HuBio 564: Principles of Pharmacology II
Case Studies
Links to the Case Study questions are on the Schedule page
Your essays will be graded by 4th yr Med students who will provide
individual feedback on your work. A very useful discussion session covering cases 1-4
and strategies for cases 5-8 will be led by the TA's on 4/22 12:30-1:20 in rooms:
- T546 students whose last names begin with A-D
- T538 students whose last names begin with E-K
- T540 students whose last names begin with L-R
- T548 students whose last names begin with S-Z
Case Study reports must be done individually. Do not work in groups to develop your answer. Feel free to use any written resource or contact the Instructor for further information, but do not ask in any way, another individual to answer the question for you. Again, these vignettes are designed to be a study guide to help you prepare for the clerkship years where you will be expected to call from your own knowledge base when facing a clinical situation.
For logistical reasons, your answers must be submitted electronically. Use the Web Submission form http://depts.washington.edu/phcol/case_sub.html and follow its instructions closely. Make sure that your name and student test ID number are entered correctly and the text of your essay is pasted completely. Your essays will be read by the course instructors, and you will get full credit for carefully prepared, clearly reasoned answers. Remember, although these patients are fictional people, we expect that you will demonstrate a high degree of professionalism in your approach to each clinical scenario. Partial credit will be given for superficial or partially correct answers. With >1400 essays to grade, do not expect feedback, but if there is a problem with your essay, we will try to point these out by return e-mail. No partial credit will be awarded if your answer might potentially harm the patient or if you overlook an important aspect of the case (e.g. misdiagnose or overlook an important contraindication). These are open-book problems; so be confident before hitting the send key.
Essays are worth 3 points each towards your course grade. Check the MyGrades web site where we will post your score as quickly as we can. You may submit answers to as many of the 8 questions as you like.
0 pts - patient harmed [this is usually because of a major omission, a misdiagnosis or
recommending a contraindicated drug. Sorry, just as in real-life, there's no partial
credit if the patient is harmed.]
1.5 pts - late, incomplete or superficial essay [the essay failed to fully explain your thinking or
failed to discuss key caveats].
3 pts - full, complete and professional answers to all parts of the question.
Turn in your essays as soon as possible, but pay attention to the posted deadlines, late answers will not be accepted without excessive groveling (and points taken off). Also, it's smart to keep a copy of your submission in case something gets lost in transit.
Information Sources:
Much of the information required to answer the questions will be covered during the lectures or can be found in the syllabus or textbook, but a goal of this exercise is to enhance your familiarity with the on-line databases. Find one that you are comfortable using:
Epocrates Rx online at https://www.epocrates.com/
UpToDate online at http://www.uptodateonline.com/
Healthlinks at http://healthlinks.washington.edu/
Micromedex at http://elektra.mcis.washington.edu/mdxdocs/mdxhome.htm
Health Central at http://www.rxlist.com/
SYSTEMATIC TREATMENT PLAN DESIGN
Case Study Template for CNS Pharmacology (psychiatry, epilepsy, stroke, pain, addiction, parkinsonism). This is an outline of steps used in the formation, evaluation, and monitoring of a treatment plan.
- Note (list) the specific concerns of the patient. Explicitly establish TREATMENT GOALS that acknowledge and address each concern.
- Complete the patient's history and physical exam (identify other meds, other qualifiers: age, gender, kidney function, liver function, pregnancy risk, drug abuse issues). Identify any co-morbidities and distinguish them from the primary problem/focus of treatment.
- Note (list) all plausible explanations and diagnoses for the condition; take natural course of the disease into consideration. Explicitly compare signs and symptoms with appropriate standardized appropriate (e.g. DSM-IV) criteria. Are there comorbid disorders or a single problem?
- Note (list) additional information (e.g. lab tests, EEG's, MRI's, etc) needed to refine diagnosis or eliminate alternative explanations. Consider possible alternative interviews to gain more information (e.g. interviews with teachers, spouse, parents, coaches, grandparents) that may be helpful in refining the diagnosis.
- Use the additional information to refine the diagnosis and develop a TREATMENT PLAN. List all medications that may be appropriate, and rank the plausible choices based on how well they: a) treat the condition, b) are compatible with the treatment goals defined by the patient, c) match the patient's health status (e.g. kidney, liver function, etc). List the plausible medications that should be excluded because of contraindications specific to this patient (e.g. treatment goals, health status, pregnancy risk). Use evidence-based literature to support your decisions.
- Initiate treatment by explaining the risk/benefit choices, expectations for progress, adverse effect monitoring plan. Engage the patient's collaboration.
