Drug Interactions Prevention in Nursing Guidelines Essay
Drug Interactions Prevention in Nursing Guidelines Essay
Prevention of Drug to Drug Interactions
Drug to drug interactions occur when a patient takes two or more medications. Such interactions have been observed to enhance, delay, or decrease the rate at which one drug (or both) is absorbed in the body (Wiggins et al., 2016). The interaction is known to affect the effectiveness of the drugs. Past studies have also indicated that drug to drug interactions can result in negative health outcomes. In order to deal with this challenge, the Centers for Disease Control and Prevention (CDC) developed new guidelines to influence different practices undertaken by caregivers and advanced practice nurses (APNs).Drug Interactions Prevention in Nursing Guidelines Essay. The guidelines offer useful incentives to dictate how and when medications should be provided. The guidelines can be used to formulate the right dosages and discontinue drugs that show negative effects. Risk factors can be analyzed continuously to mitigate every health risk (Wiggins et al., 2016). Patients who are informed about these guidelines will report such interactions and be part of the healing process.
Nurses can use the guidelines to encourage patients to monitor the nature (or complexity) of different interactions. For instance, drug testing can be done to come up with better medication plans. The use of a multi-drug interaction checker can guide both patients and nurses to analyze different medications. This practice will ensure the right drugs are administered to every patient. The guidelines offer meaningful insights to ensure positive interactions are monitored and used to deliver exemplary medical support. Patients are empowered to analyze the unique risk factors for such interactions (Wiggins et al., 2016). Issues such as old age, diseases, terminal conditions, and drug dependency should be analyzed carefully. APNs can use the current CDC guidelines in patient education to guide and empower more individuals to minimize drug to drug interactions. Drug Interactions Prevention in Nursing Guidelines Essay.
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Prevention of Food-Drug Interactions
The guidelines outlined by the CDC can be used by APNs to educate patients about food-drug interactions. For instance, patient education programs should focus on the best ways to assess the occurrence of such interactions. Patients will be informed about the best strategies to report and address the emerging side effects. The targeted persons can be guided to monitor any form of food-drug interaction and report it in a timely manner (Enwerem & Okunji, 2017). Patients can become competent decision-makers and eventually support the care delivery process. This practice will minimize the risks arising from food-drug interactions. The guidelines also outline some of the common interactions associated with various food materials. Patients who are informed about these interactions will be in a position to change their diets whenever taking specific drugs. Drug Interactions Prevention in Nursing Guidelines Essay.
The guidelines go further and outline the major side effects associated with various drug-food combinations. Patients can use such guidelines to discontinue various foods or medications. More individuals will also be willing to share every experience or side effect with their caregivers. Drug Interactions Prevention in Nursing Guidelines Essay. This form of collaboration will improve the efficiency of the healthcare delivery process. APNs can persuade more patients to engage in healthy lifestyles (Enwerem & Okunji, 2017). This practice will minimize most of the side effects or challenges associated with various food-drug interactions. The ultimate goal should be to use such guidelines to promote new practices through continuous patient education. The practice will empower more patients to identify, report, and deal with every harm (or side effect) arising from drug-food interactions.
References
Enwerem, N., & Okunji, P. (2017). Knowledge of food and drug interactions among nurses: Assessment strategy for continuing education. International Journal of Higher Education, 6(1), 122-130. Web.
Wiggins, B., Saseen, J., Page, R., Reed, B., Sneed, K., Kostis, J., … Morris, P. (2016). Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease. Circulation, 134(1), 1-28. Web.
Drug interactions can have desired, reduced or unwanted effects. The probability of interactions increases with the number of drugs taken. The high rate of prescribed drugs in elderly patients (65-year-old patients take an average of 5 drugs) increases the likelihood of drug interactions and thus the risk that drugs themselves can be the cause of hospitalization. Drug Interactions Prevention in Nursing Guidelines Essay. According to meta-analyses, up to 7% of hospitalizations are drug-related.
Methods
Selective literature review.
