Drug Interaction of St Johns Wort in Patients - Literature review Example

Annotated bibliography According to the research article, St John’s wort increases CYP3A4 activity and changes the pharmacokinetics of CYP3A4 substrates. The research studied the effects of SJW by selecting a sample of fourteen health male subjects. A single dose (10mg) of zolpidem was administered followed by 300 mg oral administration of SJW three times in a day for two weeks. However, the last dosage of SJW was administered together with zolpidem. Blood samples for analysis were obtained after every 24 hours after the zolpidem administration and findings indicated that the mean values of AUC and Cmax for zolpidem had declined and that of zolpidem had significantly increased. However, AUC showed a partial increment in three subjects after SJW treatment. The research concluded that the effects of SJW are to decrease the plasma concentration of the zolpidem thus enhancing CYP3A4 activity. Accordingly, the use of SJW should be personalized depending on the unique circumstances of the patient. Annotated bibliography Introduction St John’s wort (SJW) as known as Hypericum perforatum) is used in many countries for treatment of mild depression. St John’s wort is made up of yellow flowers is currently being researched for mood-improving benefits. Some research findings suggest that the herb increases the brain activity and prolongs the brain chemical activities such as serotonin just like ordinary anti-depressants (Hojo, Echizenya, Ohkubo & Shimizu, 711). A placebo-controlled clinical study found out that administration of SJW for fourteen days in 14 healthy subjects decreased the Cmax and AUC of quazepam. Zolpidem is a hypnotic drug and agonist of omega-1 receptor subtype. Zolpidem metabolism is mediated by CYP3A4 thus it is probable that SJW will reduce the plasma concentration of Zolpidem thus diminishing the pharmacokinetic effects (Hojo, Echizenya, Ohkubo & Shimizu, 712). Fourteen health male individuals participated in the above research study after abstaining from alcohol, herbal fruits and other medications for two weeks prior to the research. Each subject received 10 mg dosage of Zolpidem and blood samples were collected in (EDTA)-containing tubes and frozen at – 20 degrees Celsius for later analysis of plasma concentrations. After final collection of the samples at the end of the second day, subjects started their outpatient treatment with SJW extract LI160 (Kira, 300 mg; Lichtwer Pharma, Berlin, Germany). Each subject received the same dosage of 300 mg of SJW from the second day to the fifteenth day after which they returned to the laboratory and same procedures were repeated just like in day one and day two (Hojo, Echizenya, Ohkubo & Shimizu, 713). The HPLC procedure for analyzing the Zolpidem concentration entailed adding 150 ng Trazodone in methanol (ug) to 0.1 Ml of plasma as internal standard and then 0.1 Ml of acetonitrile. Supernatant (80 ul) was loaded in the HPLC pre-column in order to eliminate any interfering substances in the plasma. Zolpidem was loaded in to the pre-column using a colum-switching technique 0.5% KH2PO4 (pH 5.0). The pharmacokinetics analysis utilized a standard model. No side-effects were reported by the subjects and generally low plasma concentrations were observed after the administration of SJW. Mean value of AUC for Zolpidem was about 30 percent lower than for the zolpidem while the mean value of Cmax for zolpidem with SJW was 33.7 percent than that of Zolpidem alone. The research study did not cater for the medical history of the patients. The last dosage of SJW was concurrently administered with Zolpidem which may be the reason why three subjects reported an increase in AUC after the SJW treatment. The research study followed a scientific method in analyzing the zolpidem concentration after administering SJW. Extracts of SJW have been used for the treatment of mild depressive disorders in many countries. SJW induces P450 (CYP) 3A4 and P-glycoprotein thus altering the pharmacokinetics of any other administered drugs like warfarin, cyclosporine, digoxin, indinavir, amitriptyline, nevirapine, midazolam and alprazolam. SJW will extensively reduce the plasma concentrations of the above drugs thus acting as antidepressant. One major weakness is that pharmacodynamic effects were not evaluated, but it is generally assumed that reduction in zolpidem concentration can impede hypnotic effects of zolpidem due to reduction in pharmacodynamic effects in the concomitant administration of SJW and zolpidem. The