| Tuesday, Thursday, Friday - MoosT 1-450
Tuesday, Thursday 10:10-12:05, Friday 9:05-9:55
COURSE PREREQUISITES
Successful completion of Pharmacotherapy I-III.
All students will have completed or be in the process of completing anatomy, physiology, and pharmacology. The student is responsible for this material to the extent necessary as a framework for infectious, oncologic and toxicologic therapeutics. Thus, students are encouraged to review basic anatomy and physiology and specifically encouraged to review the section of the pharmacology textbook relevant to the classes of drugs covered.
COURSE OBJECTIVES
Infectious Diseases
The infectious diseases section of the course relates to pharmacotherapeutics and treatment of infectious diseases and aims to integrate material from MedC 6156, and other courses, with infectious disease topics important to the clinical setting. Ideally, at the end of this course the student will be able to: identify likely pathogens responsible for a particular infectious disease process; select the appropriate antibiotic(s) to provide antimicrobial coverage for these possible pathogens; select alternative antibiotics should they become necessary; and identify appropriate actions to monitor for efficacy and toxicity. To accomplish these goals, the student will be required to comprehend common microbiologic laboratory tests used to identify microorganisms.
The student will be expected to know the mechanisms of action, antimicrobial spectrum, mechanisms of bacterial resistance, common adverse reactions, pharmacokinetics, and appropriate dosing of the various antibiotics discussed in the upcoming lectures. The students will be expected, given a set of serum concentration time data, to calculate an appropriate dose and dosage interval for any one of the available aminoglycosides.
Toxicology
Upon completion of this section of the course, the student should be able to:
1. Describe the general principles in the management of all drug overdoses and chemical exposures including how to perform each of the following measures:
- Supportive care/CPR
- External decontamination (skin/eye)
- Internal decontamination (oral)
- Prevention of absorption
- Enhanced excretion
2. Know the appropriate clinical indications, uses, dosages, hazards/side effects and clinical monitoring parameters of the following agents:
- Emetics
- Lavage
- Adsorbents - Cathartics
- Whole Bowel Lavage
- Forced alkaline/acid diuresis
- Dialysis/hemoperfusion
- Antidotes
3. Describe the clinical toxicology, i.e. toxic doses, toxic blood levels, mechanism of toxicity, signs and symptoms of toxicity, clinical course, prognosis, incidence, clinical and laboratory monitoring parameters, general and specific treatments necessary to manage the following poisoning emergencies:
- Acetaminophen
- Household Products
- Carbon Monoxide
- Salicylates - Iron
- Pesticides
- Sedative Hypnotics
- Calcium Channel Blockers
- Beta Blockers
- Psychotropics
- Cyclic Antidepressants, SSRIs
- Serotonin Syndrome, Neuroleptic Malignant Syndrome
- Drugs of Abuse (e.g. cocaine, amphetamines, ethanol, etc.)
- Toxic alcohols (methanol, ethylene glycol)
- Poisonous Spiders and Snakes
- Chemical Warfare Agents Hematologic and Oncologic Malignancies
The objectives of the oncology section of the course are to provide information about the pathophysiology of common oncology disorders and to present standard therapies for treating these disorders. Emphasis will be placed on designing appropriate regimens, defining therapeutic goals, monitoring clinical and laboratory parameters, and identifying drug interactions and adverse reactions.
REQUIRED TEXTBOOKS
1. Pharmacotherapy, 6th ed, 2005, Ed. J.T. DiPiro, et. al. Reading assignments relevant to lecture topics.
2. Schwinghammer Pharmacotherapy Casebook will also be required for the Oncology Section of this course.
3. Electronic and print journal articles as outlined in the course schedules: infectious diseases, toxicology, oncology
In addition, the following references in toxicology are excellent resources for the student as additional recommended readings:
1. Ellenhorn, Matthew J. and Barceloux, Donald G. Medical Toxicology: Diagnosis and Treatment of Human Poisoning, Second Edition, Elsevier Science Publishing Company, Inc., New York, New York, 1997.
2. Goldfrank, Lewis. Goldfrank's Toxicologic Emergencies, Sixth Edition, Appleton & Lange, Norwalk, Conn., 1998.
3. Haddad, Lester & Winchester, James, Eds. Clinical Management of Poisoning & Drug Overdose, 2nd edition, WB Saunders Co., Philadelphia, 1990.
