reply w15

DQ-1

Protonix and drug-drug interactions with Warfarin for treatment of GI ulcer and deep vein thrombosis with elevated INR

The background of this study includes a patient who was at high risk for ulcers and was prescribed Pantoprazole which is commonly used as prophylaxis of ulcers (Chandelia & Dubey, 2016). The patient was also taking Warfarin daily due to a discovery of a deep vein thrombosis of the circumflex vein, common femoral vein, superficial vein, and popliteal vein (Chandelia & Dubey, 2016). This patient was also in the ICU (Chandelia & Dubey, 2016).

Initially, heparin was started on this patient and the healthcare team was able to keep the INR within normal limits of their heparin protocol (Chandelia & Dubey, 2016). However, when switching to Warfarin with a standard dose of 0.2 mg/kg (8mg/day) for this patient to maintain an INR of 2.5, there were some issues associated with it. On day 3 the INR came back elevated at 6.0, so there was a reduction of warfarin by 20% (Chandelia & Dubey, 2016). After two days, the INR was still elevated at 5.0, and another reduction by 20% without success (Chandelia & Dubey, 2016). At this time the healthcare team decided to look at the medications and foods the patient was eating.

First, the healthcare team decided to compile a list of the patient's medications and foods and found that the patient was not receiving any garlic, mango, papaya or fish (Chandelia & Dubey, 2016). The patient's medications were ceftriaxone, vancomycin, and pantoprazole, but the team was unable to stop the antibiotics, so they decided to stop the pantoprazole. After three days post discontinuation of pantoprazole, the INR had dropped to 1.4 without any change in the dose of warfarin (Chandelia & Dubey, 2016). Most importantly, at this point, the healthcare team had to increase the warfarin dose back to the original 8mg/day to get the patient's INR into the therapeutic range (Chandelia & Dubey, 2016). There was an 87.5% reduction in the dose of warfarin when given with pantoprazole (Chandelia & Dubey, 2016). The rationale behind the drug to drug interaction is that warfarin undergoes metabolism by CYP1A2, CYP2C19, and CYP3A4 (Crader, Johns & Arnold, 2019). Pantoprazole has been shown to strongly inhibit CYP2C9 activity (Chandelia & Dubey, 2016). This metabolite inhibition and interaction is what causes the low metabolism of warfarin and leads to the elevated INR (Crader, Johns & Arnold, 2019).

An alternate therapy suggested would be to use heparin subcutaneous injections through the hospital and at home until they need for pantoprazole has been resolved (Chandelia & Dubey, 2016). The issue is that the first and second-line proton pump inhibitors are inhibitors of CYP2C9 (Chandelia & Dubey, 2016). In this scenario, the only drug change that can occur is with warfarin to heparin and/or Lovenox (Chandelia & Dubey, 2016). Thought behind this is that in patients who can't tolerate oral warfarin, due to side effects, they could take pantoprazole and a lower amount of warfarin by 87.5% in order to achieve the same INR. References:

Chandelia, S., & Dubey, N. K. (2016). Warfarininduced raised international normalized ratio is further prolonged by pantoprazole. Indian Journal of Critical Care Medicine, 20(2), 127–128. https://doi-org.lopes.idm.oclc.org/10.4103/0972-5229.175934

Crader, M..F, Johns, T. & Arnold, J.K. (2019). Warfarin Drug Interactions. StatPearls Publishing. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK441964/

DQ-2

Polyethylene glycol mechanism of action is that it is an osmotic agent that binds water and retains the water in the stool (Jacobs et al., 2019). The effectiveness of polyethylene glycol is contributed to the lack of enzyme metabolism of the drug in the intestinal tract (Jacobs et al., 2019). Polyethylene glycol is also shown to increase stool weight, soften stool, increase frequency, and helps facilitate evacuation (Jacobs et al., 2019).

Polyethylene glycol pharmacokinetics is that it is administered orally in water as a solution, and mostly stays in the GI tract and is eliminated the same way (Jacobs et al., 2019). Some studies have shown 0.2% has been absorbed systemically but then quickly excreted in urine (Jacobs et al., 2019). As a side note, Polyethylene glycol is not fermented within the GI tract by colonic microflora (Jacobs et al., 2019).

The indications for Miralax is for occasional constipation in adults 17 years and older (5B Constipation and bowel cleansers, 2016). Also, polyethylene glycol is safe to use during pregnancy since it is not systematically absorbed (Jacobs et al., 2019).

