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REVIEW ARTILCE
REVIEW ON INTERACTION OF HERBAL MEDICINES WITH ALLOPATHIC
MEDICINES
P MANOJ KUMAR, SIDDHANAND S KULKARNI, SHASHIKANT D WADKAR Corresponding author email address: [email protected] Access this article online: www.jahm.in Published by Atreya Ayurveda Publications, Ilkal-587125 (India) All rights reserved. Received on: 09/02/14, Revised on: 19/01/14, Accepted on: 20/02/14 Abstract
Whenever two or more drugs are being taken, there is a chance that there will be an interaction among these drugs. These interactions may increase or decrease the effectiveness or may cause serious fatal reactions. The likelihood of drug interactions increases as the number of drugs being taken increases. Therefore, people who take several drugs are at the greatest risk for interactions. It is quite common for a patient to seek herbal treatment while taking several prescription medications. Safety has become a major issue reasonably enough, patients want to know about compatibility and possible interactions when taking herbs and allopathic medicines simultaneously. Such specific questions, unfortunately, are often difficult to answer. This review discusses the issue of drug interactions and several ways to avoid them. Key words: Herbal Drug, Ayurveda, Drug interaction, pharmacokinetics, pharmacodynamics, ADME
interaction.
unaware of the potential for herb–drug During the last decade, an explosion in the interactions1. Natural products are also liable to consumption of herbal remedies has been a great deal of variations even when witnessed. The vast majorities of these products standardized to one or more of their constituents are unlicensed and are not required to such as source material, the method by which an demonstrate efficacy, safety, or quality. extract is made will also affect its composition Although herbs are often promoted as natural and thus its interaction potential. Certain foods and therefore harmless, they are not free from and specific nutrients in foods, if ingested adverse effects. A recent observational study concurrently with some drugs, may affect the indicates that herbal supplements are associated overall bioavailability, pharmacokinetics, with adverse events that include all levels of pharmacodynamic, and therapeutic efficacy of severity, organ systems, and age groups. Recent the medications. The likelihood of drug examinations have indicated that as many as interactions increases as the number of drugs 16% of prescription drug users consume herbal being taken increases and it is estimated that if supplements. Moreover, fewer than 40% of eight or more medications are being used, there patients disclose their herbal supplement usage is a 100% chance of interaction2. The aim of this to health care providers and many physicians are Journal of Ayurveda and Holistic Medicine February, 2014 Volume 2 Issue 2 38  Manoj K Siddhanand S K, Shashikant D: Review on Interaction of Herbal Medicines with Allopathic Medicines article is to highlight the clinical interactions Distribution refers to the process in which herbs between herbal remedies and prescribed drugs. or drugs are carried and released to different parts of the body to exert their effect. Materials and methods
Interactions occur during the distribution phase A drug interaction can be defined as an if the drug has a narrow range of safety index interaction between a drug and another and is highly protein-bound. For example, substance that prevents the drug from Coumadin (warfarin) is an anticoagulant performing as expected. This definition applies medication that is very highly bound to protein to interactions of drugs with other drugs (drug- and has a very narrow range of safety index6. drug interactions), as well as drugs with food Some known examples that interact with (drug-food interactions) and other substances. Coumadin (Warfarin) include Medicago sativa One drug alters the rate or extent of absorption, (alfalfa), aspirin, ibuprofen, vitamin K and some distribution, metabolism or excretion of another types of tea, green leafy vegetables8. These items drug. A change in the blood concentration interact with Coumadin (warfarin) by either causes a change in the drug's effect. Most of the enhancing its effectiveness or thus leading to possible interactions may be classified in two prolonged bleeding, or by decreasing its major categories: Pharmacokinetic and effectiveness and thus increasing the risk of Pharmacodynamic interactions3. blood clots in the vessels, both of which may be Pharmacokinetic interactions are those that can quite dangerous to the patient. This is why affect the processes by which the drug increases patients who are taking Coumadin (warfarin) or decreases ADME interactions4 i.e. need to be exceedingly cautious when taking herbs concurrently. (Intake of Vit k 1/α effect of The Absorption of a drug into the body. Warfarin)4,9. Blood clotting times have been Distribution of the drug within the body. reported to double in patients taking Warfarin Alterations made to the drug by the body (Metabolism). and garlic (Allium sativum) supplements (WHO1999). WHO states that ginger may affect Elimination of the drug from the body. bleeding times and immunological parameters Absorption
