Stevens-Johnson Syndrome From Combined Allopurinol and Angiotensin-Converting Enzyme Inhibitors: A Narrative Review.

Stevens-Johnson syndrome (SJS) is a severe and potentially debilitating skin reaction frequently related to medication use. Allopurinol and angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for prevalent health conditions worldwide, and their interaction associated with SJS warrants further investigation. A comprehensive literature search was performed to investigate cases as studies related to SJS occurring in patients with concomitant use of allopurinol and ACE inhibitors. We identified case reports and studies detailing hypersensitivity reactions, including SJS, attributed to a combination of allopurinol and ACE inhibitors. Despite the drug-drug interactions or lack thereof seen in patient populations, there is no definitive evidence of a pharmacokinetic interaction between allopurinol and ACE inhibitors. We were only able to find one case report specifically detailing SJS in a patient on combined ACE inhibitors and allopurinol. While the exact mechanism of the interaction is unclear, those reported cases of severe hypersensitivity reactions suggest a previous history of impaired renal function as a predisposing factor in the development of SJS. The potential risk of SJS with coadministration of ACE inhibitors and allopurinol is a drug-drug interaction that physicians should be aware of. This topic requires additional attention to determine if this drug combination should be avoided entirely in certain patients.

Nonhormonal Pharmacotherapies for the Treatment of Postmenopausal Vasomotor Symptoms.

An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset. However, despite increasing prevalence, these hot flashes remain hard to treat and have a negative effect on the quality of life. Though hormone replacement therapy is commonly utilized as a standard treatment for VMSs, this therapy is not recommended for all women. Specifically, the oral form of hormone replacement therapy is associated with several contraindications, including a history of thromboembolic disease, migraine headache with aura, liver failure, heart disease, and hormone-dependent cancers. For women with these medical conditions, current literature indicates that nonhormonal therapies such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are suitable alternatives to reduce the frequency and intensity of VMSs. Currently, the only SSRI that is FDA-approved for the treatment of VMSs is paroxetine, but studies show that fluoxetine, citalopram, escitalopram, and sertraline are also proven to provide similar benefits. Similarly, the SNRI venlafaxine has also been well tolerated and has been shown to reduce the frequency and severity of hot flashes. The present investigation reviews the physiology of VMSs and examines the evidence for the use of nonhormonal pharmacologic therapies as treatment for women experiencing hot flashes. These interventions should be considered whenever hormone replacement therapy is contraindicated, with therapy individualized based on the severity of symptoms.

Chronic Administration of Melatonin: Physiological and Clinical Considerations.

BACKGROUND: Exogenous melatonin is commonly used to treat insomnia, other sleep problems, and numerous medical illnesses, including Alzheimer's disease, autism spectrum disorder, and mild cognitive impairment in adults and children. There is evolving information regarding issues with the use of chronic melatonin. METHODS: The present investigation was a narrative review. RESULTS: Melatonin usage has risen dramatically in recent years. Many countries only allow melatonin prescriptions. In the United States (U.S.), it is classified as a dietary supplement accessible over the counter and can be derived from animals, microorganisms, or, most commonly, made synthetically. No regulatory agency oversees its manufacturing or sale in the U.S. melatonin concentration of marketed preparations varies widely between product labels and manufacturers. Melatonin's ability to induce sleep is detectable. However, it is modest for most people. Sleep length appears to be less important in sustained-release preparations. The optimal dosage is unknown, and routinely used amounts vary substantially. Melatonin's short-term negative effects are minimal, resolve at medicine cessation, and do not usually prevent usage overall. Much research on long-term melatonin administration has found no difference between exogenous melatonin and placebo in terms of long-term negative effects. CONCLUSION: Melatonin at low to moderate dosages (approximately 5-6 mg daily or less) appears safe. Long-term usage appears to benefit certain patient populations, such as those with autism spectrum disorder. Studies investigating potential benefits in reducing cognitive decline and increased longevity are ongoing. However, it is widely agreed that the long-term effects of taking exogenous melatonin have been insufficiently studied and warrant additional investigation.

Osteoarthritis-Like Changes in Bardet-Biedl Syndrome Mutant Ciliopathy Mice (Bbs1M390R/M390R): Evidence for a Role of Primary Cilia in Cartilage Homeostasis and Regulation of Inflammation.

Osteoarthritis (OA) is a debilitating inflammation related disease characterized by joint pain and effusion, loss of mobility, and deformity that may result in functional joint failure and significant impact on quality of life. Once thought of as a simple "wear and tear" disease, it is now widely recognized that OA has a considerable metabolic component and is related to chronic inflammation. Defects associated with primary cilia have been shown to be cause OA-like changes in Bardet-Biedl mice. We examined the role of dysfunctional primary cilia in OA in mice through the regulation of the previously identified degradative and pro-inflammatory molecular pathways common to OA. We observed an increase in the presence of pro-inflammatory markers TGFß-1 and HTRA1 as well as cartilage destructive protease MMP-13 but a decrease in DDR-2. We observed a morphological difference in cartilage thickness in Bbs1 M390R/M390R mice compared to wild type (WT). We did not observe any difference in OARSI or Mankin scores between WT and Bbs1M390R/M390R mice. Primary cilia appear to be involved in the upregulation of biomarkers, including pro-inflammatory markers common to OA.