Tumor Necrosis Factor and Interleukin Modulators for Pathologic Pain States: A Narrative Review.

Chronic pain, a complex and debilitating condition, involves intricate interactions between central and peripheral inflammatory processes. Cytokines, specifically tumor necrosis factor (TNF) and interleukins (IL), are key mediators in the initiation and maintenance of chronic pain states. Sensory neurons expressing receptors for cytokines like TNF, IL-1, and IL-6 are implicated in peripheral sensitization, contributing to increased signaling of painful sensations. The potential of targeting TNF and IL for therapeutic intervention in chronic pain states is the focus of this review, with preclinical and clinical evidence supporting the use of TNF and IL modulators for pain management. The physiological and pathological roles of TNF in neuropathic pain is complex. Experimental evidence highlights the effectiveness of TNF modulation in mitigating pain symptoms in animal models and displays promising outcomes of clinical trials with TNF inhibitors, such as infliximab and etanercept. ILs, a diverse group of cytokines, including IL-1, IL-6, and IL-17, are discussed for their contributions to chronic pain through inflammation and peripheral sensitization. Specific IL modulators, such as secukinumab and tocilizumab, have shown potential in managing chronic neuropathic pain, as demonstrated in various studies and clinical trials. The pharmacokinetics, safety profiles, and challenges associated with TNF and IL modulators highlight the need for cautious medication monitoring in clinical practice. Comparative evaluations have revealed distinct efficacy and safety profiles among different cytokine modulators, emphasizing the need for personalized approaches based on the specific underlying causes of pain. Further research is necessary to elucidate the intricate mechanisms by which cytokines contribute to chronic pain, as well as to understand why they may affect pain differently in various contexts. Additionally, long-term safety profiles of cytokine modulators require more thorough investigation. This continued exploration holds the promise of enhancing our comprehension of cytokine modulation in chronic pain and shaping more potent therapeutic strategies for the future.

Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked to Morbidity and Mortality a Narrative Review.

Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. In this regard, there is the potential for death. Additionally, the rise in fake Xanax tablets containing etizolam and other counterfeit medications has been exacerbated by the difference in regulations regarding these substances in different countries as well as the illegal drug trade. Healthcare providers may also play a role through the over- or underprescribing of certain medications. Thus, in order to combat the rise in counterfeit medications such as fake Xanax, international cooperation, regulation, and enforcement of laws pertaining to the manufacture, prescription, and distribution of these substances are needed.

Hyponatremia With Anticonvulsant Medications: A Narrative Review.

Hyponatremia is an adverse effect of many antiseizure medications (ASMs). It occurs with interference with the normal balance of electrolytes within the body. Various risk factors associated with the development of hyponatremia in patients taking these medications include age, gender, dosage, and combinations with other drugs. ASMs such as carbamazepine (CBZ), oxcarbazepine (OXC), and valproic acid have a higher risk of hyponatremia. Hyponatremia induced by an antiseizure medication can occur through various mechanisms depending on the drug's specific mechanism of action. Hyponatremia can be a potentially fatal side effect. Patients taking these medications need to be monitored closely for the signs and symptoms of hyponatremia. Acute hyponatremia, defined as developing in <48 hours, is more likely to show symptoms than chronic hyponatremia. Signs of acute hyponatremia include delirium, seizures, decerebrate posturing, and cerebral edema with uncal herniation. Chronic hyponatremia, defined as developing in >48 hours, can cause lethargy, dizziness, weakness, headache, nausea, and confusion. Hyponatremia is associated with longer hospital stays and increased mortality. Treatment varies based on the degree of severity of hyponatremia. Choosing a treatment option should include consideration of the drug causing the electrolyte disturbance, the patient's risk factor profile, and the severity of symptoms as they present in the individual patient. Healthcare providers should be aware of hyponatremia as a potential side effect of ASMs, the signs and symptoms of hyponatremia, the different treatment options available, and the potential complications associated with rapid correction of hyponatremia.

Delirium Tremens: A Review of Clinical Studies.

Delirium tremens (DT) is a severe condition resulting from alcohol withdrawal. This review highlights the challenges in diagnosing and managing DT and emphasizes the importance of early recognition and intervention to prevent complications and ensure optimal patient outcomes. The discussion of the pathophysiology of DT, focusing on the neurochemical imbalances involving the neurotransmitters gamma-aminobutyric acid and glutamate, explains how chronic alcohol dependence leads to these imbalances and contributes to the hyperexcitability seen in DT. The management of DT involves ensuring patient safety and alleviating symptoms, primarily through pharmacological approaches, such as benzodiazepines. Closely monitoring vital signs and electrolyte imbalances is necessary due to autonomic dysregulation associated with DT. The mention of the potential complexity of DT when coexisting with other conditions emphasizes the need for additional research to advance comprehension, identify predictive factors, and enhance its management.

