• Title/Summary/Keyword: diltiazem

Search Result 120, Processing Time 0.042 seconds

Clinical trial of diltiazem on dystrophic calcinosis cutis in a dog (개의 이영양성 피부 석회증에 대한 diltiazem의 적용 1례)

  • Cho, Na-Young;Cho, Dae-Hee;Choi, Ho-Jung;Jeong, Seong-Mok;Lee, Young-Won;Park, Seong-Jun
    • Korean Journal of Veterinary Research
    • /
    • v.53 no.3
    • /
    • pp.181-184
    • /
    • 2013
  • Dystrophic calcinosis cutis associated with spontaneous hyperadrenocorticism was diagnosed in a 8-year-old female Chihuahua dog with erythematous, erosive, numerous papules, plaques, and crusts on the bilateral trunk, and inguinal region. Serum biochemical abnormalities included increases in alkaline phosphatase (ALP), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and cholesterol. Radiographs showed mild hepatomegaly and subcutaneous lobulated calcific deposits. Histopathologic examination demonstrated diffuse deposition of basophilic calcified material in the dermis. Von Kossa's stain confirmed calcium deposition. Therapy with diltiazem was useful in resolving calcinosis.

Pharmacokinetics of Diltiazem and its Major Metabolite, Deacetyldiltiazem after Oral Administration of Diltiazem in Mild and Medium Folate-Induced Renal Failure Rabbits

  • Choi, Jun-Shik;Lee, Jin-Hwan;Burm, Jin-Pil
    • Archives of Pharmacal Research
    • /
    • v.24 no.4
    • /
    • pp.333-337
    • /
    • 2001
  • The pharmacokinetic changes of diltiazem (DTZ) and its main metabolite, deacetyldiltiazem (DAD) were studied after oral administration of DTZ to normal rabbits and mild and medium folate-induced renal failure rabbits. DTZ 10 mg/kg was given to the rabbits either orally (n=6). Plasma concentrations of DTZ and DAD were determined by a high performance liquid chromatography assay. The area under the plasma concentration-time curves (AUC) and maximum plasma concentration ($C_{max}$) of DTZ were significantly increased in mild and medium folate-induced renal failure rabbits. The metabolite ratio of the DTZ to DAD were significantly decreased in mild and medium folate-induced renal failure rabbits. The volume of distribution ($V_{d}$) and total body clearance ($CL_{t}$) of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits. The elimination rate constant ($\beta$) of DTZ was significantly decreased in folate-induced renal failure rabbits, but that of DAD was significantly increased. These findings suggest that the hepatic metabolism of DTZ was inhibited and the $V_{d}$, $CL_{t}$ and $\beta$ of DTZ were significantly decreased in mild and medium folate-induced renal failure rabbits.

  • PDF

Transcutaneous Cardiac Pacing in a Dog with Diltiazem Intoxication (딜티아젬 중독증 이환견에서 경피용 체외심박조절기의 적용 증례)

  • Lee, Seung-Keun;Hyun, Chang-Baig
    • Journal of Veterinary Clinics
    • /
    • v.26 no.2
    • /
    • pp.166-169
    • /
    • 2009
  • An 11-year-old male Beagle, weighing 10.5 kg, was presented with sudden bradyarrhthmia and severe hypotension after incidental ingestion of diltiazem. The dog was treated with intravenous(IV) isotonic crystalloid solution, atropine, calcium gluconate, dobutamine, glucagon and gastric lavage under the aid of temporary transcutaneous cardiac pacing. With the short-term use of transcutaneous cardiac pacing and medical treatment, the heart rhythm and the condition of the patient were stabilized.

Involvement of Kupffer Cell in $CCl_4$ induced Liver Injury: The Role of Calcium (사염화 탄소에 의한 간손상에 있어 Kupffer cell 칼슘의 역할)

  • Yang, Mie-Rha
    • The Korean Journal of Pharmacology
    • /
    • v.32 no.1
    • /
    • pp.75-82
    • /
    • 1996
  • The hypothesis that calcium provoke $O_2^-$ formation by Kupffer cells and may contribute to carbon tetrachloride $(CCl_4)$ induced liver injury was studied in SD rats. In $CCl_4-treated$ animals, hepatic malonaldehyde (nmole/gm liver) and plasma ALT (IU/ml) levels elevated significantly from $119.63{\pm}13.00$ to $268.97{\pm}14.82$ and from $17.3{\pm}0.18$ to $806.08{\pm}37.63$, respectively, compared to those in controls. Activation of Kupffer cells with high dose of retinol (250,000 IU/kg/day, po, for 7 day) significantly enhanced ALT levels, while inactivation of Kupffer cells with gadolinium chloride (7.5 mg/kg/day, ip, for 2 day) attenuated the increase of serum ALT level following $CCl_4$ treatment. Diltiazem (10 mg/kg/day, ip for 2 day) given in combination with retinol led to a marked decrease in ALT levels compare to the level in rats treated only with retinol against $CCl_4$ treatment. In order to determine any alterations in cytochrome P450 activities, the P450 content and the CYP2E1 activity were measured and all $CCl_4-treated$ rats showed significantly lower levels compared to those in controls and vehicle-treated animals. There were significant increases in glutathione peroxidase in all $CCl_4-treated$ rats except diltiazem treated groups. No difference was found among untreated and vehicle-treated rats. It is concluded that Kupffer cells contribute to $CCl_4-induced$ liver injury and that calcium antagonist attenuated the increased $CCl_4-induced$ liver injury due to activation of Kupffer cells.

