Herb-Drug interactions

Ms.Nazneen Ratlamwala

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 own¹.

Not many people know that herbs that are regarded as safe can also interact
wit allopathic medicine and can cause adverse effects by either potentiating
the pharmacological action or reducing the therapeutic efficacy².
There are very few herb drug interaction reported up till now but they cannot
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 would
have to face disastrous consequences. In china the combination of herbs and
drugs to treat certain diseases is intentional.

According to them, herbs reduce side effects of drugs and help them to perform
better³.  Hence with such kind of mental block, little has been
devoted to investigate about herb-drug interaction. This article emphasizes
over the role of pharmacist to curb such interaction and educate the patients
by providing valuable information about the possible interaction between the
drugs and herbs that they are administering for their welfare.

Herbs and their interaction with allopathic drugs -:

Examples of herbal supplements that may possibly produce harmful side effects when used in combination with certain types of medications include: Aloe, Black cohosh, Bilberry leaf, Chamomile, Dong quai, Danshen, Echinacea, Ephedra, Fish oil, Feverfew, Garlic, Ginger, Ginkgo, Ginseng, Goldenseal, Green tea, Guarana, Licorice, Kava, Milk thistle, Scotch broom, St. John's wort, Vitamin E⁴.

Table 1.1- Herbs pharmacological action and their interaction with
allopathic drugs^{5, 6}

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. Pharmacodynamic interaction alters the way herb (or drug) interacts with receptor thereby producing toxic or pharmacological actions⁷.

Beginning with pharmacokinetic interactions, which alter drug’s absorption, metabolism and elimination, mechanism of herb-drug interaction can be clearly outlined by citing few examples and case reports. Herbs with laxative action used for treating diarrhea e.g. senna, aloe vera, cascara, rhubarb, etc interfere with intestinally absorbed drugs by speeding up intestinal transit thereby decreasing their absorption and consequently their therapeutic effect. Pharmacokinetic interactions often occur as a result of activity changes of drug-metabolizing and transporting proteins, especially cytochromeP-450 (CYP) isoenzymes and P-glycoprotein (P-gp). The activity of these enzymes and drug transporters can be enhanced or inhibited by synthetic drugs as well as by natural products. Metabolism of drug occurs in liver and any interference in enzyme function that participates in drug or herb metabolism can increase or decrease the plasma concentration of drug producing toxic effects. St. John’s wort is an example of an inducer, by increasing the rate of metabolism of indinavir; the blood levels and effectiveness of indinavir may be decreased. Drugs used against anxiety, depression, insomnia, cardiac arrythmia etc are all metabolized in liver. Hence all the drugs that are primarily metabolized by liver are susceptible to such interactions and should be taken with utmost care. Drug interactions due to alterations in elimination of drugs through the kidney can only occur if a drug is primarily eliminated from the body through the kidney. If a drug or herb causes decreased kidney function, levels of the drugs eliminated through the kidneys may be increased as a result. Herbs that have sedative properties, such as kava, nettle and sage may increase the sedative effects of some sleeping medications. Herbs that have antiplatelet activity, such as ginkgo biloba, ginger, ginseng, and garlic may increase the risk of bleeding in patients taking traditional drugs with antiplatelet activity or blood thinners. Herbs that can increase blood pressure, such as blue cohosh, ginger, licorice and bayberry can interfere with the effectiveness of drugs used to treat high blood pressure. These are pharmacodynamic interaction⁸.

Role of pharmacist in preventing herb drug interaction-:

Pharmacist can play a vital role in preventing drug herb interaction to occur by appropriately dispensing medicine and taking due care of patient’s history and medication profile. In order to ensure that the drugs that he is dispensing to the patient are safe and will not cause any interaction, he should ask following questions:

• Are you taking an herbal product, herbal supplement or other "natural remedy?"
• If so, are you taking any prescription or nonprescription medications for
  the same purpose as the herbal product?
• Have you used this herbal product before?
• Are you allergic to any plant products?
• Are you pregnant or breast-feeding?

Make sure your pharmacist and your doctor(s) know about every drug you are taking, including prescription and nonprescription drugs, herbal products, and any dietary supplements, including vitamins and minerals; Only take medication that has been specifically prescribed for you by your physician; Medication must be taken properly to ensure its safety and effectiveness; Unless otherwise instructed, take medicine on an empty stomach to achieve a faster onset of action; When taking medicine with food or around a meal time is not recommended, take medicine one hour before meal/food or two hours after meals or eating food; Take your medicine with a full glass (1 cupful or 8 oz.) of water; Avoid concurrent use of alcohol with medicine; Avoid consuming excessive quantities of chocolate and beverages containing caffeine coffee,tea,colas);and If you have any questions or concerns about your medicine or you believe you are having an adverse drug reaction or drug interaction, consult your pharmacist or physician immediately. If there is a problem, your pharmacist can contact your physician, who can prescribe other medication to avoid the risk of drug- related problems.

