Running head: CASE STUDY

Case Study: Patient Drug Interactions

Patient Characteristics

 57-year-old woman.

 The fall occurred while having lunch with recently introduced grapefruit juice.

 Has a bruise on her right arm from her recent fall.

 The patient has been experiencing dizziness for the past week.

 Overweight with a BMI of 25 and past laboratory values (presumably fasting)

demonstrate a cholesterol level of 200 and glucose of 89.

 Taking nifedipine (Procardia), atorvastatin (Lipitor), and metformin (Glucophage) for

hypertension, hypercholesterolemia, and diabetes type II mellitus (D2M), respectively.

 Blood pressure today in clinic was 85/55 after suffering from a fall.

 The patient have variations in their Cytochrome P450 genes that causes differences in

drug metabolism.

 Another important patient characteristic is the recent introduction of grapefruit juice into

the patient’s diet. Chen, Zhou, Fabriaga, Zhang, and Zhou (2018), reported that grapefruit

juice can act as an inhibitor of first pass metabolism for drugs metabolized by

cytochrome P3A4 (CYP3A4).

 As per Arcangelo, Peterson, Wilbur, and Reinold (2017), grapefruit juice can alter the

metabolism of both Procardia and Lipitor.

CASE STUDY 1

Patient Diagnosis

 The persistent feelings of dizziness for the past week, in addition to the recent episode of

syncope, suggest that the patient is experiencing drug-induced orthostatic hypotension

from the consumption of grapefruit juice.

 Arcangelo et al. (2017) reported that the effects of Procardia are exacerbated with the

consumption of grapefruit juice and therefore, the patient’s blood pressure would be

severely within hypotensive range.

 The patient’s blood pressure on presentation to the clinic was 85/55, which falls within

the hypotensive range reported by Boron and Boulpaep (2016).

Pharmacokinetics and Pharmacodynamics

Procardia (Nifedipine)

 A calcium ion influx inhibitor that exerts its action by blocking the activity of slow

calcium channels. Blocking calcium channels decreases the transmembrane influx of

calcium ions, thereby reducing the membrane contractility of vascular smooth muscle and

cardiac muscle without altering serum calcium (Skidmore-Roth, 2018).

 Procardia’s lack of effect on serum calcium makes it an appropriate anti-hypertensive

medication since it will not severely disrupt other electrochemical processes that depend

on the exchange of calcium cations. Procardia is metabolized by CYP3A4 in the liver and

grapefruit juice is an inhibitor of this cytochrome enzyme. This results in the

accumulation of Procardia and exacerbates the longitudinal effects of the anti-

hypertensive medication (Arcangelo et al., 2017).

CASE STUDY 2

 See table 1 for a concise overview of the pharmacodynamics of Procardia.

Lipitor (Atorvastatin)

 A competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)

reductase, which is responsible for the conversion of HMG-CoA to mevalonate

(Skidmore-Roth, 2018).

 Inhibition of HMG-CoA decreases the amount of lipoprotein and plasma cholesterol

synthesis in the liver (Boron and Boulpaep, 2016).

 As stated above, grapefruit juice inactivates CYP3A4, and the enzyme is responsible for

the breakdown of atorvastatin, lovastatin, and simvastatin (Arcangelo et al., 2017).

 Inhibition of CYP3A4 increases the longitudinal effects of atorvastatin and this could

potentially exacerbate some side effects of the medication, including muscle and liver

damage (Skidmore-Roth, 2018).

 The potential side effects caused by inappropriately elevated level of serum atorvastatin

do not explain the unusual side effects experienced by Ms. Rose. Therefore, it is unlikely

that atorvastatin is the underlying culprit causing the patient’s issues.

 See table 1 for a concise overview of the pharmacodynamics of Lipitor.

Glucophage (Metformin)

 A biguanide, decreases intestinal absorption of glucose, decreases a pack production of

glucose, and increases insulin sensitivity. The overall effect of Metformin is a reduction

of serum blood sugar and improved utilization of glucose (Skidmore-Roth, 2018).

CASE STUDY 3

 The exact mechanism of action of Metformin is not entirely understood, however, some

evidence suggest that it leads to activation of AMP-activated protein kinase and elevation

of cyclic adenosine monophosphate (Boron and Boulpaep, 2016).

 Modification of these regulatory molecules causes inhibition of glucose metabolism by

the liver and increase utilization of glucose by improving insulin sensitivity.

 Metformin is an unusual drug in that it is not metabolized by the body but is cleared by

tubular secretion in the kidneys. The drug has a half-life of approximately six hours and

therefore, the effects of the medication will persist until cleared by tubular epithelium

(Skidmore-Roth, 2018).

