Prevalence and Clinical Significance of Drug–Drug and Drug–Dietary Supplement Interactions among Patients Admitted for Cardiothoracic Surgery in Greece
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Ethics Approval
2.2. Evaluation of Drug Interactions with Coadministered Medications and Interactions with Dietary Supplements
3. Results
3.1. Patients’ Demographics, CTS Diagnoses, Comorbidities, and Clinical Data during Hospitalization
3.2. Medications Administered at Different Time Points
3.3. DDIs Identified and Correlation with Administered Medications
3.4. Pharmacological Mechanisms and Clinical Significance of the Identified DDIs
3.5. Dietary Supplements, Reasons for Use, and Identified DDSIs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Methods | |
---|---|
Study design | Analysis of DDIs 1 and DDSIs 2 in patients admitted to CTS 3 clinic in Greece |
Setting | Cardiothoracic surgery of University Hospital of Heraklion in Greece |
Participants | Patients that need cardiothoracic surgery (CTS) due to progressed CVD 4 |
Variables | Record of demographic characteristics, clinical values, comorbidities, medication regimens, and dietary supplement usage Analyze DDIs and DDSIs, their clinical significance, and pharmacological mechanisms |
Data sources/measurement | DDIs, DDSIs and their clinical significance based on literature search and relative databases (Medscape, Drugs.com) |
Study size | Target population: patients admitted for CTS Study population: signed informed consent form to participate |
Bias | Diligence in informing the purpose and objectives of the study Diligence in recording the medication regimens in correct time periods Recording demographics and medication regiments Analysis of data regarding significance Dietary supplement and self-medication habits feedback |
Results | |
Participants | 76 patients signed informed consent form (95% of total patients in the clinic) |
Descriptive data | 60.5% male and 39.5 female average age 66 years (min 37, max 85) Average comorbidities: 5 Average hospitalization: 10 days Admittance diagnosis 5: CABG (50%), SAVR 24%, CABG/SAVR/MVPL/CEA/BENTALL 16%, AAA 2% |
Outcome data | Comorbidities: hypertension, hyperlipidemias and diabetes were most frequent 166 unique DDIs PK-DDIs 6: 53 unique combinations PD-DDIs 7: 113 unique combinations PK-DDSIs: 18 unique combinations PD-DDSIs: 12 unique combinations |
Main results | 12% of the identified DDIs were characterized as serious and an alternative should have been used Positive trend between number of medications and prevalence of DDIs regardless the time point PK-DDIs were highly prevalent during admission and discharge whereas PD-DDIs recorded mostly during pre- and postoperation periods. 60% of patients use DS products 60% of the DDSIs were related to PK processes and 36% of the identified PK-DDSIs were due to the consumption of grapefruit juice Patients avoid or neglect seeking medical advice regarding DS usage |
Demographics 1 | Mean (±S.D.) | Min/Max |
Age (y) | 66 (±10.20) | 37/85 |
Height (m) | 1.65 (±0.1) | 1.40/1.84 |
Weight (kg) | 81.1 (±15.26) | 52.6/122.7 |
BMI (kg/m2) | 29.9 (±5.05) | 17.1/45.4 |
Comorbidities | 5 | 1/10 |
Days hospitalization (d) | 10 | 2/18 |
Preoperative hospitalization (d) | 2 | 1/8 |
Postoperative hospitalization (d) | 8 | 2/12 |
Diagnosis 2 | Number of Patients (%) | |
CABG | 38 (50%) | |
SAVR | 18 (24%) | |
MVP/CEA/Bentall/CABG-SAVR | 12(16%) | |
AAA | 2 (2%) | |
Other | 6 (8%) | |
Comorbidities | ||
Hypertension | 64 (84%) | |
Diabetes | 40 (52%) | |
Hyperlipidemias | 61 (80%) | |
Thyroid | 23 (30%) | |
Central Nervous System | 18 (24%) | |
Gastrointestinal | 4 (6%) | |
Respiratory | 5 (4%) | |
Other | 8 (10%) | |
Social Habits (Smoking & Alcohol) | Number of Patients (%) | |
Smoker | 25 (32%) | |
Ex-smoker | 32 (42%) | |
