, Question 1
A patient with heart failure and reduced ejection fraction (HFrEF) is started on
sacubitril/valsartan. Which concurrent medication requires immediate
discontinuation due to a high risk of angioedema?
A. Spironolactone
B. Lisinopril
C. Metoprolol succinate
D. Dapagliflozin
Correct Answer: B - Lisinopril
RATIONALE
Sacubitril/valsartan is contraindicated with ACE inhibitors like
lisinopril because combined neprilysin and ACE inhibition markedly
increases bradykinin levels, raising angioedema risk. A 36-hour
washout is required when switching. Spironolactone, metoprolol, and
dapagliflozin are safe and guideline-recommended companions in
HFrEF.
Question 2
Which cytochrome P450 enzyme is primarily responsible for the metabolism
of clopidogrel to its active metabolite, and what is the clinical implication for
poor metabolizers?
A. CYP3A4; poor metabolizers require higher doses.
B. CYP2C19; poor metabolizers have reduced antiplatelet effect and
increased cardiovascular risk.
C. CYP2D6; poor metabolizers experience excessive bleeding.
D. CYP1A2; poor metabolizers need alternative antiplatelet therapy.
Correct Answer: B - CYP2C19; poor metabolizers have reduced
antiplatelet effect and increased cardiovascular risk.
Page 2
, RATIONALE
Clopidogrel is a prodrug activated primarily by CYP2C19. Poor
metabolizers (e.g., *2/*2 alleles) produce less active metabolite,
leading to diminished platelet inhibition and higher rates of stent
thrombosis. CYP3A4, CYP2D6, and CYP1A2 play minor roles and
are not the primary determinants of response.
Question 3
A patient on warfarin for atrial fibrillation is prescribed
trimethoprim-sulfamethoxazole for a urinary tract infection. Which monitoring
parameter is most critical to assess within 3-5 days?
A. Serum creatinine and potassium
B. INR and signs of bleeding
C. Complete blood count with differential
D. Liver function tests
Correct Answer: B - INR and signs of bleeding
RATIONALE
Trimethoprim-sulfamethoxazole inhibits CYP2C9, which metabolizes
warfarin, and also displaces warfarin from albumin, markedly
increasing INR and bleeding risk. Close INR monitoring and dose
adjustment are essential. While renal function and CBC are relevant,
the immediate life-threatening risk is hemorrhage from
supratherapeutic anticoagulation.
Question 4
Which pathophysiologic mechanism best explains the development of diabetic
ketoacidosis (DKA) in a patient with type 1 diabetes who is nonadherent with
insulin?
A. Excessive glucose uptake by cells leading to hypoglycemia.
B. Absolute insulin deficiency causing unrestrained lipolysis and
ketogenesis.
Page 3
, C. Increased counterregulatory hormone suppression of glucagon.
D. Enhanced peripheral insulin sensitivity.
Correct Answer: B - Absolute insulin deficiency causing
unrestrained lipolysis and ketogenesis.
RATIONALE
In type 1 diabetes, absolute insulin deficiency leads to unchecked
lipolysis, producing free fatty acids that are converted to ketone bodies
in the liver, causing metabolic acidosis. Counterregulatory hormones
(glucagon, cortisol, catecholamines) are elevated, not suppressed, and
insulin sensitivity is not enhanced. Hypoglycemia is not a feature of
DKA.
Question 5
A patient with major depressive disorder has not responded to adequate trials
of two SSRIs. Which class of antidepressants is most appropriate to consider
next according to current STAR*D-informed guidelines?
A. Monoamine oxidase inhibitors (MAOIs)
B. Tricyclic antidepressants (TCAs)
C. Serotonin-norepinephrine reuptake inhibitors (SNRIs)
D. Atypical antipsychotics as monotherapy
Correct Answer: C - Serotonin-norepinephrine reuptake
inhibitors (SNRIs)
RATIONALE
After two failed SSRI trials, guidelines recommend switching to a
different class, such as an SNRI (e.g., venlafaxine, duloxetine), which
has a distinct mechanism and favorable safety profile. MAOIs and
TCAs are generally reserved for later lines due to dietary restrictions
and toxicity. Atypical antipsychotics are typically used as adjuncts,
not monotherapy, in this context.