 It is important to note that Metformin is one of the few anti-hyperglycemic medications

that does not typically cause hypoglycemia (Skidmore-Roth, 2018).

 The metabolism of the medication is not modified by different physiological states, i.e.

intense exercise or caloric input, and thus, the medication exerts a consistent effect on the

body while in circulation (Hayanga, Ngubane, Murunga, and Owira, 2009).

 Hayanga et al. (2009) reported that grapefruit juice is unlikely to affect the action of

Metformin and given its mode of excretion, the ingestion of grapefruit juice is unlikely to

cause any worrisome complications.

 See table 1 for a concise overview of the pharmacodynamics of Metformin.

Drug Interactions

 Arcangelo et al. (2017) reported that there are multiple drug-drug interactions for

Procardia. In fact, Procardia has moderate drug interactions with both Lipitor and

Metformin.
CASE STUDY 4

 Both drug-drug interactions involve an increase of the effects of both Metformin and

atorvastatin when combined with Procardia. This is due to the competition of Procardia,

Lipitor, and Metformin for the cytochrome enzymes involved in their metabolism or

secretion by the body (Skidmore-Roth, 2018). Procardia has a greater affinity for the

cytochrome enzymes and therefore, is a selectively favored for metabolism prior to

Lipitor, and Metformin’s elimination is delayed when consuming Procardia.

Plan of Care

 Immediate discontinuation of any grapefruit juice.

 Also, diabetic patients are susceptible to progressive kidney damage if improperly

controlled.

 One method of decreasing the progression of kidney damage is the combined use of

angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II receptor blockers

(ARBs). These medications act by causing dilatation of efferent arterioles in the kidney,

reducing blood pressure and kidney damage.

 These medications are effective for lowering blood pressure and the discontinuation of

Procardia is warranted with the substitution of an ACE inhibitor and ARB combination.

 The Lipitor and Metformin can remain a component of the patient’s medication regimen

due to their general lack of side effects and their effectiveness.

 Although not explicitly stated, one could assume that the health education of the patient

was poor prior to this clinic presentation. Therefore, it is essential that thorough

education is completed about the medications that the patient will be taking and their

potential side effects.

CASE STUDY 5

 The patient should be instructed that certain dietary products can modify the metabolism

of the medications and consultation with their healthcare professional should be

performed prior to any persistent changes in their diet. Per Arcangelo et al. (2017),

education on the consumption of grapefruit juice, St. John’s wort, and other herbal

supplements should be performed given the patient’s ethnicity as a Native American.

Once verbalized understanding with teach back has been performed, the patient should

follow-up in 2-4 weeks.

Table 1: Pharmacodynamics and Pharmacokinetics

Drug Name Class Mechanism Metabolism Contraindications

Lipitor HMG CoA Competitive cytochrome Grapefruit juice;
reductase inhibitor of P450 3A4 Procardia
inhibitors HMG CoA system
reductase
Metformin Biguanides Decreases Secreted Procardia
intestinal unmetabolized
absorption of in urine
glucose,
decreases a pack
production of
glucose, and
increases insulin
sensitivity
Procardia Calcium-channel Calcium channel cytochrome Grapefruit juice;
blockers inhibitor causing P450 3A4 Metformin; Lipitor
peripheral system
arterial
vasodilation
CASE STUDY 6

References

Arcangelo, V. P., Peterson, A. M., Wilbur, V., & Reinhold, J. A. (2017). 

Pharmacotherapeutics for advanced practice: A practical approach, (4th ed.).

New York: Wolters Kluwer.

Boron, W. F., & Boulpaep, E. L. (2016). Medical physiology e-book. Saint Louis, MO: Elsevier

Health Sciences.

Chen, M., Zhou, S. Y., Fabriaga, E., Zhang, P. H., & Zhou, Q. (2018). Food-drug interactions

precipitated by fruit juices other than grapefruit juice: An update review. Journal of Food

and Drug Analysis, 26(2), S61-S71.

Hayanga, J. A., Ngubane, S. P., Murunga, A. N., & Owira, P. M. (2016). Grapefruit juice

improves glucose intolerance in streptozotocin-induced diabetes by suppressing hepatic

gluconeogenesis. European Journal of Nutrition, 55(2), 631-638.

Skidmore-Roth, L. (2018). Mosby's 2019 nursing drug reference e-book. Saint Louis, MO:

Elsevier Health Sciences.

Watson, D. G. (2015). Pharmaceutical analysis e-book: A textbook for pharmacy students and

pharmaceutical chemists. Saint Louis, MO: Elsevier Health Sciences.