Recognition and Prevention of Herb-Drug Interactions, Part 2: Pharmacodynamic Interactions
By John Chen, PhD, PharmD, OMD, LAc
Editor's Note: Part 1 of Dr. Chen's article, including a complete list of references, appeared in the November 2006 issue of Acupuncture Today.
The study of pharmacodynamics gives us insight into the dynamic behavior of drugs inside the human body.
The phrase "pharmacodynamic interactions" refers, in our context, to fluctuations in the bioavailability of ingested substances as a result of synergistic or antagonistic interactions between herb and drug molecules. Pharmacodynamic interactions generally are more difficult to predict and prevent than pharmacokinetic interactions. Most of the currently known pharmacodynamic interactions have been documented through actual cases, not by laboratory experiments. The best way to prevent pharmacodynamic interactions is to follow the patient closely and monitor all clinical signs and symptoms, particularly any abnormal reactions.
A synergistic interaction occurs when two drugs with similar properties show an additive or even exponential increase in clinical impact when given together. An antagonistic interaction occurs when two drugs with similar properties are administered simultaneously and show lessened or no clinical effectiveness. Synergistic or antagonistic interactions might occur with any concurrent use of medicinal substances, regardless of whether they are herbs, drugs or both.
Chinese medicine has tracked cases of herb-to-herb pharmacodynamic interactions for centuries. The concept of synergistic interaction generally is referred to as xiang xu (mutual accentuation) or xiang shi (mutual enhancement), such as takes place in the combination of shi gao (Gypsum fibrosum) and zhi mu (Radix anemarrhenae) to clear Heat and purge Fire. The concept of antagonistic effect usually is referred to as xiang wei (mutual counteraction), xiang sha (mutual suppression) or xiang wu (mutual antagonism), such as happens in the combination of lai fu zi (Semen raphani) and ren shen (Radix ginseng), in which the therapeutic action of the latter herb is decreased by the addition of lai fu zi.
Classic Chinese texts describe numerous other herb-to-herb interactions, such as the shi ba fan (Eighteen Incompatibles) and shi jiu wei (Nineteen Counteractions). Shi ba fan (Eighteen Incompatibles) is a classic list of 18 herb-to-herb interactions. Shi jiu wei (Nineteen Counteractions) is a classic list of 19 herbal combinations in which the herbs counteract each other. Combinations of such herbs likely will lead to adverse side effects and/or toxic reactions.
Shi ba fan (Eighteen Incompatibles) is a list of herbs that are incompatible when combined. The original list contained only 18 herbs, but the list has since been expanded.
Gan cao (Radix glycyrrhizae) is incompatible with:
gan sui (Radix euphorbiae kansui);
jing da ji (Radix euphorbiae pekinensis);
hong da ji (Radix knoxiae);
yuan hua (Flos genkwa);
hai zao (Sargassum).
Fu zi (Radix aconiti lateralis praeparata), chuan wu (Radix aconiti preparata) and cao wu (Radix aconiti kusnezoffii) are incompatible with:
ban xia (Rhizoma pinelliae);
chuan bei mu (Bulbus fritillariae cirrhosae);
zhe bei mu (Bulbus fritillariae thunbergii);
gua lou shi (Fructus trichosanthis);
gua lou ren (Semen trichosanthis);
gua lou pi (Pericarpium trichosanthis);
tian hua fen (Radix trichosanthis);
bai ji (Rhizoma bletillae);
bai lian (Radix ampelopsis).
Li lu (Radix et rhizoma veratri) is incompatible with:
ren shen (Radix ginseng);
dang shen (Radix codonopsis);
nan sha shen (Radix adenophorae);
bei sha shen (Radix glehniae);
dan shen (Radix salviae miltiorrhizae);
xuan shen (Radix scrophulariae);
ku shen gen (Radix sophorae flavescentis);
chi shao (Radix paeoniae rubrae);
bai shao (Radix paeoniae alba);
xi xin (Herba asari).
Shi Jiu Wei (Nineteen Counteractions) consists of 19 herbs combined as 10 pairs that antagonize one another:
liu huang (Sulfur) and po xiao (Sal glauberis);
shui yin (Hydrargyrum) and pi shuang (Arsenolite);
lang du (Radix euphorbiae fischerianae) and mi tuo seng (Lithargyrum);
ba dou (Fructus crotonis) and qian niu zi (Semen pharbitidis);
ding xiang (Flos caryophylli) and yu jin (Radix curcumae);
ya xiao (Nitrum) and san leng (Rhizoma sparganii);
xi jiao (Cornu rhinoceri) and cao wu (Radix aconiti kusnezoffii);
xi jiao (Cornu rhinoceri) and chuan wu (Radix aconiti preparata);
ren shen (Radix ginseng) and wu ling zhi (Excrementum trogopteri seu pteromi);
rou gui (Cortex cinnamomi) and chi shi shi (Halloysitum rubrum).
