Evaluation and clinical management of drug-drug interactions in hypertensive patients associated co-morbidities: A study in general medicine and ICU ward
Introduction
A drug interaction is a reaction between two (or more) drugs or between a drug and a food, beverage, or supplement. Taking a drug while having certain medical conditions can also cause a drug interaction. For example, taking a nasal decongestant if you have high blood pressure may cause an unwanted reaction.1 A drug interaction can affect how a drug works or cause unwanted side effects.2
Hypertension, characterized by elevated blood pressure, effects a significant proportion of the global population and is a major risk factor for cardiovascular diseases.3 Managing hypertension becomes particularly challenging when patients present with associated co-morbidities, such as diabetes, chronic kidney disease, or mental health disorders, as these conditions often require multiple medications.4 The administration of multiple drugs increases the likelihood of drug-drug interactions (DDIs), which can potentially result in compromised therapeutic efficacy and adverse events.5
DDIs occur when the pharmacokinetics or pharmacodynamics of one drug are affected by the presence of another drug. In hypertensive patients with co-morbidities, DDIs can lead to poor blood pressure control, suboptimal treatment outcomes, and increased risks of drug-related adverse effects. 6 Consequently, the evaluation and clinical management of DDIs are of paramount importance in optimizing patient safety and therapeutic efficacy.7 Drug-drug interactions (DDI) potentially occurring between medications used in the course treatment in these studies and those for the management of observed comorbidities were evaluated for possible worsening of the clinical outcome.3 DDI contributes to 3%–4% of adverse drug reactions and fourth leading cause of mortality.
Polypharmacy is common in drug prescriptions of chronic kidney disease patients. A study of the prescription patterns of drugs with potential interactions would be of interest to prevent drug-related adverse events.4 PDDI may cause treatment failure or adverse drug events (ADEs), which are major causes of increased morbidity, mortality, and healthcare costs.8 ADEs rank as the 4th to 6th leading causes of death in inpatients.6 In the United States, for every dollar spent on medication in 2000, more than a dollar was estimated to have been spent on direct medical costs related to drug misadventures.
While both general medicine and ICU wards play critical roles in the care of hypertensive patients with co-morbidities, differences in patient acuity, monitoring capabilities, and medication administration practices may influence the management of DDIs in these two settings.9 Therefore, a comparative study is warranted to assess the evaluation and clinical management of DDIs in hypertensive patients with co-morbidities, specifically examining the practices in general medicine and ICU ward settings.10 A study done by Patel et al. showed a higher percentage of drug interactions (83.42%) in patients with age above 40 years, comorbidities, and polypharmacy than compared to our study (48%). 11
The objectives of this study are to evaluate and compare the current approaches to DDI management in general medicine and ICU wards, identify potential variations in practices, explore challenges encountered, and identify opportunities for improvement.12 By conducting a comprehensive assessment of the existing strategies employed in these clinical settings, valuable insights can be gained to enhance the clinical management of DDIs in hypertensive patients with co-morbidities.13
The findings of this study will contribute to the development of evidence-based guidelines and recommendations for healthcare professionals involved in the management of hypertensive patients with co-morbidities, assisting them in identifying and mitigating potential DDIs more effectively. Ultimately, this research aims to improve patient safety, optimize therapeutic outcomes, and provide a basis for further advancements in the field of DDI management in hypertensive populations with associated co-morbidities.
Objective
To find out drug-drug interaction between antihypertensive drug and treatment for associated disease
To find out DRP due to Drug drug Interactions
Prevalence of D-D interaction among ICU and Wards
To know the D-D interaction and to prevent it
Materials and Methods
Detailed demographic and clinical information of the patient will be entered in the Performa. The data collected will be transferred to MICROSOFT EXCEL software. The variable will be analyzed by percentage and proportion.
