Shadow Health Pharmacology Intermediate Patient
Case Exam 2026/2027: 250 Digital Clinical
Experience Style Q&A with Detailed Rationales
1. A patient with chronic heart failure (NYHA class III) and a left ventricular ejection fraction of
30% is initiated on sacubitril/valsartan. Which of the following concurrent medications requires
the most cautious monitoring due to a pharmacokinetic interaction that may increase the risk of
angioedema?
A. Spironolactone
B. Atorvastatin
C. Lisinopril
D. Metoprolol succinate
Answer: C
Rationale: Sacubitril/valsartan contains a neprilysin inhibitor (sacubitril) that can increase bradykinin
levels. Concurrent use with an ACE inhibitor (lisinopril) significantly raises the risk of angioedema due
to additive bradykinin elevation. A 36-hour washout period is required when switching from an ACE
inhibitor. Spironolactone requires potassium monitoring but does not interact with bradykinin.
Atorvastatin and metoprolol have no significant interaction.
2. A patient receiving a continuous infusion of heparin for acute coronary syndrome develops a
platelet count drop from 250,000/¼L to 80,000/¼L over 5 days. The clinician suspects
heparin-induced thrombocytopenia (HIT). Which of the following anticoagulants is most
appropriate to continue or initiate while awaiting confirmatory testing?
A. Enoxaparin 1 mg/kg subcutaneously twice daily
B. Fondaparinux 2.5 mg subcutaneously once daily
C. Warfarin 5 mg orally once daily
D. Argatroban intravenous infusion adjusted to aPTT 1.5-3 times baseline
Answer: D
Rationale: In suspected HIT, all heparin products (including enoxaparin) must be discontinued.
Fondaparinux has a lower risk but still carries potential cross-reactivity in some patients. Warfarin
should be avoided until platelet count recovers due to risk of venous limb gangrene. Argatroban, a direct
thrombin inhibitor, is the preferred agent for anticoagulation in HIT and does not cross-react with
heparin antibodies.
3. A patient with type 2 diabetes mellitus and stage 3 chronic kidney disease (eGFR 38
mL/min/1.73 m²) is being treated with metformin, which has been stable. Recently, the patient was
prescribed a new medication that significantly increases the risk of metformin-associated lactic
acidosis. Which of the following is most likely to have been initiated?
Page 1
,A. Sitagliptin
B. Dapagliflozin
C. Ibuprofen 800 mg three times daily
D. Lisinopril
Answer: C
Rationale: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can reduce renal perfusion and
further impair renal function, increasing the risk of metformin accumulation and lactic acidosis,
especially in patients with pre-existing CKD. Sitagliptin and dapagliflozin have minimal interaction with
metformin. Lisinopril is generally renoprotective but may cause transient hyperkalemia; it does not
significantly increase lactic acidosis risk.
4. A patient with a history of opioid use disorder is being treated with buprenorphine/naloxone.
The patient presents with acute pain from a fractured femur. Which of the following pain
management strategies is most appropriate to manage severe acute pain while minimizing the risk
of precipitating withdrawal?
A. Discontinue buprenorphine/naloxone and initiate morphine patient-controlled analgesia
B. Continue buprenorphine/naloxone and add a nonsteroidal anti-inflammatory drug only
C. Continue buprenorphine/naloxone and add a short-acting full mu-opioid agonist with higher doses to
overcome buprenorphine's high receptor affinity
D. Increase the buprenorphine/naloxone dose to 16/4 mg daily and add acetaminophen
Answer: C
Rationale: Buprenorphine has a high affinity for mu-opioid receptors, which can block the effects of
additional opioids. To manage severe acute pain, it is recommended to continue buprenorphine to
maintain stability and add a full mu-opioid agonist (e.g., fentanyl, morphine) at higher than usual doses
to overcome the receptor blockade. Discontinuing buprenorphine risks withdrawal and loss of tolerance.
NSAIDs alone are insufficient for severe pain. Increasing buprenorphine dose may not provide adequate
analgesia for acute pain.
5. A patient with a history of recurrent unprovoked venous thromboembolism (VTE) is on
long-term warfarin therapy (target INR 2-3). The patient develops a new pulmonary embolism
despite a therapeutic INR of 2.8. Which of the following is the most likely explanation for this
treatment failure?
