Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. For example, mixing a drug you take to help you sleep (a sedative) and a drug you take for allergies (an antihistamine) can slow your reactions and make driving a car or operating machinery dangerous.
Drug-food/beverage interactions result from drugs reacting with foods or beverages. For example, mixing alcohol with some drugs may cause you to feel tired or slow your reactions.
Drug-condition interactions may occur when an existing medical condition makes certain drugs potentially harmful. For example, if you have high blood pressure you could experience an unwanted reaction if you take a nasal decongestant.
A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind (drug-drug interaction). However, interactions may also exist between drugs & foods (drug-food interactions), as well as drugs & herbs (drug-herb interactions).
Generally speaking, drug interactions are to be avoided, due to the possibility of poor or unexpected outcomes. However, drug interactions have been deliberately used, such as co-administering probenecid with penicillin prior to mass production of penicillin. Because penicillin was difficult to manufacture, it was worthwhile to find a way to reduce the amount required. Probenecid retards the excretion of penicillin, so a dose of penicillin persists longer when taken with it, and it allowed patients to take less penicillin over a course of therapy.
A contemporary example of a drug interaction used as an advantage is the co-administration of carbidopa with levodopa (available as Carbidopa/levodopa). Levodopa is used in the management of Parkinson's disease and must reach the brain in an un-metabolized state to be beneficial. When given by itself, levodopa is metabolized in the peripheral tissues outside the brain, which decreases the effectiveness of the drug and increases the risk of adverse effects. However, since carbidopa inhibits the peripheral metabolism of levodopa, the co-administration of carbidopa with levodopa allows more levodopa to reach the brain un-metabolized and also reduces the risk of side effects.
Drug interactions may be the result of various processes. These processes may include alterations in the pharmacokinetics of the drug, such as alterations in the Absorption, Distribution, Metabolism, and Excretion (ADME) of a drug. Alternatively, drug interactions may be the result of the pharmacodynamic properties of the drug, e.g. the co-administration of a receptor antagonist and an agonist for the same receptor.
Metabolic drug interactions:
Many drug interactions are due to alterations in drug metabolism.[1] Further, human drug-metabolizing enzymes are typically activated through engagement of nuclear receptors.[1]
One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases. This system may be affected by either enzyme induction or enzyme inhibition, as discussed in the examples below.
Enzyme induction - drug A induces the body to produce more of an enzyme which metabolises drug B. This reduces the effective concentration of drug B, which may lead to loss of effectiveness of drug B. Drug A effectiveness is not altered.
Enzyme inhibition - drug A inhibits the production of the enzyme metabolising drug B, thus an elevation of drug B occurs possibly leading to an overdose.
Bioavailability - drug A influences the absorption of drug B.
The examples described above may have different outcomes depending on the nature of the drugs. For example, if Drug B is a prodrug, then enzyme activation is required for the drug to reach its active form. Hence, enzyme induction by Drug A would increase the effectiveness of the drug B by increasing its metabolism to its active form. Enzyme inhibition by Drug A would decrease the effectiveness of Drug B.
This is the first article in a series of three that discuss various aspects of drug interactions. This article provides a general overview of the types of drug interactions. The second and third articles will focus on pharmacokinetic and pharmacodynamic drug interactions and drug interactions involving the cytochrome P450 metabolic enzyme pathway, respectively. To assist the pharmacist in applying this information in practice, a patient case study will be included with each article. The case study will illustrate one or more drug interactions and examples of care plans that address specific drug interaction problems.
Over the past two years, approximately 80 new prescription drug products have been introduced in the United States. With increasing frequency, pharmacists are being questioned by their patients whether a new prescription drug will interact with any of their routine medications. Unfortunately, each year a number of deaths occur as the direct result of patients taking a new prescription drug in combination with their existing medication regimen. A small number of drugs are withdrawn from the market annually because patients experience harmful adverse drug reactions (ADRs) or drug interactions. Although many ADRs are detected during clinical drug trials, the side effect profiles of a new drug often require more extensive use—including use by patient populations who may not have been adequately represented in the drug’s clinical trials. Also, many drugs are generally studied in young, healthy patients who are not taking other medication. Consequently, it may take several months or years before adequate ××××××××ation of a problem exists.