4. Poisindex, by Micromedix, Inc., Medical Information Systems, Englewood, Colorado.
WORK LOAD
For undergraduate courses, one credit is defined as equivalent to an average of three hours of learning effort per week (over a full semester) necessary for an average student to achieve an average grade in the course. We expect at least that much effort from our professional students. In this 5 credit course, you should expect to spend ten hours or more a week on coursework outside the classroom.
OVERALL DIVISION OF POINTS
The weighting of the total points for the class will be done according to the number of lectures devoted to each of the three sections: infectious diseases, toxicology, and oncology.
There will be 600 total points for the class. Infectious diseases will have 240 points, toxicology will have 160 points, and oncology will have 200 points. Each section director will divide the points within their section as they see fit.
A final grade for the course will be obtained by adding up the points gained in each section and dividing by 600, the total possible. For example, if a student received 200 points in infectious diseases, 120 points in toxicology, and 170 points in oncology, s/he would have 490 total points, or 82%, which would correspond to a final grade of B-.
Unless otherwise specified, the information below pertains only to the infectious diseases section of the course.
COURSE STRUCTURE/EXAMINATIONS
INFECTIOUS DISEASES
The examinations for the infectious disease section of PHAR 6124 consist of 4 quizzes each worth 10 points, an aminoglycoside pharmacokinetic exam worth 20 points (ultimately everyone will need to demonstrate 100% competency to receive a grade in the course), and a 180 point final examination. Quizzes and the aminoglycoside pharmacokinetics exam will be given via WebCT/Vista. However, we will only score points on the kinetics exam once and that will be on the 1st exam. For example, if a student scored 70% on the kinetics exam, his/her total grade would be calculated given the initial 70% score, and although the student would be required to take the supplemental exams on aminoglycoside kinetics to demonstrate 100% competency, no other points will be awarded. If competency is not established on the 1st aminoglycoside pharmacokinetic exam, students will be provided with two other opportunities via WebCt/Vista to establish competency.
In addition to passing the kinetics competency tests, each student MUST hand in answers to Problem Set II (http://www.courses.ahc.umn.edu/pharmacy/6124/tutorials/glycoside_problem_set_2/problems2.htm) at the beginning of the “Aminoglycoside Problem Set” lecture (to be given on January 31, 2008). Failure to hand in your completed problem set PRIOR to the start of class 1/31/08 will result in the loss of 24 points or 10% of the 240 points for the class.
If a student is unable to pass the kinetics competency s/he will not receive a grade for the ID section of the class, making it impossible to pass Phar 6124.
We strongly recommend students master the material in the aminoglycoside modules and study guides so that they can insure passing the course. The modules and study guides can be found on the web page (http://www.courses.ahc.umn.edu/pharmacy/6124/index.htm). Go to the left hand side and click “Glycosides.”
During the 4 quizzes and aminoglycoside competency exam done on Vista, as well as the final, we expect students to adhere to the College of Pharmacy’s honor code.
TOXICOLOGY
This section of the class will be comprised of both lecture format and case study format presentations.
Case Studies: The students will be divided into 9 groups with each assigned a specific topic in toxicology. The groups will be informed of their topic on the first day of class. On a predetermined class period each group will be responsible for answering questions on a case involving that topic. These questions will come from the handout materials provided to the class in the syllabus. The group will be seated at the front of the class (the hot seat group) and asked a series of 8 questions pertaining to this topic by the instructor. Groups should get together to discuss potential questions and answers prior to their scheduled date to present. Use of notes during the actual case study session will not be allowed. A group leader will be assigned to each group and will be responsible for having individual group members answer questions during the case study. They will also be in charge of taking attendance for the group and turning this attendance sheet in at the end of class. For every correctly answered question by the group, each student of the group that is present will receive 2 points. The total number of points allotted will be 16 per topic and this will count as 10% of the total grade. Each week, the other 8 groups will be given 1 question to answer pertaining to the same topic. A correct answer for this question will earn the group 0.25 extra credit points for a total of 4 if all are answered correctly throughout the term.
Class Attendance: Attendance will be taken each class period in which a case study is presented. Any points awarded during the case studies described above will only be awarded to the students that are in attendance that day. On four of the days where there is a lecture presentation, an instructor evaluation will be handed out for completion.
Students will be given 1 hour to complete the final exam and midterm
QUIZZES
INFECTIOUS DISEASES
There will be four quizzes throughout the infectious diseases section of the course. When accounced, the quiz will be posted on WebCt/Vista. Students will have 24 hours to log in and take the quiz. Once you log in, you will have 30 minutes to complete the quiz. The quizzes may not be made up.
