Sri Adichunchanagiri College of Pharmacy, B G Nagara, Karnataka 571448
The rise in number of diseases, drug availability, drug users, and drug regimen complexity have all contributed to an increase in drug related problems like adverse effects, drug interactions, and follow-up complications. Although polypharmacy (taking many medications) and multimorbidity (having multiple illnesses) are becoming more prevalent, yet there is a need to assess the risks associated with the polypharmacy particularly in people who have multiple medical illness. Over the period of six months, an observational cross-sectional study was carried out in the various inpatient departments of a tertiary care teaching hospital. In order to uncover potential risks related to polypharmacy, such as adverse drug reactions and drug-drug interactions, chi-square tests were used to analyse the prescriptions of patients with multiple medical problems. In the overall study findings, the prevalence of polypharmacy among multimorbidity patients was found to be 68.9% and the prevalence of drug-drug interactions and adverse drug reactions among the multimorbidity patients who have been identified with polypharmacy was found to be 43.6% and 3.88%. Finally, our study findings demonstrated that only limited number of risks associated with having polypharmacy in the hospital settings, such as Drug-Drug Interactions, Adverse drug reactions, which could be useful to prioritize and implement the suitable actions. This study can also be extended to ambulatory care settings which helps in identifying and minimizing the DRP by auditing prescription and educating patients.
The World Health Organisation (WHO) estimates that one in nine individuals is elderly, who is being 60 years of age or older [1]. As people age, they experience a number of physiological changes, such as reduced vital capacity, elevated blood pressure, worse gas exchange in the lungs, and lower cardiac output [2]. Elderly people often have numerous medical conditions and require a variety of medications. Multimorbidity, sometimes referred to as multiple chronic conditions (MCC), is the co-occurrence of two or various chronic illnesses. Multimorbid patients are more likely to have incidents, exacerbate pre-existing conditions, unexpected hospital admissions, have greater rates of polypharmacy and adverse drug reactions (ADR), have a worse quality of life, and have a higher chance of dying. The health and social care systems are heavily burdened by the prevalence of multimorbidity and polypharmacy among the elderly [3, 4].
Multimorbidity is often linked to lower quality of life, diminished functional status, poor physical and mental health, and higher mortality. Furthermore, multimorbidity is also associated with a high treatment burden, polypharmacy, and significantly increased health-care utilization, including emergency hospital hospitalizations [5].
The use of too many medications by a patient at the same time is known as polypharmacy. According to the WHO, polypharmacy is "administration of many drugs at the same time or administration of an excessive number of drugs." Five or more drugs and/or over-the-counter medications are used weekly by 44% of men and 57% of women over 65, with 12% using 10 or more. Taking two to four drugs concurrently is known as minor polypharmacy; taking five or more medications concurrently is known as major polypharmacy; and taking ten or more medications daily is known as hyper polypharmacy [6,7].
Drug-related problems (DRPs) such as adverse drug reactions (ADRs), drug interactions (drugs, food, or diseases), and irrational use of medications that may give rise to unexpected effects are all significantly raised by age and polypharmacy [3,8].
According to the Pharmaceutical Care Network Europe (PCNE), a DRP is "any event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes." DRPs have needless detrimental health impacts, especially while a patient is in the hospital. The chance of developing certain DRPs might be considerably increased by a number of circumstances [8,9]. Polypharmacy is a serious and growing public health issue, particularly for older adults. Due to a variety of treatment regimens, a greater number of comorbid conditions, and age-related physiological changes in pharmacokinetics and pharmacodynamics with regard to specific medications, elderly individuals are more susceptible to unanticipated DRPs [10].
An ADR refers to any harm or unwanted effects brought on by a medication used at normal doses [11]. The metabolic changes and decreased medication clearance that come with ageing make older adults more susceptible to ADRs. Sometimes, polypharmacy can lead to prescription cascades, which happen when various, nonspecific signs and symptoms of an ADR are misdiagnosed as a disease and a new medication therapy is added to the previously prescribed treatment to address the ailment. This carries the risk of long-term negative consequences, which could lead to a prescription cascade [1].
