Safety of statins: focus on clinical pharmacokinetics and drug interactions.
(57/365)
Statin monotherapy is generally well tolerated, with a low frequency of adverse events. The most important adverse effects associated with statins are myopathy and an asymptomatic increase in hepatic transaminases, both of which occur infrequently. Because statins are prescribed on a long-term basis, however, possible interactions with other drugs deserve particular attention, as many patients will typically receive pharmacological therapy for concomitant conditions during the course of statin treatment. This review summarizes the pharmacokinetic properties of statins and emphasizes their clinically relevant drug interactions. (+info)
Early and vigorous fluid resuscitation prevents acute renal failure in the crush victims of catastrophic earthquakes.
(58/365)
This study analyzes the effects of fluid resuscitation in the crush victims of the Bingol earthquake, which occurred in May 2003 in southeastern Turkey. Questionnaires asking about demographic, clinical, laboratory, and therapeutic features of 16 crush victims were filled in retrospectively. Mean duration under the rubble was 10.3 +/- 7 h, and all patients had severe rhabdomyolysis. Fourteen patients were receiving isotonic saline at admission, which was followed by mannitol-alkaline fluid resuscitation. All but two patients were polyuric. Admission serum creatinine level was lower than and higher than 1.5 mg/dl in 11 and 5 patients, respectively. Marked elevations were noted in muscle enzymes in all patients. During the clinical course, hypokalemia was observed in nine patients, all of whom needed energetic potassium chloride replacement. Four (25%) of 16 victims required hemodialysis. Duration between rescue and initiation of fluids was significantly longer in the dialyzed victims as compared with nondialyzed ones (9.3 +/- 1.7 versus 3.7 +/- 3.3 h, P < 0.03). Sixteen fasciotomies were performed in 11 patients (68%), nine of which were complicated by wound infections. All patients survived and were discharged from the hospital with good renal function. Early and vigorous fluid resuscitation followed by mannitol-alkaline diuresis prevents acute renal failure in crush victims, resulting in a more favorable outcome. (+info)
Amelioration of myoglobinuric renal damage in rats by chronic exposure to flavonol-rich red wine.
(59/365)
BACKGROUND: Myoglobinuric acute renal failure causes increased oxidative stress. Since ethanol upregulates renal antioxidant enzymes and wine polyphenols behave as antioxidants, we tested the hypothesis that red wine components would ameliorate the renal damage caused by rhabdomyolysis. METHODS: Adult rats received water (control), alcohol-free red wine, ethanol 12.5% (v/v) or red wine for 10 weeks. Rhabdomyolysis was induced by glycerol injection (50%, 10 ml/kg, i.m.), and urine and blood samples were collected 6 h later to measure renal function parameters, creatine kinase (CK) activity, free F(2)-isoprostanes and total antioxidant capacity. Kidneys were then harvested for morphological studies and determinations of lipid peroxidation, protein carbonylation, (Na + K)-ATPase and antioxidant enzyme activities. RESULTS: In the control group, myoglobinuria was associated with a 68% decrease in creatinine clearance and increases in plasma creatinine and blood urea nitrogen of 3.2 and 1.8 times above baseline, respectively. Controls also showed increases in plasma free F(2)-isoprostanes levels and CK activity, together with enhanced renal expression of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase, as well as increased production of malondialdehyde and carbonyls. Rhabdomolysis reduced renal (Na + K)-ATPase activity and this reduction was associated with a 5-fold increase in fractional sodium excretion as well as morphological damage to the kidney. These changes were significantly attenuated by pretreatment with chronic red wine exposure prior to glycerol injection. A less marked degree of functional and biochemical protection was also observed in response to the administration of alcohol-free red wine and ethanol. CONCLUSIONS: The present data suggest that red wine protects against functional, biochemical and morphological damage caused by rhabdomyolysis in the rat, and this protection may be due to the synergistic effects of ethanol and non-alcoholic red wine components. (+info)
Lack of clinical utility of urine myoglobin detection by microconcentrator ultrafiltration in the diagnosis of rhabdomyolysis.