Adverse drug reactions and drug interactions present alarming problems for our society and must be addressed by all healthcare providers. Because pharmacists are the most extensively educated in the areas of pharmacology, pharmacokinetics, and therapeutics, as well as being the most accessible to patients, they need to assume a more proactive role in preventing potentially lethal situations from occurring.
The Boston Collaborative Drug Surveillance program reported a study of 9,900 patients with 83,200 drug exposures and found 3,600 adverse drug reactions, 234 (6.5%) of which were attributable to drug interactions.1 In a study where the medical charts of 1,800 surgical patients were reviewed, researchers found at least one potential drug interaction in 17% of patients.2 Other studies determined that 19% of nursing home patients received combinations of drugs with known harmful interactions,3 and adverse drug reactions on medicine wards in hospitals resulted from drug interactions in 22% of patients.4 In a study of clinic outpatients, a slightly higher ADR percentage of 23% was reported.5 Clearly, drug interactions present a health risk to patients and a medical challenge for pharmacists and physicians.
Liability For Drug-Drug Interactions
When patients are adversely affected by drug-drug interactions from medication properly ordered by their physician and obtained from their pharmacist, who is at fault and who is the gatekeeper? Are pharmacists responsible or liable for the harm suffered by patients as a result of drug-drug interactions that could have been avoided? If a pharmacist knows or should know the potential for life-threatening drug-drug interactions to occur but fails to warn patients or physicians about the problem, can the pharmacist be held liable? Is screening and monitoring a patient’s drug regimen for drug-drug interactions a standard of care expected by patients?
Growing Consensus: There is a growing body of information (i.e., laws, practice standards adopted by professional organizations, curricula of American colleges of pharmacy) addressing the issue of pharmacists’ responsibility and liability. First, colleges of pharmacy in the United States include courses in their entry level degree program designed to instruct students on aspects of drug interactions, including detection, incidence and significance, types of drug interactions, mechanisms by which interactions occur, and the role of the pharmacist in monitoring drug therapy to either avoid and/or resolve drug interactions. Second, most pharmacies in the U.S. utilize sophisticated computer software to help pharmacists manage the pharmacy’s business operation, and to screen patient medication profiles for drug-drug interactions when processing new and refill prescriptions. Third, the profession of pharmacy through its professional organizations such as the American Pharmaceutical Association, the American Society of Health-Systems Pharmacists, and the American Society of Consultant Pharmacists has publicly proclaimed that the role of the pharmacist in “pharmaceutical care as a practice standard” is to maximize patient outcomes.6,7 Fourth, OBRA-90 legislation charged pharmacists with the responsibility to minimize adverse reactions, which includes drug-drug interactions.6,8 Fifth, the Federal Department of Health and Human Services requires pharmacists who serve the needs of patients in long-term care facilities as consultant pharmacists to review the drug regimen of patients and report any irregularities, including drug interactions, to the facility’s medical director. Sixth, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) requires that hospitalized patients be educated and counseled on potential food-drug interactions by the pharmacist, dietitian, nurse and physician. The pharmaceutical care component of the JCAHO standard specifies that pharmacists are responsible for identifying drug-drug interactions as well as drug-food interactions.9,10 Finally, recent studies suggest a lack of knowledge among physicians about drug interactions, specifically drug-food interactions.10,11 These studies also report that fifth-year pharmacy students scored significantly higher than family medicine residents (in their fifth or sixth year of training) in 12 of 14 items on a standardized drug interaction questionnaire.
With such compelling ××××××××ation, it is clear why a court would find that screening for drug-drug interactions is a standard of care in pharmacy and that liability should fall on pharmacists/pharmacies who fail to comply with this standard.6
High-Risk Patients and Drug Interactions
The magnitude of the drug interactions problem increases significantly in certain patient populations and as the number of medications taken each day increases. Drug interactions that may be of minor clinical significance in patients with less severe forms of a disease can cause significant exacerbation of the clinical condition in patients with more severe forms of the disease (TABLE 1). Patient populations at high risk include the elderly, critical care patients, and patients undergoing complicated surgical procedures.12-17 The elderly population is at high risk because of the number of medications consumed, complicated drug regimens, and clinical states often presented. About 80% of elderly patients routinely take prescription and nonprescription medications concurrently. Some patients may see multiple physicians for acute and chronic conditions, as well as obtain medication from more than one community pharmacy or mail-order pharmacy.