Drug-drug interactions (DDI) are a frequent drug-related problem in individuals with polypharmacy because of age-related changes in pharmacodynamics and pharmacokinetics. DDIs fall into one of two categories: pharmacokinetic or pharmacodynamic. While pharmacodynamic interactions happen when two drugs are taken together and have an additive or opposing effect on the body at the molecular level, pharmacokinetic interactions happen when one drug influences the concentration of another through its absorption, distribution, metabolism, or excretion. A major health concern is posed by DDIs, which increase morbidity and mortality, raise the chances of being hospitalised, and pose a financial strain on healthcare systems by decreasing (or increasing by an additive impact) the effectiveness of therapy [8].
DDIs affect outcomes in two ways. On the one hand, it might cause toxicity or undesirable drug responses by increasing the serum levels of relevant drugs. On the other hand, DDI may result in subtherapeutic serum medication levels, which could cause therapy to fail. Although it is very challenging to identify the specific medication that causes ADRs, having the ability to predict DDI is essential in ensuring patient safety during multimodal treatment [7]. The study was aimed to evaluate the patient's prescription for polypharmacy & related risk among individuals with multimorbidity and to identify the dangers of polypharmacy among patients with several comorbid illnesses.
MATERIAL & METHODS:
A cross-sectional observational study was carried out over a period of six months by enrolling inpatients from different departments of the tertiary care teaching hospital, such as general medicine, general surgery, orthopaedics, ENT, etc., based on the inclusion and exclusion criteria after each patient had signed an informed consent form. The AH and RC Institutional Ethics Committee gave its approval to this study (AHRC No: IEC/AH&RC/AC/08/2024). Structured forms, in-person interviews, and case notes were used to gather data. Demographic data, medical history, medication history, and current prescriptions were all documented. The chi-square test was used to ascertain the relationship between polypharmacy and associated risks following a comprehensive revision of each patient's prescription.
DATA ANALYSIS
The collected data was then compiled and analysed to determine the prevalence of polypharmacy among the multimorbidity patients and their associated risks. We stratified the data for prescriptions having polypharmacy and not having polypharmacy. Prescriptions with polypharmacy are then divided into three categories: minor polypharmacy is when a patient takes more than two to four medications concurrently, while major polypharmacy is when a patient takes five or more medications concurrently. Additionally, concurrent usage of ten or more medications per day is referred to as hyper polypharmacy.
Following a polypharmacy analysis of the patient's medications, associated risks such adverse drug responses and drug-drug interactions are identified. The degree of drug-drug interactions is divided into three categories: mild, moderate, and major. The chi-square test was then used to determine the risk relationship of polypharmacy with adverse medication reactions and drug-drug interactions.
RESULTS
The following tables present our study's overall findings [Table 1-4]. The distribution of data on the severity of adverse drug responses, drug-drug interactions, and polypharmacy is displayed in Table-1. Table-2 displaying the correlation between polypharmacy and unfavourable medication interactions as well as drug-drug interactions. Tables 3 and 4 representing the various drug-drug interactions and adverse drug responses that have been found.
Table-1 displays the data distribution.
|
Based on severity of Polypharmacy |
||
|
Severity |
Frequency(n) |
Percentage (%) |
|
Minor |
40 |
56.33 |
|
Major |
29 |
40.8 |
|
Hyper |
2 |
2.81 |
|
Based on severity of Drug-Drug Interactions |
||
|
Severity |
Frequency(n) |
Percentage (%) |
|
Minor |
15 |
33.3 |
|
Moderate |
24 |
53.3 |
|
Major |
6 |
13.3 |
|
Based on Adverse Drug Reactions |
||
|
Adverse reaction |
Frequency(n) |
Percentage (%) |
|
Yes |
4 |
3.88 |
|
No |
99 |
96.11 |
Table-1 showing that out 103 patients, only 71 patient’s prescriptions were identified as polypharmacy, in that 40(56.33%) were having minor polypharmacy, 29(40.8%) were having major polypharmacy and only 2(2.8%) were having hyper polypharmacy. In that severity of drug-drug interactions is found to be 15(33.3%) were minor, 24(53.3%) were moderate and only 6(13.3%) were identified as major interactions. And throughout the study 4 adverse drug reactions were notified and documented.
