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HERBS AND THEIR INTERACTION WITH ALLOPATHIC DRUGS – A REVIEW

 

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About Authors:
Sharma Monish*, Kumar Bhupender, Bhardwaj Sudeep
Seth G.L Bihani S. D. College of Technical Education,
Institute of Pharmaceutical Sciences & Drug Research.
Sri Ganganagar, Rajasthan (INDIA)
*monish28sharma@gmail.com

ABSTRACT :
During the recent past, a dramatic rise in the use of herbs and herbal remedies has been witnessed in many parts of the world.  While such products had been used with apparent safety in traditional societies for many centuries, when they are being combined with pharmacological agents, posses the possibility of potential interaction between the two groups of substances. In this situation, herb-allopathic drug interaction is an important factor to be measured because there is always a chance to get undesirable therapeutic effect of the prescribed allopathic drug, as like allopathic (prescription) drugs. Herbal medicines also have different pharmacokinetic and pharmacodynamic properties which ultimately lead to produce therapeutic responses, but sometimes cause adverse actions and/or drug-herbal interactions. Drug interaction refers to the situation where two or more separate drugs have been absorbed into the body and their effects are affected by each other, i.e. the effects are increased or they produce a new effect that neither produces on its own. The aim of this article is to highlight the interactions between herbal remedies and prescribed drugs.


REFERENCE ID: PHARMATUTOR-ART-1648

INTRODUCTION:
The utilization of natural substances has increased for various diseases amongst general public over last few years not only because of their easy availability without prescription, cost and appointment to the health care professionals but also owing to the belief that natural substances has less adverse effects as compared to synthetic medicines (Ashraf Rizwan et.al.2011) but this is a dangerous oversimplification. Some herbal medicines are associated with adverse effect which include interactions with prescribed drugs (Izzo A.Angelo et.al.2009) . In this situation, herb-allopathic drug interaction is an important factor to be measured because there is always a chance to get undesirable therapeutic effect of the prescribed allopathic drug, as like allopathic (prescription) drugs. Herbal medicines also have different pharmacokinetic and pharmacodynamic properties which ultimately lead to produce therapeutic responses, but sometimes cause adverse actions and/or drug-herbal interactions . Drug interaction refers to the situation where two or more separate drugs have been absorbed into the body and their effects are affected by each other, i.e. The effects are increased or they produce a new effect that neither produces on its own (mspcindia.org /Download/Docs/Drug%20interaction%20with% 20herb.pdf). There are very few Herb-drug interaction reported up till now but they can’t be ignored as patients who are not aware about the adverse effects that can possibly occur due to concurrent administration of herbal and OTC drugs whould have to face disastrous consequence  (pharmainfo. Net/reviews/herb-drug  inte -ractions).

The use of herbal remedies for management health is more prominent in the developing world population. In developing countries, herbs have not got status of drug for the treatment of various ailment because of the problems associated with it. The concentrations of active component vary widely from one formulation to another. The problem associated with the development of herbal medicine includes presence of quite a lot of active ingredients, with fairly dissimilar pharmacological profiles, lack of quality control, lack of government regulations regarding safety and efficacy, insufficient clinical trials, and inadequate information on the adverse effects and drug-herbal interactions. Some preparations may not contain any active ingredient and the most important evidence for efficacy of a particular product may be scanty and wholly unreliable. Most of the developed countries have not given status to the herbs as medicine. Like in United States of America and Canada, herbs are currently classified as botanical or dietary supplements (Rai Amita et.al. 2012 ).

Currently, herbal products are regulated by the Dietary Supplement Health and Education Act (DSHEA) of 1994. Under DSHEA, herbal products and other dietary supplements (including vitamins, minerals, amino acids, enzymes, and organ tissues) are not regulated by the FDA as conventional prescription or over-the-counter medications or as food additives. Accordingly, the FDA has the burden of proving that a supplement is harmful rather than requiring that the manufacturer prove that the supplement is safe or effective. In addition, manufacturers are responsible for labelling of dietary supplements. Under the DSHEA, any claim that a supplement can prevent, treat, or cure a specific disease, as well as information regarding herbal-drug interactions is prohibited on the label. (Chavez Mary L. 2005).

