Lecture 11: Clindamycin, Tetracycline, Quinolones Flashcards
Cushman's Section
What is the Mechanism of action for clindamycin and compare it to erythromycin?
- Similar to Erythromycin; Inhibits protein synthesis by binding to 50s - preventing movement to the A-site
What is the main clinical use of Clindamycin?
- Gram (+): Strep & Staph
- Gram (-): Bcteroides & Fusobacterium
- TREATS bone infections with SA, Severe ance, vaginosis
- IV Clinda with pyrimethamine Treats AIDS by Toxoplama gondii
What is the Main Side Effect that limits the its clinical use of Clindamycin?
- Pseudomembranous Colitis and Diarrhea
What is the metabolic pathway of clindamycin and state the effects of metabolism on biological activity?
- By CYP450 in the liver to Sulfoxide & N-demethylated Derivative
What is the absorption, distribution, and elimination of clindamycin?
- Absorption: GI tract
- Distribution: widely even in CNS
- Elimination: Urine & Bile
Half Life of 1.5-5 h
May need to dose adjust
What are some of the adverse effects of clindamycin?
- Diarrheaa, C. Diff, Nausea, Vomiting, Stomach Cramps, Rash
What is Psudomembranous Colitis and its signifiances?
- Potentially Lethal Condition
- An overgrowth of C. Diff in the colon that SHOULD be treated with Metro or Vanco
What is the reason that Tetracyclines SHOULD NOT be given with food that are rich in Calcium, or with other drugs that are rich in Calcium, or other heavy metals?
- Tetracyclines WONT be absorbed with Calcium products
- Should be given 1 hour before or 2 hours after
What is the preferred route of administration of the Tetracyclines?
- ORAL
What is the reason that Children SHOULD NOT take Tetracycline during the period of permanent teeth formation?
- Stain the Teeth –> Brown or Grey
What is Epimerization and what effect does it have on bioloigcal activity?
- There is an elongation [amide group] that makes it inactive
- Slow in steady state & rapid at pH4
What is the pH that tetracycline epimerization is most rapid and the relative rate of epmierizatin in the sild state vs in solution?
- pH 4 = most rapid
- SLOW in solid state [capsules]
What is Tetracycline Dehydration?
- C-6 Group is antiperiplaner so a H- at C-5a kicks it off making a Methyl
What is the toxicity of Epianhydrotetracycline?
- Toxic to kidneys
- Produces Fanconi syndrome [failure of reabsorption in kidneys = malabsorption] which is FATAL
What is the why that there is selective toxicity of tetracyclines to bacteria BUT not the host?
- Eukaryotic cells DONT have uptake mechanisms
What is the reason that Minocycline and Doxycycline lack the renal toxicity of Tetracycline?
- Lack C-6 hydroxyl group
What is the way that the Tetracycline are cleaved under basic conditions?
- Cleave at pH <8.5; lactone is inactive
What is the mechanism of action for the Tetracyclines?
- Bind to 30s and inhibit synthesis by blocking tRNA to A-site = termination of chain growth
What is the Main Theraputic Use for Tetracyclines?
- ACNE
- Chlamydia, Rickettsia, Brucellosis
- Anthrax, Plague, Tularemia, Leginonnarries
What is the main advantage of using tetracycline itself rather than on of the other antibiotics in the tetracycline class?
- Generic and Inexpensive
What is the way that Demeclocycloine is more stable to dehydration than tetracycline?
- Hydroxyl group at C-6 instead of tertiary hydroxyl group
- Dehydrates slow because of secondary cation
What is the reason that Minocycline and Doxycyline do not undergo dehydration?
- Lacks C-6 hydroxyl group
What is a unique toxicity for Minocycline in comparsion to the other Tetracyclines?
- Vistibular Toxicities [Vertigo, Axtaxia, Nausea]
What is the reason that Doxycycline is widely considered the Tetracycline of Choice?
- NO 4 -epianhydrotetracycline toxicity AND fewer GI issues
