Effects of Herb Drug Interactions Essay

Effects of Herb Drug Interactions Essay

Twenty articles were considered, majority of which discussed St. John’s wort. Among the articles, the mechanism of interaction was pharmacokinetic in nature. The cytochrome P450 (CYP) enzymes and the P-glycoprotein transporter were induced by the herbs’ active components. Since these proteins are important in the metabolism of majority of drugs, interfering with their activity by the herbs results to an increased or decreased uptake of drugs. Since herb-drug interaction is highly likely, government health, and food and drugs sectors should start regulating herbal products, and health care practitioners should be aware of such interactions so that they could advise their patients about it.
Herbal medicines are plants and its parts that are used for their scent, flavor, and/or therapeutic purposes. They contain varying amounts of active components that influence their beneficial properties.Effects of Herb Drug Interactions Essay.  The Food and Drug Administration classify them as dietary supplements; hence, no regulations are placed upon the products (Bressler, 2005).
Herbal medication use has been steadily increasing globally. In the United States (US), the use of self-prescribed medication increased from 2.5% in 1990 to 12% in 1997, while patients consulting herbal medicine practitioners increased form 10.2% to 15.1%. Reasons for using herbal products include 1) efficacy and safety outlook, 2) accessibility since it is a non-prescription drug, 3) idea that it is organic, 4) desperation and dissatisfaction with conventional drugs, and 5) lower cost (Bressler, 2005). Despite using herbal products, only half of the users notify their doctors about it (Foti, wahlstrom, & Wienkers, 2006).
With the growing number of users of herbal products despite the non-regulation by the Food and Drug Administration, a lot of health institutions are bothered of the possible effects of herbal products on users, especially on herb-drug interaction. Effects of Herb Drug Interactions Essay.


Approximately 70% of the world’s population has been using medicinal herbs as a complementary or alternative medicine that has grown tremendously in both developed and developing countries over the past 20 years (World Health Organization Drugs Strategy 2002–2005). This increase in consumer demand for medicinal plants continues, although scientific data are rare to create safety and efficacy profiles. Its popularity is also related to easy availability, cost-effectiveness leading to better purchasing power, and various factors that perceive that they are generally safe. Herbs are often administered simultaneously with therapeutic drugs for the treatment of major ailments, and herb-drug interactions (HDIs) increase their potential. The main routes proposed for HDIs include cytochrome P450 (CYP450)-mediated inhibition or induction and transport and flow proteins. In our review, we highlighted herbal medicines used for the treatment of various diseases with pharmacokinetic, pharmacodynamic analysis and case reports together with their adverse effects and herb-drug interactions. Therefore, this review can be used as a quick reference database for physicians and healthcare professionals involved in therapy, aiming to maximize clinical outcomes by reducing the negative and toxic effects of plants along with avoiding herb-drug interactions.


  • herbs/plants
  • herbal products
  • natural products
  • drugs
  • interactions
  • toxicity

Herbal products are considered the best choice as complementary medicine in western countries, especially in the United States and Europe. Annual sales of dietary herbal supplements in the United States increase 6.8% year over year. In addition, China and India are the top export countries, while Hong Kong, Japan, the United States, and Germany are the leading importers. The Confederation of Indian Industry (CII) presented that the market size of the Ayurvedic industry in the country is $ 4.4 billion, and the total market size of the Indian health industry is $ 11.8 billion. There has been an increase in demand for “complementary” medicines, including those of plant origin. In addition, there is a significant increase in the self-administration of herbal medicines among the public. Effects of Herb Drug Interactions Essay. In the context of the growing demand and use of herbal medicines for patients and the public, and the subsequent interests of the regulatory authorities, comprehensive research on the safety and effectiveness of herbal products, including the possibility of interactions when simultaneous application is required, should be encouraged. This is because all herbal medicines and dietary supplements are a complex mixture containing multiple active phyto-components that increase the possibility of herb-drug interaction (HDI). Most people who consume herbal products and supplements do not show this to their pharmacist or doctor, thereby increasing the likelihood of HDI being identified and resolved over time. However, data from recent studies show that there is potential for serious interaction between some commonly used herbs/herbal products and commonly used standard medications [1].

