Response

Number 1 post: YL

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?

In Cornett et al. (2021), metabolism and elimination of diazepam is accomplished through CYP2C19 and CYP3A4 in the liver. It presents with hepatic toxicity after long-term use of oral diazepam due to the first-pass effect.

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

According to Burchum & Rosenthal (2021), first-pass effect is the rapid hepatic inactivation of certain oral drugs when passed through the hepatic portal vein. If the capacity of the liver to metabolize a drug is extremely high, the drug could be completely inactivated on its first pass via liver. In order to circumvent the first-pass effect, the authors continue to explain that a drug normally undergoes rapid hepatic metabolism could be administered parenterally to bypass the liver in order to reach therapeutic effect before being metabolized.

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?

The confusion is mostly likely caused by drug sensitivity due to her age. In Burchum & Rosenthal (2021), they explain that the rates of hepatic drug metabolism tend to decline with advanced age, and alternations in receptor properties may underlie altered sensitivity to some medications. Also, the confusion could be caused by the drug interactions with other drugs the woman is taking. If the woman is taking the MAO inhibitor in the past 14 days, a dangerous drug interaction would occur.

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

In Patel et al (2022), warfarin is hepatic metabolism, primarily through the CYP2C9 enzyme. Warfarin has two different pregnancy categories depending on the presence of a mechanical heart valve. Warfarin was listed as a Category D drug for pregnant women with a mechanical heart valve and Category X for all other indications in pregnant women. In the article, the authors explain that warfarin crosses the placental barrier causing fetal plasma levels similar to maternal values. Warfarin can cause bleeding in the fetus and use during pregnancy is commonly associated with spontaneous abortion, stillbirth, preterm birth, neonatal death, skeletal and CNS defects. In pregnant women with a high risk for thromboembolism from mechanical heart valves, the benefits and risks of warfarin therapy should undergo careful evaluation. Some professionals recommend avoiding warfarin use during the first trimester and close to delivery.

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?

As Burchum & Rosenthal (2021) explain, hepatic drug metabolism of children 1 year and older is similar to those in adults, but the metabolize drugs rate are faster than adults until age two years then gradually declines. So, increase or reduction in dosing interval may be needed for drugs that are eliminated by hepatic metabolism.

Unlike children one year older and adults, the authors state that the drug-metabolizing capacity of newborns is low, so neonates are especially sensitive to drugs that are eliminated majorly by hepatic metabolism. As a result, when these drugs are utilized, dosages must be reduced. The liver increases its capacity to metabolize many drugs about one month after birth and with compete maturation about one year old.

Q6. Explain protein binding in the neonate.

In Burchum & Rosenthal (2021), they state that binding of drugs to albumin and other plasma proteins is limited due to the following reasons: the amount of serum albumin is very low; endogenous compounds such as fatty acid or bilirubin compete with drugs for available binding sites. The authors illustrate that protein-binding capacity reaches adult values within 10 to 12 months.

Number 2 post: BI

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?

The long history of Diazepam (valium) administration and the patient’s age are contributing factors causing the patient difficulty maintaining balance. Diazepam, which is included in the class of Benzodiazepines is a potent drug used to treat various conditions like muscle spams, alcohol withdrwal and anxiety, but can also cause sedation (Scholefield, 2021). Furthermore,with increasing age  the patients has a predisposition of having to higher fat levels and lower lean body mass. Diazepam is a lipid-soluble drug. Therefore, an increase in body fat serves as a reservoir for the drug and causes a slow-release effect. This effect causes an extended half-life and a higher volume of distribution of Diazepam (Scholefield, 2021).

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

The first-pass effect is the phenomenon of drug metabolism that occurs before the drug enters the body’s systemic circulation. This phenomenon occurs in the liver as the intestine absorbs the drug via the hepatic portal vein (Scholefield, 2021).To avoid the first-pass effect, medications must not be administered thru the oral route but instead administered via sublingual intravenous, intramuscular aerosol and inhalation routes. This way allows drugs to be absorbed directly into the systemic circulation (Scholefield, 2021).

A 75-year-old woman develops symptoms of a cold and buys an over-the-counter cold medication at the grocery store. The drug 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?

Diphenhydramine is an H1 antagonist drug that can cause marked sedation and cause confusion, and disorientation to elderly patients.

A 26-year-old woman who has never been pregnant is seeking preconception care as she plans 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. However, 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 an average 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 attempts 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?

Warfarin is metabolized by the cytochrome p450 system, primarily by CYP2C9 f(Scholefield, 2021).

Warfarin can cross the placental barrier and cause bleeding disorders in the fetus (Scholefield, 2021).

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

Drugs are slowly metabolized by neonatal and elderly compared to young adults (Scholefield, 2021). However, children can metabolize medications faster because their  basic metabolic rate is higher compared to elderly. In addition, their liver enzymes are capable of almost metabolizing every drug. Because of their capacity to metabolize drugs fast, drug levels must be adjusted according to their response.

Furthermore,  the metabolic clearance in children is affected by the activity of enzymes that metabolize drugs, hepatic blood flow and perfusion, active transport process and plasma protein binding.

The speed of metabolizing drugs in infant is lower compared to adults. In addition, neonates lack in phase II conjugating system while older people have significant depression of hepatic oxidative metabolism (Scholefield, 2021).

Q6. Explain protein binding in the neonate.

Drug binding to plasma protein is an essential factor in determining drug distribution. The plasma protein with the best binding capacity is albumin (Scholefield, 2021). The protein binding of drugs in a neonate is generally reduced compared to adults. Furthermore, the bilirubin concentrations in a neonate and fatty acids are higher. The impact of reduced plasma protein binding in neonates affects protein-bound drugs significantly and have a narrow therapeutic range effect (Scholefield, 2021).