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Herb-drug interaction

For our purpose, pharmacokinetic properties entail changes in absorption, metabolism, and elimination of the drugs/herbs


 whereas pharmacodynamic behaviors refer to how the herb/drug interacts inside the body (synergistic or antagonistic).


In general, herb/drug that alters the stomach pH (anti-acids), or intestinal motility (laxatives) will have an effect on absorption. Drug/herb metabolism occurs principally in the liver.


The duration (life-span) of an herb or drug in the body depends on whether the liver’s metabolism is induced or inhibited. An herb lasts longer in the body if its metabolism is inhibited by another drug; likewise, it is excreted faster if one’s liver metabolism is induced.


Further, drug/herb elimination primarily occurs at the kidneys and is affected by the individual’s kidneys function or by drugs’ toxic side effects. Lastly, the extent to which an herb-drug interacts depends on the individual’s health condition, age, body weight, metabolic rate, and dosage (11).


Adverse potential

Drug Interactions


Ephedra and MAOI can cause dangerously high blood pressure. FDA proposed a dosage limit of 8 mg every 6 hours (or a total of 24 mg per day) and not more than 7 days of continuous use.

Ephedra, by itself, is not recommended for most people. It is never used alone in TCM

MAOI, caffeine, decongestants, stimulants

Ephedra Sinensis

(Cao Mahuang, Ma huang, Yellow astringent)

Dong Quai is safe for most adults. Women who are pregnant or breast-feeding should not take it without consulting their healthcare provider.

Women with hormone sensitive cancers such as breast, uterine, or ovarian cancer and those with endometriosis or uterine fibroids should also exercise caution.


Dong Quai

(Angelica Sinensis, Dong Gui, Chinese Angelica, Tan Kuei)

Primary use: It is most often used in oriental medicine for menstrual problems.

Dong Quai can also be widely found in traditional formulation for pain.

Decreases warfarin clearance and increases its bioavailability. Case report of hemorrhage.


Danshen (Salvia miltiorrhiza)

Primary usage: promotes blood flow and treat cardiovascular diseases i.e. angina pectoris, acute MI.

Primary actions: scavenges free radicals, inhibit platelets aggregration, and promote vasoactive.



Use of ephedrine and caffeine for weight loss


ephedrine (E) and caffeine (C) have been combined to make a pharmaceutical drug (EC) for treating obesity, and this EC combination was developed in Denmark according to strict pharmacologic research standards. Although some adverse events have been associated with the use of dietary supplements containing both E and C, most of them were related to misuse and abuse, according to the author.

Furthermore, ephedra (Ephedra sinica), which contains the alkaloids ephedrine,

pseudoephedrine, and norephedrine, has been used for thousands of years in traditional Chinese medicine as a potent but safe decongestant and bronchodilator. The importance of this herb is highlighted by the fact that pseudoephedrine is an ingredient in most over-the counter (OTC) medications for cold, flu, and sinus symptoms. Despite this history, several states banned the selling of ephedrine and ephedra in dietary supplements, and the Food and Drug Administration (FDA) also banned ephedrine in all dietary supplements in April 2004. In this op-ed article, the author considers whether this ban on ephedrine in weight-loss

products is appropriate and supported by sufficient scientific evidence.



Over 30 clinical studies of the use of EC combinations (both pharmaceutical and herbal

preparations) in humans have been conducted, and they show that when EC is used as

directed, it is safe and effective. For example, in a randomized, double-blind, placebo controlled trial, the use of herbal ephedra–caffeine for six months led to weight reduction and improvement in blood lipid concentrations without significant adverse effects.1 Similarly, the use of EC in combination with aspirin was found to safely and effectively promote weight loss both in nonexercising patients and in patients whose energy intake was not restricted.2,3 In another randomized, double-blind, placebo-controlled study, the effects of diet plus either EC, ephedrine alone, or caffeine alone were studied; EC was found to be an effective treatment whereas ephedrine and caffeine by themselves were ineffective.4



Although all of these studies were performed in adults, another randomized, double-blind,

Placebo-controlled trial in adolescents showed that EC is a safe and effective treatment for obesity in this population also. None of the reviewed studies found any serious side effects related to the use of EC as an ant obesity drug. Finally, all of the studies concluded that EC is a safe and effective weight-loss treatment in overweight and obese persons who are otherwise healthy.




In summary, the results of numerous double-blind, placebo-controlled studies indicate that

for overweight and obese adults and adolescents, the use of EC as directed is a safe weight loss treatment that is not associated with significant side effects.


