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BOOK CHAPTER

Case StudiesMark Kester PhD, Kelly D. Karpa PhD and Kent E. Vrana

Elsevier's Integrated Review Pharmacology, 227­230

Case study 1A 54­year­old homeless male, who admits to smoking cigarettes all his adult life, is admitted to thehospital with evidence of tuberculosis. This gentleman weighs 65 kg and says he was diagnosed withchronic heart failure and asthma “many years ago.” For the past 15 years, he has been obtainingtheophylline samples from a physician who volunteers at the local homeless shelter, so you decide tocontinue the drug while he is hospitalized. In the hospital, the patient has been receiving 100 mgtheophylline every 12 hours. However, you realize that theophylline is metabolized by P450microsomal enzymes, and you've placed the patient on several medications that alter the metabolismof theophylline, including ciprofloxacin, which is known to increase theophylline levels, andrifampin, which is known to induce the P450 enzymes, thus reducing theophylline levels. You decidethat it is best to obtain laboratory data to determine what the patient's plasma levels of theophyllineare because of these potential drug interactions. The laboratory report indicates that the patient'splasma concentration of theophylline is 3.6 mg/L (target range is 5 to 15 mg/L).

1. Knowing that the published value of volume of distribution (Vd) fortheophylline is 0.48 L/kg, calculate this man's Vd for theophylline.

2. Knowing that the published half­life (t 1/2 ) for theophylline in a smoker is 4.5

hours, what is the rate at which theophylline is cleared in this patient?

3. What loading dose should this patient be given to quickly increase histheophylline plasma level to 10 mg/L?

Case study 2A 68­year­old patient is transferred to your practice. She is concerned because she has been takingthe same medication for 60 years for her asthma, but it does not seem to be working very well lately.She says that she has taken the same dose of theophylline all her life—ever since she was 8 years old—and she wanted her previous doctor to increase the dose, but he did not. She is certain that the

reason her asthma has been under poor control for the past few months is because her doctor refusesto prescribe more. (In actuality, her previous doctor had suggested discontinuing the theophyllineentirely and switching her to a long­acting corticosteroid/β 2 ­agonist combination because

theophylline requires careful monitoring and has numerous drug interactions and severe toxicities.However, she refused because she had heard that steroids are “bad for you.”)

“Theophylline has worked for my entire life. When it stopped working recently, my doctor refused toincrease the dose. Why would a drug I've taken my whole life suddenly stop working?”

You review her medications and find that she is also taking cimetidine for gastroesophageal refluxand rifampin for a severe staphylococcal bone infection. You check her serum theophylline levels andfind that they are 4.0 mg/L (target range is 5 to 15 mg/L).

1. What are some of the considerations for dosing a drug with a narrowtherapeutic index (e.g., theophylline) throughout the lifespan of a patient?

2. Are there any pharmacokinetic interactions between rifampin and theophyllinethat could affect this woman's theophylline plasma levels?

3. Are there any pharmacokinetic interactions between cimetidine andtheophylline that could affect this woman's theophylline plasma levels?

Case study 3A 16­year­old female comes to the emergency department with severe abdominal cramps. She issweaty and appears feverish. On workup, she becomes nauseated and vomits pill fragments. Shereports that she ingested “a hundred pills, but I don't remember the type.” On examination, hertemperature is 101.2° F, her blood pressure is 128/72 mm Hg, her pulse is 120 beats/min, and herrespirations are 34 breaths/min.

1. What is your initial management strategy for this patient after addressing theABCs (airway, breathing, circulation)?

2. What over­the­counter medicine could be responsible for the initial symptoms?

3. Initial arterial blood gas levels are drawn (pH, 7.64; pCO 2 , 16 mm Hg; pO 2 , 98

mm Hg). What are potential mechanisms underlying this alkalosis?

4. Repeat laboratory measurements are taken 2 hours after the patient receives 2L normal saline. The results are now pH, 7.27; pCO 2 , 16 mm Hg; and pO 2 , 103

mm Hg. What are potential mechanisms leading to the secondary acidosis?

5. The patient's condition continues to worsen. What is the next course oftreatment?

Case study 4A 33­year­old female is brought to the emergency department by her husband one Saturdaymorning. She reports such a severe headache that she cannot open her eyes. Her oral temperature is104.1° F. Her husband mentions, “My wife has a rash on the back of her head.”

According to the woman's husband, she was previously in good health. On the previous day, thewoman rose early in the morning to complete her exercise routine and remarked to her husbandabout what a great workout she had. However, as the day progressed, she noted a “large painfullump” on the back of her head. By evening, she noticed additional lumps and was concerned becausethe lumps were beginning to spread down the back of her head and neck. She also began havingdiarrhea that evening. Although the woman had been seen by her family doctor “after hours” theprevious evening, no definitive diagnosis had been made, and she was sent home. Throughout thenight, the woman had severe diarrhea and vomiting.

