Levoketoconazole, sold under the brand name Recorlev, is a steroidogenesis inhibitor that is used for the treatment of Cushings syndrome. Levoketoconazole was approved for medical use in the United States in December 2021.Levoketoconazole is the levorotatory or (2S,4R) enantiomer of ketoconazole, and it is an inhibitor of the enzymes CYP11B1 (11β-hydroxylase), CYP17A1 (17α-hydroxylase/17,20-lyase), and CYP21A2 (21-hydroxylase). It inhibits glucocorticoid biosynthesis and hence circulating levels of glucocorticoids, thereby treating Cushings syndrome. In addition to its increased potency, the drug is 12-fold less potent than racemic ketoconazole in inhibiting CYP7A1 (cholesterol 7α-hydroxylase), theoretically resulting in further reduced interference with bile acid production and metabolite elimination and therefore less risk of hepatotoxicity. Levoketoconazole has also been found to inhibit CYP11A1 (cholesterol side-chain cleavage enzyme) and CYP51A1 (lanosterol-14α-demethylase), similarly but more potently relative to ketoconazole. References
External links
"Levoketoconazole". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03277690 for "A Study to Assess the Safety and Efficacy of Levoketoconazole in the Treatment of Endogenous Cushings Syndrome" at ClinicalTrials.gov
Clinical trial number NCT01838551 for "Treatment for Endogenous Cushings Syndrome (SONICS)" at ClinicalTrials.gov
Many medications cause dyspepsia, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (metronidazole, macrolides), bronchodilators (theophylline), diabetes drugs (acarbose, metformin, Alpha-glucosidase inhibitor, amylin analogs, GLP-1 receptor antagonists), antihypertensive medications (angiotensin converting enzyme [ACE] inhibitors, Angiotensin II receptor antagonist), cholesterol-lowering agents (niacin, fibrates), neuropsychiatric medications (cholinesterase inhibitors [donepezil, rivastigmine]), SSRIs (fluoxetine, sertraline), serotonin-norepinephrine-reuptake inhibitors (venlafaxine, duloxetine), Parkinson drugs (Dopamine agonist, monoamine oxidase [MAO]-B inhibitors), weight-loss medications (orlistat), corticosteroids, estrogens, digoxin, iron, and opioids. Common herbs have also been show to cause indigestion, like white willow berry, garlic, ginkgo, chaste tree berry, saw palmetto, and feverfew. Studies have shown that wheat and dietary fats can contribute to indigestion and suggest foods high in short-chain carbohydrates (FODMAP) may be associated with dyspepsia. This suggests reducing or consuming a gluten-free, low-fat, and/or FODMAP diet may improve symptoms. Additionally, some people may experience dyspepsia when eating certain spices or spicy food as well as foods like peppers, chocolate, citrus, and fish. Systemic Diseases
There are a number of systemic diseases that may involve dyspepsia, including coronary disease, congestive heart failure, diabetes mellitus, hyperparathyroidism, thyroid disease, and chronic kidney disease. Post-infectious Causes of Dyspepsia
Gastroenteritis increases the risk of developing chronic dyspepsia. Post-infectious dyspepsia is the term given when dyspepsia occurs after an acute gastroenteritis infection. It is believed that the underlying causes of post-infectious IBS and post-infectious dyspepsia may be similar and represent different aspects of the same pathophysiology. Pathophysiology
The pathophysiology for indigestion is not well understood; however, there are many theories.