HERBAL DRUGS WITH REGARD TO INDIA:
India is extremely rich in natural wealth and the knowledge of traditional medicine and the use of plants as a source of medicine is a native and an essential component  of the healthcare system. Herbal drugs constitute a major part in all the traditional system of medicine. Plants have been used for medicine from immemorial. There has been an exponential growth in the ground of herbal medicine in the last few decades, especially in developing and developed  countries. India has been referred to as the 'Medicinal Garden of the world' because; nature has given immense wealth of medicinal plants to our country.  Medicinal plants and herbal drugs have played a key role in world health According to world health  organization (WHO), about 80% of the world population  currently utilizes the herbal drugs. People are using herbal medicines from centuries for safety, efficacy,  cultural acceptability, non-toxic, lesser side effects and easily available at affordable  prices. In recent  times, there has been a move in universal trend from synthetic to herbal medicine due to side effects of synthetic  products. We can also say it 'Return to Nature'.

India has more than 45,000 plant species and it is one among  twelve huge biodiversity centers. Due to occurrence of 10 vegetative zones, 15 biotic provinces and 16 different agro-climatic zones, India's diversity is matchless. The country has 1,600 lichens, 1,800 bryophytes, 2,500 algae, 15,000-18,000 flowering plants, 23,000 fungi and 30 million micro-organisms. About 1500 plants with medicinal uses are mentioned in ancient texts and around 800 plants have been used in traditional medicine. The utilization of herbal drugs is on the flow and the market is growing step by step. The annual turnover of the Indian herbal medicinal industry is about Rs. 2,300 crore as against the pharmaceutical industry's turnover of Rs. 14,500 croreswith a growth rate of 15 percent.

The export of medicinal plants and herbs from India has been quite substantial in the last few years. India is the second largest producer of castor seeds in the world, producing about 1,25,000 tonnes per annum. The major pharmaceuticals exported from India in the recent years are isabgol, opium alkaloids, senna derivatives, vinca extract, cinchona alkaloids, ipecac root alkaloids , solasodine, Menthol, rauwolfia guar gum, Jasmine oil, agar wood oil, sandal wood oil, etc . The turnover of herbal drugs/medicine in India as over-the-counter products, ethical and classical formulations and home remedies of traditional systems of medicine is about $ 1 billion and export of herbal crude extract is about $ 80 million . It is reported that the herbal drug market in India is about $ 1 billion. Some of the medicinal plants, whose market potential is very high are: Aconitum ferox (Ranunculaceae), Aconitum heterophyllum (Ranunculaceae), Allium sativum (Liliaceae), Azadirachta indica (Meliaceae) andrographis paniculata (Acanthaceae), Asparagus recemosus (Liliaceae), Berberis aristata (Berberidaceae), Commipphora weightii (Burseraceae), Crocus sativus (Iridaceae), Nardostachys jatamansi (Valerianaceae), Embelica officinalis (Euphorbiaceae), Garcinia camboga (Guttiferae), Gymnema sylvestre (Asclepiadaceae), Holarrhena antidysenterica (Apocynaceae), Ocimum teniflorum (Labiatae), Picrorhiza kurroa (Scrophulariaceae), Plantago ovata (Plantaginaceae), Saraca indica (Leguminosae), Saussurea costus (Asteraceae), Solanum nigrum (Solanaceae), Tinospora cordifolia (Menispermaceae), Withania somnifera (Solanaceae) . People's faith in herbal drugs is reflected by a whooping turnover of rupees 450 crores annually, in herbal market. Besides, a healthy 11 % annual growth rate and increasing export potential has attracted several large and medium scale pharmaceutical industries and even some multinationals to jump on to the band wagon. ( Tyagi Lalit K. et.al.2010) .

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Mechanism of herb drug interactions :
All the herbs interact with drugs to either cause side effects or produce additive effects, the concern rises to observe cases where herbs produces side effects as they can implicit major problems to already ill patient. Herbs interact with drug pharmacodynamically or pharmacokinetically or sometimes by both ways. Pharmacokinetic interactions result in alterations of drug or natural medicine absorption, distribution, metabolism or elimination thereby affecting drug action quantitatively. Pharmacokinetic interactions are more complicated and difficult to predict because the interacting drugs often have unrelated actions; the interactions are mainly due to alteration of absorption, distribution, metabolism, or excretion, which changes the amount and duration of a drug's availability at receptor sites. Pharmcodynamic interaction alters the way herb or drug interacts with receptor thereby producing toxic or pharmacological actions. (pharmainfo.net/reviews/herb-drug interactions).