A. The patient has a lupus anticoagulant that prolongs the INR but does not reflect true anticoagulation
B. The patient has been taking a multivitamin containing vitamin K
C. The patient has been noncompliant with warfarin dosing, but the INR was drawn shortly after a dose
D. The patient has developed a heparin-induced thrombocytopenia
Answer: A
Rationale: Lupus anticoagulant (antiphospholipid syndrome) can cause a falsely elevated INR due to
interference with the phospholipid-dependent coagulation tests. In such patients, warfarin may not
provide adequate anticoagulation despite a seemingly therapeutic INR. Direct oral anticoagulants or
alternative monitoring (e.g., chromogenic factor Xa assay) may be needed. Vitamin K intake would
lower INR, not cause failure with a therapeutic INR. Noncompliance would likely result in
subtherapeutic INR. HIT is not relevant to warfarin failure.
Page 2
,6. A patient with generalized anxiety disorder has been taking sertraline 100 mg daily for 6 weeks
with minimal improvement. The clinician decides to augment therapy with a second agent. Which
of the following augmentation strategies is most supported by evidence for treatment-resistant
anxiety?
A. Add aripiprazole 2 mg daily
B. Add buspirone 10 mg twice daily
C. Add pregabalin 75 mg twice daily
D. Add propranolol 20 mg twice daily
Answer: B
Rationale: Buspirone is a 5-HT1A receptor partial agonist with established efficacy as augmentation to
SSRIs for generalized anxiety disorder, particularly when SSRI response is inadequate. Aripiprazole has
limited evidence for anxiety. Pregabalin is effective for generalized anxiety disorder but is typically used
as monotherapy or first-line, not specifically as augmentation after SSRI failure. Propranolol is used for
performance anxiety but not for generalized anxiety disorder augmentation.
7. A patient with chronic myeloid leukemia (CML) is started on imatinib 400 mg daily. After 3
months, the patient develops new-onset pleural effusions and significant peripheral edema. Which
of the following pharmacogenetic factors is most likely contributing to this toxicity?
A. CYP2D6 poor metabolizer status
B. CYP3A4 poor metabolizer status
C. UGT1A1*28 polymorphism
D. ABCB1 (P-glycoprotein) polymorphism leading to decreased efflux
Answer: B
Rationale: Imatinib is primarily metabolized by CYP3A4. Poor metabolizer status can lead to increased
drug exposure and toxicity, including fluid retention (pleural effusions, edema). CYP2D6 is not a major
pathway for imatinib. UGT1A1*28 is associated with irinotecan toxicity, not imatinib. ABCB1
polymorphisms may affect transport but are not the primary cause of imatinib-induced fluid retention.
8. A patient with a history of recurrent Clostridioides difficile infection (rCDI) is being evaluated
for fecal microbiota transplantation (FMT). Which of the following donor characteristics is an
absolute contraindication to FMT?
A. Donor has a history of irritable bowel syndrome
B. Donor has a body mass index of 32 kg/m²
C. Donor recently traveled to an area with a high prevalence of extended-spectrum beta-lactamase
(ESBL)-producing Enterobacteriaceae
D. Donor has a history of seasonal allergies
Answer: C
Rationale: FMT donor screening aims to minimize transmission of infectious agents. Recent travel to
areas with high prevalence of multidrug-resistant organisms (e.g., ESBL producers) is a
contraindication due to risk of transmitting resistant bacteria. IBS and obesity are relative but not
absolute contraindications; screening includes these but they do not automatically exclude. Seasonal
allergies are not a contraindication.
Page 3
, 9. A patient with atrial fibrillation is being considered for anticoagulation with a direct oral
anticoagulant (DOAC). The patient has a creatinine clearance of 25 mL/min, a history of
gastrointestinal bleeding, and a CHA2DS2-VASc score of 4. Which of the following DOACs is most
appropriate for this patient?
