• Korean Journal of Biological Psychiatry
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• v.16 no.4
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• pp.266-270
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• 2009

Adverse drug reactions are very common in clinical practice, and skin is one of the most frequent organs for adverse drug reactions. We report a case of a 71-year-old male patient who developed skin eruptions after switching formulation of quetiapine immediate release(IR) to quetiapine extended release(XR). He had been taking quetiapine IR(400mg/day) for treatment of manic episode which was developed one year ago. The patient showed great improvement of symptoms after taking quetiapine IR for about one year, thus dosage of medication was reduced to 50mg/day on the average. Unfortunately dose reduction has tended to worsen symptoms, so dose of quetiapine was increased again to 200mg/day with formulation changes to XR. Two days after he took new formulation, erythematous papules were occurred over his anterior neck and ventral side of left wrist. As he stopped quetiapine XR, the skin lesions gradually subsided. And he was successfully treated with readministration of quetiapine IR without any skin lesions.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.137-142
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• 1996

Effects of plantago-mucilage A (P-MA) on the immune responses were studied in ICR mice. Mice were divided into 4 groups (10 mice/group), and P-MA at doses of 7, 21 and 63 mg/kg were orally administered to mice once a day for 21 consecutive days. Mice were immunized and challenged with sheep red blood cells (SRBC). P-MA at 63 mg/kg/day significantly increased the body weight gain and the relative weights of spleen and thymus, as compared with those in controls. However, there were no significant effects on liver weight due to P-MA treatment. Plaque forming cells (PFC) and hemagglutination (HA) titers to SRBC were significantly enhanced in mice dosed at 21 and 63 mg/kg/day P-MA, as compared with those in controls. Delayed-type hypersensitivity (DTH) reaction to SRBC, phagocyte activity and circulating leukocyte were also significantly increased in mice dosed at 63 mg/kg/day P-MA. These results demonstrate that P-MA markedly enhances both humoral immune and allergic reaction to SRBC at concentrations which don't act on the relative weight of liver.

• Tuberculosis and Respiratory Diseases
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• v.77 no.3
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• pp.145-148
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• 2014

Valproic acid is one of the most common antiepileptic drugs used for the treatment of several seizure disorders. A 20-year-old man presented with a sudden decline of consciousness. He had a neurosurgery operation for intracranial and intraventricular hemorrhage. Following surgery, antiepileptic medication was administered to the patient in order to control his seizure events. On valproic acid treatment, he began to complain of fever and dyspnea. His symptoms persisted despite receiving empirical antibiotic treatment. All diagnostic tests for infectious causes were negative. A high-resolution computed tomography scan of the chest revealed predominantly dependent consolidation and ground-glass opacities in both lower lobes. The primary differential was drug associated with interstitial lung disease. Therefore, we discontinued valproic acid treatment and began methylprednisolone treatment. His symptoms and radiologic findings had significantly improved after receiving steroid therapy. We propose that clinicians should be made aware of the potential for valproic acid to induce lung injury.

• YAKHAK HOEJI
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• v.40 no.3
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• pp.326-334
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• 1996

Effects of methanol extract of Astragali Radix (AR) on the immune responses were studied using ICR mice. Mice were divided into 4 groups (10mice/group), and methanol extracts of AR at doses of 0.05, 0.25 and 1.25g/kg were orally administered to ICR mice once a day for 2 weeks. Mice were immunized and challenged with sheep red blood cells (SRBC). The results of this study were summarized as follows; (1) Methanol extract of AR at 0.05, 0.25 and 1.25g/kg didn't affect the weight ratios of thymus to body, as compared with those in controls, but significantly increased spleen weight ratio. (2)Methanol extract of AR at 0.05 and 0.25g/kg significantly increased hemagglutination titer and splenic plaque forming cells corresponding to humoral immunity, as compared with those in controls, but their enhancements were somewhat lowered at a high dose (1.25g/kg). (3) Methanol extract of AR at 0.05 and 0.25g/kg siginificantly increased delayed-type hypersensitivity reaction resulted from cell-mediated immunity, as compared with those in controls, but not so significant increases were observed at a high dose (1.25g/kg). (4) Methanol extract of AR at 0.05 and 0.25g/kg significantly increased phagocytic activity and the number of circulating leukocyte compared with those in controls, but their enhancements were lowered at a high dose (1.25g/kg). These results suggest that methanol extract of Astragali Radix increased humoral and cell-mediated immune responses, phagocytic activity and the number of circulating leukocyte, dependent upon dose, but inhibited their enhancement effects were decreased at a high dose (1.25g/kg).

• YAKHAK HOEJI
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• v.40 no.2
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• pp.202-211
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• 1996

Experiments were performed on male Sprague-Dawley rats to investigate the immunobiological effects on route of administration of amygdalin(AM). Rats were administered orally at 12.5, 25, or 50mg/kg/day of AM or injected wtih 25,50, or 100mg/kg/day of AM intravenously for 2 weeks. Rats were immunized and challenged with sheep red blood cells(SRBC). The results of this study were summarized as follows;(1) In oral administration of AM, body weight gains were significantly increased by 50mg/kg AM as compared with controls, the relative weights of liver and thymus also were significantly increased by 12.5 and 25mg/kg AM. However, 2-mercaptoethanol-resistant hemagglutination titier (2-MER HA), Plaque forming cells (PFC) and rosette forming cells (RFC) were non-dose dependently decreased. Phagocytic activity and delayed-type hypersensitivity (DTH) reaction also were significantly decreased by 50mg/kg AM. (2) In intravenous injection of AM, body weight gains, hemagglutination titer (HA), 2MER-HA, DTH reaction, PFC, RFC and circulating leukocytes were not influenced by AM. However, the relative weights of liver, spleen and thymus were significantly enhanced 100mg/kg AM. These results indicated that oral administration of AM non-dose dependently suppresses humoral and cell-mediated immunity in SD rats, and that intravenous injection of AM is unaffected humoral and cell-mediated immunity, however, the high dose of it significantly enhances phagocytic activity.

