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PMC 537 EXAMINATION 4 2001 DATE: Nov 15th FROM: Edward JN Ishac, Course Director NOTE: This exam is scheduled to last for 2 HOURS. Apportion your time to approximate 1 minute per point value. Please write the last 4 digits of your social security number on each page of the exam. Also please answer the questions from each lecturer on separate pages from those of the others. Finally, before answering the following questions, read and analyze them carefully to identify the information being requested. When you have done this, write your response, using the same organizational format as the question. Be sure to address each point raised in the question, but you are strongly discouraged from including extraneous information not asked for (even though you may be very eager to demonstrate your knowledge). There are FIVE exams scheduled for this course. The questions will be as they were in the past, i.e., short answer and/or essay type. Each exam will be worth 100 points, so figure on an 7 point question that should take 7 minutes to answer per lecture hour. There is no cumulative final exam, so all exams are weighted evenly in the final grade. GOOD LUCK 2 Opioid Analgesics & Antagonists `Dr. Selley 26 points total Question 1 (6 points). Name the six chemical classes of exogenous opioid ligands and give one example of each that is an agonist (partial agonist OK also). Question 2 (4 point). A. Pro-opiomelanocortin (POMC) is the precursor for what opioid peptide? (1 pt) B. What is the N-terminal five amino acid sequence of this POMC-derived peptide? (2 pt) C. Would you expect this peptide to be more potent, less potent or equally potent in the mouse vas deferens compared to the guinea pig ileum bioassay? (1 pt) Question 3 (7 points) Fill in the blanks (1 pt each blank). A. All opioid receptors are coupled to the _______________ subfamily of G-proteins. These Gproteins stimulate ______________ channels, inhibit _________________ channels and inhibit the activity of the second messenger synthetic enzyme ______________________. B. Chemical modifications of the _____________ position are most likely to alter morphine’s efficacy, whereas modifications at the ______________ position generally change its potency. C. The _______________________, which becomes hyperactive during opiate withdrawal, is a brainstem nucleus that contains the most norepinephrinergic neurons in the brain. 3 Opioid Analgesics & Antagonists `Dr. Selley continued Question 4 (9 points). A. Name the three types of opioid receptors that have been cloned, and for each list a highlyselective agonist and a highly selective antagonist. (6 pts) B. Activation of which one of these opioid receptor types produces respiratory depression, and why only this one? (3 pts) 4 Drug Abuse Dr. Balster 20 points total Question 1 (5 points). Why does route of drug self-administration play such an important role in drug abuse? Question 2 (7 points). What is the relevance of the phenomenon of cross-dependence to the abuse liability of opioid medications and to the approved pharmacotherapies for heroin abuse? 5 Drug Abuse Dr. Balster continued Question 3 (1 point). Name one substituted phenethylamine hallucinogen. Question 4 (1 point). What is the likely cellular mechanism of action for the hallucinogenic effects of LSD? Question 5 (1 point). What is the likely cellular mechanism of action for PCP intoxication? Question 6 (2 points). What exactly is the “crack” form of cocaine? Question 7 (3 points). What are the differences between abuse of nitrous oxide and toluene? 6 Hallucinogens Dr. Wiley 7 points total Question 1 (7 points). A. List the four major classes / targets of neurotoxicants. (2 pts) B. Briefly, describe one factor that helps to protect the central nervous system from damage. (2 pts) C. Name one substance or class of substances for which degeneration of axons is the primary mechanism of action for its neurotoxic effects. Why are some of the effects of this type of neurotoxin delayed? (3 pts) 7 Marijuana Dr. Martin 7 points total Question 1 (7 points) Please provide short answers to the following questions regarding marijuana. a. Please draw the structure of delta-9-THC. b. What is the major urinary metabolite of THC? Estimate the length of time it be detected in urine after smoking a couple of joints by routine drug screening methods. c. Describe individuals who might be at higher risk for adverse marijuana effects (high risk groups). d. Describe the pathways responsible for the synthesis and metabolism of anandamide. 8 Antidepressants/Parkinsons D. Dr Robinson 26 points total Question 1 (10 points). A B E C B D A. The diagram above depicts a dopaminergic synapse. Using the following list of drugs used in the pharmacological therapy of Parkinson's disease, match the drug with its therapeutic site of action: (Sites A–E): Benztropine______, l-Dopa______, Pergolide______, Selegiline______, & Tolcapone______ B. In the space provided, briefly explain the mechanism of action and one side effect associated with each of drugs A - E. i. Benztropine ii. l-Dopa iii. Pergolide iv. Selegiline v. Tolcapone 9 Antidepressants/Parkinsons D. Dr Robinson continued Question 2 (8 points). Briefly describe two ways in which the therapeutic and side effects of the atypical antipsychotic drug clozapine are similar to or different from those of the “classical” antipsychotics. For each difference or similarity, please provide the likely mechanism. Question 3 (8 points) Compare and contrast monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs). Give at least 2 similarities and 2 differences. 10 Lipid Metabolism Dr. Lamb 14 points Question 1 (14 points). 1. 2. 3. 4. 5. 6. 7. 8. Cholestryramine Atorvastatin Nicotinic Acid Gemfibrozil Clofibrate HDL VLDL HMGCoA Reductase 9. 10. 11. 12. 13. 14. 15. 16. LDL IDL Apoprotein CI Apoprotein CII Apoprotein E Apoprotein B-48 Apoprotein B-100 7 hydroxylase 17. 18. 19. 20. 21. 22. 23. 24. High sugar intake High fat intake Diabetes Mellitus Lipoprotein Lipase Hypothyroidism Low fat intake Adipose Tissue Lipase LCAT From the list above select the best possible answer to the following 14 questions. Some answers may be used more than once or not at all. 1. A drug that lowers plasma LDL levels by binding bile acids in the intestine. _____________ 2. An elevation in this lipoprotein reduces the risk of atherosclerosis. _______________ 3. Lowers plasma LDL levels by inhibiting cellular HMGCoA reducatase activity. ___________ 4. A dietary factor that markedly elevates plasma LDL levels. _______________ 5. A dietary factor that markedly elevates plasma VLDL levels. _______________ 6. The apoprotein that activates lecithin cholesterol acyltransferase. _______________ 7. A disease state that markedly elevates plasma VLDL levels. _______________ 8. The best drug for lowering high levels of plasma VLDL. _______________ 9. The best drug for lowering high levels of plasma LDL. _______________ 10. The best drug combination to lower high plasma levels of both VLDL and LDL. __________ 11. A drug that increases cellular cholesterol biosynthesis. _______________ 12. A disease state that lowers cellular LDL receptor levels. _______________ 13. An enzyme involved in the clearance of chylomicrons and VLDL. _______________ 14. A lipid-lowering drug that produces increased death rates compared to placebo. _________