A. Dabigatran 150 mg twice daily
B. Rivaroxaban 20 mg once daily
C. Apixaban 5 mg twice daily
D. Edoxaban 30 mg once daily
Answer: D
Rationale: Edoxaban 30 mg daily is approved for creatinine clearance 15-50 mL/min and has a lower
risk of gastrointestinal bleeding compared to other DOACs. Dabigatran is contraindicated when CrCl
<30 mL/min. Rivaroxaban 20 mg is not recommended when CrCl <30 mL/min (requires 15 mg if CrCl
15-50, but still higher GI risk). Apixaban 5 mg twice daily is appropriate for CrCl 25-50, but the
patient's history of GI bleeding makes edoxaban preferable due to lower GI bleed risk in clinical trials.
10. A patient with treatment-resistant depression is started on phenelzine, a monoamine oxidase
inhibitor (MAOI). The patient is also taking dextromethorphan for a chronic cough. Which of the
following is the most appropriate recommendation?
A. Continue both medications, but monitor for serotonin syndrome
B. Discontinue dextromethorphan and switch to an alternative antitussive such as codeine
C. Discontinue phenelzine and switch to a different antidepressant
D. Reduce the dose of phenelzine and continue dextromethorphan
Answer: B
Rationale: Dextromethorphan is a weak serotonin reuptake inhibitor and can precipitate serotonin
syndrome when combined with MAOIs. Codeine is a safer alternative as it does not have significant
serotonergic activity. Discontinuing phenelzine is not necessary if alternative cough treatment is
available. Reducing the dose of phenelzine does not eliminate the interaction risk. Continuing both is
dangerous.
11. A patient with a history of recurrent Clostridioides difficile infection (CDI) is being considered
for fecal microbiota transplantation (FMT). Which of the following best describes the
pharmacological rationale for FMT in this context?
A. FMT directly kills C. difficile spores via bacteriophage activity.
B. FMT restores colonic microbiota diversity, outcompeting C. difficile and restoring colonization resistance.
C. FMT provides passive immunity through donor antibodies against C. difficile toxins.
D. FMT acts as a probiotic supplement to enhance vancomycin efficacy.
Answer: B
Rationale: FMT works by reconstituting the gut microbiome, thereby restoring colonization resistance
against C. difficile. It does not directly kill spores (A) nor provide passive immunity (C). While it can be
used after antibiotics, it is not a probiotic supplement to enhance vancomycin (D).
Page 4
Case Exam 2026/2027: 250 Digital Clinical
Experience Style Q&A with Detailed Rationales
1. A patient with chronic heart failure (NYHA class III) and a left ventricular ejection fraction of
30% is initiated on sacubitril/valsartan. Which of the following concurrent medications requires
the most cautious monitoring due to a pharmacokinetic interaction that may increase the risk of
angioedema?
A. Spironolactone
B. Atorvastatin
C. Lisinopril
D. Metoprolol succinate
Answer: C
Rationale: Sacubitril/valsartan contains a neprilysin inhibitor (sacubitril) that can increase bradykinin
levels. Concurrent use with an ACE inhibitor (lisinopril) significantly raises the risk of angioedema due
to additive bradykinin elevation. A 36-hour washout period is required when switching from an ACE
inhibitor. Spironolactone requires potassium monitoring but does not interact with bradykinin.
Atorvastatin and metoprolol have no significant interaction.
2. A patient receiving a continuous infusion of heparin for acute coronary syndrome develops a
platelet count drop from 250,000/¼L to 80,000/¼L over 5 days. The clinician suspects
heparin-induced thrombocytopenia (HIT). Which of the following anticoagulants is most
appropriate to continue or initiate while awaiting confirmatory testing?
A. Enoxaparin 1 mg/kg subcutaneously twice daily
B. Fondaparinux 2.5 mg subcutaneously once daily
C. Warfarin 5 mg orally once daily
D. Argatroban intravenous infusion adjusted to aPTT 1.5-3 times baseline
Answer: D
Rationale: In suspected HIT, all heparin products (including enoxaparin) must be discontinued.
Fondaparinux has a lower risk but still carries potential cross-reactivity in some patients. Warfarin
should be avoided until platelet count recovers due to risk of venous limb gangrene. Argatroban, a direct
thrombin inhibitor, is the preferred agent for anticoagulation in HIT and does not cross-react with
heparin antibodies.
