Study on Salicylates and Antihypertensive Drugs Induced Hypoglycemia in a Tertiary Care Hospital

Sattu Srinivas^1*, Keerthana Valli², B. Akhila Sai², G. Kishore Swathi² and G. Sneha Krishna^2
*Correspondence: Sattu Srinivas, Department of Pharm D, Assistant Professor, CMR College of Pharmacy, India, Tel: +919550656217, Email:

Keywords

Aspirin • Blood glucose levels • Diabetes mellitus • Hypertension • Oral hypoglycemic agents

Abbreviations

HTN- Hypertension

OHG- Oral Hypoglycemics

Introduction

Diabetes mellitus is a foremost enduring disease in all over the world. In the elderly population, 1 in 4 adults of age 65 years have been diagnosed with T2DM and another 50% have prediabetes, who are at higher risk of developing diabetes in the future [1]. Hypoglycemia is a predominantly concerned problem in geriatric patients who are having diabetes mellitus because of diminished counter regulatory hormone response to hypoglycemia. It is a common acceptance that beta -blockers should be avoided in diabetic patients because they may prolong hypoglycemia and mask the hypoglycemic symptoms [2]. In healthy individuals a complicated glucoregulatory system acts rapidly to counter hypoglycemia by reducing insulin production which is important in mechanism that removes glucose from the bloodstream and activating energy assets from the fat and liver. When this glucoregulatory system does not function, there will be excessive large amounts of insulin in the blood. Which results in sudden radical drop in circulating glucose [3]. In, most of the cases hypoglycemia occurs in diabetic patients who are enduring therapeutic intervention with meglitinides, sulfonylureas or insulin [4]. Many theories about the mechanisms of antihypertensive induced glycemic effects have been hypothesized. Few of these theories have been deep-rooted and some are contradictory. In general, postulated mechanisms can be classified into Effects on peripheral blood flow, insulin receptors, liver and Insulin release [5]. Aspirin is the trade name for acetylsalicylic acid. It is used to treat pain, swelling and fever etc. Aspirin is a prototype of non-steroidal anti-inflammatory drugs. The effect of diabetes on enhancing platelets adhesion (expression of p-selectin), activation (activates protein kinase C) and aggregation. Furthermore, diabetics have less platelet lifespan, causing increased bone marrow platelet production. Finally, platelets upregulate both glycoproteins IIb, IIIa and P2Y12 signaling. Which ultimately increase platelet aggregation and adhesion. This makes aspirin therapy of potential value in these patients to diminish platelet activation and aggregation. Anti-hypertensive drugs are used to treat a patient who are having high blood pressure and also to prevent the complications. Such as myocardial infarction, stroke and other cardiovascular disease. ACE inhibitors remain as a safe choice of drug for treating patients with diabetes mellitus. Beta Blockers inhibits glycogenolysis; diminishes signs and symptoms [6].

The chemical structure of Salicylic acid is shown in (Figure 1).

Materials and Methods

Study design: A prospective observational study.

Sample size: 80 to 100.

Study duration: 6 months.

Study period: September 2019 to February 2020.

Study approval: Institutional ethical committee approval was obtained before commencing study and Study protocol was submitted to Institutional Ethical Committee (IEC), CMR College of Pharmacy, and Hyderabad for approval.

A prospective observational study will be conducted and includes the following:

Participating in the ward rounds.

Identification of cases according to inclusive criteria and document in data documentation form.

To note down the blood glucose level values.

Preparation of final report and submission.

Publication of work.

The Inclusion criteria of the study are selection of diabetic patients treating with oral hypoglycemic agents, salicylates and anti-hypertensive drugs. Patients with age group of 25-80 years of both the gender were included as in higher (>80) and lower (<25) age group the blood glucose levels may not be accurate. The Exclusion criteria of the study are patients who are absconded and patients who are non-diabetics.

Results and Discussion

According to inclusion criteria, the total 64 diabetic and hypertension patients were scrutinized. In the present study out of 64 subjects, 46 (69.6%) were females and 20(30.3%) were males. Among gender wise distribution collected data females are more than males as shown in (Figure 2). The greater number of cases were found in age group 50-59 years (28.1%) in which males were 11 and females were 7 as shown in (Table 1). According to statistical data the age groups between 50-59 years are at more risk followed by 60-69 years (Table 2). Out of 64 subjects, 19 patients who are treated with anti-diabetics and aspirin, 18 patients treated with anti-diabetics and hypertensive (Table 3), 27 patients were treated with combination (Aspirin+Hypertensive drugs+Diabetic drugs (Table 4) as shown in (Figure 3). In our study, six patients were prescribed with beta blockers and oral hypoglycemic agents in which 2 patients were showed decreased glucose levels. Among 6 patients one was treated with carvedilol and five were treated with atenolol. The patient treated with carvedilol showed no decrease in glucose levels. This result is contradicted to the study by [7] that specified that hypoglycemia was higher for carvedilol. In our study, five patients were treated with calcium channel blocker (amlodipine, cilnidipine) in which one patient administered amlodipine showed decreased glucose levels. Which results, decrease in glucose levels not only in non-diabetic patients but also in diabetic patient. The glucose levels were decreased in the age group 50-59 with drug combinations of anti-hypertensive drugs, aspirin and oral hypoglycemic agents (Table 5). The result supports the study by [8,9] conducted on calcium channel blockers use in association with lower fasting serum glucose among adults in type 2 diabetes and concludes that Calcium channel blockers use was associated with lower fasting blood glucose levels among diabetes. Out of 45 patients who were treated with aspirin and oral hypoglycemic agents. 43 patients revealed decreased glucose levels. This result supports the study which is accomplished by [10-14] determined that salicylates have been reported to lower blood glucose concentrations. And this result is also supported by they concluded that salicylates appear to be the promising treatment option for prevention or treatment of diabetes mellitus by lowering the glucose levels.

