Title: Direct Activation of Fission Yeast Adenylyl Cyclase by Heterotrimeric g protein Gpa2
Evaluation of adverse drug reactions to Shakuyaku-kanzo-to
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| Evaluation of adverse drug reactions to Shakuyaku-kanzo-to
No patients experienced adverse drug reactions except one patient who had dizziness: an 80-year-old man with a history of cerebral infarction experienced dizziness during treatment. The administration of Shakuyaku-kanzo-to was stopped and the symptom disappeared. Furthermore, regular blood tests showed no abnormal findings in any patient. One patient reported that postherpetic neuralgia (PHN), in addition to the painful muscle cramps, was alleviated. DISCUSSION Painful muscle cramps often occur in the gastrocnemius muscle. Its pathogenic mechanism was suggested to be a disorder of secondary neurons, but details of the mechanism are not clear at present (1). Underlying diseases that cause painful muscle cramps include diabetes, liver cirrhosis, chronic renal failure (hemodialysis), electrolyte abnormalities, and spondylosis deformans (lumbar spondylosis) (11). In our pain clinic, many outpatients suffer from low back and leg pain associated with lumbar spinal stenosis. They are generally treated by a nerve block that is mainly an epidural block. However, careful evaluation has shown that in many cases these symptoms occur together with painful muscle cramps. Treatments for painful muscle cramps include physical therapy such as stretching exercises, thermotherapy, traction therapy, and use of medications such as anticonvulsants, muscle relaxants, and vitamin B12 (2, 3, 10). Eperisone hydrochloride is one of the widely used muscle relaxants for muscle cramps. And Shakuyaku-kanzo-to is a Kampo medicine that is effective for crampy pain in the gastrointestinal smooth muscle and in skeletal muscle. It also reportedly has high therapeutic effectiveness for muscle cramps in patients undergoing dialysis, patients with diabetes or liver cirrhosis, and patients with dysmenorrhea (6, 7, 16). Shakuyaku-kanzo-to consists of a combination of P. lactiflora and Glycyrrhiza. Paeoniflorin, which is a major active ingredient of P. lactiflora, has sedative, antispastic, and analgesic effects and causes peripheral artery vasodilation. Glycyrrhizin, which is a major active ingredient of Glycyrrhiza, has sedative, analgesic, and anti-inflammatory effects (4, 15). In the drug information for Shakuyaku-kanzo-to extract, the prescribed dose is generally 7.5 g/day (given in divided doses twice or three times daily) for sudden muscle cramps in adult patients (13). In this study, we first prescribed 7.5 g/day of Shakuyaku-kanzo-to extract for 16 patients with lumbar spinal stenosis accompanied by painful muscle cramps. After 2 weeks, the frequency of painful muscle cramps decreased by more than 50% in about 87% of the 16 patients. The period required for the maximum therapeutic effect was less than 3 days in most patients, as well as in previous reports (7), whereas some patients required 1-2 weeks to achieve the maximum therapeutic effect. The reason for this longer time requirement may be a change in the intestinal bacterial flora caused by several days of administration of Shakuyaku-kanzo-to, which may have affected the metabolism of paeoniflorin (12). Adverse reactions to Shakuyaku-kanzo-to can include hypokalemia and pseudoaldosteronism, which should be of special concern. Such adverse reactions are caused by glycyrrhizin, which is found in Glycyrrhiza, a component of Shakuyaku-kanzo-to. A glycyrrhizin metabolite, glycyrrhizic acid, inhibits the activity of 11 -hydroxysteroid dehydrogenase, which in turn inhibits the transformation of cortisol to cortisone and thereby results in a high blood level of cortisol (8). Shakuyaku-kanzo-to has reportedly caused serious arrhythmia, cardiac failure, and hypokalemic rhabdomyolysis (9), and it should thus be administered with great care. Yoshida et al. compared the therapeutic efficacy of eperisone hydrochloride and Shakuyaku-kanzo-to for painful muscle cramps (16). They reported that the effect of Shakuyaku-kanzo-to was superior to that of eperisone hydrochloride; however, once the administration of the medicines stopped, the therapeutic effect of Shakuyaku-kanzo-to was more likely to decrease compared with that of eperisone hydrochloride. In addition, long-term administration of Shakuyaku-kanzo-to may be necessary, because painful muscle cramps accompanied by an underlying disease are considered to be intractable unless the primary disease has been cured. However, long-term routine administration of Shakuyaku-kanzo-to may cause adverse drug reactions, as previously described. We believe that in clinical practice it is important to keep the Shakuyaku-kanzo-to dosage as low as possible, in addition to following the standard cautions such as do not administer to patients with hypokalemia or muscle diseases, avoid using in combination with other drugs containing Glycyrrhiza, and conduct blood tests. In this study, we found that one patient showed pain reduction of his post herpetic neuralgia associated pain with Shakuyaku-kanzo-to. PHN causes intractable pain, and the Kampo medicines Oren-gedoku-to (Huang-Lian-Jie-Du-Tang) and Sairei-to (Chai-Ling-Tang) were reportedly effective in the treatment of PHN (5). The effect of Shakuyaku-kanzo-to on PHN has not yet been reported. Additional investigations are needed for an evaluation of the therapeutic effects of Shakuyaku-kanzo-to on PHN. The limitation of this study is that as we conducted ANOVA to evaluate the each group, there may happen alpha-error, so we should include more number of participants to avoid this error. PAINFUL MUSCLE CRAMPS TREATED BY SHAKUYAKU-KANZO-TO E137 In this study, we analyzed the effectiveness of Shakuyaku-kanzo-to for painful muscle cramps associated with lumbar spinal stenosis. The frequency of painful muscle cramps was reduced in 14 of 16 patients, whereas eperisone hydrochloride achieved the same reduction level in 4 of 14 patients. The onset of the maximum therapeutic effect was less than 3 days from the start of administration in 11 of 16 patients. No serious adverse reactions were observed, except for dizziness that was experienced by one patient. The dosage of 2.5 g of Shakuyaku-kanzo-to as needed had a therapeutic effect that was equal to the regular use of 7.5 g/day for painful muscle cramps. In conclusion, our data show that Shakuyaku-kanzo-to is effective for painful muscle cramps associated with lumbar spinal stenosis. tải về 361.3 Kb. Chia sẻ với bạn bè của bạn:
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