How Does It Structurally Resemble the Penicillins? How Does It Structure Differ (3 Ways)?

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How Does It Structurally Resemble the Penicillins? How Does It Structure Differ (3 Ways)?

STUDY GUIDE THE CARBAPENEMS 1. What is the source of thienamycin? How does it structurally resemble the penicillins? How does it structure differ (3 ways)? 2. How does thienamycin compare to penicillin G in terms of chemical reactivity? Is it’s beta- lactam ring more or less reactive? What other chemical reaction does thienamycin undergo? What is the role of pH in these reactions? How does the “aminolysis” reaction compare to the unique reactivity of ampicillin? 3. How does thienamycin compare to the pencillins in terms of metabolic stability (reactivity)? Which enzymes cleave this drug and why? What is the product and importance of the reaction? 4. How does the structure of imipenem compare to thienamycin and penicillin G? What role does the additional “formimidoyl” group play in chemical stability? Is the beta-lactam still reactive? 5. How has the metabolic stability of imipenem been improved? What is cilastatin, what does it do and what is it’s mechanism? 6. How does the structure of meropenem compare to imipenem and penicillin G? What are the structural differences and what properties do they confer? Why does meropenem not require coadministration of cilastatin to be active? 7. How do the carbpenems compare to the penicillins in terms of mechanism of action? List three reasons that account for the relatively broad antimicrobial spectrum of the carbapenems and compare these to penicillins generally. 8. Describe the key pharmacodynamic properties (PAE, time-dependent bactericidal action) of the carbapenems that contribute to clinical actions. 9.. What are the primary mechanisms of resistance to the carbapenems and how do these compare with the penicillins. Are the carbapenems resistant to hydrolysis by all beta-lactamases? Which organisms may be resistant tot he carbapenems and why? 10. Describe why certain key pathogens (P. aeruginosa, Enterobacter, Serratia, etc) may be resistant to the carbapenems. 11. Describe the spectrum of activity of the carbapenems. Which organisms are they effective and which are they not effective against and why? 12. How is each carbapenem formulated and administered? Why are they not orally bioavailable? Why should reconstituted solutions be used promptly? 13. Are the carbapenems widely distributed (including the CSF)? 14. How are these drugs cleared? Is metabolism important? What is the route and mechanism of elimination? 15. Why are the half-lives of the carbapenems relatively short? 16. How are the carbapenems similar in their adverse reaction and drug interaction profiles to the pencillins? .

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