Nonsmoker | 20 (26%) | |
Alcoholic | 6 (8%) | |
Social drinker | 34 (45%) | |
Nondrinker | 36 (47%) |
Drug A | Drug B | Drug Categories | Pharmacological Outcome | Number of Cases | |
---|---|---|---|---|---|
Pharmacokinetic drug interactions: Serious-use alternative | |||||
amiodarone | acenocoumarol | antiarrhythmic | anticoagulant | CYP * metabolism inhibition acenocoumarol levels | 4 |
amlodipine | simvastatin | Ca2+-blocker | antilipidemic | CYP3A4 inhibition (statin-rhabdomyolysis) | 4 |
aspirin | methotrexate | NSAIDs * | rheumatoid arthritis | PK-Renal clearance (methotrexate toxicity) | 2 |
esomeprazole | cilostazol | PPI * | antiplatelet | PK-CYP2C19 inhibition of cilostazol | 2 |
esomeprazole | clopidogrel | PPI | antiplatelet | Reduced antiplatelet activity -CYP2C9 metabolism | 11 |
esomeprazole | escitalopram | PPI | SSRI * | PK-CYP2C19 metabolism inhibition | 1 |
haloperidol | amiodarone | antipsychotic | antiarrhythmic | PK-CYP2D6 inhibition | 1 |
ranolazine | carvedilol | angina | β-blocker | PK-CYP2D6 metabolism (carvedilol) | 3 |
ranolazine | metformin | angina | diabetes II | PK-renal clearance (metformin) OCT2 | 2 |
ranolazine | simvastatin | angina | antilipidemic | CYP3A4 inhibition (statin-rhabdomyolysis) | 3 |
Pharmacokinetic drug interactions: Use with caution-Monitor | |||||
haloperidol | metoprolol | antipsychotic | β-blocker | PK CYP2D6 metabolism inhibition (metoprolol) | 6 |
atorvastatin | valsartan | antilipidemic | ARBs * | PK-OATB1 * transporter | 4 |
amiodarone | metoprolol | antiarrhythmic | β-blocker | PK-CYP2D6 inhibition for metoprolol (bradycardia) | 3 |
omeprazole | clopidogrel | PPI | antiplatelet | PK CYP2C9 metabolism (clopidogrel) | 3 |
ciprofloxacin | acenocoumarol | antibiotic | anticoagulant | PK-CYP1A2 inhibition acenocoumarol levels | 2 |
Pharmacokinetic drug interactions: Moderate-Minor | |||||
budesonide | acenocoumarol | corticosteroid | anticoagulant | PK-CYP3A4 induction metabolism of acenocoumarol | 13 |
amiodarone | codeine | antiarrhythmic | analgesic | PK-CYP2D6 (codeine) | 2 |
carvedilol | haloperidol | β-blocker | antipsychotic | PK-CYP2D6 inhibition | 2 |
ciprofloxacin | alprazolam | antibiotic | anxiolytics | PK CYP3A4 metabolism inhibition (alprazolam) | 3 |
ferrous (gluconate, sulfate etc.) | levothyroxine | anemia | thyroid | PK-T4 GI absorption | 4 |
Pharmacodynamic drug interactions: Serious-use alternative | |||||
alprazolam | haloperidol | anxiolytics | antipsychotic | synergism sedation | 2 |
amiloride | potassium chloride | diuretic | hypokalemia | synergism hyperkalemia | 3 |
citalopram | duloxetine | SSRI * | SNRI * | synergism (serotonin syndrome) | 1 |
fenofibrate | pitavastatin | antilipidemic | antilipidemic | synergism | 2 |
haloperidol | amiodarone | antipsychotic | antiarrhythmic | QT prolongation | 1 |
morphine | escitalopram | analgesic | SSRI | serotonin syndrome | 1 |
quetiapine | haloperidol | antipsychotic | antipsychotic | enhance antidopaminergic effect, QT prolongation | 6 |
tramadol | pethidine | analgesic | analgesic | synergism sedation | 2 |
Pharmacodynamic drug interactions: Use with caution-Monitor | |||||
alprazolam | morphine | anxiolytics | analgesic | PD-synergism sedation | 16 |
aspirin | acenocoumarol | NSAIDS | antiplatelet | PD-synergism risk of bleeding | 11 |
carvedilol | furosemide | β-blocker | diuretic | PD-antagonism and serum potassium | 9 |
ciprofloxacin | haloperidol | antibiotic | antipsychotic | PD-QT prolongation | 3 |
quetiapine | ipratropium | antipsychotic | anticholinergic | PD-synergism anticholinergic effects, hypoglycemia, QT-prolongation | 8 |
Pharmacodynamic drug interactions: Moderate-Minor | |||||
aspirin | perindopril | NSAIDs | ACE * | PD-antagonism kidney (decrease in renal function) | 11 |
bisoprolol | furosemide | β-blocker | diuretic | PD-antagonism (serum potassium) | 17 |