Pharmacodynamic herb-to-drug interactions are best identified by analyzing the therapeutic profile of the herbs, as well as that of the drugs. Concurrent use of herbs and drugs with similar therapeutic actions poses potential for herb-drug interactions. In these cases, the increased potency of treatment might interfere with optimal outcome, as the desired effect becomes less predictable and harder to obtain with precision. The highest risk of clinicallysignificant interactions occurs between herbs and drugs that have sympathomimetic, anticoagulant, antiplatelet, diuretic and hypoglycemic effects.
Herbs that exert sympathomimetic effects might interfere with antihypertensive and antiseizure drugs. The classic example of this type of herb is ma huang (Herba ephedrae), containing ephedrine, pseudoephedrine, norephedrine and other ephedrine alkaloids. Ma huang might interact with other drugs and disease conditions, and always should be used with caution in patients vulnerable to hypertension, seizures, diabetes, thyroid conditions and similar regulatory imbalances.
Herbs with anticoagulant and antiplatelet effects include herbs that have blood-activating and blood-stasis-removing functions, such as dan shen (Radix salviae miltiorrhizae), dang gui (Radix angelicae sinensis), chuan xiong (Rhizoma ligustici chuanxiong), tao ren (Semen persicae), hong hua (Flos carthami) and shui zhi (Hirudo). These herbs might interfere with anticoagulant and antiplatelet drugs, including warfarin (Coumadin), enoxaparin (Lovenox), aspirin, dipyridamole (Persantine) and clopidogrel (Plavix). Without proper supervision, concurrent use of these herbs and drugs might lead to prolonged and excessive bleeding. Thus, individuals taking anticoagulant or antiplatelet drugs must be very cautious about concurrently using herbs, and would be wise to do so only under the supervision of well-trained health care professionals.
Concomitant use of diuretic herbs and diuretic drugs might create additive or synergistic effects, making hypertension more difficult to control or hypotensive episodes more likely. The dosage of herbs and/or drugs must be adjusted to achieve optimal treatment outcome. Commonlyused diuretic herbs include fu ling (Poria), zhu ling (Polyporus), che qian zi (Semen plantaginis), and ze xie (Rhizoma alismatis).
Herbs with hypoglycemic effects might interfere with antidiabetic drugs by accentuating the decrease of plasma glucose levels. The dosage of these herbs and drugs must be balanced carefully to effectively control blood glucose levels without causing hyper- or hypoglycemia. Herbs with definite antidiabetic effects include the following pairs of herbs: zhi mu (Radix anemarrhenae) and shi gao (Gypsum fibrosum); xuan shen (Radix scrophulariae) and cang zhu (Rhizoma atractylodis); shan yao (Rhizoma dioscoreae) and huang qi (Radix astragali).
SUMMARY OF PHARACO-DYNAMIC INTERACTIONS
Understanding synergistic and antagonistic interactions from both a Chinese medicine perspective and the realm of pharmaceutical medicines helps practitioners to anticipate, prevent and/or monitor for unwanted interactions in patients who need or elect to rely on multiple therapeutic substances.
SUMMARY: CONCURRENT USE OF HERBAL MEDICINES AND PHARMACEUTICALS
Historically, herbs and drugs have been presumed to be very different treatment modalities that have rarely, if ever, been used together. The line that separates the use of herbs and drugs, however, has blurred in recent decades as the lay public gains increased accessibility to multiple treatment modalities. It's not uncommon for one patient to seek care from several health professionals for an ailment. As a result, a patient easily might be taking multiple drugs, herbs, supplements and vitamins concurrently. It becomes difficult to predict whether the combination of all these substances will lead to unwanted side effects and/or interactions. It's imprudent to assume that there will be no interactions. On the other hand, it's just as unwise to abandon treatment simply for fear of possible interactions. The solution to this situation is in the understanding of pharmacokinetic and pharmacodynamic herb-drug interactions. By understanding these mechanisms, one can recognize potential interactions and take proper actions to prevent their occurrence.
Additional information on herb-drug information can be obtained from the following sources: