ACTIVE HERBAL CONSTITUENTS

The following broad classes of active chemical constituents are found in plants: volatile oils, resins, alkaloids, polysaccharides, phenols, glycosides, and fixed oils (Hung, 1998). Volatile oils are odorous plant ingredients. Examples of plants that contain volatile oils include catnip, garlic, and citrus. Ingestion or dermal exposure to volatile oils can result in intoxication. Resins are complex chemical mixtures that can be strong gastrointestinal irritants. Alkaloids are a heterogeneous group of alkaline, organic, and nitrogenous compounds. Often, these compounds are the most pharmacologically active plant constituents. Glycosides are sugar esters that contain a sugar (glycol) and a nonsugar (aglycone). In some cases, the glycosides are not toxic. However, hydrolysis of the glycosides after ingestion can release toxic aglycones. Fixed oils are esters of long-chain fatty acids and alcohols. Herbs that contain fixed oils are often used as emollients, demulcents, and bases for other agents, and, in general, these are the least toxic of the plant constituents.

Many of these plant-derived chemicals are biologically active and, if exposure is of sufficient magnitude, potentially toxic. Numerous case reports in the medical literature document serious and potentially life-threatening adverse effects following human and animal exposure to herbal preparations. It is worth noting that in several instances the incidence of animal intoxication from an herb, herbal preparation, or dietary supplement seems to parallel its popularity (Ooms, 2001; Gwaltney-Brant, 2000). However, it must be noted that, considered as a group, herbal products do not appear to be associated with a higher incidence of serious adverse effects than is associated with ingestion of conventional prescription or over-the-counter (OTC) pharmaceuticals. Serious adverse drug reactions (ADRs) to conventional pharmaceuticals in hospitalized people have been estimated at 6.7% (Lazarou, 1998). An approximately equal incidence of hospital admissions due to ADRs has been reported (Pirmohamed, 2004). A recent study estimated that approximately 25% of all herbal remedy and dietary supplement calls to a regional human poison control center could be classified as ADRs (Yang, 2003). The most common ADRs were associated with zinc (38.2%), echinacea (7.7%), chromium picolinate (6.4%), and witch hazel (6.0%). Only 3 of 233 ADRs were considered to be serious enough to warrant hospitalization. It is likely that ADRs are underreported for both conventional drugs and herbal remedies. Unfortunately, almost no information is available regarding the overall incidence of ADRs with conventional drugs or herbal remedies in veterinary medicine.

Poisoning of an animal might occur in various ways. Use of a remedy that contains a known toxin is one possibility. For example, long-term use of an herbal remedy that contains hepatotoxic pyrrolizidine alkaloids (PAs) may result in liver failure. Pennyroyal oil containing the putative hepatotoxin, pulegone, was responsible for the death of a dog after it was applied dermally to control fleas (Sudekum, 1992). Alternatively, administration of a misidentified plant may result in poisoning. Contamination of commercially prepared herbal remedies with toxic plants has been documented in the medical literature (DeSmet, 1991; Vanherweghem, 1998). Seeds of poison hemlock (Conium maculatum) have been found in anise seed. Recently, plantain sold as a dietary supplement was found to contain cardiac glycosides from Digitalis spp. Just as with traditional prescription medications, pet intoxication following accidental ingestion of an improperly stored remedy may occur. This is particularly true with dogs because of their indiscriminant eating habits. The author was involved in a case in which a miniature poodle ingested several tablets of its owner’s medication containing rauwolfia alkaloids and developed clinical signs within 2 hours of ingestion. Reserpine was detected in the medication and the urine of the dog.

Some herbal remedies, particularly Chinese patent medicines, may contain inorganic contaminants such as arsenic, lead, or mercury or intentionally added pharmaceuticals such as nonsteroidal anti-inflammatories, corticosteroids, caffeine, or sedatives (Ko, 1998). Commonly found natural toxins in Chinese patent medicines include borneol, aconite, toad secretions (Bufo spp, Ch’an Su), mylabris, scorpion, borax, acorus, and strychnine (Strychnos nux-vomica) (Ko, 1998).

Because herbal preparations contain numerous biologically active compounds, the potential exists for diverse drug interactions when they are used in conjunction with conventional pharmaceuticals. In addition, many naturally occurring chemicals found in herbal remedies cause induction of one or more liver P-450 metabolizing enzymes (see Table 12-5). For example, eucalyptus oil induces liver enzyme activity (Blumenthal, 1998a). This can cause altered metabolism of other drugs or chemicals, resulting in enhanced or diminished drug efficacy or toxicity. Coexisting liver or renal disease can alter the metabolism and elimination of herbal constituents, thus predisposing to adverse reactions. Apparent idiosyncratic reactions with herbal remedies have been documented in people. Such reactions might be due to individual differences in drug-metabolizing capacity (Stedman, 2002; Zhou, 2004).

TABLE 12-5 Potential Drug–Herb Interactions

From Review of Natural Products, 2000a and b; Herr, 2002.

Of particular concern to veterinarians is the possibility of species differences in susceptibility to the toxic effects of herbal constituents. For example, cat hemoglobin is quite susceptible to oxidative damage. The volatile oil in garlic contains oxidants such as allicin. Thus, one can hypothesize that oxidant-induced Heinz body anemia would be more likely to occur in cats given garlic than in other species. However, no information substantiates or refutes such a hypothesis. Unfortunately, little evidence-based information exists on which informed judgments about potential hazards of specific herbs to different species can be based.

According to annual surveys of herbs sold in the United States, the most commonly used herbs include coneflower (Echinacea spp), garlic (Allium sativa), ginseng (Panax spp), gingko (Ginkgo biloba), Saint John’s Wort (Hypericum perforatum), saw palmetto (Serenoa repens), goldenseal (Hydrastis canadensis), aloe (Aloe spp), astragalus (Astragalus spp), cayenne (Capsicum spp), bilberry (Vaccinium myrtillus), and cat’s claw (Uncaria tomentosa). Presumably, these herbs are those to which pets are most likely to be exposed. According to the recently published Botanical Safety Handbook, coneflower, saw palmetto, aloe (gel used internally), astragalus, and cayenne (used internally) should be considered safe when used appropriately. Garlic, ginseng, gingko, Saint John’s Wort, goldenseal, aloe (gel used externally, dried juice used externally), and cayenne (used externally) have some restrictions regarding their use (McGuffin, 1997). For example, in humans, garlic should not be used by nursing mothers, and cayenne should not be applied to injured skin or near the eyes. Both gingko and Saint John’s Wort are contraindicated in individuals taking monamine oxidase inhibitors because of the potential for herb–drug interactions. Only insufficient data are available on which clinicians can base a determination regarding the safety of bilberry and cat’s claw, although bilberry is safe enough that it is also used as a food. Of interest is a recent study that listed the most common herb-related calls to a regional human poison control center (Haller, 2002). The most frequent calls, in descending order of frequency, involved Saint John’s Wort, ma huang, echinacea, guarana, ginkgo, ginseng, valerian, tea tree oil, goldenseal, arnica, yohimbe, and kava kava. Not all of the calls could be categorized as ADRs.