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Drugs Used As Interventional Agents in Nuclear Medicine

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Drugs Used As Interventional Agents in Nuclear Medicine THE UNIVERSITY OF NEW MEXICO HEALTH SCIENCES CENTER COLLEGE OF PHARMACY ALBUQUERQUE, NEW MEXICO The University of New Mexico Correspondence Continuing Education Courses for Nuclear Pharmacists and Nuclear Medicine Professionals VOLUMEVII, NUMBER2 Drugs Used as Interventional Agents in Nuclear Medicine by: Vivian S.bveless, PharmD, RPh, BCNP o The Univemi~ of New Mexico Health Sciencw Center Collcg. of ~armacy is mpprovd by the American Council on Pharmaceutical Wucation ~ a provider m@ of continuing pharmaceutical ducacion. Program No. 039-000-98-001 -HM. 2,5 Contnct Hours or .25 CWS Coorditi”ng Wifor and Director of Phrmacy Co&”nuing Educ&”on William B. Hladik III, MS, RPh College of Pharmacy University of New Mexico Health Sciences Center Assoctie ~tior and Production Spectitit Sharon 1. Magers Ramirez, Administrative Assistant II College of Pharmacy University of New Mexico Health Sciences Center Witotial Board George H Hinkle, MS, RPh, BCNP William B. Hladik III, MS, RPh Jeffrey P. Norenbtirg, MS, RPh, BCNP Laura L. Boles Ponto, PhD, RPh Timothy M. Quinton, PharmD, MS, RPh, BCNP Guwt Reviewer Sam C. Augustine, PharmD, RPh, BCNP While the advice and information in thi~ publication are believd to be true and accurate at press time, neither the author(s) nor the editor nor the publisher can accept any legat responsibility for my errom or omissions tbt may be made. Thc publisher makes no warranty, express or implied, with res~t to the material contained herein. Copyright 1998 University of New Mexico Health Sciences Center Pharmacy Continuing Hucation Albuquerque, New Mexico DRUGS USED AS INTERVENTIONAL AGENTS IN NUCLEAR MEDICINE STATEMENT OF OBJECTIVES The primary purpose of this lesson is to provide a basic understanding of drugs used as interventional agents in the practice of nuclear medicine. Upon successful completion of this material, the reader should be able to: 1. Identi& the indications for interventional agents used in various nuclear medicine studies. 2. Know the dosage ranges for the interventional drugs. 3. Discuss the proposed mechanism(s) of action for each of these pharmaceuticals. ● 4. Describe the precautions and contraindications associated with these drugs. 5. With selected interventional pharmaceuticals, know the treatment if an adverse reaction occurs. COURSE OUTLINE DRUGS USED AS INTERVENTIONAL AGENTS IN NUCLEAR MEDICINE I. INTRODUCTION by: II, MYOCARDIAL PERFUSION IMAGING Vivian S. Loveless, PharmD, RPh, BCNP A. Adenosine Program Manager - Clinical Suppor& B. Dipyridarnole Syncor International Corp. c. Dobutarnine Cordove, TN III. RADIONUCLIDE RENAL STUDIES A. Furosernide INTRODUCTION B. Captopril c. Enalaprilat In many nuclear medicine studies, pharmawlogic interventional agents are essential component. Care Iv. HEPATOBILMY IMAGING must be exercised with dosage determination and A. Sincalide administration of these pharmaceuticals since there is a B. Morphine risk of causing adverse drug reactions. The severity of c. Phenobarbital these reactions varies with the different drugs. In this lesson, the pharmaceuticals are categorized v. MECKEL’S DIVERTICULUM IMAGING according to the type of imaging study; the focus is on A. Cirnetidine traditional nuclear medicine rather than PET imaging. B. Pentagastrin Various aspects of these conventional drugs are c. Glucagon discussed in terms of their use as adjuncts to nuclear medicine studies. VI. CENTRAL NERVOUS SYSTEM IMAGING A. Acetazolamide MYOCARDIAL PERFUSION IMAGING VII. SCHILLING TEST Myocardial pefision imaging with the injection of a o A. Cyanocobalamin radiopharmawutical during stress can demonstrate the presence of myocardial ischemia. The uptake of VIII. CASE STUDIES radiopharmaceuticals used in myocardial perfusion A. Adenosine Case Study scintigraphy is proportional to the regional blood flow. B. Cholescintigraphy Case Study Differences in regional cardiac blood flow result in c. Renal Case Study nonhomogeneous uptake of the radiopharrnaceutical which is the primary criterion used to diagnose coronary 1x. SUMMARY artery disease. During exercise-induced vasodilation, blood flow in myocardial regions supplied by stenotic coronary arteries does not increase to the extent that it does in areas supplied by normal coronary arteries. Pharmacologic stress agents offer an alternative to exercise in patients who are unable to attain an a-table level of exertion or who are unable to exercise due to physical limitations. The three pharmacologic stress agents covered in this unit are adenosine, dipyridamole, and dobutamine. Adenosine Mechanism of Action. Adenosine is an endogenous nucleoside found in all cells of the body, and it is a potent coronary vasodilator. It is reported to exert its pharmacological effects by activating specific cel@ surface receptors Al and A2. Once adenosine interacts with A2-receptors, there is enhanced production of 2 adenylate cyclase and cyclic adenosine monophosphate dipyridamole use; and hypotension (< 80 mm Hg systolic with a reduction of sarcolemmic calcium uptake. This pressure).3’12’13’14 results in corona~ vasodilation.7’12’13 Precautions. When adenosine is administered to Once adenosine is transported into cells, it is rapidly patients rmiving drugs which have depressant effects on ● metabolized to inosine via dcamination by adenosine the SA and AV nodes, caution should be exercised dcaminase in the cytosol or via phosphorylation to because of the potential for additive or synergistic effects adenosine monophosphatc by adcnosine kinase. The of these agents. 12 rapid inward cellular transport and metabolism of Adverse Eflects. Among 1421 patients in U.S. clinical adenosine yields an ultra-short half-life which has been trials, the following reactions were reported with an reported to be less than 2 seconds, It follows, then, that incidence of 1°A or greater: flushing (440/o); chest adenosine must be administered as a constant infusion dismmfoti (40%); dyspnea or the urge to breathe duply when used for its vasodilator effects for nuclear cardiac (28%); headache (18%); throat, neck, or jaw dismmfort imaging purposes.1”12’13’14 (15%); gastrointestinal discomfort (13%); lightheaded- Methodolop. Patient preparation requires nothing ness/~ness ( 12Yo); upper extremity discomfort (4Yo); by mouth for a minimum of 4 hours with caffeine- ST segment depression (3Yo); 1st degree AV block (3%); containing beverages and foods stopped for at least 12 2nd degree AV block (3Yo);paresthesia (2VO);hypo- hours prior to the study. Long acting aminophylline or tcnsion (2Yo);nervousness (2Yo);and arrhythmias (lYo). theophylline preparations should be discontinued for 48 Even though adcnosinc has a very short half-life, 10.6% to 72 hours prior to the study. The exception to this is of the side effects occurred several hours after pentoxifyllinc since it does not inhibit the action of termination of the infusion rather than during the adenosine. Sincedipyridamoleblocks the cellular uptake infusion. It was also reported that 8.4% of adverse of adenosine which could significantly increase its level effects beginning during the infusion persisted for up to in the blood and tissues, it is recommended that patients 24 hours after mssation of the infusion; however in many taking dipyridamole chronically should not receive cmes, it was not possible to determine whether these late adenosine until 24 hours after the last dose of adverse reactions were due to the adenosinc infusion or dipyridm-nole. The mmmended adult dosing regimen is some other factor. In this same group of patients, some 140 pg/kg/min intravenously infused continuously over of the adverse reactions listed with an incidence of less 6 minutes using an infusion pump (for a total dose of than 1VO were nonfatal myocardial infarction, life- ● 0,84 mg/kg). The radiopharmaceutical is injected at 3 threatcning ventricular arrhythmia, thirddegree AV minutes into the infusion. Except when severe adverse block and bradycardia. The package insert also reports reactions prohibit, it is recommended to continue the that fatal cardiac arrest and sustained ventricular adcnosinc infision for at least 1 minute afier the tachycardia (requiring resuscitation) had been reported radiopticeutid is injected. In some cases of severe coincident with the infusion of adenosine, but it did not adverse reactions, the cardiologist may request that the provide a pcrccnt incidence.’2 infusion rate be decreased rather than stopped.34’6’7”~14 Clinidly it has been observed that the adverse effects Since ‘“’TI undergoes redistribution, imaging should of adenosinc disappear within 1 or 2 minutes when the begin immediately after the termination of the adenosine infusion is dismntinued. The package insert reports that infusion; however, imaging with ‘%Tc-tetrofosmin or in controlled clinical trials, aminophylline (thcophylline ‘gmTc-sestamibi can bc delayed for 30 minutes after 50-125 mg via slow intravenous administration) was cessation of the infusion because they only minimally neededto abort the side effects of adenosine in less than redistribute. During the adenosinc infusion and for a 27. of the patients. Even though it is generally not minimum of 5 minutes after termination of the infusion, necessary to administer aminophyllinc, the standard the patient’s ECG should bc monitored continuously with adenosine antagonist, it still should be available in all blood pressure measurements obtained every cases.3’2’4 minute.3.’4’74’75 Contraindications. The following arc contraindi- Dipyridamole cations to the use of adcnosine:
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