  • PDF

Preliminary Risk Assessment of Several Major Pharmaceutical Products In Aquatic Ecosystem

  • Park, Su-Jung;Oh, So-Rin;Jung, Jin-Yong;Kim, Young-Hee;Kim, Pan-Gyi;Choi, Kyung-Ho
    • Proceedings of the Korean Environmental Health Society Conference
    • /
    • 2005.06a
    • /
    • pp.345-350
    • /
    • 2005
  • Acute toxicities of five pharmaceutical products were evaluated with aquatic microbes, invertebrates, and fish. The test pharmaceuticals, i.e., cimetidine, carbamazepine, diltiazem, acetaminophene, and metformin have been often detected in aquatic environment, but theire cological hazard on receptors of various trophic levels has seldom been evaluated. In the present study, we conducted acute toxicity assays with a marine bacterium, Vibrio fischeri, an invertebrate, Daphnia magna, and a fish, Japanese medake (Oryzias latipes). In general, D. magna, showed the most sensitive response to the test chemicals. Diltiazem exhibited the lowest EC50 value after 96 hr of exposure at 7.6 mg/L, followed by cimetidine >acetaminophen > metformin = carbamazepine in an order of decreasing susceptibility. With the fish, diltiazem and carbamazepine showed the 96 hr EC50 values at 14.1${\sim}$35.4 mg/L while acetaminophen, cimetidine, and metformin did not cause 50% mortality at 100 mg/L. Similar pattern was noted with the Microtox Assay, with which the median effective concentrations for acetaminophen, cimetidine, and metformin were found at the range between 301.8 and 755.4 mg/L. Carbamazepine and diltiazem exposure to the microbes resulted in EC50 values around 50 mg/L. Predicted no effect concentrations (PECs) of these pharmaceuticals derived from the EC5O values obtained from this study, and predicted environmental concentrations (PECs) obtained from available literatures were utilized to estimate ecological risks of the test compounds. No test pharmaceuticals resulted in risk quotients (PEC/PNEC) greater than 1, which suggests no serious potential ecological concerns. It should be noted however that further studies including the refinement of PEC derivation, identification and toxicity assessment of the metabolites and/or their interactions with other stressors may be warranted to better understand the environmental consequences of the residual pharmaceutical discharge to the waterway.

  • PDF

Effect of Calcium Channel Blocker on Acetaminophen-induced Hepatotoxicity in Rats and Histopathologic Examination (Acetaminophen에 의해 유도된 흰주의 간손상에 미치는 Calcium channel Blocker의 효과 및 조직학적 소견)

  • 이은경;정기화;정춘식
    • Journal of Food Hygiene and Safety
    • /
    • v.13 no.3
    • /
    • pp.258-267
    • /
    • 1998
  • The acetaminophen (AP AP), an antipyretic and analgesic agent, induces the hepatotoxicity by increasing influx of calcium and destabilizing the cellular membrane which can be caused by N-acetyl-p-benzoquinoneimine generated by cytochrome P-450 (CYF-450) when it is overdosed. Diltiazem (DIL), a calcium channel blocking agent, has been known to suppress the CYF-450 activities. To study the effect of DIL in APAP treated rats, the serum biotransformational enzyme analyses and the liver histopathologic examination were conducted on the rats which had been administered DIL at 3, 6, 9 and 12 hours after the 3,000 mg/kg of APAP administration. Following a single dose of DIL administered 12 hours after AP AP administration, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, malondialdehyde and calcium contents of liver and microsome were significantly reduced. Glutathione S-transferase (GST) activity was significantly increased. Histopathologic studies showed that DIL had prevented the development of centrilobular necrosis induced by AP AP in liver tissue. Our results suggested that diltiazem could inhibit the formation of free radical and the influx of calcium and could increase GST activity. Therefore, diltiazem can be administered at the time of 12 hours after overdosed AP AP to diminish the liver damage.