Table 1
Conditions that Place Patients at High Risk for Drug Interactions
High risk associated with the severity of disease state being treated
Aplastic anemia
Asthma
Cardiac arrhythmia
Critical care/intensive care patients
Diabetes
Epilepsy
Hepatic disease
Hypothyroid
High risk associated with drug interaction potential of related therapy
Autoimmune disorders
Cardiovascular disease
Gastrointestinal disease
Infection
Psychiatric disorders
Respiratory disorders
Seizure disorders
Not only do drug interactions present a danger to the patient, but they can also greatly increase healthcare costs. For example, a study revealed an increased length of stay of 3.1 days for patients who received warfarin with potentially interacting drugs compared with a control group.18 Patients on a combination of drugs also required more laboratory tests to monitor resolution of these interactions.
Drugs identified as having a high risk of being involved in a clinically significant drug interaction frequently have a narrow therapeutic index, a very steep dose-response curve or potent pharmacologic effects.12,19-21 A listing of drugs with a narrow therapeutic index appears in TABLE 2. A toxic dose of these drugs may be only slightly above the therapeutic dose. A slight increase in the dose may produce a large increase in serum drug levels and clinical effect. Conversely, a slight decrease in the plasma level of drugs with a steep dose-response curve may result in a significant loss of therapeutic effect. Examples of such drugs include corticosteroids, carbamazepine, quinidine, oral contraceptives, and rifampin.12 Patients receiving drugs with a narrow therapeutic index should be monitored closely for possible clinically significant drug interactions.
Table 2
Drugs With Narrow Therapeutic Index
Aminoglycoside antibiotics
(gentamicin, tobramycin)
Anticoagulants (warfarin, heparins)
Aspirin
Carbamazepine
Conjugated estrogens
Cyclosporine
Digoxin
Esterified estrogens
Hypoglycemic agents
Levothyroxine sodium
Lithium
Phenytoin
Procainamide
Quinidine sulfate/gluconate
Theophylline
Tricyclic antidepressants
Valproic acid
Adverse Drug Reactions (ADRs)
An adverse drug reaction can be defined as an unexpected diminished or enhanced pharmacologic activity or toxicity of a drug when used alone, or any noxious response to a drug that occurs at doses used in humans for prophylaxis, diagnosis, or therapy. (A drug’s failure to achieve its intended effect is not considered an ADR.) This definition also includes any undesirable or unexpected event requiring discontinuation of the drug, modification of the dose, prolonged hospitalization, or the administration of supportive treatment.
Type A Reactions: Adverse drug reactions are generally classified as type A or type B, but some drug reactions do not fit well into either category. Type A (augmented) reactions are normal pharmacologic effects of the drug exaggerated to the point of being undesirable or intolerable for patients.23 These ADRs are often dose-dependent, and the percentage of patients who might experience these effects is generally predictable. Examples of drugs indicated as causing type A reactions include warfarin or heparin, which cause bruising; or diphenhydramine, which causes drowsiness. Another form of type A reaction involves a drug’s recognized pharmacologic property other than the primary desired one. For example, b-adrenergic blocking agents exert their effect on receptors other than those targeted in the heart and vasculature, leading to the potential of bronchospasm due to b-blockade of certain receptors in the pulmonary tree.
Type B Reactions: Type B (bizarre) reactions are often more severe adverse effects unrelated to the known pharmacologic action of the drug and include most immunologic reactions.23 Unless patients are tested for antibody markers, these reactions are unpredictable and may or may not be dose-dependent. An example of a type B reaction is an anaphylactic reaction to penicillin. The term “idiosyncratic reactions” has also been used in place of type B adverse reactions.
