1.2.11: Develop and implement individualized treatment plans, taking into consideration pharmacodynamic, pharmacokinetic, and pharmacogenomic principles
Which of the following is important to consider when initiating combination hydralazine and isosorbide dinitrate in an African American patient with heart failure?
(A) Initiate hydralazine 37.5 mg and isosorbide dinitrate 20 mg one tablet three times daily
(B) Discontinue background ACE inhibitor therapy
(C) Add concurrent digoxin therapy
(D) Therapy is well tolerated and lacks significant adverse reactions
In African American patients with HF, hydralazine 37.5 mg and isosorbide dinitrate 20 mg tid (A) is the starting dose, while hydralazine 75 mg and isosorbide dinitrate 40 mg tid is the target dose. Hydralazine and isosorbide dinitrate therapy should be initiated in addition to background ACE inhibitor therapy in this patient population (B). Concurrent digoxin therapy (C) is not required. Dizziness and headache are common dose-limiting side effects of this therapy, with no significant adverse reactions (D).
BV is a 50-year-old African American male patient with a new diagnosis of heart failure. His past medical history includes hypertension, diabetes mellitus, bilateral renal artery stenosis, and previous myocardial infarction. Which medication should be initiated to decrease pre-load and afterload for appropriate management of his heart failure?
Hydralazine and isosorbide dinitrate (B) consist of a venous and arterial vasodilator, and may be used in addition to the standard heart failure therapy of ACE inhibitors and beta blockers in African Americans or any patient who cannot tolerate an ACE inhibitor or ARB.
Lisinopril (Prinivil), (A), is an ace inhibitor and should be initiated in heart failure patients. However, BV has an absolute contraindication to ACE inhibitor therapy, bilateral renal artery stenosis. Other absolute contraindications for ACE inhibitors are pregnancy and angioedema. Valsartan (Diovan), (C), is an ARB and may be initiated in heart failure patients as an alternative to ACE inhibitors. BV has an absolute contraindication to ARB therapy, bilateral renal artery stenosis. Eprelenone (Inspra), (D), is an aldosterone antagonist used in the management of systolic heart failure after the patient is on standard therapy with an ACE inhibitor and beta blocker.
UGT1A1*28 mutations have been shown to cause what change in pharmacokinetics?
(A) Decreased fluorouracil clearance
(B) Increased fluorouracil clearance
(C) Decreased irinotecan clearance