Table-2 Showing association between polypharmacy and their associated risks.
|
Association between Polypharmacy and Severity of Drug-Drug Interactions |
|||||||
|
|
Severity of Drug-Drug Interactions |
||||||
|
No |
Minor |
Moderate |
Major |
Total |
|||
|
Polypharmacy |
0 |
Count |
26 |
3 |
1 |
2 |
32 |
|
Expected Count |
18.0 |
4.7 |
7.5 |
1.9 |
32.0 |
||
|
1 |
Count |
32 |
12 |
23 |
4 |
71 |
|
|
Expected Count |
40.0 |
10.3 |
16.5 |
4.1 |
71.0 |
||
|
Total |
Count |
58 |
15 |
24 |
6 |
103 |
|
|
Expected Count |
58.0 |
15.0 |
24.0 |
6.0 |
103.0 |
||
|
Association between Polypharmacy and Adverse drug reactions |
|||||||
|
|
Adverse Reactions |
|
|||||
|
0 |
1 |
Total |
|
||||
|
Polypharmacy |
0 |
Count |
32 |
0 |
32 |
|
|
|
Expected Count |
30.8 |
1.2 |
32.0 |
|
|||
|
1 |
Count |
67 |
4 |
71 |
|
||
|
Expected Count |
68.2 |
2.8 |
71.0 |
|
|||
|
Total |
Count |
99 |
4 |
103 |
|
||
|
Expected Count |
99.0 |
4.0 |
103.0 |
|
|||
Table-3 Showing the number of Drug-Drug interactions identified and explanation
|
Drug-Drug interaction |
Description |
Frequency(n) |
|
Doxycycline – Heparin |
Leads to increased effect of Heparin by Pharmacodynamic Synergism. |
1 |
|
Hydrocortisone -Furosemide |
Decreased Excretion of Hydrocortisone, Pharmacodynamic synergism. |
2 |
|
Pregabalin -Nortriptyline |
One enhances the other's effects through pharmacodynamic synergism. |
1 |
|
Doxycycline -Ceftriaxone |
Doxycycline decreases the effect of Ceftriaxone by Pharmacodynamic Antagonism. |
1 |
|
Carvedilol -Aspirin |
By pharmacodynamic antagonism, aspirin reduces the effects of carvedilol, and both medications can raise potassium levels in the blood. |
4 |
|
Potassium Citrate -Glimepiride |
Potassium citrate can increase the effects of glimepiride by Pharmacodynamic Synergism. |
2 |
|
Ciprofloxacin -Ondansetron |
Concurrent use of both can increase the risk of an irregular heart rhythm. |
2 |
|
Clopidogrel -Oseltamivir |
Clopidogrel may decreases the serum concentrations of oseltamivir. |
1 |
|
Bisoprolol -Valsartan/Sacubitril |
Synergistic Effect can lead to decreased blood pressure. |
1 |
|
Ceftriaxone -Furosemide |
Leads to increased toxicity of Furosemide by Pharmacodynamic Synergism. |
6 |
|
Nicardipine -Atorvastatin |
Leads to decreased metabolism of Atorvastatin. |
2 |
|
Bisoprolol -Telmisartan |
Concurrent use can raise serum potassium level and Pharmacodynamic Synergism. |
1 |
|
Amlodipine -Metformin |
Amlodipine reduces the pharmacodynamic antagonistic effects of metformin. |
2 |
|
Hydrochlorothiazide - Oral hypoglycaemic agents |
Hydrochlorothiazide decreases the effects of oral hypoglycaemic agents by Pharmacodynamic Antagonism. |
3 |
|
Aspirin -Warfarin |
Aspirin increases the Effects of Warfarin by Anticoagulation. |
1 |
|
Telmisartan -Aspirin |
Aspirin decreases the effect of Telmisartan by Pharmacodynamic Antagonism. |
1 |
|
Telmisartan -Atorvastatin |
Telmisartan increases the toxicity of Atorvastatin leads to risk of myopathy. |
1 |
|
Furosemide -Thiamine |
Furosemide increases renal clearance, which lowers thiamine levels. |
1 |
|
Aspirin -Heparin |
Either raises the danger of bleeding or makes the other harmful by anticoagulation. |
1 |
|
Ceftriaxone -Heparin |
Ceftriaxone will increase the effect of heparin by Anticoagulation. |
1 |
|
Pantoprazole -Cilostazol |
Pantoprazole increases the toxicity of cilostazol by affecting hepatic enzyme CYP2C19 metabolism. |
1 |
|
Aspirin -Potassium Chloride |
Concurrent use of both can increase the level of serum potassium. |
1 |
|
Hydralazine -Carvedilol |
Either increases effects of the other by Pharmacodynamic Synergism. |
1 |
|
Ascorbic Acid -Aspirin |
Acidic (anionic) drugs compete with ascorbic acid for renal tubular clearance, which will boost the action of aspirin. |
