Myeloma bone disease is due to the overexpression of receptor activator for nuclear factor κ B ligand (RANKL) by bone marrow stroma. RANKL activates osteoclasts, which resorb bone. The resultant bone lesions are lytic (cause breakdown) in nature, and are best seen in plain radiographs, which may show "punched-out" resorptive lesions (including the "raindrop" appearance of the skull on radiography). The breakdown of bone also leads to the release of calcium ions into the blood, leading to hypercalcemia and its associated symptoms. Anemia
The anemia found in myeloma is usually normocytic and normochromic. It results from the replacement of normal bone marrow by infiltrating tumor cells and inhibition of normal red blood cell production (hematopoiesis) by cytokines. Impaired kidney function
Impaired kidney function may develop, either acutely or chronically, and with any degree of severity. The most common cause of kidney failure in multiple myeloma is due to proteins secreted by the malignant cells. Myeloma cells produce monoclonal proteins of varying types, most commonly immunoglobulins (antibodies) and free light chains, resulting in abnormally high levels of these proteins in the blood. Depending on the size of these proteins, they may be excreted through the kidneys. Kidneys can be damaged by the effects of proteins or light chains. Increased bone resorption leads to hypercalcemia and causes nephrocalcinosis, thereby contributing to kidney failure. Amyloidosis is a distant third in the causation.
Cenobamate, sold under the brand names Xcopri (US) and Ontozry (EU), is a medication used for the treatment of partial-onset seizures, a kind of epilepsy, in adults. It is taken by mouth.Cenobamate was approved for medical use in the United States in November 2019 and placed in Schedule V of the Controlled Substances Act in March 2020. Cenobamate was approved for medical use in the European Union in March 2021. Medical uses
In the United States, cenobamate is indicated for the treatment of partial-onset seizures in adults.In the European Union, it is indicated for the adjunctive treatment of focal-onset seizures with or without secondary generalization in adults with epilepsy who have not been adequately controlled despite a history of treatment with at least two anti-epileptic medications. Contraindications
Cenobamate shortens the QT interval of the heart rhythm. It is therefore contraindicated in people with familial short QT syndrome, a very rare disease of the electrical system of the heart. Adverse effects
The most common side effects are drowsiness (in 37% of people taking the drug), dizziness (33%), and fatigue (24%). Sight disorders, headache and elevated potassium levels in the blood (over 5 mmol/L) are also common. Hypersensitivity occurs in fewer than 1% of patients, drug reaction with eosinophilia and systemic symptoms (DRESS) in fewer than 0.1%. Overdose
There are few data regarding cenobamate overdose. It is expected that the described adverse effects such as drowsiness, dizziness and fatigue would occur, as well as possibly problems with the heart rhythm. No specific antidote exists.