- MONITOR THE EFFECTIVENESS of the treatment plan at appropriate intervals. Anticipate and adjust plan in response to adverse effects. Adjust dosage, if appropriate. Substitute alternative drug, if appropriate. Assess compliance.
- FOLLOW UP. Decide how long treatment will be required and when termination of treatment will be appropriate. Discuss this with the patient. Use evidence-based literature to support your decisions.
The following is an example of a question and answer from last years course to give you a sense of instructors' expectations.
Example Case Study from 2004 (do not answer this one in 2009):
You are performing a routine physical examination on a 65-year-old woman. You discover that she has an irregularly irregular heart rhythm and perform an EKG. It turns out that she is in atrial fibrillation. You perform an echocardiogram that shows an enlarged left atrium but normal left ventricular function. She was already taking atenolol for hypertension; her heart rate is therefore controlled at approximately 60-70 beats per minute. Her blood pressure on atenolol 100 mg po qd is 150/90.
What do you tell this woman about her risk of stroke?
How can you best prevent a stroke in this patient?
She is lost to follow up. Approximately 6 months later, she presents to the emergency room with the acute onset of aphasia and right hemiparesis. You are evaluating her within 45 minutes of her symptom onset (according to her coworkers who called 911). Given her aphasia, it is unclear what medications she was taking. Her BP is 200/120. Her glucose is 215 mg/dL, hematocrit is 45, platelets are 300K and the INR is 1.1.
What do you think happened?
What is the most appropriate initial therapy for her?
You treat her within 90 minutes of symptom onset and she experiences a near complete recovery.
How can you best prevent this from happening again?
What do you tell her about her stroke risk now?
One student's answer:
Having atrial fibrillation with a controlled, within normal limits heart rate, this woman may only experience symptoms such as uncomfortable palpitations. But perhaps the most serious consequence of atrial fibrillation with left atrial hypertrophy is thrombus formation due to atrial stasis (particularly in the atrial appendages) and consequent embolization, most devastatingly to the cerebral circulation. Her gender, age adjusted relative risk for stroke with atrial fibrillation is 3.0 in comparison with her non-a-fib counterparts - stroke rate in comprehensive study was 2.2 in her age stratum (up-to-date).
As with most chronic illness, prevention is the best policy. Generally speaking, the best way to prevent stroke with this woman would be to tighten-up control of her hypertension, think about nutritional intake that may promote less viscous blood, and reduce the coagulation abilities of her blood.
This patient's hypertension may have a large role in elevating her risk for left appendage thrombotic emboli. With further history about other risk factors including potential coagulation disorders, diabetes or prior history of TIAs among many other established criteria, one could further stratify this patient's risk. It should be made clear to this woman how important risk stratification is with regard to her atrial fibrillation-associated embolic risk in making informed decisions treatment plans that maximize anticoagulation and minimize bleeding.
Bringing her blood pressure down is a reasonable approach in reducing risk of stroke. At 150/90, there is room to improve especially if there are additional behavioral/thought/lifestyle modifications she could make in addition to her atenolol. Stressing the importance of her hypertension in conjunction with her other heart conditions and risks would be appropriate - ensuring patient understanding.
Diuertic therapy including the ACE-inhibitor ramipril or the thiazide derivative chlorthalidone have shown success in stroke prevention. If her status is compatible and she elects to not use aspirin, then I may add ramipril at 1.25 mg once daily and perhaps titrating upward depending on her response.
Increasing water intake to a reasonable level (depending on how much she currently drinks) may be of some benefit in preventing viscous blood. If this woman is not hypersensitive to warfarin or does not have any of a large list of hemorrhagic tendencies, recent or upcoming surgeries, or a number of other contraindications (see up-to-date), then she may want to seriously consider trying 0.5-1 mg warfarin per day, slowly titrating to level as determined by thoughtful risk stratification (probably 2-3 mg/day range).
If warfarin use is too risky and she is not on ramirpil, then daily aspirin, perhaps in the area of 200-300 mg per day, would be another option this woman may try if compatible with her condition.
It appears that this woman has thrown a thrombotic emboli perhaps to the arterioles in her left basal ganglia, pons, cerebellum, and/or anterior limb of the internal capsule, which is indicative of a lacunar infarct.