The Evolving Role of Monomethyl Fumarate Treatment as Pharmacotherapy for Relapsing-Remitting Multiple Sclerosis.

Multiple sclerosis is the most common autoimmune disease affecting the central nervous system (CNS) worldwide. Multiple sclerosis involves inflammatory demyelination of nerve fibers in the CNS, often presenting with recurrent episodes of focal sensory or motor deficits associated with the region of the CNS affected. The prevalence of this disease has increased rapidly over the last decade. Despite the approval of many new pharmaceutical therapies in the past 20 years, there remains a growing need for alternative therapies to manage the course of this disease. Treatments are separated into two main categories: management of acute flare versus long-term prevention of flares via disease-modifying therapy. Primary drug therapies for acute flare include corticosteroids to limit inflammation and symptomatic management, depending on symptoms. Several different drugs have been recently approved for use in modifying the course of the disease, including a group of medications known as fumarates (e.g., dimethyl fumarate, diroximel fumarate, monomethyl fumarate) that have been shown to be efficacious and relatively safe. In the present investigation, we review available evidence focused on monomethyl fumarate, also known as Bafiertam®, along with bioequivalent fumarates for the long-term treatment of relapsing-remitting multiple sclerosis.

Odevixibat: A Novel Bile Salt Inhibitor Treatment for Pruritus in Progressive Familial Intrahepatic Cholestasis.

Chronic pruritus is defined as an itch lasting greater than six weeks. It can manifest from a wide variety of etiologies, as many different substances can act as pruritogens, such as steroids, histamine, progesterone, endogenous opioids, and serotonin. In the setting of cholestatic liver disease, increased bile acids play a major role in chronic pruritus. The itching in cholestatic liver disease is worsened in intensity at night and localized frequently to the palms, soles, knees, and other pressure sites. It can be hard to manage, affecting the quality of sleep and causing irritability, poor attention, and, in some cases, depression. One such disease that results from chronic pruritus is progressive familial intrahepatic cholestasis (PFIC), a group of uncommon hereditary disorders that affects the formation of bile and its outflow from the liver. Previously, the drug ursodeoxycholic acid was used to help manage pruritus or surgical procedures, e.g., partial external biliary diversion or partial internal biliary diversion, to help control complications of the disease. This literature review will discuss three clinical studies covering the effectiveness of odevixibat in treating pruritus in patients with PFIC. Odevixibat (Bylvay) is an oral drug that has been FDA-approved to treat pruritus in patients three months of age and older with PFIC. Odevixibat prevents the reabsorption of bile salts in the intestines, resulting in decreased levels of bile salts via their excretion in stool. Several studies have determined that the drug is well tolerated and provides a nonsurgical, pharmacological treatment alternative for those with PFIC.

Fluoroquinolones: Neurological Complications and Side Effects in Clinical Practice.

Fluoroquinolones, a popular antibiotic class that inhibits nucleic acid synthesis of bacteria by disrupting the activity of the enzyme's topoisomerase IV and DNA gyrase, are used to treat bacterial infections. However, the widespread use of these drugs has allowed for the development of microbial resistance in recent years. Quinolones also have many clinically relevant side effects, including psychosis, confusion, seizures, headaches, dizziness, and nausea. Common side effects include tendinitis, myopathy, depression, and fatigue. Cardiovascular side effects include increased risk of aortic aneurysm, aortic dissection, and QT interval prolongation. Overall, quinolones can be an effective choice for treating bacterial infections. Still, the side effect profile and decreased efficacy secondary to microbial resistance no longer make the quinolone class an ideal choice for many types of infection. A better understanding of the role of quinolone-mediated or neurological damage, cardiovascular impairment, and musculoskeletal involvement is imperative to determine the risks/benefits for the clinician.

Xylazine: A Drug Adulterant of Clinical Concern.

