St. John's Wort (Hypericum perforatum) is an herbal medication that consists of anthraquinones, which have displayed anti-inflammatory and anti-cancer effects. It has also been used as an antidepressant. It derives from a flowering plant found in Europe and Asia. It is common in the form of a tablet, capsule, tea, or liquid extract used to treat a handful of medical conditions which include but are not limited to the following:
St John's Wort is a xenobiotic or a plant-derived compound composed of five various forms of hypericin and other flavonoids. Many mechanisms of action have been proposed. One of the main mechanisms used in health care is the report that St. John's Wort acts as a serotonin reuptake inhibitor. This works to reduce the uptake of serotonin at neuronal synapses, as well as dopamine and norepinephrine. The elevated levels of neurotransmitters are believed to be helpful when treating depression. The supplement works by activating pregnane-X-receptor (PXR) Cytochromes, which induces the cytochrome P450 system, specifically the CYP3A4 enzyme and P-glycoprotein. P450s or monooxygenase enzymes act through hydroxylation reactions onto the xenobiotic or St. John's Wort to make it more polar and thus increasing its reactivity for conjugation into various polar groups. In the monooxygenase reaction, molecular oxygen (O2) is broken into water and alcohol (R-OH); because of this, only one oxygen of the pair is given to the xenobiotic substrate. To prepare for the monooxygenase reaction, other reactions take place in xenobiotic metabolisms such as hydrolysis, deamination, epoxidation, preoxygenation, reduction, desulfurization, and dehalogenation. St. John's Wort's ability to inhibit monoamine oxidase allows an increase in the formation of norepinephrine. Hyperforin, a St. John's wort component, is believed to be the responsible factor for inducing CYP3A4 by activating a xenobiotic receptor and nuclear steroid/pregnane. Hyperforin itself could be the P-glycoprotein activating compound. Another mechanism that leads to antidepressant activity is the capability of binding to GABA receptors to decrease the binding of GABA, which results in lowered CNS depression. Although St. John's Wort is not yet FDA approved, it is worth noting to acknowledge that some of its proposed mechanisms are in FDA approved drugs that are used for the same variety of health complications.[8][9][10][11]
St John’s Wort has shown encouraging data in its effectiveness and safety when used as a monotherapy. It is prepared by the grinding of the flowers of the plant as well as its dried leaves. The dried flowers can be used in a tea and ingested orally, or be made into an oil by infusion for topical use. Usually, one would find the ground plant in capsules taken as a dietary supplement.
Suggested Use: As a dietary supplement, adults are to take one 300 mg capsule with 0.3% hypericin content three times a day. One to three capsules daily can be taken with meals, or as directed by health care providers. The herbal supplement must be stored in a cool and dry place, away from direct light.
One of the primary adverse effects is the risk of a life-threatening increase in serotonin when combined with certain antidepressants and the inhibition of monoamine oxidase. Using the supplement with other antidepressant medications may cause serotonin syndrome. Serotonin syndrome may first cause tachycardia, increased blood pressure, mydriasis, and sweating. Some may have a fever, and temperatures can rise above 106 degrees F. Treatment can include serotonin antagonists, benzodiazepine to target GABA receptors. Increased blood pressure can have treatment with short-acting antihypertensives.
Caution:
The positive effects of St John’s Wort are negated when used in conjunction with other medications; sometimes, the effects of drug interactions can be life-threatening. Drugs that also utilize the cytochrome P450 system, specifically CYP3A4, or are substrates of P-glycoproteins in metabolism can have reduced efficacy and produce adverse effects when taken in conjunction with St. John’s Wort. These drugs include HIV protease inhibitors, CYP3A4 HIV non-nucleoside reverse transcriptase inhibitors, ciclosporin, tacrolimus, irinotecan, imatinib mesylate, digoxin, oxycodone, and warfarin. Those on hormonal contraceptives must be aware when taking St. John’s Wort that there have been incidences of unplanned pregnancies and irregular menstrual cycles. Clinicians must be aware that when prescribing serotonergic agents and other antidepressants, there is a potential risk of pharmacodynamic interactions occurring when taken with St. John’s Wort.[8][12][9][13][14]
Healthcare professionals must understand and provide precautions as well as awareness of the contraindications of St. John’s Wort to administer safe and knowledgeable healthcare. As the medication has use for a plethora of medical conditions, health care providers need to be aware of why the patient is using it and monitor as needed.
Any health care provider (Md, DO, NP, or PA) can encourage the use of St. John's Wort as it can be found over-the-counter. Clinicians should be aware of its use in their patients. Often, general practitioners' lack the knowledge that their patients are using the herbal supplement when they self medicate. The use of H. perforatum without knowledge by a healthcare provider increases the likelihood of harmful implications on the efficacy and safety of the supplement as there are dangerous drug interactions. Patients should receive counsel and monitoring when taking St. John's Wort.
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