ABSTRACT
PURPOSE OF REVIEW: This review provides an overview of neuromuscular side effects associated with statin use, their diagnosis, and treatment. RECENT FINDINGS: The discovery of anti-HMGCR antibodies led to a better understanding of clinical aspects of statin-associated anti-HMGCR myopathy and its treatment. Statins are widely prescribed medications with well-established benefits in the treatment of cardiovascular diseases and stroke. Adherence to statins is influenced by development of side effects, especially muscle related. There is wide range of neuromuscular side effects associated with statin therapy. Documented neuromuscular side effects include asymptomatic elevation of muscle enzymes, mild-moderate myalgias and cramps, toxic and immune-mediated severe necrotizing myopathy, and rare cases of rhabdomyolysis. In addition, statins can lead to unmasking or triggering of underlying muscle and neuromuscular junction disorders. This article identifies the risk factors and provides a review of neuromuscular side effects associated with statin use, their diagnosis and treatment.
Subject(s)
Autoimmune Diseases , Drug-Related Side Effects and Adverse Reactions , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Muscular Diseases , Autoantibodies , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Muscular Diseases/chemically inducedABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used therapeutic agents that exhibit frequent and sometimes severe adverse effects, including gastrointestinal ulcerations and cardiovascular disorders. In an effort to obtain safer NSAIDs, we assessed the direct cyclooxygenase (COX) inhibition activity and we investigated the potential COX binding mode of some previously reported 2-(trimethoxyphenyl)-thiazoles. The in vitro COX inhibition assays were performed against ovine COX-1 and human recombinant COX-2. Molecular docking studies were performed to explain the possible interactions between the inhibitors and both COX isoforms binding pockets. Four of the tested compounds proved to be good inhibitors of both COX isoforms, but only compound A3 showed a good COX-2 selectivity index, similar to meloxicam. The plausible binding mode of compound A3 revealed hydrogen bond interactions with binding site key residues including Arg120, Tyr355, Ser530, Met522 and Trp387, whereas hydrophobic contacts were detected with Leu352, Val349, Leu359, Phe518, Gly526, and Ala527. Computationally predicted pharmacokinetic profile revealed A3 as lead candidate. The present data prove that the investigated compounds inhibit COX and thus confirm the previously reported in vivo anti-inflammatory screening results suggesting that A3 is a suitable candidate for further development as a NSAID.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Cyclooxygenase 1/chemistry , Cyclooxygenase 2/chemistry , Cyclooxygenase Inhibitors/chemistry , Phenols/chemistry , Thiazoles/chemistry , Amino Acid Motifs , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Binding Sites , Cyclooxygenase Inhibitors/chemical synthesis , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Kinetics , Meloxicam , Molecular Docking Simulation , Phenols/chemical synthesis , Protein Binding , Protein Interaction Domains and Motifs , Sheep , Structure-Activity Relationship , Thermodynamics , Thiazines/chemistry , Thiazoles/chemical synthesisABSTRACT
OBJECTIVES: To report the prevalence and characteristics of headaches in veterans with mild traumatic brain injury (TBI) and to describe most common treatment strategies after neurological evaluation. METHODS: We conducted a retrospective cohort study. The setting was a United States Veterans Healthcare Administration Polytrauma Network Site. The study participants consisted of 246 veterans with confirmed diagnosis of mild TBI. The main outcome measures were: Self-reported head pain occurring 30 days prior to initial mild TBI screening; headache severity measured by the Neurobehavioral Symptom Inventory; headache characteristics; and treatment prescribed by neurologists. RESULTS: The majority (74%) of veterans with a confirmed diagnosis of mild TBI (N=246), due largely to blast exposure, reported headaches in the 30 days preceding the initial mild TBI evaluation. Thirty-three percent of these veterans (N=81) were referred to neurology for persistent headaches. Of the 56 veterans attending the neurology evaluation, 45% were diagnosed with migraine headaches and 20% with chronic daily headaches. The most commonly used abortive agents were triptans (68%) and the most common preventive medications were anticonvulsants (55%) and tricyclics (40%). CONCLUSION: There was an increased prevalence of headaches in veterans with mild TBI. Most of the TBI veterans in our study group were exposed to blast injury and findings indicate that the nature of head trauma may be contributing to headaches. Findings highlight the need for developing effective headache prevention and treatment strategies for all persons with mild TBI and in particular for veterans with blast-related mild TBI.