research findings showed inter-variability since three subjects reported a small increase in AUC after administration of SJW. One generalization of the research is that zolpidem is a substrate for transport by enteric pgp or transporter systems. Another generalization was that SJW induces CYP3A4 but not CYP2C9, CYP2D6 and CYP1A2 since CYP2CI9 to zolpidem metabolism is low (Hojo, Echizenya, Ohkubo & Shimizu, 714). The practical implication is that repeated administration of SJW will decrease plasma concentration of Zolpidem by enhancing CYP3A4 activity and thus can be used as a mild depressant. However, cautionary approach should be undertaken while administering SJW and Zolpidem at the same time thus the advice should be personalized depending on unique circumstances of the patient (Hojo, Echizenya, Ohkubo & Shimizu, 714). The above clinical research has shown that SJW can be effective for the cure of mild depression with fewer side effects. The main chemical extract for the cure of depression is hyperforin which is greatly concentrated in SJW herb. Hyperforin acts as reuptake inhibitor of serotonin leading to greater concentrations of the serotonin in the brain thus reducing depression (Martin, Scahill & Kratochvil, 2010). High serotonin concentrations influence positive moods. According to Journal of Clinical Psychopharmacology, SJW is better in the treatment of social anxiety disorder that placebo since the potential side effects are mild and include mainly gut problems and dry mouth (Wolraich, 2008). However, adequate care should be exercised when combining the treatment with other drugs since it can reduce the medical effects of some drugs and cause addictive effects on other drugs (Wolraich, 2008). For instance, birth control pills and cancer treatment drugs should never be administered at the same time with SJW since SJW will alter the medical effects of those drugs (Wolraich, 2008). SJW can also be used for treatment of other depression related disorders such as tiredness, difficulties in sleeping, seasonal affective disorder, attention deficit-hyperactivity disorder and obsessive disorders (Wolraich, 2008). According to this article, these are the implications that might happen under long term use of SJW. The drug can increase the sensitivity of the skin to sunlight, cause dizziness and gastrointestinal discomforts after chronic use (Martin, Scahill & Kratochvil, 2010). From the article, SJW chronic use may lead to headaches and irritability of the skin due to the addictive nature of the drug. Chronic use will also lead to insomnia or retinal harm when the herb is taken for long term and eyes exposed to sunlight. Hypericin component in SJW induces changes in lens protein leading to the formation of cataracts that eventually lead to blindness. Chronic use of SJW may lead to increase in the metabolism of drugs such as indinavir that is used in HIV treatment since SJW includes cytochrome P450 3A that breaks down certain medical drugs. SJW may also reduce levels of digoxin in the blood stream ultimately leading to heart failures. It is apparent clear that long term use of SJW will lead to behavioral changes of the individual such as skin rashes, sleep disturbances and other withdrawal symptoms such as extreme fatigue, nausea and vomiting. Chromic use of SJW may lead to serotonin syndrome thus leading to complications of the brain that are manifested in behaviors such as poor coordination, fever, restlessness, sweating and confusion. The herb should not be used in treatment of bipolar disorder since it can lead muscle contractions especially in pregnant women (Bratman, 1997). SJW is only suited for mild depression that is related to serotonin deficiency since the powerful nutrients work within hours (Bratman, 1997). Low dosages of SJW should be recommended and interactions with other medications should be avoided. The dosage should be personalized according to medical needs of each individual and a dosage of 300 mg per day is recommended (Martin, Scahill & Kratochvil, 2010). References: Hojo, Y., Echizenya, M., Ohkubo, T & Shimizu, T. “Drug interaction between St John’s wort and zolpidem in healthy subjects”, Journal of clinical pharmacy and therapeutics, (2011) 36, 711-115. Martin, A., Scahill, L & Kratochvil, C. (2010). Pediatric psychopharmacology principles and practice. New York. Oxford University Press. Wolraich, M. (2008). Developmental-behavioral pediatrics: evidence and practice. Philadelphia. Elsevier. Bratman, S. (1997). Beat depression with St John’s wort. Rocklin. Prima Publications. Read More