1 |
|
Acetazolamide -Aspirin |
Either increases levels of the other by other by inhibiting each other’s renal tubular secretion |
1 |
|
Ticagrelor -Ivabradine |
Ticagrelor will increase the effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. |
1 |
|
Aspirin -Folic Acid |
Aspirin decreases the levels of folic acid by inhibition of GI absorption. |
1 |
|
Timolol -Aspirin |
Aspirin decreases effects of timolol by pharmacodynamic antagonism. |
1 |
|
Aspirin -Bisoprolol |
Aspirin decreases the effects of bisoprolol by Pharmacodynamic Antagonism. |
1 |
|
Diltiazem -Bisoprolol |
Either raises the risk of bradycardia or makes the other worse through an unknown interaction mechanism. |
1 |
|
Telmisartan -Spironolactone |
Concurrent use of both can increase the serum potassium level. |
2 |
|
Torsemide -Metformin |
Torsemide decreases the effects of metformin by Pharmacodynamic Antagonism. |
2 |
|
Piperacillin -Heparin |
Piperacillin will increase the effect of heparin by Anticoagulation. |
1 |
|
Amiodarone -Carvedilol |
Amiodarone will increase the effect of carvedilol by affecting hepatic enzyme CYP2C9/10 Metabolism. |
1 |
|
Sodium Bicarbonate -Carvedilol |
Sodium bicarbonate decreases the effect of carvedilol by inhibition of GI absorption. |
1 |
|
Spironolactone -Aspirin |
Aspirin lowers the effects of spironolactone by unknown interaction mechanism. |
1 |
Table-3 shows that out of 118 Drug-Drug interaction, major drug interaction was by non-steroidal anti-inflammatory drugs (NSAIDs), Antihypertensive, Antidiabetic class of drug. Major drug interaction causing drugs was Aspirin, Ceftriaxone, Clopidogrel, Telmisartan, Carvedilol, Furosemide, Ciprofloxacin, Metoprolol and so on.
Table-4 Showing the numbers of Adverse drug reaction identified
|
Drug |
Brand |
Description |
Frequency(n) |
|
Acetazolamide |
DIAMOX |
Hyponatremia |
1 |
|
Vancomycin |
VANCIN |
Hot flushes and itching over forehead |
1 |
|
Ciprofloxacin |
CIPRO |
QT Interval Prolongation |
1 |
|
Spironolactone |
ALDALACTONE |
Increase in Serum Potassium |
1 |
Table-4 representing different 4 adverse drug reactions identified, out of which one patient had hot flushes and itching over the forehead as soon after the vancomycin infusion has started, another patient experienced hyponatremia due to acetazolamide, increase in serum potassium level due to spironolactone and prolongation of QT interval respectively.
DISCUSSIONS:
The major goals of medication therapy are to minimise patient risk, improve the patient's quality of life, and attain the specified therapeutic objectives. However, taking too many medications to treat pre-existing ailments and utilising drugs inappropriately to treat diseases can result in a number of drug-related issues, including polypharmacy, adverse effects, and drug-drug interactions. In a tertiary care teaching hospital, this study was conducted to evaluate the patient's prescription in order to detect the presence of polypharmacy and to determine the risks connected with it. 103 patients admitted to the various wards of the tertiary care hospital, including general medicine, ophthalmology, cardiology, surgery, orthopaedics, and others, participated in an observational cross-sectional study.
A prospective study was conducted by Vrettos I et al. including 310 patients over 65, they found that 158 were women (51%) and 152 were men (49%). 166 individuals (53%) were belonged to polypharmacy group. similarly In our study also, out of 103 individuals, 57 were male and 46 were Female in total. The majority of the patients, 55 (53.39%) were aged around 61-80 years, followed by the age group of (41-60) 33(32.03%), age group of (21-40) 8(7.76%) and the remaining 7(6.79%) were between the ages of 80-100 [12].