In our review, we highlighted herbal medicines used for the treatment of various diseases with their adverse effects and herb-drug interactions, and stated recommendations for proper use of plants that might prevent possible risks for future incidents.

2. Toxicological risks of plants and herbal products

General risks associated with herbs and/or herbal products include:

  • Misidentification without assigning with Latin names. Possible causes of misidentification include contamination of cultivated plants with weeds, and resembling plants mistaken for herbs collected in the wild.

  • Contamination with harmful substances such as heavy metals, polycyclic aromatic hydrocarbons, dioxins, as well as natural toxins or microorganisms.

  • Interaction with other drugs, such as antagonism or synergism, and medical tests that potentially lead to misdiagnosis.

  • Adulteration with other medicinal drugs.

  • Intrinsic toxicity caused by the presence of natural toxins, such as aristolochic acids [2].

2.1 Nephrotoxicity

The drug or toxin that causes kidney damage when exposed to a certain level cannot pass the excess urine, and the waste product is what is called nephrotoxicity. In this case, there is an increase in blood electrolytes, such as potassium and magnesium. This situation begins temporarily but can be serious if it is not detected before. Blood urea nitrogen (BUN) test and creatinine levels in the blood are two simple tests called as kidney function tests used to detect the nephrotoxicity. For healthy individuals, the normal levels of BUN and creatinine are between 10–25 mg/dl and 0.7–1.4 mg/dl, respectively. The following factors may increase these values:

  1. Dehydration.

  2. Obstruction of blood flow to or from kidney caused by a tumor, stone, or irregular heart rhythms.

  3. Nephritis or urinary tract infection.

  4. The aftermath of diseases such as diabetic neuropathy, congestive heart failure, and enlarged prostate gland in man.

  5. Gastrointestinal bleeding. Effects of Herb Drug Interactions Essay.

  6. Prolonged hypotension.

  7. Protein-rich diets.

  8. Radiocontrast dye injected intravenously to improve visibility.

  9. Drug toxicity with some chemotherapeutics (carboplatin, carmustine, cisplatin, methotrexate, and mitomycin) and biological therapeutic agents (interleukin-2 and interferon-alpha), antibiotics (amphotericin B, gentamicin, and vancomycin), NSAIDs (ibuprofen), diuretics (furosemide), and ACE inhibitors (captopril, benazepril, and enalapril).

  10. Nephrotoxicity after taking herbal medicine.

The cause of nephrotoxicity after taking herbal medicine may be the addition of toxins during careless preparation, addition of adulterants, heavy metals, and some pharmaceutical products intentionally reducing costs or increasing effectiveness [3].

About 50 plants were related to kidney damage case reports published in PubMed in the last 50+ years (from 1966 to May 2016). Herbs include Aristolochia fangchiY.C.Wu ex L.D.Chow & S.M.Hwang, Artemisia herba-albaAsso, Callilepis laureola DC., Cupressus funebris Endl., Ephedra sinica Stapf, Hypericum perforatum L., Taxus celebica (Warb.) H.L.Li, Tribulus terrestris L., and Tripterygium wilfordii Hook.f. Aristolochia species containing aristolochic acid, Aristolochia fangchi, had the highest number of publications (not actual cases) [4].

2.2 Hepatotoxicity

Hepatotoxicity (“Hepar means liver and “Toxiconmeans poison in ancient Greek) implies liver damage caused by medication, chemical, herbal, or dietary supplements. Stomach pain, vomiting, nausea, chance in urine and stool color, rash, jaundice, frequent tiredness, weakness, fatigue, and fever are the main symptoms of the damage. Some liver function tests performed on blood samples allow detecting hepatotoxicity in the laboratory. These tests include alanine transaminase test (normal range 7–55 U/l), alkaline phosphatase test (normal range 45–115 U/l), albumin test (normal range 3.5–5.0 g/dl), aspartate transaminase test (normal range 8–48 U/l), and bilirubin test (normal range 0.1–1.2 mg/dl). Increased ALT, ALP, AST, and bilirubin and decreased albumin levels demonstrate hepatotoxicity. The levels of ALP also increase during pregnancy [3]. Effects of Herb Drug Interactions Essay.