Almost as soon as the patient arrived in the emergency department, she began complaining of anirregular heartbeat. An electrocardiogram revealed premature ventricular contractions; the womandenied a prior history of cardiovascular problems. On examination of the patient's head, the “rash”on the back of her head appeared to be spreading down her neck and across her face. At theemergency department, an astute attending physician correctly diagnosed the woman as havingerysipelas. The patient has no history of drug allergies.

1. What is erysipelas, and which microorganisms are the most likely culprits?

2. What is the most likely cause of the patient's cardiac arrhythmias?

3. A scab is identified on the patient's scalp, and both group A streptococci andstaphylococci are isolated and cultured. Blood cultures are negative, which iscommon with erysipelas (blood cultures are positive in only 5% of cases). Discussan antimicrobial that is appropriate for this patient.

4. After 5 days of receiving an intravenous antibiotic, her fever finally subsidedand she was discharged with a prescription for 10 additional days of therapy withoral dicloxacillin. In addition, at the time of discharge, a first­year residentinformed the patient that the laboratory had just called with results of a stoolculture that had been conducted during admission because the patient'sabdominal pain and diarrhea had worsened while she was hospitalized.Clostridium difficile toxins were identified in the patient's stool culture. What isthe source of this gastrointestinal microorganism, and how is this secondaryinfection treated?

Case study 5

A 70­year­old man with a history of long­standing hypertension and recently diagnosed type 2diabetes mellitus comes to the oncology clinic. He has just found out the gastric pain that heattributed to a “flare­up” of his peptic ulcer disease is actually giant large­cell lymphoma, anaggressive neoplasm. As the director of the oncology clinic, you tell the patient that he will bereceiving six to eight cycles of a chemotherapeutic regimen known as CHOP, followed byconsolidative radiation therapy to his stomach and lymph nodes. The patient asks for additionalinformation about the CHOP regimen, and you explain that this is a combination of four differentdrugs: cyclophosphamide, doxorubicin, vincristine, and prednisone.

1. When explaining the long­term complications of doxorubicin to the patient,what do you warn him about and what can be done to prevent or minimize thedrug's effects?

2. When explaining long­term complications associated with vincristine, of whatdo you warn the patient?

3. What long­term complications are associated with cyclophosphamide, and howcan they be prevented?

Case study 6A clinical study is conducted in which a healthy volunteer is administered norepinephrine,epinephrine, and isoproterenol. Blood pressure, total peripheral resistance, and heart rate aremonitored during drug infusions. The results of this study are depicted in the accompanying figure.

1. Explain the widely disparate results for these three adrenergic agonists.Specifically address the receptors responsible for the various hemodynamicchanges.

HR, heart rate; TPR, total peripheral resistance; BP, blood pressure; MAP, mean arterial pressure.

Case study 7A 75­year­old male complains of “stomach pain” and massive rectal bleeding when passing stools. Heis also gingerly holding his left shoulder. On questioning, he tells you that last week, he slipped onthe ice and fell while shoveling snow. He was prescribed celecoxib by his family doctor for persistentshoulder pain and swelling. When the pain failed to resolve after a few days, this man scheduled asecond appointment with his family physician. This time, his regular doctor was out of town, so hewas seen instead by another partner in the practice, who prescribed ibuprofen. The pain haspersisted for several weeks and during this time, he has been taking both celecoxib and ibuprofenregularly. In the middle of the night, the man was brought to the emergency department when hefilled the toilet bowl with bloody stools twice. He was feeling faint and had nearly passed out beforehis wife was able to summon an ambulance. His medical history includes hypertension and pepticulcer disease. The hypertension is controlled with medication, and there have been no ulcers in morethan a decade. The following are the patient's pertinent laboratory values from his complete bloodcount, with normal values shown in parentheses:

Hemoglobin = 11.9 g/dL (13.8 to 17.2 g/dL)

Hematocrit = 34% (40.7 to 50.3%)

Mean corpuscular volume = 75.9 μm 3 (80.0 to 97.6 μm 3 )

Mean corpuscular hemoglobin = 24.0 pg/cell (26.7 to 33/7 pg/cell)

Mean corpuscular hemoglobin concentration = 30.0 g/dL (32.7 to 35.5 g/dL)

1. You suspect that because of his massive gastrointestinal bleeding, the patient isiron­deficient. What other tests might you order to confirm your diagnosis?

2. What do you suppose contributed to patient's loss of iron?

3. Ultimately, surgical intervention was needed to halt the severe gastrointestinalbleeding, and the patient was discharged home with a prescription for ironsupplements. What might you tell the patient and note in his chart regarding thisiron therapy?

Case study 8A 45­year­old man enters a clinic for the first time. He tells the doctor, “I feel fine, but the nurse atwork took my blood pressure. It was 150/100 mm Hg and 160/102 mm Hg on two different days. Shesays I need a checkup.”