PURPOSE OF REVIEW: The opioid epidemic has been responsible for significant morbidity and mortality in the USA and worldwide. As a result, it is essential to recognize the threat these potent drugs can cause when illicitly used. Specifically, introducing fentanyl as a drug adulterant has been shown to impact overdose rates drastically. In this regard, the Drug Enforcement Agency recently released a public safety alert announcing the new threat of a new adulterant called xylazine. Xylazine is a powerful animal sedative with a different mechanism of action when compared to illicit opioids such as heroin and fentanyl. Xylazine is typically injected intravenously via a syringe, often in combination with multiple other drugs. One of the most common drugs, xylazine, is taken in combination with fentanyl, with users of this drug combination describing xylazine as prolonging the euphoric sensation produced by fentanyl. RECENT FINDINGS: Xylazine may cause adverse effects such as bradycardia, brief hypertension followed by hypotension, premature ventricular contractions, ataxia, slurred speech, sedation, and respiratory depression. Much of the recent literature on xylazine use in humans comes from case reports and review articles. Related to widespread use in veterinary medicine and increasing circulation in illicit drug markets, there is a critical need for public awareness and additional clinical-based studies to further increase understanding of mediated or modulated pharmacological effects of xylazine in humans. Further research is urgently needed to more clearly understand the implications of unregulated xylazine in the illicit drug market, to formulate public health interventions, and to implement harm reduction strategies.

A Comprehensive Review of Solriamfetol to Treat Excessive Daytime Sleepiness.

Purpose of Review: This is a comprehensive review of the literature regarding the use of Solriamfetol for excessive daytime sleepiness. It covers the background and current therapeutic approaches to treating excessive daytime sleepiness, the management of common comorbidities, and the existing evidence investigating the use of Solriamfetol for this purpose. Recent Findings: Excessive daytime sleepiness leads to worse quality of life, a medical sequela and significant economic cost. There are multiple phenotypes of excessive daytime sleepiness depending on the comorbidity making treatment challenging. Due to the complexity of etiology there is not a cure for this ailment. Solriamfetol is a norepinephrine/dopamine dual reuptake antagonist that can be used to manage daytime sleepiness. Solriamfetol was first approved by the FDA in 2018 for use in excessive daytime sleepiness associated with obstructive sleep apnea and narcolepsy. Ongoing literature has proved this drug to be a safe and effective alternative pharmacotherapy. Summary: Recent epidemiological data estimate up to one-third of the general adult population suffers from excessive daytime sleepiness. There is no cure to daytime somnolence and current pharmacotherapeutic regimens have worrisome side effect profiles. Solriamfetol is a new class of drug that offers a safe and effective alternative option for clinical providers treating excessive daytime sleepiness.

A Comprehensive Review of Lemborexant to Treat Insomnia.

Purpose of Review: This is a comprehensive review of the literature regarding Lemborexant for the treatment of insomnia. It covers the background and management of insomnia and then reviews the body of existing evidence evaluating the use of Lemborexant for this purpose. Recent Findings: Insomnia leads to significant decreased in quality of life and economic burden due to decreased workplace performance and increased health care costs. Insomnia manifests as a single common pathway of hyperarousal due to a highly complex network of interactions between activation of the sympathetic system and the endocrine system. Lemborexant is a dual orexin 1/2 antagonist that blocks cortical arousal and promotes sleep state transition. Lemborexant was approved by the FDA in 2019 for use in insomnia. It belongs to a class of orexin neuropeptide inhibitors that is growing in popular clinical application. Summary: Insomnia is a crippling disorder of the sleep wake cycle that drives significant morbidity and mortality in the United States. It carries a high societal and economic toll due to direct and indirect effects to the healthcare system. Lemborexant is a new addition to the orexin antagonist class of drugs that already includes Almorexant and Suvorexant that has superior pharmacokinetic properties. While Lemborexant does have a mild side effect profile, its clinical safety and efficacy make it a promising insomnia drug of the future.

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.

Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging. OBJECTIVES: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. METHODS: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed. The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain. Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations. LIMITATIONS: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. CONCLUSION: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded - and herein recommended - that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments.

Acromegaly: Pathophysiological Considerations and Treatment Options Including the Evolving Role of Oral Somatostatin Analogs.

Acromegaly is a condition most commonly diagnosed in the fifth decade of life and has numerous treatment options. In this regard, Mycapssa® is the first FDA-approved oral octreotide capsule for treating acromegaly, combining the efficacy of the somatostatin receptor ligand, octreotide, with the ease of a twice-daily oral capsule. Where surgical treatment is not an option, somatostatin analogs, including octreotide, are the first line of medical treatment for acromegaly, requiring regular subcutaneous or intramuscular injections administered by a patient's healthcare provider. Octreotide capsules (Mycapssa®) provide an alternative to these somatostatin receptor ligand injections by combining octreotide with other excipients to produce a transient permeability enhancer technology that improves paracellular transport of octreotide across the gastrointestinal wall into the small intestine. Across multiple trials, including open-label (CH-ACM-01), double-blind placebo-controlled (CHIASMA OPTIMAL), and open-label extension of the trial period (CHIASMA OPTIMAL OLE), Mycapssa® octreotide capsules maintained a consistent biochemical normalization of IGF-1 and GH levels, safety profiles similar to injected somatostatin receptor ligands, and patient preference to continued treatment with octreotide capsules. While clinical trial data supports the use of octreotide capsules (Mycapssa®) in the pharmacological management of GH and IGF-1 levels, very little data exist regarding the drug's efficacy, tolerability, and use in female or pediatric-specific populations. A better understanding of the efficacy, application, and role of oral octreotide capsules in the long-term medical management of acromegaly in a diversity of populations is imperative to best determine the risks/benefits for the clinician.