owing to its ability to inhibit thromboxane ¾ Depends on surface area of synthase and to act as a prostacyclin agonist10. absorption(less in stomach and more in Metabolism
intestines) 5,6. Many drug interactions are due to alterations in Alteration in stomach HCL (HCL secretion α break down α absorption) drug metabolism. Most herbs and drugs are e.g. avoid antacids with antibiotics metabolized by the liver to inactive derivatives. which reduces the activity of The rate at which the liver metabolizes these herbs and drugs determines the length of time these herbs or drugs stay active in the body. If Intestinal/Gut motility (Gut motility 1/α absorption) e.g. the liver were induced to speed up its Capsicum annum increases gut motility there by decreases metabolism, herbs and drugs would be absorption of aspirin4,7. inactivated at a faster pace and the overall effectiveness of ingested substances would be Blood flow to the site (blood flow α absorption) e.g. lower and vice versa5,6. Although all the Capsicum annum increases blood flow to GIT absorption mechanism is undoubtedly relevant to interaction with herbal medicines, the main focus will be on the cytochrome p 4505 and drug transporter proteins. Drug metabolism goes in Journal of Ayurveda and Holistic Medicine February, 2014 Volume 2 Issue 2 39  Manoj K Siddhanand S K, Shashikant D: Review on Interaction of Herbal Medicines with Allopathic Medicines the serum, the kidneys, the skin and the Pharmacodynamic interactions are those where intestines but the greatest portion is carried out the effects of one drug are changed by the by enzymes that are found in the liver mainly presence of another drug at its site of action. cytochrome p 45011,12. (Metabolism α enzymatic Pharmacodynamic refers to the study of how activity 1/α effect of same drug or other drug) drugs actually behave inside the human body2; e.g. Rifampicin which increases liver one drug causes a change in patient response to metabolism and decreases the effect of oral another drug without altering that drug's contraceptive when used together, Grape juice pharmacokinetics4. (Vitis vinifera) inhibits cytochrome p 450 • E.g. Shankapushpi (Convolvulus preventing midazolam, alprazolam to metabolise pluricaulis) may decrease phenytoin before entering blood stream4,11. levels as well as diminishes drug Excretion
Drugs are eliminated from the body as an Pharmacodynamic interactions refer to the unchanged drug or changed by a process of fluctuation in bioavailability of ingested excretion or converted to metabolite. Renal substances as a result of synergistic or excretion the major route of elimination; antagonistic interactions between herb/drug affected by renal function and urinary pH, some molecules. Pharmacodynamic interactions are drugs are eliminated in bile and other by body generally more difficult to predict and prevent Loop diuretics (furosemide, than pharmacokinetic interactions4,6. bumetanide) increase excretion of potassium, Garlic (Allium sativum) and ginseng (Panux magnesium, sodium, chloride, calcium and ginseng) should be discontinued at least seven corticosteroids (prednisolone) decrease sodium days before surgery because both herbs have excretion, resulting in sodium and water been reported to aggressive bleeding. Ginkgo retention; increases excretion of potassium and biloba should be discontinued three days before calcium so that electrolyte imbalance should be surgery because it inhibits platelets aggregation Pharmacodynamic interaction
Possible drug interactions4,7,11,14,15,16
Herb Drug
Interaction
Aloe vera Digoxin and Thiazide Increases cardiac toxicity Capsicum annum May effect blood glucose levels Capsicum annum May increase absorption Echinacea purpurea Warfarin Decreases Antihypertensive drugs Herb may decrease BP (Allium sativum) Aspirin/Warfarin Irreversible inhibition of platelet Allium sativum) Ginko biloba Acetaminophen Subarachnoid Ginko biloba Anticonvulsants Journal of Ayurveda and Holistic Medicine February, 2014 Volume 2 Issue 2 40  Manoj K Siddhanand S K, Shashikant D: Review on Interaction of Herbal Medicines with Allopathic Medicines Increase oral bioavailability Vitis vinifera) Sodium and fluid retention (Glycyrrhiza glabra) Drug interactions are complex and chiefly your health care practitioners to unpredictable. A known interaction may not eliminate unnecessary medications. occur in every individual. This can be explained Discussion
