• What are Herb-drug interactions???
• Whether they are diagnoised??????
• Are they neglected????
• Any reports?????
• What is the significance????
Need for the study
• Early humans recognized their dependence on nature in
both health and illness.
• The World Health Organization (WHO) estimates that 80
percent of the world population use herbal medicine for
some aspect of primary health care.
• More than 60% Asians resort to herbal products to treat
a variety of recalcitrant chronic disorders such as
anxiety, depression, dementia and memory impairment,
headache, weight loss, etc..
• FDA Recent research estimates 50% of adult Americans
use at least one prescription medication and with that,
16% also take herbal supplements.
• Herbal medicines (HMs) are readily available in the
market from health food stores without prescriptions and
are widely used in India, China, USA and all over the
• According to recent survey the majority of people who
use HMs do not inform their physicians about their
consumptions that can cause abnormal test results and
confusion in proper diagnosis.
• The medical and scientific literature is abundant with
reports suggesting that the concomitant oral
administration of natural products and prescription drugs
or over- the counter products may affect human drug
metabolism and significantly increase the risk for serious
clinical adverse reactions.
Nature of Herb Drug interaction:
• The nature of herb-drug interactions is not a chemical interaction
between a drug and an herb component to produce something toxic.
• Instead, the interaction may involve having an herb component,
causing either an increase or decrease in the amount of drug in the
• Herbs and drugs may interact either pharmacokinetically or
• Many drug interactions are due to alterations in drug metabolism
and drug absorption, thereby altering the bioavailability of the drug.
• One notable system involved in metabolic drug interactions is the
enzyme system comprising the cytochrome P450 oxidases.
• Another major player in herb-drug interaction is the P-glycoprotein
Interacting drug comments
St. John’s Wort Theophyline,
Lower concentration may
cause treatment failure
Garlic Warfarin Increases effectiveness of drug,
Saqinavir Decreases drug effect
Kava Kava Additive effects with CNS
Decreases drug effect
Ginkgo biloba aspirin, warfarin Bleeding, Hemorrhage,
Increases Drug toxicity
Licorice Spironolactone Decreases drug effect
Common herb –drug interactions
Some of the important documented herbs causing interaction
The Cytochrome P450 enzymes:
• Cytochrome P450 is a superfamily of heme-containing mono-oxygenase
enzymes, crucial for the oxidative, peroxidative, and reductive metabolism
of a diverse group of substances. The basic reaction catalysed by CYPs
is the addition of one oxygen atom to the substrate, while the other oxygen
atom is further reduced to water with reducing equivalents derived from
• They are responsible for most of the oxidative metabolism of both
xenobiotics and endogenous substrates.
Role of cytochrome P450 in drug metabolism
• Most drugs are lipophilic and can not be easily eliminated from the body unless they
are metabolised to more hydrophilic derivatives .
• A large number of enzymes exist which metabolise foreign compounds. They have
been classified as belonging to phase I or phase II pathways of metabolism.
• Phase I enzymes include oxidases, hydrolases and reductases, while the phase II
enzymes are all transferases .
• Among the large number of Phase I enzymes, the CYPs (cytochrome P450s) are the
most important superfamily of enzymes which account for the majority of oxidative
biotransformations of xenobiotics and endogenous biochemicals .
• The phase II transferases serve to transfer various water-soluble molecules such as
glucuronic acid, sulfonic acid and glutathione to other chemicals .
• Often, drugs undergo both phase I and phase II reactions sequentially, but excretion
after only one metabolic reaction is also possible.
• Quantitatively, the smooth endoplasmic reticulum of the liver cell is the principal organ
of drug metabolism, although every biological tissue has some ability to metabolize
Relative levels and importance of cytochrome p450 isozymes
Herb-drug interactions involving CYP enzymes
• During the past few years a revolution has
taken place in our understanding of drug
interactions, mostly as a result of
advances in the molecular biology of the
CYP enzyme system. Several factors
directly or indirectly influence the CYP
activity. Many drug interactions are a result
of induction or inhibition of CYP enzymes.
• Many herbal constituents have been reported to inhibit various
CYPs . The nature of inhibition may be competitive,
noncompetitive, or mechanism based. The later is characterized by
NADPH, time and concentration dependent enzyme activation,
occurring when some herbal constituents are converted by CYPs to
reactive metabolites that are capable of irreversibly binding to CYPs
. Mechanism based inhibitors require atleast one cycle of the
CYP catalytic process to form reactive metabolites. The resultant
metabolites lead to CYP inactivation by chemical modification of the
heme, the apoprotein, or both as a result of covalent binding of
modified heme to the apoprotein. An in vitro study indicated that
Licorice, which is used as anti-allergic and anti-inflammatory agents
inactivated CYP3A4 and 2B6 in a time and concentration dependent
manner, but 2C9 is competitively inhibited. Similarly, Clinical
studies have shown that Kava, which is an effective herbal medicine
for the therapy of anxiety and insomnia, inhibited CYP1A2, 2C9,
2C19, 2D6, 3A4 and 4A9.
• Herb-drug interactions involving enzyme induction are not as
common as inhibition based drug interactions but equally profound
and clinically important. The most common mechanism is
transcriptional activation leading to increased synthesis of more
CYP enzyme proteins. Increased metabolism of the affected
drug leads to decreased intensity and duration of drug effects. If the
drug is a prodrug or it is metabolized to an active or toxic metabolite
then the effect or toxicity is increased. It is somewhat difficult to
predict the time course of enzyme induction because several factors
including the half-life of drug and enzyme turnover determine the
time course of induction. Several recent reports provide
evidence that St. John,s wort, an ancient herbal remedy for
antidepressants, promotes the metabolism of coadministrated drugs,
including the HIV protease inhibitor indinavir, the immunodepressant
cyclosporine, and oral contraceptives[27 ]. Because each of these
drugs is metabolised by CYP3A4, these findings suggested that
St.John wort induces CYP 3A4 expression.
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