Lyme Disease and Post-treatment Lyme Disease Syndrome: Current and Developing Treatment Options.

Lyme disease and its treatment implications have become an ever-increasing area of concern within the United States related to the markedly increased prevalence of infection within the last two decades. The presentation, pathophysiology, and epidemiology of Lyme disease have been well studied, and thus treatments for this disease are widely available. While the treatment of its early and late stages is relatively simple with 10-14 day and four-week courses of doxycycline, respectively, the main problem rests in the understanding of the etiology and pathology of post-treatment Lyme disease syndrome (PTLDS). With the time of symptoms onsetting approximately six months after treatment and potentially lasting indefinitely, this syndrome's effect on patients' quality of life could be devastating. Searching on PubMed, Google Scholar, MEDLINE, and ScienceDirect using keywords including Lyme disease, PTLDS, doxycycline, erythema migrans, azlocillin, and treatment, the authors have tried to make clear the different aspects. The authors have reviewed and discussed clinical studies of Lyme disease and its treatments/potential therapeutics as well as PTLDS and its sparse treatments/potential therapeutics.

Impact of a Neuropsychiatric Therapeutics Course and a Case-Based Course on Pharmacy Students' Mental Health Stigma.

OBJECTIVE: Mental health education can reduce the stigma held by medical and nursing students; however, findings in this regard are limited in pharmacy academia. This study investigated the impact of a neuropsychiatric therapeutics course followed by a case-based course on the mental health stigma held by pharmacy students. METHODS: A survey was conducted of second-year pharmacy students (n = 202) on the first and last day of a neuropsychiatric therapeutics course and 4 months later, at the end of a case-based course. The questionnaires included the Opening Minds Stigma Scale for HealthCare Providers (OMS-HC) scale, Recovery scale, Empowerment scale, and Attribution Questionnaire (AQ-9). Omnibus Friedman tests evaluated the main effect of time, followed by Wilcoxon signed-rank post hoc tests to compare baseline and postcourse scores. RESULTS: Friedman test outcomes showed significant main effects of Time for OMS-HC, Recovery, Empowerment, and AQ-9 scales. Post hoc analysis indicated that compared to the baseline scores, the scores on Recovery and Empowerment scales significantly increased, OMS-HC scores decreased, but AQ-9 scores did not change after the therapeutics course. Compared to the baseline, OMS-HC and AQ-9 scores decreased, Recovery scale score increased, but the Empowerment scale score did not change after the case-based course. The scores did not decrease further after the case-based course compared to those after the therapeutics course. CONCLUSION: The decreases in OMS-HC and AQ-9 scores and increases in Recovery and Empowerment scores indicate reductions in mental health stigma. Stigma among students was overall reduced after the therapeutics course and this reduction was maintained after the case-based course.

Cebranopadol for the Treatment of Chronic Pain.

PURPOSE OF REVIEW: Regardless of the etiology, if pain persists chronically, it can detrimentally impact multiple aspects of a patient's well-being. Both physical and psychological effects are significant in many chronic pain patients. In this regard, psychological consequences can alter a patient's quality of life, functionality, and social functioning. Opioids have been the long-established gold standard for acute pain treatment in settings such as the postoperative period. An alternative to opioids in pain management has been highly sought after. Through a non-selective mechanism, cebranopadol is a first-in-class oral drug which combines agonism of the mu and nociceptin opioid peptide (NOP) receptors to provide improved analgesia, while reducing the occurrence of many typically opioid side effects. This manuscript is a narrative review of the possible use of cebranopadol in pain management. RECENT FINDINGS: In pre-clinical studies, cebranopadol was similar to morphine in its pain control efficacy. In a phase IIa trial, cebranopadol was superior to placebo in reducing pain. In a randomized clinical trial, cebranopadol was superior to morphine. Another study concluded that cebranopadol had a lower misuse potential when compared to hydromorphone. In summary, cebranopadol offers new opportunities in treating chronic moderate to severe pain, while also countering risks of addiction. Additional studies are warranted to further evaluate the safety and efficacy of cebranopadol. In this regard, cebranopadol could prove to be a promising alternative to current pain treatment options.

