To compensate for this deficit in function, the colon increases its potassium secretion as part of an adaptive response. However, serum potassium remains elevated as the colonic compensating mechanism reaches its limits. Elevated potassium
Hyperkalemia develops when there is excess production (oral intake, tissue breakdown) or ineffective elimination of potassium. Ineffective elimination can be hormonal (in aldosterone deficiency) or due to causes in the kidney that impair excretion.Increased extracellular potassium levels result in depolarization of the membrane potentials of cells due to the increase in the equilibrium potential of potassium. This depolarization opens some voltage-gated sodium channels, but also increases the inactivation at the same time. Since depolarization due to concentration change is slow, it never generates an action potential by itself; instead, it results in accommodation. Above a certain level of potassium the depolarization inactivates sodium channels, opens potassium channels, thus the cells become refractory. This leads to the impairment of neuromuscular, cardiac, and gastrointestinal organ systems. Of most concern is the impairment of cardiac conduction, which can cause ventricular fibrillation and/or abnormally slow heart rhythms. Diagnosis
To gather enough information for diagnosis, the measurement of potassium must be repeated, as the elevation can be due to hemolysis in the first sample. The normal serum level of potassium is 3.5 to 5 mmol/L. Generally, blood tests for kidney function (creatinine, blood urea nitrogen), glucose and occasionally creatine kinase and cortisol are performed.
Mobocertinib, sold under the brand name Exkivity, is used for the treatment of non-small cell lung cancer.The most common side effects include diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.Mobocertinib is a small molecule tyrosine kinase inhibitor. Its molecular target is epidermal growth factor receptor (EGFR) bearing mutations in the exon 20 region. Mobocertinib is an irreversible kinase inhibitor, forming a covalent bond with the cysteine 797 in the EGFR active site, leading to sustained inhibition of EGFR enzymatic activity. The irreversible binding leads to increased potency via higher affinity binding, more sustained EGFR kinase activity inhibition, and greater overall selectivity, as only a limited number of other kinases possess a cysteine in the equivalent position.Mobocertinib was approved for medical use in the United States in September 2021. It is a first-in-class oral treatment to target EGFR Exon20 insertion mutations. Medical uses
Mobocertinib is indicated for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. Mechanism of action
Mobocertinib acts to inhibit EGFR exon 20 insertion mutations at a lower concentration than it does on wild-type proteins. Pharmacokinetics
The volume of distribution of Mobocertinib at steady state is 3,509 L.  The mean oral bioavailability of Mobocertinib is 37%. The median Tmax is 4 hours. The average half-life of Mobocertinib and its metabolites is 18 hours. Mobocertinib is metabolized by CYP3A enzymes.