Results
Drug interactions occur on pharmacodynamic and pharmacokinetic levels. Examples of pharmacodynamic interactions are simultaneous administration of a NSAID and phenprocoumon (additive interaction), or of aspirin and ibuprofen (antagonistic interaction). Pharmacokinetic interactions occur at the levels of absorption (e.g., levothyroxine and neutralizing antacids), elimination (e.g., digoxin and macrolides), and metabolism, as in the competition for cytochrome P450 enzymes (e.g., SSRIs and certain beta-blockers).
Conclusion
The systematic knowledge of drug interaction, in particular on the level of absorption, elimination, transport and drug metabolism may help to prevent adverse effects. Predicting pharmacodynamic interactions often demands a deeper understanding of the mechanisms of effect. Electronic prescribing systems are helpful.
Increasing multimorbidity with age often makes it necessary to prescribe several drugs for one patient at a time. As a consequence, the average 65-year-old patient is on five drugs simultaneously (1). Prescription peaks in the 75- to 84-year-old group; a European study showed among patients with a mean age of 81 years that 34% to 68% were taking six drugs or more (2).
A necessary consequence of this is the danger that interactions between drugs will lead to serious adverse effects or will reduce the therapeutic effect of some compounds. Potential interactions can arise at any age in life, but the frequency of polypharmacy in older life increases the risk substantially. Meta-analyses of the reasons for inpatient admission to medical wards showed that in 7% of cases serious drug interactions were the cause for admission or for prolonged hospital stays (3, e1, e2). Similar conclusions were reached in an earlier Austrian study of 543 newly admitted elderly patients (median age: 82 years), who were taking 7.5 ± 3.8 drugs at the time of their admission (4). The authors regarded 36% of the drugs as unnecessary and 30% as inappropriate for elderly people (see recommendations in the PRISCUS list [5]). For 10% of the patients, adverse drug effects were regarded as the reason for their inpatient admission, and in 18.7% a drug interaction very probably played a part in these effects (6). Adverse drug effects are also a—sometimes avoidable—problem during inpatient treatment. One of the frequent causes here is incorrect or wrongly adjusted dosages, especially in patients with reduced kidney function (7). A British study of 3695 patients demonstrated that almost 15% of the patients suffered adverse drug effects during their stay in hospital, which in a quarter of these cases prolonged the hospital stay. Once sex, age, and type of ward (medical, surgical) were taken into account, the number of simultaneously prescribed drugs was the only significant predictor (7). Drug Interactions Prevention in Nursing Guidelines Essay. In a survey in Sweden, the contribution of drugs to overall mortality was estimated at 3%; gastrointestinal and central nervous bleeding alone contributed a third of the incidence (e3).
Knowing about interactions and their causes may help to avoid them. One study, in which hospital personnel on an intensive care unit were informed of drug interactions by written drug information based on a computerized clinical decision support system, was very successful, reducing the number of interactions from 66% to 54% and the number of unwanted events from 44% to 25% (e4) (Box 1).
Learning goals
This CME article gives examples of interactions at the pharmacodynamic level, mainly using the example of nonsteroidal anti-inflammatory drugs (NSAIDs). The focus is on demonstrating the systematics of pharmacokinetic interactions. The learning goals follow from this: knowledge of important and frequent
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pharmacodynamic interactions
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pharmacokinetic interactions at the absorption and excretion levels, and
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pharmacokinetic interactions at the drug metabolism level, chiefly of cytochrome P450 enzymes
The review article is based on a selective literature search in PubMed and publicly accessible databases such as http://medicine.iupui.edu/clinpharm/ddis/. The clinical manifestation of interactions can vary greatly. Inadequate lowering of blood pressure and a blood pressure drop that may be so extreme as to cause hypovolemic shock can both result from pharmacodynamic and/or pharmacokinetic interactions. To avoid serious consequences so far as possible from the outset, therefore, requires the ability to make better predictions about drug interactions.Drug Interactions Prevention in Nursing Guidelines Essay. In some cases, however, desired interactions can improve the therapeutic effect, e.g., if local bioavailability is increased by inhibition of the metabolic pathways.
Pharmacodynamic interactions
The term “pharmacodynamic interactions” refers to interactions in which drugs influence each other’s effects directly. As a rule, for example, sedatives can potentiate each other. The same is true of alcohol, which can potentiate the sedative effects of many drugs.