TOXICOLOGY
Two exams will be given during the course and will consist of both multiple choice, short answer and T/F questions. Each will be worth 72 points. Exams will be reviewed with the students at an assigned time.
HEMATOLOGY/ONCOLOGY
Quizzes in the hematology and oncology section are announced and will be given in the first ten minutes of class on scheduled days. They will consist of true/false, multiple choice, and short answer questions, and may not be made up.
EXAM POLICIES
• Use of programmable calculators is permitted so long as programmable features are not used providing an unfair advantage to other students. This would be an honor code violation.
• Your working area should be clear of all books, personal organizers, etc.. You need only your calculator, two #2 pencils, examination, and answer sheet. Graph paper will be provided if required.
• Once examinations begin, no one is allowed to leave the room (i.e. to go to the restroom, etc.) until they have completed the examination.
• Write your name and ID# on the test, answer sheet, and graph paper.
• Number your answer sheet with the number on your test and remember to fill in the dots corresponding to your name and ID#.
• If students have any questions that arise while taking the exam, then they should approach the test proctor alone.
• Hand in all three items: your exam, graph paper, and answer sheet at the end of the exam.
• No grade will be assigned until each exam item is returned.
• Exams and quizzes will not be graded on a curve
MAKE-UP POLICY
There will be no make-up exams or any other opportunity to pass the course other than the scheduled exams, unless approval by the instructor is obtained in advance of the examination date. If you are ill or have a family emergency, call in advance and speak with the section director or one of the course teaching assistants. Email messages regarding absence from exams will not be accepted as an excused absence.
ABSENCE POLICY
We expect all students to attend and participate in all scheduled classes. If you must miss a class, notify the section director or one of the teaching assistants PRIOR TO your absence. If you miss one of the optional kinetic exams, we will consider this a missed opportunity to satisfy the course requirement.
GRADING
% Total Points Grade
> 93 A
90-92 A-
87-89 B+
83-86 B
80-82 B-
77-79 C+
73-76 C
70-72 C-
67-60 D
< 60 F
*minimum passing grade is 60%
*Grades will be posted on the course website as soon as all exams have been scored.
PROBLEMS/OFFICE HOURS
Any problems concerning the presentation of this curriculum or any problems related to this course should be directed to the section or course director. Teaching assistants are also available for feedback. All three section directors (Drs. Rotschafer, Kirstein, Sioris, Filandrinos, and Gualtieri) will have office hours by appointment. Please call any of them to make arrangements; they will be more than happy to get together with you.
TEACHING ASSISTANTS
*Office hours to be determined at a later date
Infectious Diseases: Isaac Mitropoulos, 612-626-6116 (mitro004@umn.edu) and
Mary Ullman, 612-626-6116 (ullma020@umn.edu)
Toxicology: TBA
Oncology:: TBA
COURSE WEB PAGE
The course web page has been developed extensively and we will be relying on it as an integral tool in this class. http://www.courses.ahc.umn.edu/pharmacy/6124/index.htm
EVALUATION OF INSTRUCTORS AND TEACHING ASSISTANTS
There is a great deal of time and effort devoted to the presentation of this curriculum. We are always looking for ways in which we might improve. We would greatly appreciate any comments you might have which might improve the way in which this course is presented to students. A formal evaluation will be held at the end of the course.
HONOR CODE
Each student is bound by the following specific provisions as part of the Code: Academic misconduct is any unauthorized act which may give a student an unfair advantage over other students, including but not limited to: falsification, plagiarism, misuse of test materials, receiving unauthorized assistance and giving unauthorized assistance. Specifically, each student will be required to do their own work on all quizzes and tests.
CLASSROOM ETIQUETTE
You signed the following statement upon accepting a class place in the University of Minnesota College of Pharmacy
I hereby affirm that I have read and understood the provisions and stipulations of the University of Minnesota Pharmacy Student Code of Ethical Responsibility and Professional Behavior
The Code was established in the belief that central to any intellectual and professional endeavor is an atmosphere of mutual trust and respect, based on individual maintenance of community standards. Your professional community starts here...at the College of Pharmacy with your peers, faculty, preceptors, staff and administration. It is our expectation that you will exhibit professional behavior towards other students and to faculty in the classroom at all times. In turn, we will treat you with the professional respect you deserve.