(60/365)
BACKGROUND: In the diagnosis of rhabdomyolysis, the microconcentrator qualitative assay for urine myoglobin (uMb) is often used as a screening tool. The accuracy and clinical utility of this assay in screening patients with rhabdomyolysis have not been examined. METHODS: We conducted a retrospective analysis of the relationship between creatine kinase (CK), serum myoglobin (sMb), the urine qualitative assay for myoglobin and the semi-quantitative assay for urine haem pigments (uH) in patients evaluated for rhabdomyolysis. RESULTS: There were 673 patients with CK and uMb recorded on the same day. The uMb assay had a sensitivity of only 26.4% [95% confidence interval (CI): 23.1-29.7%] and specificity of 96.8% (95% CI: 95.5-98.1%) for the detection of severe rhabdomyolysis, defined as a CK >10 000 U/l. SMb and CK measured simultaneously in 83 patients were highly correlated (R(2) = 0.72 for log-transformed values), suggesting that the negative uMb test was not a result of the absence of sMb. In 241 patients who had CK, uMb and uH measured on the same day, the presence of 'moderate' or 'large' uH in the absence of haematuria, indicating presence of myoglobinuria, had a sensitivity of 81% (95% CI: 76-86%) for the detection of CK >10 000 U/l vs a sensitivity of 22% (95% CI: 17-27%) for the uMb assay. CONCLUSIONS: The microconcentrator-based uMb assay has a poor and clinically inadequate sensitivity in the detection and diagnosis of rhabdomyolysis. (+info)
A 55 yr-old man presented with progressive muscle weakness and oliguria for 5 days. Laboratory findings suggested rhabdomyolysis complicated with acute renal failure. A diagnosis of polymyositis was based upon the proximal muscle weakness on both upper and lower limbs, elevated muscle enzyme levels, muscle biopsy findings and the needle electromyography findings. The muscle biopsy showed extensive muscle necrosis and calcification. Investigations for underlying malignancy demonstrated hepatocellular carcinoma. The patient was managed with hemodialysis and high dose prednisolone. His renal function was fully recovered and his muscle power did improve slightly, but he died of a rupture of the hepatic tumor. In our view, this is an interesting case in that the hepatocellular carcinoma was associated with polymyositis and fulminant rhabdomyolysis-induced acute renal failure requiring hemodialysis. (+info)
Rhabdomyolysis in 119 students after repetitive exercise.
(62/365)
Exercise induced rhabdomyolysis is well known, but has rarely been reported in high school students. This is the report of 119 cases in high school students who exercised vigorously (120 push ups in five minutes) in cold weather. Most of them developed muscle pain and dark urine within two to four days of the exercise. (+info)
The role of mitochondrial uncoupling in 3,4-methylenedioxymethamphetamine-mediated skeletal muscle hyperthermia and rhabdomyolysis.
(63/365)
Use of the popular club drug ecstasy (3,4-methylenedioxymethamphetamine, MDMA) can result in life-threatening hyperthermia and rhabdomyolysis. Recent studies show a link between skeletal muscle uncoupling proteins in MDMA-mediated hyperthermia. The mechanisms by which MDMA interacts with skeletal muscle mitochondria are largely unknown. The present study was designed to comprehensively evaluate the effects of MDMA on bioenergetics and toxicity of skeletal muscle. Using (31)P nuclear magnetic resonance (NMR) and serum creatine kinase levels, we demonstrate evidence for uncoupling of oxidative phosphorylation in the skeletal muscle of MDMA (40 mg/kg)-treated rats. In vivo, rats treated with MDMA had significantly elevated serum creatine kinase levels, a marker of rhabdomyolysis, 4 h post-MDMA treatment (955 +/- 132 IU/l) compared with saline-treated controls (373.2 +/- 59 IU/l). beta-ATP signal areas after MDMA treatment showed significant reductions (15%) from the baseline values with corresponding increases in inorganic phosphate (88% increases) and decreases in intracellular pH. Clark electrode experiments on isolated skeletal muscle mitochondria in vitro (1-5 mM MDMA) and ex vivo in MDMA-treated animals demonstrated no evidence of uncoupling of oxidative phosphorylation. In vitro experiments using L6 myotubules cocultured with primary hepatocytes demonstrated the presence of uncoupling protein-3 in the L6 myotubules, but no evidence of a direct effect of MDMA or its potential metabolites on cellular creatine kinase concentrations. These findings suggest that MDMA uncouples skeletal muscle mitochondria in vivo but that this uncoupling is the result of indirect mechanisms. (+info)
Indices of muscular damage in the perioperative period of peripheral revascularization procedures.
(64/365)
AIM: We evaluated the perioperative levels of plasma myoglobin (Mb) and creatine kinase (CK) in patients submitted to peripheral revascularization surgery for a variety of conditions. METHODS, DESIGN AND SETTING: Observational study in a surgical ward of a community hospital. subjects: 50 consecutive patients were included in the study: 30 were admitted for elective peripheral revascularization (Group 1), 10 for urgent peripheral revascularization (Group 2), and 10 for major elective abdominal surgery with minimal risk of rhabdomyolysis. These latter patients served as Control Group. INTERVENTIONS: CK and Mb levels were measured immediately before intervention, 24 and 48 h postoperatively, and were compared in each group. Patients with CK >1,000 UI/l within this period were submitted to standard prophylaxis of acute renal failure (ARF), and further monitored. RESULTS: Preoperative values of CK and Mb were normal in Group 1 and Control Group, but not in Group 2. After the intervention, CK and Mb levels increased in all groups, although in a different degree. This increase was maximal in Group 2, where 9 patients showed CK >1,000 UI/l within the first 48 postoperative hours, and were submitted to ARF prophylaxis. In Group 1 CK and Mb values increased moderately, and maximal CK values were below 1,000 UI/l in all cases. The postoperative increase in CK and Mb values was minimal in Control Group, where these parameters were already in the normal range 48 hours after the intervention. CONCLUSIONS: Persistently increased CK and Mb at 48 h after a peripheral revascularization procedure are consistent with a significant ischemia-reperfusion injury. (+info)