3. A patient with type 2 diabetes mellitus and stage 3 chronic kidney disease (eGFR 38
mL/min/1.73 m²) is being treated with metformin, which has been stable. Recently, the patient was
prescribed a new medication that significantly increases the risk of metformin-associated lactic
acidosis. Which of the following is most likely to have been initiated?
Page 1
,A. Sitagliptin
B. Dapagliflozin
C. Ibuprofen 800 mg three times daily
D. Lisinopril
Answer: C
Rationale: Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen can reduce renal perfusion and
further impair renal function, increasing the risk of metformin accumulation and lactic acidosis,
especially in patients with pre-existing CKD. Sitagliptin and dapagliflozin have minimal interaction with
metformin. Lisinopril is generally renoprotective but may cause transient hyperkalemia; it does not
significantly increase lactic acidosis risk.
4. A patient with a history of opioid use disorder is being treated with buprenorphine/naloxone.
The patient presents with acute pain from a fractured femur. Which of the following pain
management strategies is most appropriate to manage severe acute pain while minimizing the risk
of precipitating withdrawal?
A. Discontinue buprenorphine/naloxone and initiate morphine patient-controlled analgesia
B. Continue buprenorphine/naloxone and add a nonsteroidal anti-inflammatory drug only
C. Continue buprenorphine/naloxone and add a short-acting full mu-opioid agonist with higher doses to
overcome buprenorphine's high receptor affinity
D. Increase the buprenorphine/naloxone dose to 16/4 mg daily and add acetaminophen
Answer: C
Rationale: Buprenorphine has a high affinity for mu-opioid receptors, which can block the effects of
additional opioids. To manage severe acute pain, it is recommended to continue buprenorphine to
maintain stability and add a full mu-opioid agonist (e.g., fentanyl, morphine) at higher than usual doses
to overcome the receptor blockade. Discontinuing buprenorphine risks withdrawal and loss of tolerance.
NSAIDs alone are insufficient for severe pain. Increasing buprenorphine dose may not provide adequate
analgesia for acute pain.
5. A patient with a history of recurrent unprovoked venous thromboembolism (VTE) is on
long-term warfarin therapy (target INR 2-3). The patient develops a new pulmonary embolism
despite a therapeutic INR of 2.8. Which of the following is the most likely explanation for this
treatment failure?
A. The patient has a lupus anticoagulant that prolongs the INR but does not reflect true anticoagulation
B. The patient has been taking a multivitamin containing vitamin K
C. The patient has been noncompliant with warfarin dosing, but the INR was drawn shortly after a dose
D. The patient has developed a heparin-induced thrombocytopenia
Answer: A
Rationale: Lupus anticoagulant (antiphospholipid syndrome) can cause a falsely elevated INR due to
interference with the phospholipid-dependent coagulation tests. In such patients, warfarin may not
provide adequate anticoagulation despite a seemingly therapeutic INR. Direct oral anticoagulants or
alternative monitoring (e.g., chromogenic factor Xa assay) may be needed. Vitamin K intake would
lower INR, not cause failure with a therapeutic INR. Noncompliance would likely result in
subtherapeutic INR. HIT is not relevant to warfarin failure.
Page 2
,6. A patient with generalized anxiety disorder has been taking sertraline 100 mg daily for 6 weeks
with minimal improvement. The clinician decides to augment therapy with a second agent. Which
of the following augmentation strategies is most supported by evidence for treatment-resistant
anxiety?
A. Add aripiprazole 2 mg daily
B. Add buspirone 10 mg twice daily
C. Add pregabalin 75 mg twice daily
D. Add propranolol 20 mg twice daily
Answer: B
Rationale: Buspirone is a 5-HT1A receptor partial agonist with established efficacy as augmentation to
SSRIs for generalized anxiety disorder, particularly when SSRI response is inadequate. Aripiprazole has
limited evidence for anxiety. Pregabalin is effective for generalized anxiety disorder but is typically used
as monotherapy or first-line, not specifically as augmentation after SSRI failure. Propranolol is used for
performance anxiety but not for generalized anxiety disorder augmentation.
7. A patient with chronic myeloid leukemia (CML) is started on imatinib 400 mg daily. After 3
months, the patient develops new-onset pleural effusions and significant peripheral edema. Which
of the following pharmacogenetic factors is most likely contributing to this toxicity?