because there are several factors that affect the likelihood that a known interaction will occur. Demand for herbal products worldwide has These factors include differences among increased at an annual rate of 8% during the individuals in their genes, physiology, age2, period of 1994–2001, and according to WHO lifestyle (diet, exercise), underlying diseases2, forecast, the global herbal market would be drug doses2, and the relative time of worth $5 trillion by the year 2050. As of today, administration of the two substances. Europe and the United States are two major (Sometimes, interactions can be avoided if two herbal product markets in the world, with a drugs are taken at different times) market share of 41% and 20%, respectively. • Additive effects of alcohol and The explosion in popularity of herbs dates to the benzodiazepines17 Dietary Supplement Health and Education Act of 1994 (DSHEA), in which the FDA • Beta-blocker given with beta-agonist9 recognized herbal preparations as dietary Ways to prevent drug interactions
supplements outside of its direct regulatory control. Supplements are permitted to have Best way to prevent is close monitoring of patient itself. "structure–function" statements on their label stating only the product's supposed When therapeutic goals are not met, clinicians should ask questions about physiological function 20. how and when drugs are being taken in The present paper includes various aspects of relation to foods and nutritional drug interactions commonly occurring knowingly or unknowingly which pose serious threat to human health due to limited scientific Give health care practitioners a complete list of all of the drugs that you evidence from randomized, controlled trials to are using or have used within the last support the safety and efficacy of the majority of herbal products and represent an important issue to be tackled. It becomes very difficult to predict 4. Inform health care practitioners when whether the combination of all these medications are added or discontinued18. medications will lead to unwanted side-effects 5. Inform health care practitioners about and/or interactions. It is imprudent to assume changes in lifestyle (for example, that there will be no interactions. On the other exercise, diet, alcohol intake). hand, positive herb-drug interactions having beneficial effects also need to be elucidated. Ask your health care practitioners about the most serious or frequent drug According to the scoring system described by interactions with the medications that Fugh-Berman and Ernst, 68.5% of the cases you are taking since the frequency of reported were classified as ‘unavailable' (i.e. drug interactions increases with the reports contained inadequate information to number of drugs used19, 2, work with assess the likelihood of an interaction), 18.5% Journal of Ayurveda and Holistic Medicine February, 2014 Volume 2 Issue 2 41  Manoj K Siddhanand S K, Shashikant D: Review on Interaction of Herbal Medicines with Allopathic Medicines were classified as ‘possible' (i.e. reports medications, it is becoming increasingly provided some evidence for an interaction, but important for health care providers to be aware there may be other causes of the event) and 13% of potential adverse effects and interactions. It is as ‘well documented' (reports appeared to not uncommon for one patient to seek care from provide reliable evidence for an interaction)1. several doctors for an ailment. As a result, a Lastly it is important for every physician to patient may easily be taking multiple drugs, identify and monitor high risk patients those on herbs and vitamins concurrently. On the other multiple medications and marginal diets, and ask hand, it is just as unwise to abandon treatment them about their use of herbs and provide simply for the fear of possible interactions education about potential herb-drug interactions. therefore researchers should strive to fill the gaps in our present understanding of this Conclusion
problem. On the other hand, positive drug With the increasing prevalence of the use of interactions having beneficial effects also need herbal products, and the fact that many to be elucidated, where it should be possible to consumers and patients are using herbal exploit the increased bioavailability of the drugs products in conjunction with conventional for reducing the dosage. References
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