Page 4
A patient with heart failure and reduced ejection fraction (HFrEF) is started on
sacubitril/valsartan. Which concurrent medication requires immediate
discontinuation due to a high risk of angioedema?
A. Spironolactone
B. Lisinopril
C. Metoprolol succinate
D. Dapagliflozin
Correct Answer: B - Lisinopril
RATIONALE
Sacubitril/valsartan is contraindicated with ACE inhibitors like
lisinopril because combined neprilysin and ACE inhibition markedly
increases bradykinin levels, raising angioedema risk. A 36-hour
washout is required when switching. Spironolactone, metoprolol, and
dapagliflozin are safe and guideline-recommended companions in
HFrEF.
Question 2
Which cytochrome P450 enzyme is primarily responsible for the metabolism
of clopidogrel to its active metabolite, and what is the clinical implication for
poor metabolizers?
A. CYP3A4; poor metabolizers require higher doses.
B. CYP2C19; poor metabolizers have reduced antiplatelet effect and
increased cardiovascular risk.
C. CYP2D6; poor metabolizers experience excessive bleeding.
D. CYP1A2; poor metabolizers need alternative antiplatelet therapy.
Correct Answer: B - CYP2C19; poor metabolizers have reduced
antiplatelet effect and increased cardiovascular risk.
Page 2
, RATIONALE
Clopidogrel is a prodrug activated primarily by CYP2C19. Poor
metabolizers (e.g., *2/*2 alleles) produce less active metabolite,
leading to diminished platelet inhibition and higher rates of stent
thrombosis. CYP3A4, CYP2D6, and CYP1A2 play minor roles and
are not the primary determinants of response.
Question 3
A patient on warfarin for atrial fibrillation is prescribed
trimethoprim-sulfamethoxazole for a urinary tract infection. Which monitoring
parameter is most critical to assess within 3-5 days?
A. Serum creatinine and potassium
B. INR and signs of bleeding
C. Complete blood count with differential
D. Liver function tests
Correct Answer: B - INR and signs of bleeding
RATIONALE
Trimethoprim-sulfamethoxazole inhibits CYP2C9, which metabolizes
warfarin, and also displaces warfarin from albumin, markedly
increasing INR and bleeding risk. Close INR monitoring and dose
adjustment are essential. While renal function and CBC are relevant,
the immediate life-threatening risk is hemorrhage from
supratherapeutic anticoagulation.
Question 4
Which pathophysiologic mechanism best explains the development of diabetic
ketoacidosis (DKA) in a patient with type 1 diabetes who is nonadherent with
insulin?
A. Excessive glucose uptake by cells leading to hypoglycemia.
B. Absolute insulin deficiency causing unrestrained lipolysis and
ketogenesis.
Page 3
, C. Increased counterregulatory hormone suppression of glucagon.
D. Enhanced peripheral insulin sensitivity.
Correct Answer: B - Absolute insulin deficiency causing
unrestrained lipolysis and ketogenesis.
RATIONALE
In type 1 diabetes, absolute insulin deficiency leads to unchecked
lipolysis, producing free fatty acids that are converted to ketone bodies
in the liver, causing metabolic acidosis. Counterregulatory hormones
(glucagon, cortisol, catecholamines) are elevated, not suppressed, and
insulin sensitivity is not enhanced. Hypoglycemia is not a feature of
DKA.
Question 5
A patient with major depressive disorder has not responded to adequate trials
of two SSRIs. Which class of antidepressants is most appropriate to consider
next according to current STAR*D-informed guidelines?
A. Monoamine oxidase inhibitors (MAOIs)
B. Tricyclic antidepressants (TCAs)
C. Serotonin-norepinephrine reuptake inhibitors (SNRIs)
D. Atypical antipsychotics as monotherapy
Correct Answer: C - Serotonin-norepinephrine reuptake
inhibitors (SNRIs)
RATIONALE
After two failed SSRI trials, guidelines recommend switching to a
different class, such as an SNRI (e.g., venlafaxine, duloxetine), which
has a distinct mechanism and favorable safety profile. MAOIs and
TCAs are generally reserved for later lines due to dietary restrictions
and toxicity. Atypical antipsychotics are typically used as adjuncts,
not monotherapy, in this context.
Page 4