The results according to our study are as follows:

The patients from OP department who are prescribed with oral hypoglycemic and aspirin were observed for 8 months and there is a considerable decrease in blood glucose levels as shown in (Figure 4).

The patients from OP department who are prescribed with oral hypoglycemic and anti-hypertensive drugs were observed for 8 months and there was a slight decrease in blood glucose levels as shown in (Figure 5).

The patients from OP department who are prescribed with oral hypoglycemic drugs, aspirin and anti-hypertensive drugs were observed for 8 months and there was a considerable decrease in blood glucose levels as shown in (Figure 6).

The patients from IP department who are prescribed with hypoglycemic agents along with aspirin were observed for 10 days and there was a slight decrease in blood glucose levels as shown in (Figure 7).

The patients of IP department who are prescribed with hypoglycemic agents along with anti-hypertensive drugs were observed for 10 days and there was a slight decrease in blood glucose levels e as shown in (Figure 8).

The patients from IP department, who are prescribed with hypoglycemic agents along with anti-hypertensive and aspirin. Were observed for 10 days and there is a considerable decrease in blood glucose levels as shown in (Figure 9).

Conclusion

In Outpatient Department and in Inpatients, there is abundant decrease in blood glucose levels by taking combination of drugs like aspirin, oral hypoglycemic agents and anti-hypertensive drugs and in patients taking oral hypoglycemic agents along with aspirin also showed decreased blood glucose levels but when compared with these two combination Aspirin +OHA+HTN group has shown much decrease in glucose levels. In Inpatient Department, there is much more decrease in blood glucose levels in patients taking combination of aspirin, oral hypoglycemic agents, anti-hypertensive.

Acknowledgements

The authors convey their sincere regards to the medical and paramedical staffs of the Department of General Medicine, Outpatient department, Gandhi Hospital, Secunderabad. They have helped throughout the case collection and also discussed various points related to the case whenever asked to them. Without their support this work would not have been successfully completed smoothly. The greater number of patients are taking combination of anti-hypertensive, anti-diabetics and aspirin that is 27patients.

References

1. https://www.researchgate.net/publication/226588719_Antihypertensive_drug_therapy_and_hypoglycemia_in_elderly_diabetic_patients_treated_with_insulin_andor_sulfonylureas
2. Cadavid, Angela P. "Aspirin: the mechanism of action revisited in the context of pregnancy complications." Front Immunol 8 (2017): 261.
3. Smith, Jamie W., and Bradley J. Goad. Geriatric Notes. Jones & Bartlett Learning, 2018.
4.  Bharati, Sandesh M., and Nishith Singh. "Effect of losartan and amlodipine on insulin sensitivity in non-diabetic hypertensive patients." IJBCP 5 (2016): 202-208.
5. Blackburn, David F., and Thomas W. Wilson. "Antihypertensive medications and blood sugar: theories and implications." Can J Cardiol 22 (2006): 229-233.
6. Rizos, Christos V., and Moses S. Elisaf. "Antihypertensive drugs and glucose metabolism." World J Cardiol 6 (2014): 517.
7. Dungan, Kathleen, Jennifer Merrill, Clarine Long, and Philip Binkley. "Effect of beta blocker use and type on hypoglycemia risk among hospitalized insulin requiring patients." Cardiovasc Diabetol 18 (2019): 1-9.
8. Khodneva, Yulia, Anath Shalev, Stuart J. Frank, April P. Carson, and Monika M. Safford. "Calcium channel blocker use is associated with lower fasting serum glucose among adults with diabetes from the regards study." Diabetes Res Clin Pract 115 (2016): 115-121.
9. https://www.researchgate.net/publication/221917930_Drugs_and_Hypoglycemia
10. Rumore, Martha M., and Katelynn S. Kim. "Potential role of salicylates in type 2 diabetes." Ann Pharmacother 44 (2010): 1207-1221.
11. Vue, Mays H., and Stephen M. Setter. "Drug-induced glucose alterations part 1: drug-induced hypoglycemia." Diabetes Spectr 24 (2011): 171-177.
12. https://www.ncbi.nlm.nih.gov/books/NBK534841/
13. https://www.britannica.com/science/hypoglycemia
14. Khalil, Salam, Fahed Darmoch, Zeel Shah, and M. Chadi Alraies. "Should all diabetic patients be on aspirin for primary prevention?." Expert Rev Cardiovasc Ther 17 (2019): 557-560.