You, a 34-year-old veterinarian with a husband and three children, are preparing for your day packed with surgeries and procedures. Your technician is performing the intake for Charlie, a 10-year-old neutered male golden retriever who will be receiving a dental cleaning and one or more dental extractions. The form she is completing asks about any new developments or medications since Charlie’s last exam six weeks ago. The client, Claudia, denies changing anything; she does reinforce that Charlie has severe separation anxiety at times like this. The technician remarks that he seems calm now and assures the client that she’ll take good care of Charlie. They say their goodbyes and nothing seems unusual. What’s wrong with this picture? What the technician failed to ask and what Claudia neglected to mention was that Charlie had been taking St. John’s wort (SJW) for many weeks and, in fact, had a double dose before they left the house. Claudia had seen abundant ads and blogs on the Internet advocating SJW for dogs with anxiety, phobias and depression. Having planned this dental procedure weeks earlier, she decided to give the herb a try and see how he did well in advance of his scheduled date. Claudia found the herbal in extract form at the feed store; she figured because it was liquid, it would be absorbed well before anesthesia began so as not to pose an aspiration risk. Flower Power The label bore no warnings about herb-drug interactions. Instead, the dainty yellow SJW flowers on the package may have subliminally suggested that this supplement was natural and, therefore, safe. Other than dosage recommendations and naming ingredients, no information was offered about side effects, interactions or even the amount of active ingredient(s). As you prepared Charlie for anesthesia, what you didn’t know (because the technician didn’t ask and the client didn’t volunteer) was that the SJW had reached levels capable of causing unanticipated herb-drug interactions. SJW is the herbal poster child in this regard. Its pharmacokinetic interactions involve the cytochrome P450 (CYP450) pathway—the most common method by which herbs interfere with drug effects. Some herbs and dietary supplements inhibit the metabolic actions of CYP450 isoenzymes, while others, such as SJW, induce them. By enhancing the elimination of active drugs, SJW can lower plasma drug levels and shorten their duration of action. Furthermore, the CYP450 3A4 isoenzyme family generates the most concern about interactions because over half of all pharmaceuticals are metabolized to some degree by CYP3A4. SJW induces CYP3A4 specifically. This makes the body more efficient at destroying drugs that depend on this pathway for detoxification. In fact, the ability of SJW to interact with medications has been shown to affect dogs. That is, SJW lowered the maximum whole-blood concentration and AUC (area under the plasma concentration time curve) of cyclosporine within one week of administration. Brain Game Much has also come to light about the mechanisms of action of SJW. It affects brain function by inhibiting the reuptake of several neurotransmitters, including glutamate, serotonin, dopamine and norepinephrine. New evidence reveals that SJW may promote the release of glutamate from vagal afferents that synapse with the nucleus tractus solitarius in the brainstem. The NTS controls several homeostatic functions and behaviors, and the benefits of vagal stimulation range from anti-depressant activities to digestive health, immune wellness and anti-inflammatory benefits. Thus, while clinicians should remain cognizant about the potential for herb-drug interactions, SJW also offers opportunities to treat a range of conditions with far fewer medications and side effects inherent in pharmaceuticals. Some contend that the safest way to sidestep herb-drug interactions during surgery and anesthesia is to require that patients discontinue the botanical agents two to three weeks earlier. However, this could cause clients consternation if, as in Charlie’s case, they are trying to help their dog through the event itself. It also involves the abrupt cessation of a supplement on which the patient has come to rely. There are, in fact, several herbs that may interact with conventional pharmaceuticals. This could confuse the clinical picture and lead to unexpected results, as noted in human practice from pediatric oncology to perioperative analgesia/anesthesia. The lack of sufficient regulatory oversight, awareness about botanicals among practitioners, and product standardization raise the possibility of surprises when mixing drugs and herbs. In Charlie’s case, a six-week history of SJW administration could conceivably affect his level of sedation during anesthesia as well as his postoperative analgesia. Other herbs could raise the risk of intraoperative bleeding. In the spirit of One Health, there is another reason for veterinarians to keep herb-drug interactions on their radar. Let’s say, for example, that the stress of practice is getting you down, and you begin taking SJW for depression and anxiety. Let’s say, as well, that you neglect to mention this to your doctor and she fails to ask about herbs the next time you go in for a checkup regarding your oral contraceptive prescription. This would be important to know, as oral contraceptives as well can be reduced by SJW isoenzyme induction. Better to know before becoming unintentionally pregnant.
