Serum creatine

In vivo, patients treated with AZT develop a mitochondrial myopathy with mitochondrial DNA depletion, deficiency of cytochrome c oxidase (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion (Lewis and Dalakas 1995 Dalakas 2001). Clinically, the patient presents with fatigue, myalgia, muscle weakness, wasting and elevated serum creatine kinase. Muscle biopsy shows ragged red fibers , the characteristic histopathologic changes of mitochondrial myopathy, cansed by subsarcolemmal accumulation of mitochondria (Lewis and Dalakas 1995). 

A 33-year-old female patient treated with haloperidol for a history of schizophrenia is seen in the ED because of complaints of fever, stiffness, and tremor. Her temperature is 104°F, and her serum creatine kinase (CK) level is elevated. What has occurred ... 

Even between episodes, most patients have increased serum creatine kinase (CK) forearm ischemic exercise causes no rise of venous lactate concentration. This is a... 

Sidell, F.R., Calver, D.L. and Kaminskis, A. (1974). Serum creatine phosphokinase activity after intramuscular injection. JAMA 228 1884-1887. 

Intramuscular injections have been shown to produce elevations in serum enzyme activities presumably due to either inflammatory areas in the muscle or actual breakdown of cells and release of enzyme. In one study, preinjection values of creatine phosphokinase were in the normal range of 24-100 units. Multiple intramuscular injections of penicillin, diuretics, and narcotics every 6 hours caused the creatine phosphokinase values to rise to levels between 160 to 240 units, or up to 2.5 times the upper limit of normal. When the injections were stopped, the creatine phosphokinase values returned to normal within 48 hours (B7). Similar observations of aspartate aminotransferase activities were made in patients receiving intramuscular injections of penicillin every 4 hours. Activities rose to values as high as 200 units. Other workers have reported injection related serum creatine phosphokinase elevations following intramuscular administration of chlorpromazine and suxamethonium (HIO, M11,T6). 

The stress of cold produced increased urinary excretion of norepinephrine but not of epinephrine or vasopressin (K8). Cold in the form of accidental hypothermia also resulted in increased serum creatine phos-phokinase (M2). Mental stress (problem solving) resulted in increases of urinary vasopressin from 33 to 47.6 units, epinephrine from 5.5 to 11.3 mg, and norepinephrine from 17 to 21 mg (K8). 

Myopathy and neuropathy Colchicine myoneuropathy appears to be a common cause of weakness in patients on standard therapy who have elevated plasma levels caused by altered renal function. It is often unrecognized and misdiagnosed as polymyositis or uremic neuropathy. Proximal weakness and elevated serum creatine kinase are generally present, and resolve in 3 to 4 weeks following drug withdrawal. Maiabsorption of vitamin B-f2- Colchicine induces reversible malabsorption of vitamin B-12, apparently by altering the function of ileal mucosa. 

Sldell, F.R., Culver, D.L., Kaminskis, A. 1974. Serum creatine phosphoklnase activity after intramuscular injection. The effect of dose, concentration, and volume. J. Am. Med. Assn. 229 1894-1897. 

SGPT, serum creatine phosphokinase, or serum lactic dehydrogenase were found in rabbits treated dermally with 20 mL isophorone (Dutertre-Catella 1976). No other indices of liver toxicity were examined therefore, the 20 mL dose cannot be considered a NOAEL for liver effects. 

Correct answer = D. The CK isoenzyme pattern at admission showed elevated MB isozyme, indicating that the patient had experienced a myocardial infarction in the previous 12 to 24 hours. [Note 48 to 64 hours after an infarction, the MB isozyme would have returned to normal values.] On day 2, 12 hours after the cardioconversions, the MB isozyme had decreased, indicating no further damage to the heart. However, the patient showed an increased MM isozyme after cardo-conversion. This suggests damage to muscle, probably a result of the convulsive muscle contractions caused by repeated cardioconversion. Angina is typically the result of transient spasms in the vasculature of the heart, and would not be expected to lead to tissue death that results in elevation in serum creatine kinase. 

Myopathy, which is manifested by rhabdomyolysis, muscle pain and cramps, elevated serum creatine and phosphokinase levels, and myoglobinuria. 

Figure 16-3 Assay for serum creatine kinase (CK) activity.

Why do you think that serum creatine kinase levels might be elevated in patients with seemingly unrelated conditions such as alcoholism and epilepsy ... 

A 24-year-old man took 4 g of amoxapine and developed gross hematuria and a high serum uric acid concentration on the second day of hospitalization (15). As in previously reported cases, serum creatine phosphokinase was grossly raised. The patient remained obtunded and stuporose for 7 days but eventually recovered. 

Boot E, de Haan L. Massive increase in serum creatine kinase during olanzapine and quetiapine treatment, not during treatment with clozapine. Psychopharmacology (Berl) 2000 150(3) 347-8. 

A 67-year-old man with bipolar disorder became confused, delirious, and manic (99). His only medications were olanzapine 10 mg/day and divalproex sodium 500 mg bd. On day 6, typical neuroleptic malignant syndrome developed. He had a fever (39.9°C), obtundation, rigidity, tremor, sweating, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and raised serum creatine kinase. Olanzapine was withdrawn and the syndrome resolved by day 12. 

However, serum creatine kinase activity did not increase. The symptoms disappeared when olanzapine was withdrawn. 

An 85-year-old man developed fever, muscle rigidity, and changes in mental state, but his serum creatine kinase activity was not increased (105). 

A 30-year-old man who had taken olanzapine 20 mg/ day for 10 days developed typical neuroleptic malignant syndrome with raised body temperature (39.7°C), obtundation, tremor, rigidity, sweating, fluctuating pupillary diameter, tachycardia, labile hypertension, raised serum creatine kinase activity, and severe hypernatremia (190 mmol/1) (108). 

Marcus EL, Vass A, Zislin J. Marked elevation of serum creatine kinase associated with olanzapine therapy. Ann Pharmacother 1999 33(6) 697-700. 

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