This study was mainly focused on patients with multiple chronic conditions (MCC), a population inherently at higher risk of polypharmacy, drug–drug interactions (DDIs), and adverse drug reactions (ADRs). Among the participants, the majority had two comorbidities (64%), while 23.3% had three, and a smaller proportion had four or more.
The high prevalence of patients with two or more chronic conditions in our study aligns with global trends. For instance, Marengoni et al. and Salisbury et al. emphasized that multimorbidity is increasingly common, particularly among older adults, and is a key driver of polypharmacy [13,14]. Similarly, Guthrie et al. found that over 50% of patients with multimorbidity were prescribed five or more medications, indicating the strong link between chronic disease burden and increased medication use [15].
According to our study, the majority of patients (40, or 56.33%) received 3-5 medications per day during their hospital stay, which qualifies as minor polypharmacy. Meanwhile, 29 patients (40.8%) received 6-10 medications, indicating major polypharmacy, and two patients (2.81%) were prescribed more than ten medications, classified as hyper polypharmacy. These findings are consistent with those of Sidamo T et al. at Edna Adan University Hospital, where 71% of patients exhibited polypharmacy. In that study, 775 prescriptions (68%) with two to four medications reflected minor polypharmacy, while 35 prescriptions (3%) with five or more drugs represented significant polypharmacy, also leading to DRPs in multimorbid patients [7].
The drug–drug interaction data further highlight the impact of MCC. Our findings showed 53.3% moderate and 13.3% major DDIs. These figures are comparable to those reported by Aljadhey et al., who found that patients with MCC are more likely to experience clinically relevant DDIs. Rong et al., also demonstrated a direct correlation between the number of medications prescribed and the severity of DDIs, supporting our observation that patients with higher comorbidity counts are at greater risk [16,17].
Interestingly, the rate of adverse drug reactions (ADRs) in our study was 3.88%, which is lower than in several other studies. For example, Beijer and de Blaey et al. reported ADR rates of up to 17% in similar populations. Nonetheless, even a low incidence of ADRs can have serious implications, especially in multimorbid patients [18].
Overall, our findings reinforce the interconnected relationship between multimorbidity, polypharmacy, and medication-related risks. As highlighted by Rankin et al., patients with multiple chronic conditions benefit most from comprehensive medication reviews and individualized treatment plans to reduce unnecessary drug use and minimize harm [19]. Interventions such as pharmacist-led medication reconciliation and the use of clinical decision support systems have been proven effective in reducing inappropriate prescribing in this vulnerable group.
CONCLUSIONS
This study revealed that the associated risk factors among patients having polypharmacy, who got admitted to the wards of various departments. The most prevalent risk factors were Drug-Drug interaction, and followed by Adverse drug reactions. Non-steroidal anti-inflammatory drugs (NSAIDs), antidiabetic and antihypertensive medications, and other antibiotic classes were determined to be the most often occurring drug class producing drug-related issues. Drug-drug interactions and adverse drug responses were more likely to occur in patients with comorbidity and polypharmacy. The participation of clinical pharmacists into the multidisciplinary team promotes the detection and solution of DRP in the majority of cases, and should be considered as a rule in general clinical practice.
Last but not least, only a limited number of risks such as medication-drug interactions and adverse drug reactions—may be connected to polypharmacy in a hospital context, which could be useful to prioritise interventions. Additionally, this study can be expanded to ambulatory care settings, which aid in recognising and minimising the DRP by monitoring prescriptions and educating patients.
ACKNOWLEDGEMENT
We express our sincere gratitude to individuals and organizations who provided immense support and guidance.
REFERENCES
M S Pallavi, K C Shobhitha Nanje Gowda, B N Ravindra, B P Satish Kumar, Assessment of Polypharmacy and Associated Risk Among the Patients with Multimorbidity: A Cross-Sectional Study in Tertiary Care Teaching Hospital, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 7, 3063-3071. https://doi.org/10.5281/zenodo.16313587
10.5281/zenodo.16313587
