Plasma creatine

Henry, P. D. Roberts, R. and Sobel, B. E. Rapid separation of plasma creatine kinase isoenzymes by batch absorption on glass beads. Clin. Chem. (1975), 21, 884-849. 

Pretreatment of rats with chlorpromazine (10 mg/kg intramuscularly) and sodium thiosulfate (1,000 mg/kg intraperitoneally) greatly decreased or abolished the increase in plasma creatine kinase observed in rats exposed to hydrogen cyanide at 200 ppm for 12.5 minutes (O Flaherty and Thomas 1982). In an in vitro study, chlorpromazine and 4,4 -diisothiocyano-2,2 -stilbene disulfonic acid reduced cyanide-induced contractions in vascular smooth muscle (Robinson et al. 1985a). It was suggested that chlorpromazine prevents cyanide-induced calcium influx and reduces peroxidation of membrane lipids (Maduh et al. 

Rhabdomyolysis is a problem with several lipid-lowering drugs (SEDA-13, 1325 SEDA-13, 1328 SEDA-13, 1330 SEDA-19, 409), especially when they are used in combination (37). In individuals with pre-existing renal insufficiency this can lead to an earlier need for chronic dialysis (38). All statins can cause myopathy and rhabdomyolysis, but not all statins are alike. For example, the evidence to date, based on almost 2 decades of experience, points to an extremely low risk of myopathy and rhabdomyolysis with lovastatin, and lovastatin 20 mg tablets are being considered for non-prescription availability in several countries (39). Furthermore, muscle adverse effects do not necessarily occur after a change from one statin to another (40). Interactions between various hypolipidemic drugs and other drugs also sometimes cause rhabdomyolysis (SEDA-18, 426). For instance, itraconazole markedly increases plasma concentrations of lovastatin, and in one subject plasma creatine kinase was increased 10-fold within 24 hours of administration of this combination (41). 

Plasma CHE was determined by a radiometric assay (9) using acetylcholine and Btf 284c51. Plasma creatine kinase fCK) was determined by a spectrophotometric method (10). 

Raised plasma creatine kinase concentration and white cell count are suggestive (but not conclusive) of neuroleptic malignant s)mdrome. There is some clinical overlap with the serotonin syndrome (see... 

Tomlinson B, Cruickshank JM, Hayes Y, Renondin JC, Lui JB, Graham BR, Jones A, Lewis AD, Prichard BN. Selective beta-adrenoceptor partial agonist effects of pindolol and xamoterol on skeletal muscle assessed by plasma creatine kinase changes in healthy subjects. Br J Clin Pharmacol 1990 30(5) 665-72. 

SEDA-19, 409), especially when they are used in combination (26). In individuals with pre-existing renal insufficiency this can lead to an earlier need for chronic dialysis (27). Interactions between various hypolipidemic drugs and other drugs also sometimes cause rhabdomyo-lysis (SEDA-18,426). For instance, itraconazole markedly increases plasma concentrations of lovastatin, and in one subject plasma creatine kinase was increased 10-fold within 24 hours of administration of this combination (28). 

Vinardell MP, Vives MA. Plasma creatine kinase activity after intramuscular injection of oily vehicles in rabbits. Pharm Pharmacol Lett 1996 6(2) 54—55. 

Skeletal muscle Cases of rhabdomyolysis (muscle fiber breakdown), leading to acute renal failure secondary to myoglobinuria, have been reported with cerivastatin and other drugs in this class. Myopathy, defined as muscle aching or muscle weakness, associated with increases in plasma creatine kinase values to greater than 10 times the upper limit of normal, was seen in 0.4% of patients in US cerivastatin clini cal trials. 

Type V, also called McArdle s disease, usually presents in the second or third decade with muscle cramps after exercise. Moderate exercise can be sustained, and patients have a second wind, when symptoms disappear if exercise is continued. Increased plasma creatine kinase activities at rest, the failure of ischemic exercise to increase serum lactate concentrations while producing an exaggerated increase in ammonia, myoglobinuria, and diminished activity of muscle phosphorylase establish the diagnosis. Patients respond to oral glucose administration or injections of glucagon. 

Stable Strontium. Rats injected intraperitoneally with 315 mg/kg of strontium as strontium chloride showed significant temporary hypercalcemia, transient hypophosphatemia, and a slight temporary rise in plasma creatine, but no change in plasma urea or glucose levels (Appleton 1995). 

Fayoll, R, H. Lefebvre, and J. P. Braun. 1992. Effects of incorrect venepuncture on plasma creatine kinase activity in dog and horse. British Veterinary Journal 148 161-162. 

In mice orally administered 3,6, or 9 g/kg of dried shiitake daily for 5 days, an increase in plasma creatine kinase activity was observed at the 9 g/kg dose. No other changes in blood chemistry were observed (Nieminen et al. 2009). 

In the resting muscle, at least 95 per cent, of the creatine is in the bound form of creatine phosphagen, and is maintained at this level by the plasma creatine, which is in equilibrium with the free creatine of the muscle. Creatine is continually being synthesised in accordance with the phosphagen requirements of the muscular and possibly other systems, the surplus being excreted as creatinine. 

When deprived of dietary choline, healthy male subjects have diminished plasma concentrations of choline and phosphatidylcholine, and they develop liver cell death (elevated plasma alanine aminotransferase). In similarly deprived animal models, the liver cell death is caused by apoptosis, a regulated form of cell suicide. In an ongoing study of choline deficiency in humans, muscle cell death (elevated plasma creatine phosphokinase, MM form) has also been noted. 

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