Often, however, a pharmacodynamic interaction is actually desired, if mutually potentiating effects in the same direction (synergistic effects) are aimed at, e.g., in the use of anti-infectives or in pain therapy. When the effect of one drug is impeded by another, the effects of these drugs are antagonistic.
Even barely observable undesired effects can potentiate each other in a dangerous manner. For example, if fluoroquinolones are combined with macrolides such as erythromycin, this can result in QT prolongation. The combination of ACE inhibitors with potassium-sparing diuretics such as amiloride can increase potassium retention so strongly that life-threatening hyperkalemia ensues. Interactions of nonsteroidal anti-inflammatory drugs (NSAIDs) are demonstrated below as an example of pharmacodynamic interactions. Drug Interactions Prevention in Nursing Guidelines Essay.
Pharmacodynamic interactions of NSAIDs
Platelet-related interactions—It is generally known that simultaneous administration of NSAIDs increases the COX-1-mediated inhibition of thromboxane synthesis and hence the risk of gastrointestinal bleeding in a synergistic manner. A particular property of the acidic anti-inflammatory ibuprofen is its specific, reversible binding to COX-1, which prevents acetylsalicylic acid (ASA) from acetylating the serine residue at position 529 of the COX-1 protein. Irreversible and hence long-lasting inhibition of COX-1-mediated thromboxane A2 synthesis by ASA can thus be prevented and the cardiac risk of patients with coronary heart disease can increase (8).
Long-term clinical observations confirm these ex vivo observations (e5), which appear also to hold for naproxen (e6). Accordingly, patients with coronary heart disease on ASA prophylaxis should not take ibuprofen or naproxen on a regular basis.
Increased gastrointestinal bleeding also occurs when selective serotonin reuptake inhibitors (SSRIs) such as citalopram are taken simultaneously with NSAIDs (e7). SSRIs inhibit the transport of serotonin into the platelets, leading to further impairment of function and doubling of the risk of bleeding. The SSRI-mediated impairment of platelet function can also increase the risk of bleeding due to vitamin K antagonists such as warfarin and phenprocoumon (9, e8). SSRIs were associated with an increased risk of gastrointestinal bleeding with an odds ratio of 2.6 (95% confidence interval [CI] 1.5 to 4.3), whereas other antidepressants barely increase the risk. NSAIDs and specific COX-2 inhibitors, on the other hand, also increased the risk of bleeding, with an odds ratio of 2.6 (95% CI 1.6 to 4.2) and 3.1 (95% CI 1.4 to 6.7), respectively. Drug Interactions Prevention in Nursing Guidelines Essay.These study results thus indicate that SSRIs increase the risk of bleeding associated with vitamin K antagonists as much as NSAIDs do. Since the absolute number of bleeding events under SSRI treatment is quite low, however, simultaneous treatment with SSRIs and anticoagulants or NSAIDs should chiefly be avoided in at-risk patients with a known history of bleeding (e7).
Interactions with the vascular system—NSAIDs can reduce the blood-pressure-lowering effect of ACE inhibitors. The main mechanism is via a reduction in glomerular perfusion through a reduction of local prostaglandin E2 synthesis with corresponding reactive secretion of renin. In a controlled clinical study, the blood pressure of healthy volunteers treated with lisinopril rose by 7 to 9 mmHg when they were given piroxicam (e9). It was recently reported that these important interactions of NSAIDs are also true for AT1-receptor blockers (10). Low-dose ASA, on the other hand, appears to have no effect on arterial blood pressure (e10). Nevertheless, doses of 300 mg ASA and higher can reduce the effects of ACE inhibitors.
Other interactions of inhibitors of the renin–angiotensin system (RAAS)—The aldosterone-antagonistic effect of ACE inhibitors and AT1-receptor antagonists can, in combination with potassium-sparing diuretics or specific aldosterone antagonists such as spironolactone and eplerenone, induce dangerous hyperkalemia or renal failure. After the introduction of spironolactone for the treatment of cardiac failure, the number of hospitalizations for hyperkalemia increased markedly (11).Drug Interactions Prevention in Nursing Guidelines Essay. Apparently there now exists an increased awareness of this potential problem, however; although, according to the guidelines of the European Society of Cardiology (ESC), aldosterone antagonists are the drug of choice for patients with NYHA class II heart failure, alongside RAAS inhibitors, and consequently are being used more widely, more recent studies do not show significant hyperkalemia when they are used in combination with RAAS inhibitors (e11, e12).
