Drug induced rhabdomyolysis

Abstract

Rhabdomyolysis is a clinical condition of potential life threatening destruction of skeletal muscle caused by diverse mechanisms including drugs and toxins. Given the fact that structurally not related compounds cause an identical phenotype pinpoints to common targets or pathways, responsible for executing rhabdomyolysis. A drop in myoplasmic ATP paralleled with sustained elevations in cytosolic Ca²⁺ concentration represents a common signature of rhabdomyolysis. Interestingly, cardiac tissue is hardly affected or only secondary, as a consequence of imbalance in electrolytes or acid-base equilibrium. This dogma is now impaired by compounds, which show up with combined toxicity in heart and skeletal muscle. In this review, cases of rhabdomyolysis with novel recently approved drugs will be explored for new target mechanisms in the light of previously described pathomechanisms.

Graphical abstract

Figure 1

Schematic presentation of a skeletal muscle cell. Diseases label the location and site of injury and defect. Sarcoplasmic reticulum (SR), the ryanodine receptor (RyR), DHP receptor (the voltage sensitive L-Type Ca²⁺ channel) and sarcomeres (myocontractile machinery). During rhabdomyolysis reduced myoplasmic ATP concentrations facilitate elevated Ca²⁺ concentrations.

Figure 2

Analogs to Figure 1 drugs label the site of action within a skeletal muscle cell to trigger rhabdomyolysis. Question marks indicate postulated targets.