline and doxycycline
b/c they lack a C-6 hydroxyl group
Cleavage in base - Tetracyclines
undergo cleavage in base at pH values of 8.5 or above
the lactone product is inactive
Mechanism of action of tetracycline
bind to the 30S ribosomal subunit and inhibit 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
Therapeutic use of tetraclines
Broad-spectrum antibiotics
- Most common use is for treatment of acne
- Drug of choice for chlamydia, rickettsia, brucellosis, and spirochetal infections
Also used for
- anthrax
- plague
- tularemia
- Legionnaries’ disease
What are specific agents within the tetracycline class?
- Tetracycline
- Demeclocycline
- Meinocycline
- Oxytetracycline
- Doxycycline
tetracycline
- generic and relatively inexpensive
2. food and milk lower oral absorption by about 50%
demeclocycline - how is it different than tetracycline?
how is it similar?
it has a secondary hydroxyl group at C6 instead of the tertiary hydroxyl group, therefore, it dehydrates more slowly than tetracycline
food and milk lower oral absorption by about 50%
minocycline - how is minocycline different than the rest?
oral bioavailability?
lacks C6 hydroxyl group and therefore does not undergo acid-catalyzed dehydration – so no potential for 4-epianhydrotetracycline mediated toxicity
oral bioavailability is 90-100%
absorption is lowered by ~20% when taken with food or milk
minocycline is the only tetracycline that causes
vestibular toxicity (vertigo, ataxia, nausea)
oxytetracycline - what is notable about its properties?
oral bioavailability?
most hydrophilic tetracycline
oral bioavailability is ~60%
– reduced by 50% when taken with food or milk
doxycycline - synthesized from?
structural differences from other tetracyclines?
oral bioavailability?
half life?
synthesized from oxytetracycline
lacks C6 hydroxyl - does not undergo acid-catalyzed dehydration - no potential for 4-epianhydroxtetracycline-mediated toxicity
oral bioavailability 90-100%
– reduced by 20% when taken with food or milk
half life 18-22 hr which permits once a day dosing
what is considered to be the tetracycline of choice? why?
doxycycline
no potential for 4-epianhydrotetracycline mediated toxicity and it produces fever GI symptoms than other tetracyclines
