Learning Drug-Herb Interactions 101

Drug-drug interactions is referring to the changes in the effect of one drug in the presence of another drug. It is usually described as an increase or decrease in the action of either substance, or associated with an adverse effect that is not normally associated with either drug.

Drug interactions are usually categorised into three broad classes of underlying mechanisms:

• Pharmacodynamic interactions occur between drugs with similar or opposite pharmacological effects. The underlying mechanisms include competition at molecular or cellular sites of action.

• Pharmacokinetic interactions occur when one drug alters the absorption, distribution, metabolism or excretion of another drug.

• Pharmaceutical interactions relating to chemical or physical incompatibility between the drug preparations.

In pharmacodynamic interactions, one drug alters the sensitivity or responsiveness of tissues to another drug by having the same (agonistic) or a blocking (antagonistic) effect. These effects usually occur at the receptor level but may occur intracellularly. Hence, in pharmacodynamic interactions, drugs influence each other’s effects directly.  Let's explore further.

In pharmacokinetic interactions, a drug usually alters absorption, distribution, protein binding, metabolism, or excretion of another drug. Thus, the amount and persistence of available drug at receptor sites change. Let's look at how interactions can affect drug absorption.

Drug interactions can occur at the distribution phase of pharmacokinetics. Different drugs will have different distribution patterns and rate. Distribution depends on lipid solubility and blood flow to specific tissues. Let' s explore the interactions that may affect or alter drug distribution.

There are two major pathways of drug elimination are drug metabolism and drug excretion. These pathways are important to convert drugs which are usually lipophilic to metabolites which are water soluble (hydrophilic or ionised). Drug-drug interactions can slow or increase these processes can can lead to either toxicity of loss of pharmacology or therapeutic effects. Let's explore how interactions of the drug metabolism can occur.

At the level of drug excretion, a drug can affect another drug's excretion by various mechanisms, including affecting the reabsorption or tubular secretion of another drug. Let's explore the mechanisms and the drug transporters involved in the process.

Pharmaceutical incompatibility is the interaction between drug or substances with excipients, resulting in their physical and chemical properties change and thus affects the stability and pharmacological properties of the medicine. In resolving the issue of compatibility of substances in a formulation, it is crucial to take into account not only the therapeutic effect of the ingredients, but also their physical and chemical properties and the possibility of interaction with excipients or other substances. Let's learn more about this.

The principles of drug-herb interactions are similar with drug-drug interactions. Herbal components are capable of interacting pharmacodynamically or pharmacokinetically with drug substances.

Let's look at some of the herbs and supplements that are commonly implicated in drug-herb interactions.

Let's look at the common drug-herb interactions with antidiabetic drugs.

The use of herbal medicines among patients under cardiovascular pharmacotherapy is widespread and more common than expected. Drug-herb interactions are prevalent when cardiovascular medications with a narrow therapeutic index, such as digoxin and warfarin, are co-administered with herbs which can potentiate or reduce pharmacologic effects, and or affect the  pharmacokinetics (ADME) of the drugs. This can be especially important in vulnerable patient populations such as the elderly, chronically ill and compromised immune systems.

Some herbs, including garlic, ginkgo, ginseng, and St John's wort, can have a significant influence on concurrently administered drugs.  Hence, health care professionals are responsible in probing patients about their use of herbal products. They should have a good knowledge base about herbal remedies and should inquire about their use, discuss adverse effects, and monitor and identify possible herb-drug interactions.

A large number of herbal remedies are used by cancer patients for treating the cancer and/or reducing the toxicities of chemotherapeutic drugs. Some herbal medicines have shown potentially beneficial effects on cancer progression and may reduce chemotherapy-induced toxicities. However, there is lack of scientific basis for the clinical use of these herbal medicines in cancer management and almost none of these plant medicines have been tested in rigorous clinical trials.

Let's look at some of the herbal medicine that may interact with chemotherapeutic or anticancer agents.

Solid organ transplant recipients depend on long term immunosuppressive drugs to prevent organ rejection. However, the same patients may require other drugs or may consume herbal supplements to treat underlying or concurrent diseases. Any drugs or herbal medicine capable of altering the plasma drug concentration of these immunosuppressant agents can lead to serious complications, such as infection and toxicity due to over-immunosuppression or acute organ rejection due to under-immunosuppression.

There are a number of herbal medicine which may interact with common immunosuppressant agents.

Although some safety data are required for herbal/botanical product registration, unfortunately not for drug-herb interactions data. Hence,  in vitro or clinical evaluations were not needed prior to these categories of product registration, unlike the conventional pharmaceutical agents.

The current challenges with drug-herb interactions data include:

• Herbal products frequently consist of multiple constituents.

• Modulation of drug metabolizing enzymes and transporters by herbal products can reflect interactions with one or more herbal product constituent in the product.

• Lack of knowledge of the pharmacokinetics of the herbal product or components of the herbal product.

• Drug-herb interactions data are not mandatory for product registration in most countries

• Most drug-herb interactions are based on isolated in vitro and in vivo studies and published case reports.

However, there are various drug-drug or drug-herb interactions database you can use to search for a potential interaction between a drug and a herbal medicine. Try to explore!