The causes of liver damage are both hepatocellular and extracellular mechanisms such as hepatocyte disruption, transport protein disruption, T-cell activation, hepatocyte apoptosis, disruption of mitochondria, injury of bile duct, drug toxicity, and drug interaction [3].

Drug toxicity mechanisms: drugs are the main cause of hepatotoxicity. About 900 drugs, toxins, and herbs have been reported for hepatotoxicity. There are two types of drug reactions: the first is the reaction that directly affects the liver, called internal drug reactions; and the other is the reaction that mediates the immune response, called idiosyncratic drug reactions. In the first category, the drug itself or its metabolite produces a dose-dependent injury, such as paracetamol and carbon tetrachloride. In the second category, hypersensitivity reactions, for example, phenytoin reaction, cause an immunoallergic or metabolic idiosyncratic reaction due to fever, rash, eosinophilia and indirect drug reaction for a short time. The second reaction type response rate is variable, for example, halothane [3].

Drug interaction mechanisms: when some drugs are taken at the same time, they react together and cause liver damage. For example, the combination of tylenol with INH, histamine, laniazide, and nydrazide can be hepatotoxic [3].

When hepatotoxicity caused by herbal drug intake is discussed, case rates are often reported. The severity of toxicity varies greatly between mild hepatitis and acute liver failure. The scoring system for allopathic drugs can be evaluated, but not suitable for herbal medicines and needs validation. Many Ayurvedic and Chinese herbal medicines are reported to cause hepatotoxicity. The main hepatotoxic herbs are Cimicifuga racemosa (L.) Nutt., Larrea tridentata (Sessé & Moc. ex DC.) Coville, Scutellaria baicalensis Georgi, Scutellaria lateriflora L., Teucrium chamaedrys L., etc. [3].

2.3 Cardiotoxicity

Cardiotoxicity is a term used for damage to the heart or change heart functions. It is a condition where there is a change in the electrophysiological function of the heart or damage to the heart muscle, weakening the heart and causing poor blood circulation. Effects of Herb Drug Interactions Essay.This can be detected by symptoms such as dry, unproductive cough; inflammation in the ankles, hands, feet, and neck vessels; irregular heartbeat; tachycardia; cardiomegaly; weakness; dizziness; etc. [3].

Herbal drugs that have a direct effect on the heart include medicine prepared from plants such as Aconitum napellusL.Atropa belladonna L., Catharanthus roseus (L.) G.Don, Digitalis purpurea L.Ephedra distachya L., Glycyrrhiza glabra L., Mandragora officinarum L., etc. [3].

2.3.1 Potential precautions of plants on hypertension

Herbal products are widely used in the general population and many are encouraged for the natural treatment of hypertension. Patients with hypertension often prefer to use these products in addition to or instead of pharmacological antihypertensive agents. Due to the frequent use of herbal products, both consumers and healthcare providers should be aware of the major issues surrounding these products and factors affecting both effectiveness and damages (Table 1) [5].

Herbal/natural products for evidence of benefit Herbs/herbal products for evidence of harm Causes
Coenzyme Q10 Ephedra spec. (Ephedra) Cardiac effects, hypertension, palpitations, tachycardia, stroke, seizures
Fish oil Citrus × aurantium L. (Bitter orange) Blood pressure increases occur in healthy people
Allium sativum L. (Garlic) Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Siberian Ginseng) Hypertension, tachycardia, palpitations
Vitamin C Glycyhrriza glabra (Licorice) Mineralocorticoid excess syndrome, subsequent hypertension

Table 1.

Herbal/natural products in hypertension for their benefits and disadvantages.

Figure 1.

The important risk factors that influence the occurrence of interactions between herbal products and conventional drugs [13].