Drug-Drug Interactions
Drug-drug interactions can be defined as the modulation of the pharmacologic activity of one drug (i.e., the object drug) by the prior or concomitant administration of another drug (i.e., the precipitant drug).23-24 In these reactions, the pharmacologic properties of the object drug and/or the precipitant drug can be either severely enhanced or diminished. The interaction can be potentiated, or synergistic, when the combined effect of the two drugs is greater than the total effects of the drugs used separately. The interaction can be expressed as antagonized when the resulting effect is less than the combined effects of the two drugs when used separately or when the effect partially or completely nullifies the effect(s) of each drug. In some instances, predictable drug-drug interactions in patients are beneficial, and clinicians allow them to occur because they result in lower doses of the drug(s) being administered while still achieving therapeutic serum drug levels. For example, administering penicillins (renally excreted) with the drug probenecid significantly elevates serum levels of penicillin and prolongs its half-life.
The causes and significance of drug interactions are multifaceted and include drug dose; serum drug level; route of administration; drug metabolism; duration of therapy; and patient factors, such as age, gender, weight, genetic predisposition, and other factors. Drug interactions are frequently characterized as pharmacokinetic or pharmacodynamic in nature.23-24 Pharmacokinetic interactions influence the disposition of a drug in the body and involve the effects of one drug on the absorption, distribution, metabolism and/or excretion of another drug. These interactions frequently cause marked shifts in serum drug levels and alter clinical response. Pharmacodynamic interactions are related to the pharmacologic activity of the interacting drugs. These interactions are frequently associated with synergism, antagonism, or altered cellular transport, and they affect organ systems and/or receptor sites.
Drug-Nutrient Interactions
Generally, administering oral medication along with food or at a mealtime is a convenient manner of drug dosing. However, drug interactions can occur that modify the activity of the drug (decrease or increase drug effects) or impair the nutritional benefit of certain food.23-24 The most commonly observed type of drug-food interaction affects drug absorption.
Food’s Effect on Drug Absorption: Food can decrease a drug’s rate of absorption and/or decrease the extent of absorption of numerous drugs. Examples of drugs whose absorption is decreased when taken with food include penicillin, tetracycline (TCN), erythromycin, levodopa, phenytoin, and digoxin.23 Drugs whose absorption increases when taken with food include spironolactone,26 griseofulvin,27 and itraconazole. With some drugs, this food-drug interaction may be utilized to achieve higher serum drug levels or to use lesser amounts of drug per dose. For example, administering the drug ketoconazole with acidic beverages (colas) leads to high and prolonged serum levels for ketoconazole. Generally, these interactions have an insidious onset and may not be clinically evident except for failure to achieve the therapeutic goals of therapy or loss of disease control. Continuous long-term monitoring of patients is needed when drugs and food must be taken together. See TABLE 3 for a listing of other drugs influenced by food and nutritional products.
In addition to affecting absorption of drugs, food can interact with drugs in a variety of other ways.
Table 3
Foods Containing High Amounts of Tyramine
Ale
Avocados
Bananas
Beans (lima beans, butter beans, bean pods)
Caviar
Cheese (especially aged)
Chocolate
Coffee
Figs
Fish (smoked or pickled herring)
Processed meat (bologna, fermented meat, salami, pepperoni, summer sausage)
Liver (beef or chicken)
Raspberries
Raisins
Sour cream
Soy beans or sauce
Tofu
Wines (especially red)
Yeast preparations
Yogurt
MAOIs and Tyramine: One of the most clinically significant interactions occurs when monamine oxidase inhibitors (MAOIs [e.g., phenelzine, tranylcypromine, isocarboxazid, and procarbazine]) are taken with foods containing high amounts of the compound tyramine.23-25,28 Normally, tyramine is metabolized by monoamine oxidase before it enters the body’s systemic circulation. When MAOIs and foods high in tyramine are taken concurrently, large amounts of tyramine can potentially reach systemic circulation, resulting in acute exacerbation of blood pressure. In some instances, this reaction has been so severe that hypertensive emergencies/crises have been reported. See TABLE 3 for a listing of foods that contain high amounts of tyramine.
