Clindamycin and Tetracycline Flashcards
Be able to describe the mechanism of action of clindamycin and compare it to erythromycin.
a) Similar to that of the macrolide antibiotics like erythromycin. It inhibits protein synthesis by binding to the bacterial 50S ribosome. It binds to the same site at erythromycin.
b) Binding involves RNA and not protein.
Be able to specify the main clinical uses of clindamycin
a) Effective against aerobic gram-(+) cocci and anerobic gram-(-) bacilli.
b) May be used systemically to treat bone infections with staphylococcus aureus or topically to treat severe acne. As a vaginal cream for bacterial vaginosis.
c) Treatment of lung abscesses and anerobic lung and pleural space infections. Treats MRSA.
d) Administered IV with pyrimethamine and leucovorin to treat AIDS in pts with encephalitis.
Be able to state the main side effect of clindamycin that limits its clinical use.
a) High incidence of pseudomembranous colitis and diarrhea limit the use of clindamycin to infections.
Be able to describe the main metabolic pathways of clindamycin and state the effects of metabolism on biological activity.
a) Extensively metabolized by cytochrome P450 enzymes in the liver to the sulfoxide and the N-demethylated derivative. The metabolites are pharmacologically inactive.
Be able to describe the absorption, distribution, and elimination of clindamycin.
a) 90% of the dose is absorbed from the GI tract.
b) Widely distributed and penetrates the CNS in high enough concentrations to be useful in the treatment of cerebral toxoplasmosis in HIV pts.
c) Mainly excreted in the urine and bile.
Be able to specify the main adverse effects of clindamycin.
a) Diarrhea, pseudomembranous colitis, N/V, abdominal cramps, and rash.
Be able to describe pseudomembranous colitis and its significance.
a) This is a potentially lethal condition commonly associated with clindamycin. Overgrowth of C diff, which is inherently resistant to clindamycin, results in the production of a toxin that causes a range of adverse effects ranging from diarrhea to colitis and toxic megacolon. Treat with metronidazole or vancomycin.
Be able to show how the tetracyclines bind to heavy metals.
a) Chelation. Tetracyclines form stable chelates with polyvalent metal ions such as Ca++, Al+++, Cu++, and Mg++.
Be able to state why the tetracyclines should not be administered with foods that are rich in calcium, or with other drugs that are rich in calcium or other heavy metals.
a) Because the insoluble calcium chelates are not absorbed from the GI tract. Do not administer with antacids that contain multivalent metals or with hematinics containing iron.
b) Do not take tetracyclines with milk or food.
Be able to specify the preferred route of administration of the tetracyclines.
a) Oral, since oral absorption is adequate in the absence of multivalent metal ions in the GI tract.
Be able to explain why children should not take tetracycline during the period of permanent teeth formation.
a) Tetracyclines chelate calcium during formation of teeth, resulting in permanently brown or gray teeth. The discoloration of the teeth becomes worse with time as a result of a photooxidation reaction.
b) Should also be avoided after the 4th month of pregnancy in order to avoid undesirable effects on fetal bones and teeth.
Be able to describe tetracycline epimerization, and the effect that this has on biological activity.
a) The hydrogen on the amine-bearing carbon atom is acidic, resulting in enolization and epimerization. Epimerization is the process by which one stereoisomer is converted to another. They differ in configuration at only one chiral center. The epitetracycline product is pharmacologically inactive.
Be able to state the pH at which tetracycline epimerization is most rapid, and the relative rate of epimerization in the solid state vs. in solution.
a) Epimerization is slow in the solid state and most rapid in solution at pH 4.
Be able to describe tetracycline dehydration.
b) This is a chemical reaction in which a tetracycline molecule loses a water molecule, resulting in the formation of a dehydrated derivative. This reaction involves the elimination of a hydroxyl group and a proton; the hydroxyl group at C-6 is protonated under acidic conditions and water is eliminated anhydrotetracycline (inactive) which epimerizes to form 4-epianhydrotetracycline
Be able to describe the toxicity of epianhydrotetracycline.
a) It is toxic to the kidneys and can produce a Fanconi-like syndrome (failure of the reabsorption mechanism in the proximal convoluted tubules) that can be fatal.