  • PDF

Prevention of Ischemic Damage in Working Rat Hearts by Calcium Channel Blocker and Calmodulin Inhibitors (흰쥐심장의 허혈손상에 대한 Calcium 통로봉쇄제와 Calmodulin 억제제의 예방효과에 대한 연구)

  • 성시찬
    • Journal of Chest Surgery
    • /
    • v.22 no.6
    • /
    • pp.901-913
    • /
    • 1989
  • This study was investigated under the postulation that activation of intracellular calcium- calmodulin complex during ischemia-reperfusion leads to myocardial injury. The protective effects of calcium channel blocker, diltiazem and calmodulin inhibitors, trifluoperazine, flunarizine and calmidazolium from ischemic injury in rat hearts were observed by using Langendorff apparatus when the antagonists were infused for 3 min in the beginning of ischemia. Thereby, an increase in resting tension developed during 30-min ischemia was analyzed with regard to [1] the degree of cardiac functional recovery following 60-min reperfusion, [2] changes in biochemical variables evoked during 30-min ischemia. The results obtained were as follows: l. In the ischemic group, the resting tension was increased by 4.1*0.2 g at 30-min ischemia. However, the increase in resting tension was markedly reduced not only by pretreatment with diltiazem [3.3 p M] but also with calmodulin inhibitors, trifluoperazine [3.3 p M], flunarizine [0.5 p M] and calmidazolium [0.5 p M], respectively. 2. Recovery of myocardial contractility, +dF /dt and coronary flow were much reduced when evoked by reperfusion in the ischemic group. These variables were significantly improved either by pretreatment with diltiazem or with calmodulin inhibitors. 3. The resting tension increment evoked during ischemia was significantly inversely correlated with the degree of cardiac function recovered during reperfusion. 4. Following 30-min ischemia, the production of malondialdehyde and release of lysosomal enzyme were much increased in association with a decrease in creatine kinase activity. 5. The increases in malondialdehyde production and release of free lysosomal enzyme were suppressed by pretreatment with calmodulin inhibitors as well as diltiazem. Likewise, the decrease of creatine kinase activities was prevented by these calcium antagonists. With these results, it is indicated that a increase in resting tension observed during ischemia has an inverse relationship to the cardiac function recovered following reperfusion, and further, the later may be significantly dependent on the degree of biochemical alterations occurred during ischemia such as decrease in creatine kinase activity, increased production of malondialdehyde and increased release of free lysosomal enzyme. Thus it is concluded that calmodulin plays a pivotal role in the process of ischemic injury.

  • PDF

HPLC Determination of Diltiazem and Deacetyldiltiazem in Rat Plasma (HPLC를 이용한 랫트 혈장중의 딜타아젬 및 데아세틸딜티아젬의 정량)

  • Lee, Yong-Hee;Shim, Chang-Koo;Lee, Min-Hwa;Kim, Shin-Keun
    • Journal of Pharmaceutical Investigation
    • /
    • v.22 no.4
    • /
    • pp.317-321
    • /
    • 1992
  • A high-performance liquid chromatographic (HPLC) method was developed for the determination of diltiazem (DTZ) and its major metabolite, deacetyldiltiazem (DAD), in rat plasma. DTZ, DAD and imipramine, the internal standard, were selectively fractionated from plasma on a $C_{18}$ reversedphase column $({\mu}-Bondapak,\;10\;{\mu}m\;silica,\;300{\times}3.9\;mm\;ID)$. The composition of the mobile phase was methanol: acetonitrile: 0.04 M ammonium bromide: triethylamine (40:24:36:0.06 in volume). The pH of the mobile phase of their method was lowered to 6.4. The eluents from the column were detected for DTZ and DAD using a UV detector at 237 nm. The recovery was >85% for DTZ and DAD, and average intra-day and inter-day coefficients of variation were <6% for DTZ and DAD at the concentration ranges of 20-1000 ng/ml. Detection limit of DTZ and DAD in plasma was 20 ng/ml with signal-to-noise ratio of 3. This method would be applicable to practical pharmacokinetic studies without detriment to the HPLC column.

  • PDF

Effect of Poloxamer Content on Dissolution of Diltiazem Hydrochloride from Core Pellets (딜티아젬 함유 코아 펠렛으로부터 약물의 용출에 미치는 폴록사머 함량의 영향)

  • Lee, Seung-Woo;Kam, Sung-Hoon;Hong, Ji-Woong;Choi, Ki-Song;Park, Eun-Seok;Chi, Sang-Cheol
    • Journal of Pharmaceutical Investigation
    • /
    • v.32 no.4
    • /
    • pp.305-311
    • /
    • 2002
  • In order to evaluate the effect of poloxamer 407 content on the dissolution profiles of pellets, diltiazem HCl (DTL) core pellets were prepared with poloxamer 407 (50-90% w/w, with lactose as filler) using an extruder and a spheronizer. Any possible interaction between the drug and excipients was evaluated using DSC, IR and TLC. Dissolution tests were performed using USP basket method. In addition, scanning electron micrograph was performed to examine the surface roughness and cross sections. The release of DTL from the core pellets was decreased with increasing poloxamer 407 content. Cracks appeared on the surface of the core pellets with increasing the poloxamer 407 content, which may play a role on the retardation of the release of DTL from core pellets. There was no any significant interaction between the drug and excipients employed to prepare the core pellets.