How is warfarin metabolized?

Discussion Prompt

Post your answers to the 6 questions corresponding to this week’s content on primary care medication management. Provide your responses and rationales. Support your rationales with high-level evidence. (See Post Expectations)

A 70-year-old woman is in your office complaining of recently having trouble maintaining her balance after taking diazepam (valium). She occasionally takes diazepam when she feels anxious and has trouble sleeping. She has a 15-year history of taking diazepam.

Q1. Explain the cause of this patient’s difficulty in maintaining her balance?

Q2. Diazepam experiences a significant first-pass effect. What is the first-pass effect, and how can first-pass metabolism be circumvented?

A 75-year-old woman develops symptoms of a cold and buys an over-the-counter cold medication at the grocery store. The medication contains diphenhydramine, acetaminophen, and phenylephrine. She takes the recommended adult dose but soon after taking the medication she becomes very confused and disoriented.

Q3. What is likely causing the signs of confusion?

A 26-year-old woman who has never been pregnant is seeking preconception care as she is planning to pursue pregnancy in a couple of months. Currently, she has no symptoms to report and on review of body systems, there were no concerns. Her past medical history is significant for a history of rheumatic fever as a child. She subsequently underwent valve replacement with a mechanical heart valve. She is followed by a cardiologist who has already evaluated her cardiac function and she has received clearance from her cardiologist to pursue pregnancy. Records from her cardiologist include a recent cardiac echocardiography report that reveals a normal ejection fraction indicating normal cardiac function.

She has no alterations in her daily activities related to her heart. She has no other significant medical or surgical history. She is a non-smoker, drinks occasionally but has stopped as she is attempting to conceive, and does not use any non-prescription drugs.

Current Medications: Her current medications include only prenatal vitamins, which she has begun in anticipation of pregnancy, and warfarin. She has no known drug allergies.

Vital Signs: On examination, her pulse is 80 beats per minute, blood pressure is 115/70 mm Hg, respiratory rate is 18 breaths per minute, and she is afebrile.

Measurements: Weight = 152 pounds, Height = 5′5 ″, BMI= 25.29

Q4. How is warfarin metabolized? Does warfarin cross the placental barrier?

Q5. Explain the hepatic drug metabolism of children 1 year and older. How do they compare with the hepatic drug metabolism of infants and adults?

Q6. Explain protein binding in the neonate.