With pharmacodynamic interactions, it is not possible to demonstrate a simple systematics as it is in pharmacokinetic interactions; instead, they require a careful weighing up of which drug groups cause desired and which undesired effects, which can in turn either potentiate or weaken each other (Table 1).
Table 1
| Substance I | Substance II | Possible effect | |
| Additive interactions | |||
| NSAIDs | SSRI, phenprocoumon | Increased risk of bleeding | |
| NSAIDs | Glucocorticoids | Increased risk of gastric bleeding | |
| ACE inhibitors | Spironolactone, amiloride | Hyperkalemia | |
| SSRIs | Triptans | Serotonin syndrome | |
| Tricyclic antidepressants | Low-potency neuroleptics | Increased anticholinergic effects | |
| Quinolones | Macrolides, citalopram | QT-interval prolongation, torsade de pointes | |
| Antagonistic interactions | |||
| Acetylsalicylic acid | Ibuprofen | Reduced effects | |
| ACE inhibitors | NSAIDs | Reduced effects | |
| Levodopa | Classical neuroleptics | Reduced effects | |
| Phenprocoumon | Vitamin K | Reduced effects | |
SSRI, selective serotonin reuptake inhibitor; NSAID, nonsteroidal anti-inflammatory drug
Pharmacokinetic interactions
Reciprocal influencing of absorption, distribution in the various compartments, metabolization, and elimination can affect the effective concentrations at their sites of action. The causes can be formation of complexes, competition for uptake transporters, or induction of metabolizing enzymes and efflux transporters (Figure 1).Drug Interactions Prevention in Nursing Guidelines Essay.
Example of induction: P-glycoprotein, the most important efflux transporter at several interfaces can be induced by rifampicin.
PXR, pregnane X receptor; RXR, retinoid X receptor
The systematics are becoming increasingly better understood, so that some of the interactions of various drugs can be well predicted, partly with the help of computer programs, at least for certain drug groups (12). Quantification of the extent of the interaction, however, is not usually subject to any simple rule, such as in dose adjustment of renally eliminated drugs depending on the patient’s glomerular filtration rate.
Interactions at the absorption level—formation of complexes
Complexes can considerably reduce the bioavailability of drugs. The bisphosphonates used in osteoporosis, such as alendronate, have a very low bioavailability of only 0.5% to 2%. Calcium ions in mineral water or milk reduce this markedly still further. Multivalent cations can also form complexes with tetracycline or quinolones and also reduce the bioavailability of levothyroxine; simultaneous intake of calcium-containing foods or neutralizing antacids containing aluminum or magnesium ions, must therefore be avoided. Recently, a reduction of the protective properties of alendronate with reference to avoiding hip fractures was observed when proton pump inhibitors were given at the same time (13).
Interactions at the absorption level—membrane transport
Multidrug efflux transporters such as P-glycoprotein (P-gp, ABCB1) were first described as one of the causes of chemotherapy resistance in tumors.Drug Interactions Prevention in Nursing Guidelines Essay. P-glycoprotein is expressed in many tissue barriers such as intestine, liver, kidney, and blood–brain barrier, and in the placenta, testis, lymphocytes, and tumor cells, and extrudes predominantly lipophilic connections/bindings from inside the cell via the apical membranes of epithelial or endothelial cells.
Inhibition of this efflux transporter could therefore help to overcome chemoresistance. P-gp-mediated efflux transport also contributes to reducing the responsiveness of lymphocytes to HIV protease inhibitors. Ritonavir, which causes many side effects at high doses, simultaneously inhibits P-gp and also the drug-metabolizing cytochrome P450 3A4 (CYP3A4). The fixed combination of ritonavir with, for example, 200 mg lopinavir improves the bioavailability of the protease-inhibiting substance and the efflux of lopinavir out of the lymphocytes, thus reducing the breakdown in the liver. So far, however, the attempt to overcome the chemoresistance of tumors by inhibiting efflux transporters, especially by means of P-glycoprotein, has been unsuccessful.