Other Effects of Foods: Other examples of drug-food interactions are as follows:29,30 1) vitamin K found in green leafy vegetables, tomatoes, coffee, beef liver, green tea, alfalfa tablets, etc. (TABLE 5) and some nonprescription vitamin-mineral products can antagonize the anticoagulant effect of warfarin, resulting in decreased anticoagulant activity and lowered prothrombin time (PT) laboratory blood tests;25,28,29 2) vitamin B6 (pyridoxine) found in avocados, beans, peas, sweet potatoes, bacon, beef liver, pork, tuna, and some nonprescription vitamin-mineral products, increases the metabolism of levodopa, producing decreased blood levels of dopamine and antiparkinsonism effects;23,25,28 3) calcium, magnesium and aluminum found in food supplements or antacid compounds bind (chelate) with TCN to form an insoluble complex resulting in significantly decreased absorption of TCN and decreased antibiotic effect;23,27,28 and 4) calcium in vitamin-mineral products and liquid enteral nutritional supplements interact with some fluoroquinolone antibiotics (ciprofloxacin, enoxacin, and others) and with phenytoin, reducing their bioavailability and resulting in decreased antibiotic activity and loss of seizure control, respectively.
Table 5
Foods and Products High in Vitamin K
Alfalfa tablets
Broccoli
Brussels sprouts
Cabbage
Cauliflower (raw)
Green leafy vegetables (spinach, collard greens)
Green tea
Liver
Soybean
Vegetable oils (canola, soybean)
Watercress
Drug-Disease Interactions
Certain drugs have the capability to exacerbate acute and/or chronic disorders.23,24,27,27 Beta-adrenergic blocking agents can precipitate and exacerbate diseases such as asthma, chronic obstructive pulmonary disease, and peripheral vascular disease. These drugs can also blunt the typical signs and symptoms of a hypoglycemic reaction in diabetic patients and alter insulin utilization in the body. These drugs and calcium channel modulators, particularly verapamil, have negative inotropic and negative chronotropic effects on the heart and can exacerbate diseases such as congestive heart failure. Prednisone can aggravate congestive heart failure and cause fluid overload. Because a number of these interactions may have an insidious onset, continuous long-term monitoring of patients may be needed.
Drug-Herbal Interactions
The use of herbal or natural products in the U.S. is growing significantly every year. In 1997, it was estimated that 33% of U.S. adults used one or more herbal products, and spent $3 billion on these products.31 Although there are very few well designed clinical trials to support their use, these products are considered both safe and effective alternatives to traditional medicine by American society. This acceptance was perpetuated by the Dietary Supplement Health and Education Act (DSHEA) of 1994, enacted by Congress, which classified herbal products not as drugs, but as dietary supplements. The premise for this enactment by DSHEA was that dietary supplements were safe and adverse effects from these products were rare; however, no statements were included to support their effectiveness. Because about 70% of patients may not be informing their physician or pharmacist of their herbal product use, the potential and incidence for adverse reactions and drug-drug interactions is unknown and not being monitored. Other reasons that make adverse reactions to these products likely include a lack of standardization of content of natural products, variations in the strength of the active ingredient, contamination by fungal organisms, and adulteration with other potentially harmful natural products.31 Potential adverse effects of herbs and drug-herb interactions of selected herbs are listed in TABLE 6. Patients generally do not consider these products as drugs, and may not mention their use during medication history interviews performed by pharmacists, nurses, or physicians. Patients should be asked about use of herbal or natural product(s) and other medications in order to evaluate the potential of these products to interact when used concurrently with prescription medication.
» لوحــــــــات التــــــــــوزيع M.V Distribution Board
» كيف نحافظ على الأجهزة الإلكترونية
» تعلم قواعد الفرنسية بالكامل في ساعة و احدة
» خدمه العملاء
» كورس الجامعة الامريكية لدراسات الجدوي للمشروعات الهندسية,Global Feasibility Study For Engi
» ((~~العبارات التحفيزية الايجابيه لك وللاخرين~~))
» ادارة الازمــات
» عشر نصائح لمكافحة التوتر النفسي