Etiology of Drug-Induced Edema: A Review of Dihydropyridine, Thiazolidinedione, and Other Medications Causing Edema.

Edema is an accumulation of fluid in the body's tissues that affects millions of Americans yearly. It can affect multiple body parts, for example, the brain or eyes, but often occurs in the periphery, including the feet and legs. Medications, such as dihydropyridine and thiazolidinediones (TZDs), can be the etiology of edema. Edema can develop in association with problems in the vasculature or lymphatic flow. In recent years, a better understanding of these drug-induced mechanisms has been appreciated. Specifically, dihydropyridines can increase hydrostatic pressure and cause selective pre-capillary vessel vasodilation. TZDs can cause edema through increased vascular permeability and increased hydrostatic pressure. Specifically, peroxisome proliferator-activated receptor gamma (PPARγ) stimulation increases vascular endothelial permeability, vascular endothelial growth factor (VEGF) secretion, renal sodium, and fluid retention. Other drugs that can cause edema include neuropathic pain agents, dopamine agonists, antipsychotics, nitrates, nonsteroidal anti-inflammatory (NSAIDS), steroids, angiotensin-converting enzyme (ACE) inhibitors, and insulin. There are various clinical presentations of edema. Since multiple mechanisms can induce edema, it is important to understand the basic mechanisms and pathophysiology of drug-induced edema. Edema can even become fatal. For example, angioedema can occur from ACE inhibitor therapy. In this regard, it is considered a medical emergency when there is laryngeal involvement. This review aims to thoroughly appreciate the multiple causes of drug-induced edema and the ways it can be treated or prevented.

Avacopan, a Novel Competitive C5a Receptor Antagonist, for Severe Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis.

Avacopan is a relatively novel drug with complement antagonizing properties, and it has demonstrated promising outcomes in treating antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. This review article seeks to investigate the current standard of care for ANCA vasculitis with the combination of avacopan. The current standard therapy involves the usage of daily corticosteroids in addition to either cyclophosphamide or rituximab; however, prolonged use of corticosteroids is known to be associated with various adverse effects. Avacopan was introduced as a possible substitution to alleviate high-corticosteroid dosages. It functions through competitive inhibition of the C5a receptor in the complement system and results in the reduction of neutrophil activation and migration to sites of inflammation. Clinical trials have observed the efficacy of avacopan both in conjunction with standard therapy with corticosteroids and without corticosteroids. The use of avacopan was able to achieve disease remission and improve renal function in patients with ANCA-associated vasculitis. Additionally, the novel treatment did not increase the risk of adverse events during treatment, while also lowering the toxic effects associated with corticosteroid usage. In summary, current evidence supports the success and safety of administering avacopan to treat patients with ANCA-associated vasculitis. Additional clinical trials are warranted to identify optimal dosage and method in using avacopan in the clinical setting.

Bupropion Mediated Effects on Depression, Attention Deficit Hyperactivity Disorder, and Smoking Cessation.

Bupropion had been in use since the late 1980s as an unconventional treatment for depression. Unlike other antidepressants, bupropion has no serotonergic activity and inhibits the reuptake of norepinephrine and dopamine. The drug has been used to treat depression, Attention Deficit Hyperactivity Disorder (ADHD), and smoking cessation. This investigation reviews the pharmacokinetic and pharmacodynamic effects of bupropion and its mechanisms of action and interactions with other drugs. We evaluated the efficacy of major on and off-label uses of bupropion, focusing on the indications, benefits, and adverse effects. Our review demonstrates that bupropion is superior to placebo and non-inferior to SSRIs such as escitalopram in treating major depressive disorder. More research is needed to determine positive patient-centered outcomes such as increases in quality of life. In the case of ADHD, the evidence for efficacy is mixed with poorly conducted randomized clinical trials, small sample sizes, and a lack of long-term assessments. The same is true in the case of bipolar disorder in which there is still limited and controversial data available on bupropion's safety and efficacy. In the case of smoking cessation, bupropion is found to be an effective anti-smoking drug with synergistic benefits when used as a combination therapy. We conclude that bupropion has the potential to provide benefit for a subset of patients who do not tolerate other typical antidepressants or anti-smoking therapies or for those whose treatment goals align with bupropion's unique side effect profile, such as smokers who wish to quit and lose weight. Additional research is needed to determine the drug's full clinical potential, particularly in the areas of adolescent depression and combination therapy with varenicline or dextromethorphan. Clinicians should use this review to understand the varied uses of the drug and identify the situations and patient populations in which bupropion can lend its greatest benefit.