An example of a typical drug interaction at the P-gp level is the much higher bioavailability of the cardiac glycoside digoxin when accompanied by oral administration of the calcium antagonist verapamil.
A selection of P-gp substrates, inhibitors, and inducers is shown in Table 2.Drug Interactions Prevention in Nursing Guidelines Essay.
Table 2
| Group | Substance |
| Substrates | |
| Opioids | Loperamide, morphine |
| Antihypertensives | Aliskiren, carvedilol |
| Anticoagulants | Dabigatran |
| Cardiac glycosides | Digoxin |
| Immunosuppressants | Ciclosporin, tacrolimus, sirolimus |
| Protease inhibitors | Indinavir, saquinavir |
| Statins | Atorvastatin, lovastatin, simvastatin |
| Antineoplastic agents | Paclitaxel, anthracyclines, vinca alkaloids, etoposide, imatinib |
| Inducers | |
| Anticonvulsants | Carbamazepine (oxcarbazepine less so), phenytoin, phenobarbital, primidone |
| Tuberculostatics | Rifampicin |
| Antiretroviral | Efavirenz |
| St. John’s wort extract | Hyperforin |
| Inhibitors | |
| Antimycotics | Itraconazole, ketoconazole |
| Calcium channel blockers | Diltiazem; felodipine; nicardipine; nifedipine; verapamil especially |
| Macrolide antibiotics | Erythromycin, clarithromycin, not azithromycin |
| HIV protease inhibitors | Indinavir; nelfinavir; ritonavir especially; saquinavir |
| Immunosuppressants | Ciclosporin |
| Antiarrhythmic drugs | Amiodarone, quinidine, propafenone |
P-gp induction can, on the other hand, accelerate efflux transport and reduce the bioavailability of drugs. For ciclosporin, this means that simultaneous administration of the tuberculostatic rifampicin can lead to subtherapeutic concentrations. Rifampicin binds intracellularly to the nuclear receptor PXR, one of the main regulators of transcriptional control of P-gp expression (14, e13) (Figure 2). Drug Interactions Prevention in Nursing Guidelines Essay. Other PXR ligands, and thus inducing drugs, are the anticonvulsants carbamazepine (oxcarbazepine to a lesser extent), phenobarbital, and phenytoin, and the HIV therapeutic efavirenz. A case of unexpected clinical significance was one where ingestion of St. John’s wort extract led to such a pronounced fall in ciclosporin concentration that an acute transplant rejection occurred (15). The substance responsible for this was hyperforin, which is present in St. John’s wort extract and was identified as another PXR ligand.
Inhibition of CYP34A-catalyzed metabolization of the vitamin K antagonist phenprocoumon by the macrolide antibiotic clarithromycin. The result is an increase in bioavailability, in turn increasing the risk of bleeding
Leber_Fotolia abhijith3747
In addition to P-gp, the efflux transporters ABCC2 (MRP2) and ABCG2 (BCRP) are also responsible for the efflux transport of many medical drugs and can be subject to interactions with inhibitors.
The opposite also occurs: inhibition of uptake transporters leads to a reduction in bioavailability. An example is inhibition by repaglinide of the uptake of metformin via the organic cation transporter OCT1 (e14).
Interactions at the metabolic level
Inhibition of drug metabolism is a frequent cause of drug interactions. Most metabolic interactions are due to competition for the cytochrome P450 enzyme (CYP), which is expressed in the liver and catalyzes the phase I oxidation of more than half of all medical drugs (16).
Interactions with CYP3A4 are particularly marked, since this isoenzyme has a particularly broad substrate spectrum (e15). Some of the CYP3A4 substrates, inhibitors, and inducers are identical with those of P-gp, indicating a synergistic defense mechanism against foreign matter that has developed in the course of evolution (Tables 3 and 44). Drug Interactions Prevention in Nursing Guidelines Essay.