Although ephedrine abuse can lead to serious and even deadly side effects, the statistics associated with such abuse pale in comparison with those associated with the abuse of ibuprofen, paracetamol (acetaminophen), and aspirin. Yet these OTC products remain in the marketplace whereas ephedrine is banned. This ban was enacted even though a panel of experts convened by the FDA concluded in 1997 that the use of improved warning labels on ephedrine-containing products rather than a ban was the most appropriate course of action. The author also cites a review6 that showed that the FDA misinterpreted the adverse-reaction data for ephedrine.



Licorice (Glycyrrhiza glabra) contains glycyrrhizin,

which inhibits 11b-dehydrogenase, 5a-reductase, and

5b-reductase. Glycyrrhizin is metabolized largely to

glycyrrhetinic acid (an even more potent inhibitor of

5a-, 5b-reductase and 11b-dehydrogenase). Liquorice

has been shown to increase plasma concentrations of

prednisolone [22, 23]. It also potentiated the cutaneous

vasoconstrictor response of hydrocortisone [24]. Licorice

is a common herb in Chinese and Japanese herbal

mixtures. The effect of several such mixtures on

prednisolone concentrations has been tested. Both Shosaiko-

To and Xiao Chai Hu Tang decreased the plasma

AUC of prednisolone [25] whereas Saiboku-To increased

it. Sairei-To did not affect it [26]. Both Sho-saiko-To

and Rikkunshi-to were found not to affect the pharmacokinetics

of a single oral dose of o¯oxacin [26]


St John's wort affects the clearance of many drugs,

including cyclosporin, antidepressants (predominantly

SSRIs), digoxin, indinavir, and phenprocoumon. The

underlying mechanism appears to be multifactorial. There

is evidence of a strong interaction with P-glycoprotein

(PgP), an ATP-dependent drug ef¯ux transporter known

to pump drugs out of the cell membrane, thus decreasing

intracellular concentrations [27]. St John's wort increases

expression of duodenal PgP/MDR1 [28]. The herb also

induces the activity of an important form of cytochrome

P450, CYP3A4. However, results of studies of the

effect of St John's wort on CYP3A4 are con¯icting.

While three enzyme marker studies indicated a potent

inducing effect of St John's wort (300 mg three times

dailyr14 days) on CYP3A4 activity [29, 30], two others

found no effect (both 300 mg three times daily, one for

3 days [31], the other for 8 days [32]) on CYP2D6 or 3A4

activities. It is possible that the negative trials were simply

too short in duration. Alternatively, differences in quality

of the HMPs used might explain the discrepancy. One

study examining the effect of St John's wort on CYP1A2

activity (using a caffeine/dextromethorphan probe) found

that it (300 mg three times daily for 8 days) had no effect

on 17 DMX/caffeine ratios [33], indicating that this

HMP has a low potential for drug interactions involving

CYP 1A2.


Cases of serotonin syndrome could arise if St John's

wort increased serotonin levels. However, it cannot be

considered an SSRI, because in vitro, St John's wort

inhibits the uptake of serotonin, noradrenaline and

dopamine only at high concentrations with IC50s of

2.4, 4.5, and 0.9 mg mlx1, respectively [34] which are

unlikely to be achieved with oral dosing. However,

enough cases of interactions with SSRIs have been

reported that a serotonergic (or serotonin-amplifying)

effect of St John's wort could occur.

There is reasonable documentation of interactions

between coumarin anticoagulants and St John's wort,

danshen, dong quai, ginseng, and ginkgo [35]. Most of

these case reports are probably not true interactions but

result from additive anticoagulant effects. Dong quai

contains coumarins, and would be expected to augment

the effects of a coumarin-derived anticoagulant. Ginkgo

and garlic interfere with platelet function, and have been

associated with bleeding even in the absence of warfarin

or other anticoagulant treatment. Danshen also interferes

with platelet function but appears to decrease the elimination

of warfarin at least in rats [37]. In a recent case

report, the INR of a patient taking warfarin who drank

0.5±1 gallon of green tea (Camellia sinensis) was seen to

decrease [36].

Inadequate reporting makes it dif®cult to determine

whether a herb±drug interaction has occurred. Authors

should be required to document all relevant information

(see above). The adverse event should be clearly

described, alternative explanations should be explored and

a rechallenge should be considered. The HMP should

be analysed to ascertain the contents of the product. Even

well-documented case reports can only serve as a critical

early warning system.

Herb±drug interactions occur but are under-researched.

In many cases there is no plausible mechanism to explain

the observed phenomena and causality is uncertain.

Patients taking St John's wort or anticoagulants are at

the highest risk of an interaction. Patients on coumarin

anticoagulants should be speci®cally advised to avoid

taking herbal medicines or to have their INR measured

within 2 weeks of starting the product. Patients

taking garlic, ginkgo, danshen, or other HMPs affecting

platelet function should also be monitored. The

risks of combining St John's wort with drugs or

anticoagulant drugs with herbal medicines should be

publicised further.

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