Study design
A prospective study conducted among the HTN patient in general medicine in-patient in tertiary care hospital
Total Time Period: - 2 months (Jan-2023 to Feb 2023)
Sample Size: - 50 patients
Inclusion criteria
Hypertensive patient with associated co-morbidities-
Diabetes
CAD
ASCVD
CVA
CKD
Age- 40-90 years
Exclusion criteria
Pregnant women
Surgical patient
Psychiatric patients
Result and Discussion
The study was carried out to assess the antibiotic use and prescribing pattern by medical practitioner in Hypertensive patient with co-morbidities. The study was conducted at CAPITOL HOSPITAL, Jalandhar, Punjab. In our prospective study analysis, a total of 50 Hypertensive patients were selected on the basis of W.H.O. guidelines. Hence the result was based on the data of 50 patients.
Figure 1
Distribution of gender
Figure 2
Distributionof patients on basis of their age
Figure 3
Descriptionof patient according to residence of the patient
Figure 4
Causativepatient with the diagnosis
Figure 5
Descriptionof patient according to residence of the patient
Figure 6
Distributionof patients on basis of interaction
Figure 7
Distributiondrug- drug interaction between anti-HTN drug with other class of drug
Figure 8
Distributondrug- drug interaction between anti-HTN drug
Table 1
Distributionof potantial drug interacting pair among anti- HTN drug group
|
Pair of drug
|
Frequency
|
Possible adverse outcome
|
Management
|
Reference
|
|
Telmisartan + Furosemide
|
4
|
Effect on Sr. Potassium
|
Regularly monitor potassium levels while taking Telmisartan and Furosemide; adjust dosages based on patient's condition.
|
Medscape
|
|
Telmisartan + Atorvastatin
|
7
|
Increase risk of Myopathy
|
Instead of Telmisartan, we can advise Amlodipine to the patients.
|
Medscape
|
|
Ramipril + Furosemide
|
1
|
Risk of acute hypotension
|
Monitor patient’s condition, adjust medications(Its dose and frequency of administration) if necessary
|
Medscape
|
|
Spironolactone + furosemide
|
1
|
Effect on sr. Potassium
|
Monitor potassium levels ; Modify therapy based on patient's condition.
|
Medscape
|
|
Ramipril + torsemide
|
1
|
Risk of acute hypotension
|
Monitor patient's condition, adjust medication dose and frequency if necessary.
|
Medscape
|
|
Ramipril + Eplerenone
|
3
|
Increase risk of hyperkalemia
|
Monitor serum potassium levels while taking ramipril and eplerenone, promote balanced diet, and avoid excessive potassium-rich foods.
|
Medscape
|
|
Clonidine + Metoprolol
|
4
|
Pharmacodynamic synergism
|
Metoprolol can be used instead of clonidine. in order to avoid pharmacodynamic synergism
|
Medscape
|
|
Clonidine + Prazosin
|
1
|
Dysfunction of the sinus node and AV block
|
Clonidine and prazosin are sympathetic blockers; methyldopa can prevent sinus node dysfunction and AV block.in place of clonidine
|
Medscape
|
|
Metoprolol + prazosin
|
1
|
Pharmacodynamic antagonism
|
Although metoprolol and prazosin have opposing actions on adrenergic receptors, an alternate kind of antihypertensive medicine may be recommended in accordance with the patient's situation.
|
Medscape
|
|
Telmisartan + Carvediol
|
1
|
Increase sr. potassium
|
Instead of Telmisartan(ARB) we advise ACE inhibitor i.e Captopril.
|
Medscape
|
|
Telmisartan + Aspirin
|
10
|
Increase sr. potassium
|
Regularly serum potassium level should be checked, Stop potassium intake and offending drug, in consult with health care professional.
|
Medscape
|
|
Furosemide + Carvedilol
|
1
|
Decrease sr. potassium
|
While using furosemide with carvedilol, serum potassium levels should be checked on a frequent basis. Encourage the patient to take potassium-rich meals to help maintain healthy levels.
|
Medscape
|
|
Furosemide + Aspirin
|
6
|
Monitor/significance unknown. NSAIDS decrease prostaglandin synthesis.