A. CYP2D6 poor metabolizer status
B. CYP3A4 poor metabolizer status
C. UGT1A1*28 polymorphism
D. ABCB1 (P-glycoprotein) polymorphism leading to decreased efflux
Answer: B
Rationale: Imatinib is primarily metabolized by CYP3A4. Poor metabolizer status can lead to increased
drug exposure and toxicity, including fluid retention (pleural effusions, edema). CYP2D6 is not a major
pathway for imatinib. UGT1A1*28 is associated with irinotecan toxicity, not imatinib. ABCB1
polymorphisms may affect transport but are not the primary cause of imatinib-induced fluid retention.
8. A patient with a history of recurrent Clostridioides difficile infection (rCDI) is being evaluated
for fecal microbiota transplantation (FMT). Which of the following donor characteristics is an
absolute contraindication to FMT?
A. Donor has a history of irritable bowel syndrome
B. Donor has a body mass index of 32 kg/m²
C. Donor recently traveled to an area with a high prevalence of extended-spectrum beta-lactamase
(ESBL)-producing Enterobacteriaceae
D. Donor has a history of seasonal allergies
Answer: C
Rationale: FMT donor screening aims to minimize transmission of infectious agents. Recent travel to
areas with high prevalence of multidrug-resistant organisms (e.g., ESBL producers) is a
contraindication due to risk of transmitting resistant bacteria. IBS and obesity are relative but not
absolute contraindications; screening includes these but they do not automatically exclude. Seasonal
allergies are not a contraindication.
Page 3
, 9. A patient with atrial fibrillation is being considered for anticoagulation with a direct oral
anticoagulant (DOAC). The patient has a creatinine clearance of 25 mL/min, a history of
gastrointestinal bleeding, and a CHA2DS2-VASc score of 4. Which of the following DOACs is most
appropriate for this patient?
A. Dabigatran 150 mg twice daily
B. Rivaroxaban 20 mg once daily
C. Apixaban 5 mg twice daily
D. Edoxaban 30 mg once daily
Answer: D
Rationale: Edoxaban 30 mg daily is approved for creatinine clearance 15-50 mL/min and has a lower
risk of gastrointestinal bleeding compared to other DOACs. Dabigatran is contraindicated when CrCl
<30 mL/min. Rivaroxaban 20 mg is not recommended when CrCl <30 mL/min (requires 15 mg if CrCl
15-50, but still higher GI risk). Apixaban 5 mg twice daily is appropriate for CrCl 25-50, but the
patient's history of GI bleeding makes edoxaban preferable due to lower GI bleed risk in clinical trials.
10. A patient with treatment-resistant depression is started on phenelzine, a monoamine oxidase
inhibitor (MAOI). The patient is also taking dextromethorphan for a chronic cough. Which of the
following is the most appropriate recommendation?
A. Continue both medications, but monitor for serotonin syndrome
B. Discontinue dextromethorphan and switch to an alternative antitussive such as codeine
C. Discontinue phenelzine and switch to a different antidepressant
D. Reduce the dose of phenelzine and continue dextromethorphan
Answer: B
Rationale: Dextromethorphan is a weak serotonin reuptake inhibitor and can precipitate serotonin
syndrome when combined with MAOIs. Codeine is a safer alternative as it does not have significant
serotonergic activity. Discontinuing phenelzine is not necessary if alternative cough treatment is
available. Reducing the dose of phenelzine does not eliminate the interaction risk. Continuing both is
dangerous.
11. A patient with a history of recurrent Clostridioides difficile infection (CDI) is being considered
for fecal microbiota transplantation (FMT). Which of the following best describes the
pharmacological rationale for FMT in this context?
A. FMT directly kills C. difficile spores via bacteriophage activity.
B. FMT restores colonic microbiota diversity, outcompeting C. difficile and restoring colonization resistance.
C. FMT provides passive immunity through donor antibodies against C. difficile toxins.
D. FMT acts as a probiotic supplement to enhance vancomycin efficacy.
Answer: B
Rationale: FMT works by reconstituting the gut microbiome, thereby restoring colonization resistance
against C. difficile. It does not directly kill spores (A) nor provide passive immunity (C). While it can be
used after antibiotics, it is not a probiotic supplement to enhance vancomycin (D).
Page 4