Pharmacokinetic Interactions: These interactions take place when an herbal drug changes the absorption, distribution, metabolism, protein binding, or excretion of a drug that results in altered levels of the drug or its metabolites. Most of the pharmacokinetic drug interactions involve oxidative metabolism by the cytochrome P-450 system (CYF) or by the effect of herbal on the efflux drug transporter P-glycoprotein. The CYF system is a family of monooxygenase enzymes that are mainly found in intestinal and liver cells and catalyzes several Phase I metabolic processes, including oxidation, hydroxylation, S- and O-demethylation and oxidative deamination of more than 70% of prescription drugs.

Absorption: The term Absorption is describes the process of the physical passage of herbs or drugs from the outside to the inside. The majority of all absorption occurs in the intestines, where herbs or drugs must pass through the intestinal wall to enter the bloodstream. Several mechanisms may interfere with the absorption of drugs through the intestines. The absorption of herbs may be adversely affected if they are administered with drugs that may promote binding in the gastrointestinal tract. Herb absorption may be adversely affected in the presence of drugs that change the pH of the stomach. Drugs that affect gastrointestinal motility may also affect the absorption  of herbs. Slower gastrointestinal motility means the herbs stay in the intestines for a longer period of time, thereby increasing the potential absorption. Conversely, more rapid gastrointestinal motility means the herbs stay in the intestines for a shorter time, which may decrease absorption.


[FIGURE:  DOSE-EFFECT RELATIONSHIP STDY]

(Katzung G.Bertram et.al. 2009)

Distribution: Distribution refers to the process in which herbs or drugs are carried and released to different parts of the body. After absorption, herbs or drugs need to be presented to the affected area to exert their effect. Interactions occur during the distribution phase if the drug has a narrow range of safety index and is highly protein-bound. For example, Coumarin (warfarin) is an anticoagulant medication that is very highly bound to protein and has a very narrow range of safety index.

Metabolism: In most cases, drugs that stimulate greater liver metabolism do not exert an immediate effect. The metabolism rate of the liver changes slowly, over several weeks. Therefore, the effect of accelerated liver metabolism is not seen until weeks after the initiation of drug therapy. Once metabolized by the liver, most of the herbs and drugs become inactive derivatives. The rate at which the liver metabolizes a substance determines the length of time it stays active in the body. If the liver was induced to speed up its metabolic rate, herbs and drugs would be deactivated at a more rapid pace and the overall effectiveness of ingested substances would be lower. On the other hand, if the liver was made to slow down its metabolism, herbs and drugs would be deactivated at a slower pace and the overall impact of the substances would be greater.

Elimination: One more possible mechanism for producing herbal-drug interactions is modifying in renal clearance of a drug. Herbals that can inhibit tubular uptake or in other ways that can interfere with the renal clearance of a drug should be considered as having potential to produce pharmacokinetic herbal-drug interactions. The liver neutralizes incoming drugs and herbs, the kidneys are responsible for eliminating the substances and their metabolites  from the body. ( Tyagi Lalit K. et.al.2010)

REFERENCES
1.    Ashraf, Rizwan et.al.(2011) Garlic ( Allium sativum ) supplement with standard Antidiabetic agent provides better Diabetic control in Type-II Diabetes patients. Pakistan Journal of Pharmaceutical sciences.24(4), pp.565-570.
2.    Izzo, A.Angelo et.al.(2009) Interactions Between Herbal medicines and Prescribed drugs-Review Article. Adis Data information. 69(13), pp.1777-1798.
3.    Herb- Allopathic drug interactions. Maharashtra State Pharmacy Council’s Drug Information Center. mspcindia.org/Download/Docs/Drug%20interaction%20with%20herbs.pdf [Accessed on 24/5/2012]
4.    Herb-Drug interactions. pharmainfo.net/reviews/herb-drug interactions [Accessed on 24/5/2012]
5.    Rai, Amita et.al. (2012) . Interaction of Herbs and Glibenclamide: A Review. International Scholarly Research Network (ISRN Pharmacology). pp.  1-5.
6.    Chavez Mary, L. (2005) Herbal-Drug Interactions. Internet Continuing Education-InetCE (9), 1-30.
7.    Tyagi Lalit, K. et.al.(2010) Herb-Drug interactions : Emerging Threat and Their management. Botany Research International 3(1), 1-13.
8.    Katzung, G. Bertram et.al. (2009) Basic & Clinical Pharmacology.11th edition. McGraw-Hill Medical, p. 50.

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