bromazepam | morphine | anxiolytics | analgesic | PD-synergism sedation | 25 |
ceftriaxone | furosemide | antibiotic | diuretic | nephrotoxicity | 35 |
perindopril | enoxaparin | ACE | antiplatelet | PD-hyperkalemia | 7 |
Drugs | DS | PK-PD Mechanism | Drug Category | Clin. Sign. | Potential Clinical Outcome | No Cases |
---|---|---|---|---|---|---|
metformin | aloe vera | PD | diabetes II | 2 | hypoglycemia | 2 |
levothyroxine | caffeine | PK-GI absorption | thyroid | 2 | decreased T4 levels | 5 |
aspirin | fish oil | PD | anticoagulate | 2 | bleeding | 2 |
clopidogrel | fish oil | PD | anticoagulate | 2 | bleeding | 1 |
eplerenone | grapefruit | PK-CYP3A4 inhibition | diuretic | 2 | hyperkaliemia | 1 |
amlodipine | grapefruit | PK-CYP3A4 inhibition | Ca2+-blocker | 3 | mlodipine-ADRs | 2 |
clopidogrel | grapefruit | PK-CYP3A4 inhibition | antiplatelet | 2 | reduced bioactivation | 6 |
simvastatin | grapefruit | PK-CYP3A4 inhibition | antilipidemic | 1 | statin-ADRs | 1 |
ranolazine | grapefruit | PK-CYP3A4 inhibition | chronic angina | 1 | QT prolongation | 1 |
atorvastatin | grapefruit | PK-CYP3A4 inhibition | antilipidemic | 1 | statin-ADRs | 7 |
tamsulosin | grapefruit | PK-CYP3A4 inhibition | prostatic hyperplasia | 2 | tamsulosin-ADRs | 1 |
alfuzosin | grapefruit | PK-CYP3A4 inhibition | a1-antagonist-prostate | 3 | alfuzosin-ADRs | 1 |
finasteride | grapefruit | PK-CYP3A4 inhibition | prostatic hyperplasia | 3 | finasteride-ADRs | 1 |
alprazolam | grapefruit | PK-CYP3A4 inhibition | anxiety | 2 | cilostazol-ADRs | 1 |
cilostazol | grapefruit | PK-CYP3A4 inhibition | antiplatelet | 2 | risk for bleeding | 1 |
ivabradine | grapefruit | PK-CYP3A4 inhibition | angina | 1 | ivabradine-ADRs | 1 |
ticagrelor | grapefruit | PK-CYP3A4 inhibition | antiplatelet | 1 | risk for bleeding | 1 |
prasugrel | green tea | PD | antiplatelet | 3 | Increased drug action | 1 |
aspirin | green tea | PD | antiplatelet | 3 | bleeding | 7 |
clopidogrel | green tea | PD | antiplatelet | 3 | bleeding | 5 |
cilostazol | green tea | PD | antiplatelet | 3 | risk for bleeding | 1 |
ferrous sulfate | green tea | PK-GI absorption | iron deficiency | 2 | reduced Fe absorption | 1 |
folic acid (FA) | green tea | PK-GI absorption | iron deficiency | 2 | reduced FA absorption | 1 |
metformin | sage | PD | antidiabetic | 3 | hypoglycemia | 4 |
alprazolam | sage | PD | anxiety | 3 | increased sedation | 2 |
gabapentin | sage | PD | anticonvulsant | 3 | convulsions | 1 |
insulin | sage | PD | diabetes I | 3 | hypoglycemia | 1 |
sigagliptin | sage | PD | diabetes II | 3 | hypoglycemia | 1 |
aspirin | B12 | PK-GI absorption | B12-deficiency | 2 | B12-deficiency | 1 |
ensomeprazole | B12 | PK-GI absorption | B12-deficiency | 3 | B12-deficiency | 1 |
Total | 62 |
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Spanakis, M.; Melissourgaki, M.; Lazopoulos, G.; Patelarou, A.E.; Patelarou, E. Prevalence and Clinical Significance of Drug–Drug and Drug–Dietary Supplement Interactions among Patients Admitted for Cardiothoracic Surgery in Greece. Pharmaceutics 2021, 13, 239. https://doi.org/10.3390/pharmaceutics13020239
Spanakis M, Melissourgaki M, Lazopoulos G, Patelarou AE, Patelarou E. Prevalence and Clinical Significance of Drug–Drug and Drug–Dietary Supplement Interactions among Patients Admitted for Cardiothoracic Surgery in Greece. Pharmaceutics. 2021; 13(2):239. https://doi.org/10.3390/pharmaceutics13020239
Chicago/Turabian StyleSpanakis, Marios, Maria Melissourgaki, George Lazopoulos, Athina E. Patelarou, and Evridiki Patelarou. 2021. "Prevalence and Clinical Significance of Drug–Drug and Drug–Dietary Supplement Interactions among Patients Admitted for Cardiothoracic Surgery in Greece" Pharmaceutics 13, no. 2: 239. https://doi.org/10.3390/pharmaceutics13020239