General Anesthesia Capstone Project - General Information amp; Thinking Questions You will not be able to access the thinking questions...

General Anesthesia Capstone Project – General Information & Thinking Questions You will not be able to access the "thinking questions" drop box until you score at least 80% on one take of the “information review questions”. General Information : Before taking the Information Review Questions, it is recommended that you review the following topics: Attractive Forces in Compounds Chemical Reactions Diffusion Enantiomers & Chiral Receptors Functional Groups Gases Hydrophilic Definition Organic Reac tions Polarity of Bonds Polarity of Molecules Scientific Method Solubility Project Overview & Thinking Questions : Surgical procedures took a major leap forward in patient comfort with the advent of anesthetic agents in the mid -1800s. The first demonstrated use of nitrous oxide was in 1844 and that of diethyl ether in 1846. While nitrous oxide is still commonly used in dental applications, diethyl ether has been supplanted by a new generation of anes thetics which offer fewer side e ffects and are notably non -flammable. One class of the new anesthetics is fluorinated hydrocarbons. In this capstone project, you will examine the chemistry of these fluorinated hydrocarbons, one proposal for how general anesthetics work, and how inhalation anesthetic s are delivered. Two examples of fluorinated hydrocarbon anesthetics are Isoflurane and Sevoflurane. 1.) (3 points) Identify the different functional groups in Isoflurane and Sevoflurane. One of the general characteristics of general anesthetics is that they are lipophilic compounds. Lipophilic means lipid loving; in other words, lipophilic compounds would want to dissolve in lipids. A related term you have learned about is hydrophilic. In pharmacology, it is important to understand how lipophilic a drug is as well as how hydrophilic a drug is. O F F F F F Cl Isoflurane O F F F F Sevoflurane F F F 2.) (3 points) Explain what characteristics of functional groups make a n organic compound lipophilic and what ones make a compound hydrophilic. Explain why these characteristics are lipophilic or hydrophilic. 3.) (3 points) Based on what you have learned in Modules 5 and 8 this semester, why should you be surprised that these compounds are lipophilic? Explain your answer. NOTE – Do not say that you are not surprised as you really should be . The exact mode of action for general anesthetics has not been elucidated. Many hypotheses have been proposed as to how they work. One hypothesis that has been proposed is that all lipophilic compounds act as general anesthetics by dissolving in the lipophilic cell membrane of nerve cells causing the membrane to bloat and that t he lipophilic compounds do n ot interact with any chiral receptors within the membrane, but rather it is just the quantity of compounds in the membrane that cause the effect. Two experiments (given below) were performed to test this hypothesis. For each experiment, you will need to indicate whether it proves or disproves the hypothesis given above. Experiment #1 : An experiment run to test the hypothesis found that cyclopropane act ed as a general anesthetic. 4.) (2 points) Is cyclopropane a lipophilic or hydrophilic compound? 5.) ( 3 points) Does the fact that cycloproane acts as a general anesthetic support or dispr ove the hypothesis listed above? Explain your answer. Experiment #2 : An experiment run found that the two enantiomers of Isoflurane do not act the same as anesthetics, in that it took a smaller amount of one to produce the same anesthetic effect as the other. 6.) (2 points) What roles do chiral receptors play in biological systems? 7.) ( 3 points) Does the fact that the two enantiomers of Isoflurane do not act the same support or disprove the hypothesis listed above? Explain your answer. Mode of delivery for drugs plays a very important part of the design of compounds. Inhalation anesthetics as their name implies are delivered to the body via the lungs. The anesthetic enters the lungs and is absorb ed through the alveoli by passive diffu sion. It then passively diffuses into the blood stream which in turn delivers it to all tissue throughout the body, where once again the anesthetic passively diffuses into the tissue. inhaled/exhaled gases ⇋ alveoli ⇋ blood ⇋ tissue 8.) (3 points) Explai n why an anesthetic diffuses from the inhaled air into the lungs onward to the tissue in terms of partial pressure. 9.) (3 points) Explain why anesthetics must be continually administered to keep a patient from waking up? Hint – the anesthetics are not metabolized by the body. 10 .) (3 points) Explain how an anesthesiologist can use the partial pressure of anesthet ic being delivered to a patient to determine amount delivered ? Hint – in chemistry, amount refers to moles. One concern with using any drug is the potential for harmful metabolites or degradation products to occur. One concern with Sevoflurane is that it reacts with chemicals used in the absorbents that capture exhaled carbon dioxide. This reaction create s the toxic degradation product (call ed Compound A) shown below . 11 .) (2 points) While this exact reaction is not in your textbook, there is a similar reaction where atoms are removed to form an alkene. What type of reaction is the one in the textbook? 12 .) (2 poi nts) What atoms are removed in the reaction shown in the book? 13 .) (3 points) Pr opose a valid balanced chemical equation for Sevoflurane forming Compound A. Your balanced chemical equation must show molecular formulas for all reactants and products involved in the reaction. For the organic molecules, remember the molecular formulas are written as C #H#F#O#. Think about what atoms are different between Sevoflurane and Compound A. For full credit, y ou must justify your proposal. 14 .) (2 po ints) Please give constructive feedback regarding this Capstone Project. Was it worthwhile? Did it illustrate CHE 106 concepts? What did you gain/learn from doing the project that you did not learn from the modules individually? What would you keep/re commend in future semesters? What would you change? What other information would you like to convey to your instructor with respect to this project? References: Lemke, T.L, Williams, D.A., Roche, V.F., & Zito, S.W. FOYE’S Principles of Medicinal Chemis try, 6 th ed. (2008). Philadelphia: Wolters Kluwer O F F F F F F