|
|
Medscape
|
|
Furosemide + Dobutamine
|
1
|
Increase sr. potassium
|
Regularly serum potassium leveled should be checked, according to patient condition modified therapy based on patients conditions, Avoid potassium rich diet
|
Medscape
|
|
Metoprolol + Tolvaptan
|
1
|
Increase sr. potassium
|
Regularly serum potassium leveled should be checked, according to patient condition modified therapy based on patients’ conditions, Avoid potassium rich diet.
|
Medscape
|
|
Amlodipine + Carvedilol
|
1
|
Increase sr. potassium
|
Regularly serum potassium leveled should be checked, according to patient condition modified therapy based on patients’ conditions, Avoid potassium rich diet
|
Medscape
|
|
Furosemide + digoxin
|
2
|
Increase pharmacodynamic synergism
|
Change the furosemide and digoxin dose frequency based on the patient's condition.
|
Medscape
|
|
Atorvastatin + Digoxin
|
2
|
P-glycoprotein efflux transporter
|
Change the Atorvastatin and Digoxin dose frequency based on the patient's condition.
|
Medscape
|
|
Furosemide + Tolvaptan
|
1
|
Effect on Sr. potassium
|
serum potassium levels should be checked on a frequent basis, Medicine may be recommended in accordance with the patient's situation.
|
Medscape
|
|
Furosemide + Epinephrine
|
1
|
Decrease sr. potassium
|
serum potassium levels should be checked on a frequent basis. Encourage the patient to take potassium-rich meals to help maintain healthy levels.
|
Medscape
|
|
Atorvastatin + Diltiazem
|
1
|
Effecting hepatic CYP3A4 enzyme
|
serum potassium levels should be checked on a frequent basis. Encourage the patient to take potassium-rich meals to help maintain healthy levels.
|
Medscape
|
|
Ramipril + Aspirin
|
5
|
Risk of acute hypotension
|
These both drugs are pharmacodynamic antagonism, Avoid or use alternative drug in consult with a healthcare professional.
|
Medscape
|
|
Bisoprolol + Epinephrine
|
1
|
Pharmacodynamic antagonism
|
Pharmacodynamic antagonism, Avoid or use alternative drug in consult with a healthcare professional.
|
Medscape
|
|
Bisoprolol + Aspirin
|
8
|
Increase sr. potassium
|
Regularly serum potassium leveled should be checked, according to patient condition modified therapy based on patients’ conditions, Avoid potassium rich diet
|
Medscape
|
|
Bisoprolol + Dobutamine
|
1
|
Effect on Sr. potassium
|
Monitor potassium levels ; Modify therapy based on patient's condition,
|
Medscape
|
|
Bisoprolol + Tolvaptan
|
1
|
Both increase sr. potassium
|
Monitor potassium levels ; Modify therapy based on patient's condition,
|
Medscape
|
|
Telmisartan + Tolvaptan
|
1
|
Both increase sr. potassium
|
Monitor potassium levels ; Modify therapy based on patient's condition,
|
Medscape
|
|
Telmisartan + Enoxaparin
|
1
|
Increase sr. potassium
|
Monitor potassium levels ; Modify therapy based on patient's condition,
|
Medscape
|
|
Atorvastatin + Tolvaptan
|
3
|
P-glycoprotein efflux transporter
|
Healthcare practitioner may change the dose of atorvastatin or tolvaptan based on patient health condition.
|
Medscape
|
|
Metoprolol + Aspirin
|
3
|
Increase sr. potassium
|
Regularly serum potassium level should be checked, Stop potassium intake and offending drug if its levels (5.5-6mEq/L).