Tianeptine, an Antidepressant with Opioid Agonist Effects: Pharmacology and Abuse Potential, a Narrative Review.

Tianeptine is an antidepressant drug approved for the treatment of major depressive disorder in countries other than the US. It is classified as an atypical tricyclic antidepressant and has shown potential benefits in addressing anxiety and irritable bowel disease. However, it is important to note that tianeptine is not approved for any use by the United States Federal Drug Administration (FDA). Despite its lack of approval by the FDA, tianeptine has been distributed online and at small retail locations. The term "gas station drugs" refers to a wide range of substances typically available for purchase from gas stations, corner stores, bodegas, mini marts, smoke shops, and the Internet. These substances may be produced commercially by drug manufacturers or in clandestine laboratories to mimic the effects of more well-known illicit/controlled substances such as marijuana, cocaine, opioids, etc. Tianeptine has made its way to convenience stores and gas station shelves, branded as "Zaza" and "Tianna Red." It can also be obtained online from independent vendors without a prescription. Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance. Overdose and use in suicide attempts have also been documented. This manuscript is a narrative review, highlighting the dangers of tianeptine and other gas station drugs and underscoring the urgent need to regulate these substances.

The Emerging Role of Ketamine in Acute Postoperative Pain Management.

PURPOSE OF REVIEW: Postoperative pain (POP) is among the most unpleasant experiences that patients face after surgery. Interest in and use of N-methyl-D-aspartate (NMDA) receptor antagonists for the management of POP has increased over the years with ketamine being the most popular drug of this class. RECENT FINDINGS: Several randomized controlled trials found that the use of ketamine either alone or in combination with other medications leads to decreased postoperative pain and opioid consumption. However, there are other studies that have not found these benefits. The results as of now suggest that the role of intraoperative ketamine in postoperative pain control varies among different operative procedures. While some studies have shown promise in ketamine's potential use as a postoperative analgesic, there is still a great deal of proposed research and randomized controlled trials needed to deduce the most efficacious and tolerable form and dose of ketamine.

Proton Pump Inhibitors, Kidney Damage, and Mortality: An Updated Narrative Review.

Since their approval by the Food and Drug Administration (FDA) in 1989, proton pump inhibitors (PPIs) have become one of the most highly utilized drugs in the United States, assuming a position as one of the top 10 most prescribed medications in the country. The purpose of PPIs is to limit the amount of gastric acid secreted by the parietal cells via irreversible inhibition of the H+/K+-ATPase pump, therefore maintaining an elevated gastric acid pH of greater than 4 for 15-21 h. Even though PPIs have many clinical uses, they are not without their adverse effects, mimicking achlorhydria. Besides electrolyte abnormalities and vitamin deficiencies, long-term use of PPIs has been linked to acute interstitial nephritis, bone fractures, poor COVID-19 infection outcomes, pneumonia, and possibly an increase in all-cause mortality. The causality between PPI use and increased mortality and disease risk can be questioned since most studies are observational. Confounding variables can greatly affect an observational study and explain the wide-ranging associations with the use of PPIs. Patients on PPIs are generally older, obese, sicker with a higher number of baseline morbidities, and on more medications than the compared PPI non-users. These findings suggest that PPI users are at a higher risk of mortality and complications based on pre-existing conditions. This narrative review aims to update readers on the concerning effects that proton pump inhibitor use can have on patients and give providers a resource to create informed decisions on appropriate PPI use.

Low-Dose Initiation of Buprenorphine: A Narrative Review.

PURPOSE OF REVIEW: Opioid use disorder (OUD) is a chronic disorder in which a person loses control over the use of opioids, develops a compulsive behavior, and defends the use despite knowing the negative consequences. There are numerous treatments for OUD, including buprenorphine. Since it is displacing a full agonist opioid, precipitated withdrawal can occur with standard inductions involving buprenorphine. RECENT FINDINGS: Case reports have noted success with a low-dose initiation of buprenorphine, which is different from typical protocols, relatively limited by adverse effects when patients were recently administered full agonists. A cohort investigation studied the use of a transdermal patch as part of the protocol, which was fairly well tolerated. While ongoing research is being conducted on this topic, recent case studies and smaller cohort studies have demonstrated the feasibility of a trial to treat OUD with low-dose initiation of buprenorphine.