Despite a thorough examination to determine an identifiable cause for his hypertension, none wasfound, and the patient was given a diagnosis of stage 2 essential hypertension. The patient wasinstructed on lifestyle changes including (a) smoking cessation, (b) regular exercise, (c) alcohollimitations (no more than two beers per day), and (d) a low­fat, low­cholesterol, low­salt diet.

The patient was motivated to initiate these lifestyle modifications, so the physician prescribed onlyhydrochlorothiazide initially and scheduled a follow­up examination for 2 months later. The patientreturned 2 weeks later with a painful, swollen, red big toe joint. His potassium level was 3.2 mEq/L(normal, 3.5 to 5.0 mEq/L), and his uric acid level was 11.9 mg/dL (normal, 3 to 8 mg/dL).

1. Account for the patient's painful toe and his abnormal laboratory values.

2. The patient's pharmacologic therapy was changed to atenolol. Although thepatient's blood pressure had lowered to 132/94 mm Hg with atenolol, his heartrate was only 50 beats/min. The patient reported easy fatigability and a reductionin exercise tolerance. Explain how atenolol causes these adverse effects.

3. Because the patient reported other adverse effects associated with the β­blocker(e.g., reduced libido, sleep disturbances), it was decided that instead of loweringthe dose, a drug from a different class would be tried. Atenolol was graduallytapered over a period of 1 week. Why was the dose of atenolol tapered slowly?

4. The patient was started on lisinopril. How does lisinopril work, and whatadverse effects might the patient experience?

Case study 9A 60­year­white male weighing 170 pounds is brought to the emergency department by his wifebecause his “ankles are swollen.” You view the patient's extremities and note that he has stage 4pitting edema in his ankles. The patient tells you that he has a history of poorly controlled

hypertension. Before prescribing any medications, you ask the laboratory to check his Na + , K + , andserum creatinine. Pertinent laboratory values are:

K + : 3.5 (3.3 to 4.9 mmol/L)

Na + : 140 mmol/L (135 to 145 mmol/L)

Creatinine: 2.5 mg/dL (0.5 to 1.7 mg/dL)

1. What is this patient's creatinine clearance?

2. What is the best choice of medication to reduce this patient's edema on anoutpatient basis?

3. At your suggestion, the patient follows up with the internal medicine

department. In addition to having hypertension, he also finds out that he has type2 diabetes. The internist gives the patient an additional prescription.Unfortunately, you see the patient again in the emergency department 2 weeksafter his appointment with internal medicine. This time, he is reporting anirregular heartbeat. An electrocardiogram reveals that the patient has aprolonged P­R interval and QRS duration, atrioventricular conduction delays,and a loss of P waves. Laboratory work reveals that his potassium level is elevatedat 5.7 mEq/L. Which class of medication did the internist most likely prescribe forthe patient's hypertension?

Case study 10An 8­year­old boy with asthma has recently developed a nonproductive cough. His asthma has beenwell controlled over the past 3 years since he started allergy desensitization immunotherapy (allergyshots). He is presently taking cromolyn (four puffs per day) as well as albuterol (two puffs) whenneeded or before exercise. He demonstrates good inhaler technique and uses a spacer. During yourworkup, you discover that the family has just “adopted” a puppy and the boy's asthma symptomshave been flaring up. His peak flow rates have been falling, and he has been having more nocturnalsymptoms.

1. What is your plan to minimize and manage the child's asthma symptoms, giventhat the puppy remains in the household?

2. What adverse effects are especially of concern in a young child using inhaledcorticosteroids?

Case study 11A 49­year­old male has been given a diagnosis of hyperreactive airway disease and asthma. After about with influenza, he developed a recurrent cough that interferes with his job and active lifestyle.The cough and associated tight chest are unresponsive to over­the­counter cold and flu medications.The patient is somewhat surprised when you start working him up for gastroesophageal refluxdisease (GERD). He states that his stomach is fine and he has never had heartburn.

1. What is the connection between asthma and GERD?

2. What agents can be given to the patient to treat his GERD symptoms?

Case study 12A . A 41­year­old woman is admitted for severe chest pains. She appears as a thin, flushed, nervouswoman. Her complaints include nervousness, palpitations, weight loss despite strong appetite, andunexplained bruising. She states she is being treated for deep vein thrombosis with warfarin 5

mg/day. Physical examination reveals a blood pressure of 190/95 mm Hg, pulse of 125 beats/min,and temperature of 102.6° F. Your exam also reveals droopy eyes, decreased visual acuity, anenlarged thyroid, atrial fibrillation, pitting edema, and tremor.

1. What is your initial diagnosis, and how would you treat the patient?

B . A 37­year­old female wants to breastfeed her first child. She requests information oncontraception choices before leaving the hospital. She has a strong family history of cardiovasculardisease and is presently a two­pack­per­day smoker. She previously had a conventional intrauterinedevice that was removed because of severe bleeding. She also states that spermicidal foams andcondoms cause her itching and burning.

2. What type of contraception would you recommend to the patient?

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