Muscle cramps and elevated serum creatine phosphokinase levels induced by β-adrenoceptor blockers

Y. Imai, N. Watanabe, J. Hashimoto, A. Nishiyama, H. Sakuma, K. Omata, K. Abe, H. Sekino

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26 Citations (Scopus)


We have assessed the propensity of β-adrenoceptor blockers to cause muscle cramps and to raise the serum creatine phosphokinase (CPK) level in 78 patients with essential hypertension. After a control period, a β-adrenoceptor blocker without intrinsic sympathomimetic activity (ISA; propranolol, metoprolol or arotinolol) was administered for three months. Thereafter, the patients were randomised to receive a β-adrenoceptor blocker with ISA (pindolol or carteolol) for three months or a β-adrenoceptor blocker without ISA for a further three months. This pattern was continued until all β-adrenoceptor blockers had been given. At the end of each period, CPK and CPK-MB levels were measured. Of the 78 subjects, muscle cramps occurred in 27 during treatment with pindolol and 32 during treatment with carteolol. No complaints were made by subjects treated with propranolol and arotinolol, but muscle cramps were reported in 2 treated with metoprolol. While muscle cramps were caused both by pindolol and carteolol in 16 subjects, they were caused by either of these drugs in the remainder of the subjects. Muscle cramp occurred mainly in the calves when the patients were in bed at night. Serum CPK and CPK-MB levels increased significantly during treatment with pindolol (control period vs pindolol, CPK=96 vs 133 IU · ml-1, CPK-MB=14 vs 18 IU · ml-1) or carteolol (CPK=117 IU · ml-1, CPK-MB=18 IU · ml-1) while the levels during treatment with propranolol, arotinolol and metoprolol did not change from those in the control period. The change in serum CPK during treatment with carteolol or pindolol was significantly correlated with the control serum CPK level. No correlation was observed between muscle cramps and serum CPK level. There were individual differences in the severity of muscle cramps, with some subjects complaining frequently of severe muscle cramps. Because muscle cramps are frequently experienced at night, they disturb sleep and lower the quality of life in patients. This problem should be considered during treatment with β-adrenoceptor blockers with ISA.

Original languageEnglish
Pages (from-to)29-34
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Issue number1
Publication statusPublished - 1995 Mar
Externally publishedYes


  • CPK
  • CPK-MB
  • arotinolol
  • carteolol
  • intrinsic sympathomimetic action
  • metoprolol
  • muscle cramps
  • propanolol
  • β-Adrenoceptor blocker

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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