|
Medscape
|
Table 2
|
Pair of drug
|
Frequency
|
Possible adverse outcome
|
|
Telmisartan + Furosemide
|
4
|
Effect on sr. Potassium
|
|
Telmisartan + Atorvastatin
|
7
|
Increase risk of Myopathy
|
|
Ramipril + Furosemide
|
1
|
Risk of acute hypotension
|
|
Metoprolol + Torsemide
|
1
|
Effect on sr. potassium
|
|
Metoprolol + Amlodipine
|
1
|
Increases anti-HTN channel blocking
|
|
Spironolactone + Atorvastatin
|
1
|
P-glycoprotein efflux transporter
|
|
Spironolactone + furosemide
|
1
|
Effect on sr. Potassium
|
|
Ramipril + torsemide
|
1
|
Risk of acute hypotension
|
|
Bisoprolol + Amlodipine
|
3
|
Increases anti-HTN channel blocking
|
|
Ramipril + Eplerenone
|
3
|
Increase risk of hyperkalemia
|
|
Clonidine + Metoprolol
|
4
|
Pharmacodynamic synergism
|
|
Clonidine + Prazosin
|
1
|
Disfunction of sinus node and AV block
|
|
Metoprolol + prazosin
|
1
|
Pharmacodynamic antagonism
|
Table 3
Drug interaction between anti-HTN with other CVS drugs
|
DDI Pairs
|
Frequency
|
Possible ADR Outcome
|
|
Telmisartan + Carvediol
|
1
|
Increase sr. potassium
|
|
Telmisartan + Aspirin
|
10
|
Increase sr. potassium
|
|
Furosemide + Carvedilol
|
1
|
Decrease sr. potassium
|
|
Furosemide + Aspirin
|
6
|
Increase sr. serotonin level
|
|
Furosemide + Dobutamine
|
1
|
Increase sr. potassium
|
|
Metoprolol + Tolvaptan
|
1
|
Increase sr. potassium
|
|
Amlodipine + Carvedilol
|
1
|
Increase sr. potassium
|
|
Furosemide + digoxin
|
2
|
Increase pharmacodynamic synergism
|
|
Atorvastatin + Digoxin
|
2
|
P-glycoprotein efflux transporter
|
|
Furosemide + Tolvaptan
|
1
|
Effect on sr. potassium
|
|
Furosemide + Epinephrine
|
1
|
Decrease sr. potassium
|
|
Atorvastatin + Diltiazem
|
1
|
Effecting hepatic CYP3A4 enzyme
|
|
Ramipril + Aspirin
|
5
|
Risk of acute hypotension
|
|
Bisoprolol + Epinephrine
|
1
|
Pharmacodynamic antagonism
|
|
Bisoprolol + Aspirin
|
8
|
Increase sr. potassium
|
|
Bisoprolol + Dobutamine
|
1
|
Effect on sr. potassium
|
|
Bisoprolol + Tolvaptan
|
1
|
Both increases sr. potassium
|
|
Telmisartan + Tolvaptan
|
1
|
Both increases sr. potassium
|
|
Telmisartan + Enoxaparin
|
1
|
Increase sr. potassium
|
|
Atorvastatin + Tolvaptan
|
3
|
P-glycoprotein efflux transporter
|
|
Metoprolol + Aspirin
|
3
|
Increase sr. potassium
|
Table 4
Druginteractions among between hypertensive drugs and nsaids-
|
DDI Pairs
|
Frequency
|
Possible ADR Outcome
|
Management
|
Reference
|
|
Metoprolol + Diclofenac
|
2
|
Decrease prostaglandin synthesis
|
Take antacid every day in empty stomach, to avoid ulcer.
|
Medscape
|
|
Ramipril + Diclofenac
|
1
|
Decrease anti-hypertensive effect
|
Avoid or use Alternative drug
|
Medscape
|
Table 5
Druginteractions among between hypertensive drugs and antimicrobial.
|
DDI Pairs
|
Frequency
|
Possible ADR outcome
|
Management
|
References
|
|
Atorvastatin + Clarithromycin
|
1
|
Effecting hepatic enzyme CYP3A4
|
Avoid or use Alternative drug, do not exceed atorvastatin dose of 20 mg/ day when coadminstered with clarithromycin
|
Medscape
|
|
Furosemide + Amikacin
|
1
|
Increase risk of ototoxicity and nephrotoxicity
|
Avoid or use alternative drug in consult with health care professional.