Hence patients prescribed with certain “known herbs” which are likely to produce interaction with conventional drugs should be periodically monitored. Interactions reported earlier can help to avoid their concurrent use.

Clinical Management:

Clinical management of drug-drug interactions should include prospective and concurrent patient-, disease-and drug-monitoring measures that are sensitive enough to alert the pharmacist or healthcare provider to monitor specific patient-, disease- or drug-therapy parameters and, whenever possible, correlate these findings with clinical laboratory tests. Follow-up monitoring of a patient’s therapy and making appropriate adjustments in the drug regimen can circumvent potentially significant drug interactions. Patients at high risk for drug interactions who also take drugs with a narrow therapeutic index should be monitored more closely for drug interactions, especially when a new drug is added or discontinued. Depending on the drugs in question, likely drug interactions will generally occur within a few days following a change in drug regimen. If two drugs have been identified as having high potential to interact and cause harm, the pharmacist can contact the patient’s physician to obtain an order for another medication that will not cause the troublesome interaction. In some instances a patient’s diet or lack of adherence to a specified diet may be part of the problem. These situations may require the assistance of a dietitian to resolve^{9, 10,11}.

In addition to the above guide, it is possible to predict when herb/drugs interact by knowing their pharmacokinetic properties, and their pharmacodynamic behaviors. 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) and interfere with the 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. In summary, patients should not try to mix drugs that have a narrow therapeutic range (digitalis, theophylline, lithium, and warfarin) with potassium lowering herbs (licorice, and aloe), herbal stimulants (ephedra, caffeine, guarana, green tea), and antiplatelet herbs (Ginkgo, bilberry leaf, ginger, black cohosh, and Chamomile).

Herbs can also interact with food and pharmacist should also consider diet
of the patient and counsel the patient about probable interactions.

Most commonly occurring interaction between food and herb are:

• Monoamine oxidase inhibitors interact with compounds containing tryptamine
  like cheese and as it is known that ST. JOHN’S WORT have antidepressant properties
  like MAO inhibitors, it should be avoided.
• Milk should not be taken with aloe, as it doesn’t mix well with laxatives.
• Oatmeal interferes with absorption of digoxin, making it ineffective in
  therapeutic dosage.
• Licorice increases level of digoxin 4 times and may precipitate adverse
  events^{12, 13}.

Reported cases of herb-drug interaction-:

Danshen-: Interaction of danshen with warfarin was reported in 48 year old woman suffering from rheumatic heart disease, leading to abnormal clotting profile (prothrombin time (PT) was greater than 60 seconds and international normalized ratio (INR) was 5.62) ¹⁴.

Kava-: A 54-year-old man was admitted in comatose state as he was taking
kava and alprazolam together.Kava like alprazolam has sedative and calming action
¹⁵.

St john’s wort-: A 50-year-old woman taking paroxetin and St John wort complained of lethargy, weakness, nausea and fatigue¹⁶.

Garlic-: An 87-year-old man reported hematoma after he ingested high amount of garlic along with warfarin¹⁷.

Ginseng-: Due to its monoamine oxidase inhibiting action it leads to psychoactive stimulation. When taken with phenelzine, it was reported in a 64-year-old woman who experienced hallucination and irritability¹⁸.

In the past, very few case reports related to herb-drug interactions were reported, and many of the reactions could only be explained theoretically. Recently, however, there have been several reported cases of possible herb-drug interactions. For clinicians, case reports provide more relevance than theoretical, in vitro, or animal data, allowing them to examine the components of the interaction and their relevance in terms of its onset, severity, and outcome.

Summary-:

Its high time now that patients seeking both ayurvedic and allopathic treatment
remain aware of potential herb-drug interaction and avoid taking medications
which might prove hazardous to their already deteriorating health. This article
provides brief idea about pharmacist can change the present scenario and utilize
their knowledge in providing healthy information about herb-drug interaction. 

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About Authors

Mrs.S.P.Ingale
Lecture in Pharmacology, MAEER’S Maharashtra Institute of Pharmacy, Pune-411038
E.mail-suvarnabhirud@rediffmail.com
Mobile.no-: 9423219990

Ms.Nazneen Ratlamwala* , MAEER’S Maharashtra Institute of Pharmacy, Pune-411038, e-mail : nazkulsum@yahoo.com

*Author for correspondance