DISABILITY ACCOMMODATIONS
Any student with a documented disability (e.g., physical learning, psychiatric, vision, hearing, etc.) who needs to arrange reasonable accommodations must contact the Course Director (651-221-3896) and Disability Services (612-626-1333) at the beginning of the quarter. All discussions will remain confidential. If you need special accommodations for testing, please provide a copy of the letter from disability seervices within the 1st week of class.
BACKGROUND/EXPECTATIONS (Infectious Diseases)
A requirement for PHAR 6124 is a working knowledge of antibiotics listed below, which have been presented in previous courses (MedC 5164). Please review the following for both the midquarter and final exams. Further information on these antibiotics may not be given in class lectures.
You are responsible for:
• Mechanism of action
• Spectrum
• Mechanism of resistance (i.e., penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant Enterococcus)
• Common side effects
PENICILLINS:
Know the difference in spectrum and uses of penicillin, aminopenicillins (e.g. amoxicillin), penicillinase resistant penicillins, broad spectum penicillins, and beta lactam/beta lactamase inhibitors combination products.
CEPHALOSPORINS:
Know the difference in spectrum and uses of common first, second, third, and fourth generation cephalosporins. Pay particular attention to which agents have anti anaerobic activity, and which are active against P. aeruginosa. MISCELLANEOUS:
• Imipenem/cilastatin
• Aztreonam
• Daptomycin
• Tigecycline
• Telithromycin
• Rifampin
• Nitrofurantoin
• Clindamycin
• Doxycycline/Minocycline
• Trimethoprim/Sulfamethoxazole
• Metronidazole
• Vancomycin
• Chloramphenicol
• Erythromycin/Azithromycin/Clarithromycin
• Quinupristin/dalfopristin
• Linezolid
• Fluoroquinolones: older (e.g., ciprofloxacin), and newer (e.g., gatifloxacin, moxifloxacin)
HEURISTICS (Infectious Diseases)
• Respiratory fluoroquinolones including levofloxacin, moxifloxacin, and gemifloxacin have increased activity against gram-positive bacteria (particularly S. pneumoniae) compared to older quinolones such as ciprofloxacin.
• In the United States, about 35% of S. pneumoniae are not susceptible to penicillin, and half of these meet the laboratory criteria for resistance.
• Penicillin-resistant S. pneumoniae tend to show laboratory resistance to a number of other antibiotic classes.
• In the United States, 25%-30% of macrolide resistant S. pneumoniae.
• Methicillin resistant S. aureus (MRSA) also tend to be quinolone resistant.
• 10 to 40% of Haemophilus influenzae are ampicillin resistant.
• 80% of Staphylococcus epidermidis are methicillin resistant (MRSE).
• 50% of Staphylococcus aureus are methicillin resistant (MRSA).
• Almost all staphylococci are penicillinase producing.
• Enterococcus is preferably treated with a combination of penicillin or ampicillin or vancomycin plus either streptomycin or gentamicin when a systemic infection is suspected. Multiple antibiotic resistant enterococci are becoming much more common and traditional therapeutic approaches will usually not work for these organisms.
• Vancomycin is the drug-of-choice for methicillin-resistant Staphylococcus epidermidis (MRSE) and Staphylococcus aureus (MRSA) however, rising MIC values and alternative agents may change vancomycin’s current status.
• No currently marketed cephalosporin should be used to treat methicillin resistant staphylococcal infections except ceftibiprole or ceftaroline.
• No currently marketed cephalosporin should be used to treat enterococcal infections.
• First and second generation cephalosporins do not provide adequate coverage for Pseudomonas aeruginosa.
• Of the cephalosporins only ceftazidime, cefepime, ceftibiprole and ceftaroline provide reasonable coverage for Pseudomonas aeruginosa infections. (Although these drugs may represent the cephalosporins of choice of Pseudomonas infections they may not be the drug of choice of Pseudomonas infections.
• Only some select third generation cephalosporins should be considered for treating meningeal infections (Selection of third generation cephalosporins should be based on the likely microorganism and penetration into cerebrospinal fluid and their CSF MIC.
• Of the currently marketed cephalosporins only cefoxitin and possibly ceftizoxime should be considered as adequate coverage for Bacteroides fragilis infections.
• Of the currently available cephalosporins, only cefoxitin, cefotaxime, ceftriaxone and possibly some of the other third generation cephalosporins should be considered for penicillinase producing Neisseria gonorrhea infections.
• No currently marketed cephalosporins should be considered as adequate therapy for Listeria infections especially central nervous system infections.
• The need for totally empiric or "blind" therapy is rare.
• The likely source of infection is a strong indicator of the likely cause of infection.
• The causes of community-acquired infection are different from the causes of hospital-acquired infection.
• The sources and causes of infection are more diverse in immunosuppressed patients than in normal hosts.
• Signs and symptoms of infection are more subtle and obscure in immunosuppressed patients.
• All empiric therapy regimens should be modified to a regimen appropriate for the susceptibility of the causative agent(s) once known.
• Antibiotic regimens should be the least toxic that is appropriate to the causative agent.
• The sicker the patient, the greater the need for immediate antimicrobial treatment.
• Neutropenic patients (100/mm3) require immediate institution of antimicrobial therapy if they appear to have infection.
• Infections of specialized body sites require special antimicrobial consideration (e.g. meningitis require high penicillin dosage to achieve adequate CSF levels endocarditis requires prolonged high dose therapy to prevent relapse).
• With a first order PK drug, an increase or decrease in dose will result in a proportional increase or decrease in serum concentrations.
• The time between the peak and the trough of an antibiotic given intravenously is T-t'.
• Ko is an infusion rate and not a dose. Dose is equal to Ko x t'.
• With a first order drug, half-life and Kd are dose independent parameters. Any factor that prevents the patient from receiving the assumed dose of aminoglycoside will not change the determination of t1/2 or Kd providing post infusion data is used.
• Any factor that prevents the patient from receiving the assumed amount of aminoglycoside will result in an error in the calculation of distribution volume.
• Trough concentration drawn prior to the intravenous administration of an antibiotic must be extrapolated to the start of the antibiotic infusion.
• With aminoglycoside trough/peak checks, the trough concentration is used both in the calculation of Kd and in the calculation of volume of distribution at steady-state. Whereas with first- or second-dose kinetics the trough is used only in the calculation of volume of distribution.
• To accurately perform trough/peak pharmacokinetic studies, the patient must be at steady-state using the same dose, dosage interval, and infusion time while on the same schedule. The patient also must have received the drug for at least 5 half-lives and the clinical status (serum creatinine and fluid status etc.) are not undergoing dramatic change.
• An aminoglycoside dosage interval usually approximates two or three patient drug half-lives.
• The elimination rate constant, half-life, and distribution volume are similar between aminoglycosides (except for inactivation with beta-lactam antibiotics) i.e. pharmacokinetic data from one aminoglycoside can be used to develop a dosage and dosage interval for another aminoglycoside.
ABBREVIATIONS
• AAPMC = Antibiotic associated pseudomembranous colitis
• ABW = Actual body weight
• AG = Aminoglycosides
• ARF = Acute renal failure
• AUC = Area under the antibiotic concentration curve
• BLIC = Beta lactam inhibitor combination
• caMRSA = Community acquired MRSA
• CLcr or CrCl = Creatinine clearance
• CNS = Central nervous system
• CRF = Chronic renal failure
• CSF = Cerebral spinal fluid
• DBW = Dosing body weight
• GISA = Glycopeptide intermediate S. aureus
• GNB = Gram negative bacilli
• HIV = Human Immunodeficiency Virus
• H-MRSA = MRSA hereroresistant MRSA
• LBW = Lean body weight
• LRTI = Lower respiratory tract infection
• MAC = Mycobacterium avium complex
• MBC = Minimum bactericidal concentration
• MIC = Minimum inhibitory concentration
• MOA = Mechanism of action
• MOR = Mechanism of resistance
• MRSA = Methicillin-resistant Staphylococcus aureus
• MRSE = Methicillin-resistant Staphylococcus epidermidis
• PAE = Post antibiotic effect
• PCN = Penicillin
• PD = Pharmacodynamics
• PK = Pharmacokinetics
• PMN = Polymononuclear cell
• SBE = Subacute bacterial endocarditis
• SBT = Serum bactericidal titer
• SDD = Single daily dosing
• SE = Side effects
• SIT = Serum inhibitory titers
• S/STI = Skin/soft tissue infection
• STD = Sexually transmitted diseases
• TB = Tuberculosis
• TMP/SMX = Trimethoprim/sulfamethoxazole (Bactrim/Septra)
• UA = Urinary analysis
• UO = Urinary output
• UTI = Urinary tract infections
• URTI = Upper respiratory tract infection
• VISA = Vancomycin intermediate S. aureus
• VRE = Vancomycin resistant Enterococcus
• VRSA = Vancomycin resistant S. aureus
• WBC = White blood cell(s) |
