Cynthia is a 55-year-old female patient whose labs indicate that she has diabetes, hypertension, and hyperlipidemia. As such, Glipizide, an insulin stimulating drug, has been recommended for her care. Hydrochlorothiazide may also be suggested for the control of her hypertension in addition to dietary and lifestyle changes. Finally, Simvastatin has been recommended for the treatment of hyperlipidemia. The dosages for each of these drugs are as follows:
2.5mg of Glipizide once daily
12.5mg of Hydrochlorothiazide once daily
20mg of Simvastatin once daily, orally before bedtime

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These dosages may need to be adjusted dependant on the patient’s reaction and their efficacy in controlling her health conditions.

How will you properly monitor each medication for efficacy and toxicity?
Each of the drugs that Cynthia has been prescribed require different monitoring regimens in terms of both efficacy and toxicity. The major recommendation for Glipizide is to assess the creatinine at baseline and then periodically (once a month initially) reassess creatinine levels (Foretz, Guigas, Bertrand, Pollak, and Viollet, 2014). In addition to this, the patient should have blood and urine glucose monitored: urine can be tested with laboratory testing once a month and blood glucose can be tested by the patient using an at-home blood glucose monitor (Foretz et al., 2014). These values are important as there is currently no strict regimen recommendation for Glipizide and it can cause hypoglycaemia if the dosage is too high (Foretz et al., 2014).

Hydrochlorothiazide is a tablet that works as a diuretic, and the removal of sodium and chloride from the body during this process is the likely mechanism of action in terms of reducing hypertension (Roush, Ernst, Kostis, Kaur, & Sica, 2015). There is no strict monitoring protocol for this drug, and as such it is recommended that Cynthia comes in for regular check-ups for her blood pressure and concentrations of electrolytes.

Simvastatin can have significant effects on renal function, even at lower dosages of 5mg. The patient should have renal function monitored when taking this drug in order to protect against damage to the kidneys. Another major side effect of Simvastatin is myopathy, defined as muscle pain and tenderness. This should also be monitored through the patient’s reporting of adverse symptoms (Brault, Ray, Gomez, Mantzoros, & Daskalopoulou, 2014).

Are you concerned with any drug-drug interactions?
There is a potential moderate interaction between glipizide and hydrochlorothiazide. There is a potential severe interaction between simvastatin and grapefruit juice, which the patient should be advised to avoid.

If so, what are they, and what is the mechanism of the interaction?
The moderate reaction between glipizide and hydrochlorothiazide is due to the fact that the efficacy of glipizide can be reduced by many different classes of medications (Brault et al., 2014). The management of this issue should be monitored in terms of the glycemic control of the patient and for any negative effects on glucose metabolism (Brault et al., 2014). This can occur due to the increased urination frequency of hydrochlorothiazide, which then expels the glipizide from the body and reduces its efficacy (Brault et al., 2014).

The Simvastatin interaction with grapefruit juice has the effect of increasing plasma concentrations of the drug. This is because grapefruit and its juice has the effect of inhibiting CYP450 first-pass metabolism, leading to a potential increase of simvastatin systemic exposure of up to 16 times the dosage (Brault et al., 2014). This can also increase the chance of the patient developing myopathy (as noted above) and lead to an increase in creatinine kinase (Brault et al., 2014). Again, this means that the patient should be advised to avoid grapefruit and its juice, and continually monitored for creatinine levels, renal function, and the presence of myopathy and muscle weakness.

There are no other significant interactions between the drugs or potential food ingested by the patient.

    References
  • Brault, M., Ray, J., Gomez, Y.-H., Mantzoros, C. S., & Daskalopoulou, S. S. (2014). Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metabolism, 63(6), 735–745.
  • Foretz, M., Guigas, B., Bertrand, L., Pollak, M., & Viollet, B. (2014). Metformin: from mechanisms of action to therapies. Cell Metabolism, 20(6), 953–966.
  • Roush, G. C., Ernst, M. E., Kostis, J. B., Kaur, R., & Sica, D. A. (2015). Not just chlorthalidone: evidence-based, single tablet, diuretic alternatives to hydrochlorothiazide for hypertension. Current Hypertension Reports, 17(4), 31.