• Korean Journal of Clinical Pharmacy
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• v.20 no.2
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• pp.128-137
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• 2010

This review summarizes gender differences in pharmacokinetics, pharmacodynamics, and adverse drug reactions. Gender differences in pharmacokinetics are categorized by four major factors: absorption/bioavailability, distribution, metabolism, and elimination. There are sex-based differences in gastric emptying time, gastric alcohol dehydrogenase activity, apparent volume of distribution, ${\alpha}1$-acid glycoprotein level, phase I (CYP) and phase II metabolizing enzymes, glomerular filtration rate, and drug transporters. This review also reports gender differences in pharmacokinetics and pharmacodynamics of cardiovascular agents, central nervous system acting agents and antiviral agents. In addition, it has been reported that females experience more adverse reactions such as coughing, tachycardia, nausea, vomiting, rash, hypersensitivity, hepatotoxicity, and metabolic disorder after taking cardiovascular, central nervous system acting and antiviral agents. Therefore, in order to provide optimal drug dosage regimens both in male and female, gender differences in pharmacokinetics, pharmacodynamics, and adverse drug reactions must be considered.

• Tuberculosis and Respiratory Diseases
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• v.59 no.4
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• pp.423-426
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• 2005

Imatinib-mesylate (Gleevec, Glivec) is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Imatinib is also used to treat patients with c-kit (CD 117)-positive unresectable tumors, or metastatic malignant gastrointestinal stromal tumors, or both. Imatinib is a welltolerated drug with few side effects. However, it has been associated with gastrointestinal irritation, fluid retention and edema, skin rashes, depigmentation, hepatotoxicity, hemorrhage, and hematological toxicity (anemia, neutropenia, and thrombocytopenia). In addition, imatinib has been associated with dyspnea and cough, which are mainly secondary to the pleural effusion and pulmonary edema, which represent local or general fluid retention. These events appear to be dose related and are more common encountered in the elderly. However, there has been no report of hypersensitivity pneumonitis associated with imatinib-mesylate in Korea. We report a case of 51-year old woman who developed hypersensitivity pneumonitis that might have been induced by imatinib-mesylate during the treatment of a gastrointestinal stromal tumor.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.456-464
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• 2020

Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC₅₀, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED₅₀, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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• pp.143-149
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• 2017

Background: L-asparaginase (L-ASP) is a critical agent for the treatment of acute lymphoblastic leukemia and lymphoma, which is associated with serious toxicities including hypersensitivity, pancreatitis and thrombosis. Methods: To evaluate the toxicity of L-ASP in real clinical settings, we included the patients with L-ASP adverse drug reactions (ADRs) reported in a regional pharmacovigilance center of Seoul St. Mary's hospital from January 2014 to December 2015. Results: A total of 83 cases of L-ASP related ADRs were reported in 54 patients. Of these 83 cases, 65 cases (78.3%, 65/83) were spontaneously reported and 18 cases (21.7%, 18/83) were detected by further medical records review. Of the patients with ADRs, pediatric patients accounted for 83.3% of the cases (45/54) and median age was 9 years. The most common clinical manifestations of ADRs were hematology manifestations (31.3%, 26/83), followed by hepatobiliary manifestations (18.1%, 15/83). Thirty-four serious ADRs were reported in 19 patients. The sserious ADR group showed significantly longer hospitalization and higher rate of discontinuation of L-ASP than the non-serious ADR group (p = 0.005, 0.03). The most common clinical manifestations of serious ADRs were hepatobiliary manifestations (41.2%, 14/34). In total, 8 cases (9.6%, 8/83) of unlabeled ADRs were identified. They were serious ADRs. Conclusion: We identified unlabeled serious ADRs of L-ASP. Also, correlations were observed between serious ADRs and length of hospitalization, discontinuation rate respectively. Further investigations and developed spontaneous ADR reporting systems are needed to evaluate these correlations.

• Archives of Plastic Surgery
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• v.47 no.4
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• pp.297-300
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• 2020

Hyaluronidase, an enzyme that breaks down hyaluronic acid, has long been used to increase the absorption of drugs into tissue and to reduce tissue damage in cases of extravasation of a drug. With the increasing popularity of hyaluronic acid filler, hyaluronidase has become an essential drug for the correction of complications and unsatisfactory results after filler injection. For this reason, when performing procedures using hyaluronic acid filler, a sufficient knowledge of hyaluronidase is required. In order for hyaluronidase to dissolve a hyaluronic acid filler, it must interact with its binding sites within the hyaluronic acid. The reaction of a filler to hyaluronidase depends on the hyaluronic acid concentration, the number of crosslinks, and the form of the filler. Hyaluronidase is rapidly degraded and deactivated in the body. Therefore, in order to dissolve a hyaluronic acid filler, a sufficient amount of hyaluronidase must be injected close to the filler. If the filler is placed subcutaneously, injection of hyaluronidase into the filler itself may help, but if the filler is placed within a blood vessel, it is sufficient to inject hyaluronidase in the vicinity of the vessel, instead of into the filler itself. Allergic reactions are a common side effect of hyaluronidase. Most allergic reactions to hyaluronidase are local, but systemic reactions may occur in infrequent cases. Since most allergic responses to hyaluronidase are immediate hypersensitivity reactions, skin tests are recommended before use. However, some patients experience delayed allergic reactions, which skin tests may not predict.