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PMC 537 EXAMINATION 5 2000 DATE: December 11th 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 Multiple Choice Questions Answers: Balster 1.____ Egle 1.____ 2.____ 2.____ 3.____ 3.____ 4.____ 4.____ 5.____ 5.____ 6.____ 6.____ 7.____ 7.____ 8.____ 8.____ 9.____ 9.____ 10.___ 10.___ 11.___ 11.___ 12.___ 12.___ 2 Diuretics Dr. Costanzo 12 points total 1. For each group of diuretics, give the name of one drug in this class, the site of action in the nephron, and the transporter (or transport process) that is inhibited when the drug produces an increase in Na+ excretion. (3 points, 1/4 point each response). Diuretic class Name of drug Site in nephron Transporter inhibited CA inhibitors Loop diuretics Thiazide diuretics K-sparing diuretics 2. For each diuretic group below, name the acid-base disorder it produces and, in one or two sentences, explain why. (3 points, 1 point for each diuretic group.) CA inhibitors Loop diuretics K-sparing diuretics 3. For each diuretic group below, state the expected effect on Ca2+ excretion and, in a few sentences, why this effect on Ca2+ occurs. (3 points, 1.5 points for each diuretic group.) Loop diuretics Thiazide diuretics 4. What is the effect of loop diuretics on the ability to concentrate the urine in a person who is dehydrated? (1.5 points) 5. What happens to the serum Na+ concentration in a person taking a thiazide diuretic who is drinking large volumes of water, and why? (1.5 point) 3 Drug Abuse 1. B. C. D. E. D. E. Receptor down-regulation Receptor upregulation Changes in biodisposition Altered signal transduction Changes in levels of endogenous opioids Relative to drugs with short durations of action, long-acting drugs A. B. C. D. E. 6. they have no positive reinforcing effects most do not produce cross-dependence with heroin they have a slow onset of action they are not available clinically more than one of the above The cellular basis for opioid tolerance probably involves A. B. C. 5. N-methyl-D- aspartate (NMDA) gamma-amino-butyric acid (GABA) 5-HT2 D2 5-HT1A Opioid mixed-agonist/antagonists have lower abuse potential than full opioid agonists because. A. B. C. D. E. 4. The ability of antagonists to maintain opiate dependence insures patient participation in the treatment program. The primary use of antagonists is to precipitate abstinence. Patients are usually medicated with antagonists before being placed on methadone. Patients are detoxified before being placed on antagonist therapy. Antagonists are particularly suited for in-patient treatment Which of the following receptors is most likely to serve as the basis of hallucinogen intoxication? A. B. C. D. E. 3. 12 points total Which of the following statements is true about the use of opiate antagonists such as naltrexone in the treatment of heroin abuse. A. 2. Dr. Balster have a less intense withdrawal syndrome require more frequent use to produce physical dependence have a delayed emerging withdrawal syndrome have a prolonged withdrawal syndrome more than one of the above Alcohol withdrawal symptoms are similar to the withdrawal symptoms from A. B. C. D. E. heroin barbiturates phenothiazines benzodiazepines more than one of the above 4 7. Which of the following is a representative indolamine hallucinogen? A. B. C. D. E. 8. A heroin addict receives this drug and experiences an immediate, severe withdrawal syndrome. He was probably given A. B. C. D. E. 9. heroin cocaine barbiturate haloperidol marihuana Which drug(s) of abuse can produce a personality deterioration which resembles paranoid schizophrenia? A. B. C. D. E. 12. physical dependence psychological dependence cross-dependence tolerance drug addiction Convulsions are more likely to occur with____________withdrawal. A. B. C. D. E. 11. naloxone methadone dextropropoxyphene disulfiram heroin A heroin addict seeks a prescription from a physician for hydromorphone (Dilaudid) for the treatment of back pain. If, in truth, the patient is trying to relieve heroin withdrawal symptoms, this is best considered an example of A. B. C. D. E. 10. LSD PDQ PCP MDMA mescaline toluene marihuana amphetamine LSD more than one of the above To which drug are the effects of phencyclidine (PCP) most similar? A. B. C. D. E. LSD dimethyl-tryptamine amphetamine ibogaine ketamine 5 Neurobehavioral Toxicology Dr. Wiley 7 points total 1. List the four major classes / targets of neurotoxicants. (2 points) 2. Which of these targets is the primary target of MPTP? (one word answer, 1 point). 3. Describe the presumed mechanism of action for the neurotoxic effects of MPTP, including specification of which system it affects and why it affects that system. Use a diagram if desired (4 points) Antiarrhythmics/Calcium Blockers Dr. Satin 20 points total 1. For each of the Vaughan-Williams classes and subclasses of antiarrythmic drugs, provide a brief description of the typical class effect, and list a prototype drug (12 points). 2. Briefly mention two limitations of the Vaughan-Williams classification? (1 points) 3. Briefly describe reentry arrythmias, and how antiarrytmic drugs in general interfere with their generation (3 points) 4. Discuss the relative clinical usefulness of the Ca channel blockers nifedipine vs. verapamil, and describe their mechanisms of action in very basic terms (4 points) Renal Pharmacology 1. Dr. Lichtman 7 points total Select acetaminophen, cadmium, or chloroform to illustrate why the kidney is more susceptible to the toxic effects of the selected agent than other organs. (In your answer, include the most likely mechanism of action for the drug you selected, describe the clinical signs that would be observed, the primary site of damage, and of course why the kidney is particularly susceptible to toxicity). Remember to select only one agent (7 points). 