2.4 Neurotoxicity

The physical brain damage occurred by exposure to neurotoxin is stated as neurotoxicity. Neurotoxin is a substance that causes changes in the nervous system activity by disrupting or killing neurons.Effects of Herb Drug Interactions Essay.  Neurotoxicity symptoms are generally emotional disorders, visual impairment, extremity failing, sexual dysfunction, headache, and behavioral alteration. Atropa belladonnaBrugmansia species, Catharanthus roseusCannabis sativaL., Conium maculatum L., Coscinium fenestratum(Goetgh.) Colebr.Datura stramonium L., Hyoscyamus niger L., and Papaver somniferum L. are the common medicinal herbs that have potential neurotoxic effects [3].


2.4.1 Psychiatric and neurological adverse effects

Psychiatric and neurological patients often try herbal medicines assuming they are safe. Numerous case reports include various adverse events such as cerebral arteritis, cerebral edema, delirium, coma, confusion, encephalopathy, hallucinations, intracerebral hemorrhage and other cerebrovascular accidents, movement disorders, mood disorders, muscle weakness, paresthesia, and seizures. Some deaths have been recorded. Misuse is caused by toxicity of herbal ingredients, contamination and adulteration, and herb-drug interactions [6] (Table 2).

Herbs Adverse effects Potential drug interactions
Panax ginsengC.A.Mey. Insomnia, vaginal bleeding, mastalgia, mania Phenelzine, hypoglycemic drugs
Valeriana officinalis L. (Valerian) Headache, GI symptoms, hangover Other CNS depressants
Datura stramonium(Jimson weed)* Ataxia, blurred vision, disorientation, other cholinergic signs Other anti-cholinergic agents
Glycyrrhiza glabra(Licorice) Mineral corticoid effects Antihypertensives, corticosteroids, digoxin
Passiflora incarnataL. (Passionflower) Nausea, drowsiness, ventricular tachycardia Other CNS depressants
Mentha pulegiumL. (Pennyroyale) GI symptoms and cramps, confusion, hallucination, liver failure Inhibitors of cytochrome P-450 system
Piper methysticumG.Forst. (Kava)* GI symptoms, restlessness, allergies, hepatitis Other CNS depressants
Ephedra sinica (Ma Huang)* Anxiety, confusion, insomnia, psychosis Other CNS-stimulants, beta-blockers, MAO-inhibitors, phenothiazines, theophylline
Ginkgo biloba L. GI symptoms, allergies, headache, dizziness, bleeding Anticoagulants
Tripterygium wilfordii (Thunder God Vine)* Dryness of mouth, nausea, GI symptoms, leukopenia Not known
Eucalyptus sp. Cyanosis, delirium, GI symptoms Not known
Hypericum perforatum (St. John’s wort) GI symptoms, allergies, fatigue, anxiety Serotonin reuptake inhibitors, hepatic enzyme inducer
Aconitum sp. (Aconite)* Acidosis, bradycardia, diarrhea, hypokalemia Antiarrhythmics, antihypertensives

Table 2.

Herbal remedies implicated in causing neurological adverse effects [6].

Although we know the unconscious use of plants or their products, some of the plants given in the table are potent plants that are undesirable to be used in phytotherapy, but they are generally used in Traditional Chinese Medicine. Effects of Herb Drug Interactions Essay.

2.5 Skin toxicity

Cutaneous toxicity is a term used for a pronounced negative effect such as skin irritation, inflammation, or rashes of the epidermal growth factor receptor caused by exposure to a plant, chemical, or environmental factor. Skin consisting of a layer of dead cells and several layers of living cells is the largest organ and a defensive barrier of the body. When irritant influences into the skin, the living cells react due to cause inflammation or dermatitis. Inflammation consists of four parts including redness, pain, heat, and swelling. Skin toxicity can be detected easily as the reaction is observed immediately. The most common sources of skin toxicity are food and cosmetics, and others are medicated lotions, balms, creams, inhalers, and essential oils. Various herbal ingredients are available in all the cosmetics and medicinal products mentioned above. Types of skin sensitization reactions include: Effects of Herb Drug Interactions Essay.