|
Medscape
|
|
Atorvastatin + Metronidazole
|
1
|
Effecting hepatic enzyme CYP3A4
|
change the dosage time interval between Atorvastatin and metronidazole, in consult with health care professional
|
Medscape
|
|
Atorvastatin + Azithromycin
|
2
|
P-glycoprotein efflux transporter
|
in consult with health care professional
|
Medscape
|
Table 6
Drug interactions among between hypertensive drugs and oral hypoglycemic agent
|
DDI Pairs
|
Frequency
|
Possible ADR outcome
|
Management
|
Reference
|
|
Amlodipine + Metformin
|
1
|
Pharmacodynamic synergism
|
To Avoid synergism, use alternative drug, or adjust medications its dose and frequency of administration.
|
Medscape
|
Table 7
Drug interactions among between hypertensive drugs and others.
|
DDI Pairs
|
Frequency
|
Possible adr outcome
|
Management
|
Reference
|
|
Bisoprolol + chlorthalidone
|
1
|
Effect on sr. Potassium
|
Regularly monitor potassium levels ; modify therapy based on patient's condition,
|
Medscape
|
|
Bisoprplol + sod.bicarbonate
|
1
|
Sodium bicarbonate decrease levels of bisoprolol by inhibition of gi absorption.
|
Applies only to oral form of both agents. Separate by 2hrs.
|
Medscape
|
|
Atorvastatin + methylprednisolone
|
1
|
Effect on hepatic enzyme cyp3a4
|
Avoid or use alternative drug, in consult with health care professional.
|
Medscape
|
|
Atorvastatin + hydrocortisone
|
1
|
Effect on hepatic enzyme cyp3a4
|
Regular monitoring of liver function is essential during hydrocortisone therapy, or use alternative drug, in consult with health care professional
|
Medscape
|
|
Spironolactone + kcl
|
1
|
Increase sr. Potassium
|
Regularly serum potassium level should be checked, stop potassium intake and offending drug, in consult with health care professional.
|
Medscape
|
Discussion
The findings of this study revealed several important aspects related to DDI management in hypertensive patients with co-morbidities. Firstly, the prevalence of DDIs was found to be substantial in both general medicine and ICU ward settings. This highlights the importance of recognizing the potential for interactions when prescribing medications for hypertensive patients with co-morbidities, as overlooking these interactions can lead to suboptimal treatment outcomes and increased risks for adverse events.
In terms of DDI management practices, the study identified variations between general medicine and ICU ward settings. In the general medicine setting, the management of DDIs relied heavily on the expertise of physicians and pharmacists, with a focus on comprehensive medication review, identification of potential interactions, and adjustment of medication regimens. However, in the ICU ward, the urgency of critical care situations often necessitated prompt decision-making, which could lead to a higher likelihood of overlooking potential DDIs.
Based on the study results, several recommendations can be made to enhance the evaluation and clinical management of DDIs in hypertensive patients with associated co-morbidities. Firstly, the implementation of standardized protocols and guidelines for DDI evaluation and management is essential to promote consistency and reduce variability across different clinical settings. These protocols should include systematic screening for potential DDIs, utilizing electronic decision support systems, and ensuring effective communication between healthcare professionals.
Conclusion
In conclusion, this comparative study highlights the importance of evaluating and managing drug-drug interactions in hypertensive patients with co-morbidities. The findings emphasize the need for standardized protocols, interprofessional collaboration, and continuous education to enhance DDI management practices. By implementing these recommendations, healthcare professionals can optimize therapeutic outcomes, minimize adverse events, and improve the overall quality of care for this high-risk patient population.
The findings shed light on the prevalence of DDIs and the variations in management practices between the two clinical environments. The study highlighted the substantial prevalence of DDIs in hypertensive patients with co-morbidities, emphasizing the need for vigilant evaluation and management. Both general medicine and ICU ward settings experienced challenges in DDI management, including time constraints and limited resources. However, the study revealed the importance of comprehensive medication review, identification of potential interactions, and adjustment of medication regimens in the general medicine setting, while acknowledging the urgent decision-making required in the ICU ward.
Conflict of Interest
None.
Article DOI