Drug interactions with polyethylene glycol are extensive when the drugs are taken by the oral route (Jacobs et al., 2019). This is mostly due to the increase in movement in the GI system, which decreases the time allowed for the absorption of oral medications (Jacobs et al., 2019). Closer monitoring of oral drugs when polyethylene glycol is recommended as well as titration for the efficacy of desired effects and outcomes (Jacobs et al., 2019).

Side effects include bowel obstruction, nausea, vomiting, abdominal pain, and irritable bowel syndrome (5B Constipation and bowel cleansers, 2016). Contraindications include bowel obstruction, renal insufficiency, hepatic impairment, and avoid prolonged use (5B Constipation and bowel cleansers, 2016).

In terms of use of polyethylene glycol for the use of constipation and the incidence of C. Diff, studies have shown that out of seven hundred and fifty tests, five hundred and thirty-five C. Diff tests were done where the patient had ingested polyethylene glycol 48 hours prior to the test, compared to the control group, causes an unnecessary rise in the testing of patients (Carter & Malani, 2018). This study theorized that the increase in test frequency also led to a rise in false-positive tests due to colonization and not infection, and unnecessary treatment of C-Diff (Carter & Malani, 2018). A secondary thought in the study was that if the increase of unnecessary treatment occurred, so did the risk of creating antibiotic resistance, leading to worse outbreaks as 20% of C-diff infections are hospital-acquired (Carter & Malani, 2018). A proposed solution was to create a questionnaire for staff to complete that includes the signs and symptoms of C. Diff as well as information regarding laxatives and stool softeners and last administration date (Carter & Malani, 2018). References:

5B Constipation and bowel cleansers. (2016). MPR - Physician Assistants’ Edition, 23(2), 54–55.

Carter, K. A., & Malani, A. N. (2019). Laxative use and testing for Clostridium difficile in hospitalized adults: An opportunity to improve diagnostic stewardship. American Journal of Infection Control, 47(2), 170–174. https://doi-org.lopes.idm.oclc.org/10.1016/j.ajic.2018.08.008

Jacobs, C., Brar, T., Riverso, M., Perbtani, Y. B., & Yang, D. (2019). Abdominal Pain due to Opioid-Induced Constipation. ACG Case Reports Journal, 6(11), 1–2. https://doi-org.lopes.idm.oclc.org/10.14309/crj.0000000000000288

DQ-3

There are frequent drugs that interact with antacids. One of the drugs that frequent is in high alert for antacids interactions is tetracycline. People that may suffer from an upset stomach are often told to take some sort of antacid. Antacids contain calcium, magnesium, aluminum, sodium bicarbonate, iron and zinc. Antacids are known to alter and increase the Ph of the stomach content. This creates a problem towards the absorption of tetracycline. With higher Ph the less the breakdown of tetracycline and the slower the absorption (Deglin,Vallerand,Sanoski,2018). Magnesium can bind to the tetracycline antibiotic and decrease its absorption. This may have an effect on magnesium concentrations as well. Low body magnesium can have some side effects. Some side effects of low magnesium are nausea, fatigue, numbness, tingling, unwanted muscle contraction (Beware Mixing Antibiotics With Magnesium,2015). Magnesium deficiencies can worsen existing medical conditions. Studies have shown that having hypomagnesemia and electrolyte imbalance may lead to recurrent acute asthma episodes (Mohammad,Abdulazez, Mahmoud, Emam, (2014). The patient must wait 1 to 2 hours after taking tetracycline in order to begin supplementation of magnesium or calcium. This will ensure that maximum absorption of tetracycline can enter the patient’s body. If I were the provider, I will instruct the patient to take their prescribed antacid only when needed. I will also inform the patient that antacids need to be taken 3 hours apart from antibiotic therapy. In the case where the patient is having difficulty coordinating the specific instructions, I will probably switch the antibiotic therapy to something less controversial such as Keflex.

 Reference

Bai, G. P., & Ravikumar, P. (2013). Study of prevalence of hypomagnesemia and its impact on the severity of acute asthma. Journal of Evolution of Medical and Dental Sciences, 30, 5693.

 Deglin, J. H., Vallerand, A. H., & Sanoski, C. A. (2018). Daviss drug guide for nurses. Philadelphia: F.A. Davis (380-385).

Hala A. Mohammad, Mohammad T. Abdulfttah, Ali O. Abdulazez, Ahmed M. Mahmoud, & Rasha M. Emam. (2014). A study of electrolyte disturbances in patients with chronic stable asthma and with asthma attacks. Egyptian Journal of Chest Disease and Tuberculosis, 3, 529. https://doi.org/10.1016/j.ejcdt.2014.03.010