6 Antihypertensive/Cardiac Stimulants Dr. Ishac 30 points total You have a choice of four (4) questions, answer any three (3) questions. Each question is worth 10 points. Question 1 (10 points). A 38 year old man over four separate office visits, has documented blood pressure of 160/100 mmHg. Upon further examination and many (expensive) tests, no underlying cause of the hypertension can be found and he is given a diagnosis of essential hypertension. A. The managing physician wishes to give a single drug treatment to control the hypertension. Assuming there is no other complicating disease present. List the four front-line classes of drugs that would be suitable to treat the hypertension in this individual (4 points). B. Assuming the use of a single agent was not sufficient to lower the blood pressure to an acceptable level. What combination therapy (2 or 3 agents) would complement each other in the treatment of the hypertension with fewer side-effects. Use flow diagrams with arrows to explain your rationale (6 points). Question 2 (10 points). A. Describe the mechanism of action of the Angiotensin converting enzyme (ACE) inhibitors. Use flow diagrams with arrows to illustrate your answer. Name one commonly used ACE inhibitor (5 points). B. Describe the proposed mechanism of action of the beta-adrenoceptor blocking agents. Use flow diagrams with arrows. Name two commonly used betaadrenoceptor antagonists (5 points). Question 3. (10 points) A. Briefly discuss the cellular mechanism(s) of action of the cardiac glycosides in the treatment of Congestive heart failure (CHF) (5 points). B. Discuss the significance of the Therapeutic index in relationship to the cardiac glycosides (2 points). C. Discuss the importance of serum K+ level on the actions of cardiac glycosides. List a drug class which may affect the serum potassium level (3 points). 7 Question 4. (10 points) Ishac continued For the follow individuals select a suitable agent or agents to treat their medical conditions with the least potential for side-effects. Also any drug class which may be contraindicated. You have a choice of ten (10) scenarios, answer any five (5) scenarios. Each scenario is worth 2 points. 1. A 55 year old, hypertensive white male with CHF and angina pectoris. 2. A 45 year old, hypertensive afro-American woman with diabetes. 3. A 65 year old, hypertensive white woman who is also obese. 4. A 50 year old, hypertensive white woman who has asthma. 5. A 55 year old, hypertensive white male with benign prostrate hypertrophy 6. A 70 year old, afro-American male with CHF. 7. A 35 year old, balding, vain, white male with hypertension. 8. A 45 year old, hypertensive white woman who suffers from migraines. 9. A 50 year old, hypertensive white woman with glaucoma 10. A 50 year old, hypertensive afro-American woman with diffuse pheochromocytoma. 8 Antianginal Agents 1. ATP, NO, NO, disulfide bonds, beta receptors, calmodulin calmodulin cGMP calcium MLCK exhibit, exhibit, not exhibit, not exhibit, cellular dispositional cellular dispositional According to the Needleman hypothesis, the development of tolerance to the nitrates is due to the formation of: a. b. c. d. e. 5. decreased unchanged increased unchanged decreased You would expect an isolated aortic strip taken from an animal chronically administered nitroglycerin (GTN) to __________ tolerance to GTN administered in vitro, indicating that GTN tolerance has a __________ basis. a. b. c. d. 4. unchanged, decreased, unchanged, increased, increased, It appears that the vasodilator action of nitrates involves the formation of ________ and an increase in the amount of ________ in the vascular smooth muscle cell. a. b. c. d. e. 3. 12 points total In typical (or effort, exertional, etc.) angina, 02 supply to the heart is and 02 demand is: a. b. c. d. e. 2. Dr. Egle cyclic AMP sulfhydral groups excessive amounts of NO disulfide bonds inactive metabolites at an unusually high rate An increase in cGMP in a vascular smooth muscle cell results in __________ of myosin-LC and a(n) __________ in calcium uptake by the sarcoplasmic reticulum. a. b. c. d. phosphorylation, phosphorylation, dephosphorylation, dephosphorylation, increase decrease increase decrease 9 6. Which of the following observations would not support the concept that cGMP is a mediator of nitroglycerin (GTN) action? a. b. c. d. e. 7 The duration of action of nitroglycerin is approximately __________ hours for the sublingual tablet and __________ hours for the transdermal membrane. a. b. c. d. e. 8 3, 0.5, 12, 0.5, 3, 12 6 24 24 72 Adverse effect(s) closely associated with nitroglycerin and related drugs: a. b. c. d. e. 9. inhibition of cyclic guanoside phosphodiesterase enhances the relaxant effect of GTN GTN activates the cGMP-producing enzyme guanylyl cyclase inhibition of guanylyl cyclase activity reduces the relaxant effect of GTN tolerance development to GTN is accompanied by decreased guanylyl cyclase activity all of the above support the stated concept increased hepatic transaminases headache GI irritation nephrotoxicity all of the above Which of the following combinations of antianginal drugs would pose the lowest risk of cardiac depression (contractility, conduction) or reflex tachycardia? a. b. c. d. propranolol and nitroglycerin nifedipine and nitroglycerin propranolol and verapamil the risk would be equal for the three combinations Select the drug(s) most closely related to each statement below a. b. c. d. e. nitrate beta blocker dihydropyridine calcium blocker a and c all of the above 10 May cause a reflex tachycardia 11 Tolerance associated with chronic use 12 Reduce(s) cardiac preload more than afterload through peripheral vasodilation 10 Extra A 50 year old, hypertensive white woman with arrhythmias.