Intravenous thrombolytic therapy with recombinant tissue plasminogen activator may be helpful in reducing her neurological deficit, but tPA is contraindicated with systolic pressures above 185 mmHg and/or diastolic pressures above 110 mmHg. Attempts to reduce hypertension immediately following stroke are generally avoided as there is speculation of loss of cerebral autoregulation maintaining an elevated intracranial pressure following a stroke and lowering blood pressure may further compromise ischemic areas. However, it may be wise to try to get her blood pressure securely below 200 mg (around 170) in this acute situation. In due time (some sources say in a couple of days, others say couple of weeks), her hypertension needs to be aggressively worked-up and treated.
Assuming a cardiac source of embolization, treatment is with intravenous heparin while warfarin is introduced. The target is an INR of around 2.0-3.0 for the prothrombin time. This treatment can be started right away with no evidence of intracranial hemorrhage or blood in her CSF. Oral aspirin should be provided for its neuroprotective (anti-inflammatory) and anti-platelet characteristics. Also, her highly elevated glucose levels need to also be vigorously addressed. Insulin therapy should be initiated immediately and a through diabetic work-up and intervention plan ought to be persistently and caringly pursued. Active physical therapy also will play an important role in this woman's initial stroke therapy in order to improve regaining of motor and coordination control as well as strength and mobility.
After considering this woman's lifestyle including exercise, nutrition and drug intake, the best way to prevent stroke reoccurrence is to help her pharmacologically maintain tight control of her hypertension, cholesterol, and blood glucose levels as well as continuing with anticoagulation treatment. Aspirin has been referred to as the mainstay of secondary stroke prevention as far as anticoagulation is concerned. Other, newer, more expensive antiplatelet medications such as clopidogrel and extended release dipyridamole in combination with aspirin may be considered as well. But some sources indicate that chronic warfarin therapy is more effective at reducing stroke especially in higher risk patients with severe heart disease or hypercoaguable states. Further studies would need to be gathered with regards to patient's cardiac performance (ejection fraction, etc.), protein C & S levels, antithrombin III levels, anticardiolipin antibodies, as well as other indicators of hypercoaguability. If it is determined that more assertive therapy is appropriate, this woman may be served best by prescribing low dose warfarin for maximal stroke prevention if she her condition is not contraindicated in any way.
The patient's risk for recurrent stroke is now significantly increased having just experienced her first cerebral embolic event - assuming this was her first event. Her hypertension, atrial fibrillation with enlarged left atrium, and apparent diabetes all leave her at a seriously increased risk for recurrent stroke. She must closely adhere to the treatment plan that we agree upon, and communicate closely with her providers for monitoring and support.
The Instructors's Answer Key for this Case:
What do you tell this woman about her risk of stroke?
Based on the fact that she is female, is 65 years old, is in atrial fibrillation and is hypertensive, her yearly risk of stroke is significant - at least 5% per year.
How can you best prevent a stroke in this patient?
The most appropriate treatment for stroke prevention in this patient with atrial fibrillation is anticoagulation. At present, warfarin adjusted to maintain an INR ~ 2.5 is standard of care. In the near future, ximelagatran will likely be used in clinical practice as well. Aspirin does decrease the risk of stroke in patients with atrial fibrillation but is not nearly as effective as warfarin. Finally, she is quite hypertensive. A second anti-hypertensive agent should therefore be added to her drug regimen. Which anti-hypertensive agent is probably not as important as whether or not her BP is controlled, but there may be some advantage to diuretics and ARBs (data exists for losartan).
What do you think happened?
She has clearly had a stroke. Given the fact that her INR is 1.1, she obviously hasn't been taking her warfarin.
What is the most appropriate initial therapy for her?
Given that the patient presented within 45 minutes of symptom onset, she is theoretically a candidate for thrombolysis. Her BP, however, is too high for administration of tPA. She therefore needs to be treated so that she can receive the medication. Labetalol is the most appropriate anti-hypertensive to achieve a BP<185/110. One could also make and argument to start her on an insulin drip to normalize her glucose. Aspirin and anticoagulants should be held for 24 hours after thrombolysis.
How can you best prevent this from happening again?
She needs to be anticoagulated long term. There is no benefit to acute anticoagulation with heparin in patients who experience stroke due to atrial fibrillation. Aspirin should probably be started while initiating therapy with warfarin (or possibly ximelagatran).
What do you tell her about her stroke risk now?
Given that she has now had a stroke due to atrial fibrillation, her yearly risk of stroke is even greater than before - probably on the order of 10% or so. Anticoagulation can decrease that risk by about 67%.
END OF EXAMPLE
Grades
The School of Medicine Online Curriculum Web site (SOMOC) will be used to post grades. By clicking on the My Grades link in the upper right corner, you can log in to check which of your case studies have been received and graded, and you can check your grade on the two exams.
