Sodium-Glucose Cotransporter 2 Inhibitors Mechanisms of Action: A Review

Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i), or gliflozins, are a group of antidiabetic drugs that have shown improvement in renal and cardiovascular outcomes in patients with kidney disease, with and without diabetes. In this review, we will describe the different proposed mechanisms of action of SGLT2i. Gliflozins inhibit renal glucose reabsorption by blocking the SGLT2 cotransporters in the proximal tubules and causing glucosuria. This reduces glycemia and lowers HbA1c by ~1.0%. The accompanying sodium excretion reverts the tubuloglomerular feedback and reduces intraglomerular pressure, which is central to the nephroprotective effects of SGLT2i. The caloric loss reduces weight, increases insulin sensitivity, lipid metabolism, and likely reduces lipotoxicity. Metabolism shifts toward gluconeogenesis and ketogenesis, thought to be protective for the heart and kidneys. Additionally, there is evidence of a reduction in tubular cell glucotoxicity through reduced mitochondrial dysfunction and inflammation. SGLT2i likely reduce kidney hypoxia by reducing tubular energy and oxygen demand. SGLT2i improve blood pressure through a negative sodium and water balance and possibly by inhibiting the sympathetic nervous system. These changes contribute to the improvement of cardiovascular function and are thought to be central in the cardiovascular benefits of SGLT2i. Gliflozins also reduce hepcidin levels, improving erythropoiesis and anemia. Finally, other possible mechanisms include a reduction in inflammatory markers, fibrosis, podocyte injury, and other related mechanisms. SGLT2i have shown significant and highly consistent benefits in renal and cardiovascular protection. The complexity and interconnectedness of the primary and secondary mechanisms of action make them a most interesting and exciting pharmacologic group.

Neurological problems

This chapter provides an overview of the care and management of neurological disorders commonly seen in critical care, starting with an outline of the anatomy and physiology of the nervous system. The concepts of awareness, consciousness, and arousal, and the use of the Glasgow Coma Scale (GCS) to assess conscious level are discussed. The management and monitoring of raised intracranial pressure, cerebral perfusion pressure, and the impact on cerebral blood flow are detailed. The management of sodium and water balance, including diabetes insipidus, is outlined. There are overviews of the management and nursing of patients who have suffered traumatic brain injury, subarachnoid haemorrhage, status epilepticus, myasthenia gravis, Guillain–Barré syndrome, meningitis, encephalitis, and intracranial abcess. The concept, ethics, and testing of brainstem death, organ donation, and the care of the family are detailed.

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) in Traumatic Spinal Cord Injury

Hyponatraemia is a known complication associated with neurosurgical conditions including acute spinal injury. The prevalence of hyponatraemia in acute spinal cord injury has been known to be much higher than in the general population. Hyponatraemia is a marker of different underlying diseases and it can be a cause of morbidity itself; this implies the importance of a correct approach to the problem. The syndrome of inappropriate antidiuretic hormone (SIADH) is one of the most common causes of hyponatraemia; it is a disorder of sodium and water balance characterised by urinary dilution impairment and euvolaemic/hypotonic hyponatraemia, in the absence of renal disease or any identifiable nonosmotic stimulus able to induce antidiuretic hormone (ADH) release. It is a diagnosis of exclusion. We are reporting a case of hyponatraemia in a patient with lumbar spinal cord injury who was initially managed as any other hyponatraemia and was later diagnosed as suffering from SIADH.