Narrative Review of Topiramate: Clinical Uses and Pharmacological Considerations.

Due to the diverse mechanisms of action of antiseizure drugs, there has been a rise in prescriptions of these drugs for non-epileptic pathologies. One drug that is now being used for a variety of conditions is topiramate. This is a narrative review that used PubMed, Google Scholar, MEDLINE, and ScienceDirect to review literature on the clinical and pharmacologic properties of topiramate. Topiramate is a commonly prescribed second-generation antiseizure drug. The drug works through multiple pathways to prevent seizures. In this regard, topiramate blocks sodium and calcium voltage-gated channels, inhibits glutamate receptors, enhances gamma-aminobutyric acid (GABA) receptors, and inhibits carbonic anhydrase. Topiramate is approved by the Food and Drug Administration (FDA) for epilepsy treatment and migraine prophylaxis. Topiramate in combination with phentermine is also FDA-approved for weight loss in patients with a body mass index (BMI) > 30. The current target dosing for topiramate monotherapy is 400 mg/day and 100 mg/day to treat epilepsy and migraines, respectively. Commonly reported side effects include paresthesia, confusion, fatigue, dizziness, and change in taste. More uncommon and serious adverse effects can include acute glaucoma, metabolic acidosis, nephrolithiasis, hepatotoxicity, and teratogenicity. Related to a broad side effect profile, physicians prescribing this drug should routinely monitor for side effects and/or toxicity. The present investigation reviews various anti-seizure medications before summarizing indications of topiramate, off-label uses, pharmacodynamics, pharmacokinetics, adverse effects, and drug-drug interactions.

Update on Overactive Bladder Therapeutic Options.

BACKGROUND: Millions of Americans are burdened by overactive bladder (OAB) syndrome and the psychogenic and economic hardships that accompany it. Several theories attempt to explain OAB as a neurogenic dysfunction, myogenic dysfunction, urothelial dysfunction, or decreased expression of a channel protein secondary to bladder outlet obstruction. Given that the etiology of OAB is a working theory, the management of OAB is also an evolving subject matter in medicine. There are uncertainties surrounding the pathophysiology of OAB, the strength of a clinical diagnosis, and accurate reporting because of the disease's stigma and decreased use of health care. DATA SOURCES: This is a narrative review that used PubMed, Google Scholar, Medline, and ScienceDirect to review literature on current and future OAB therapies. RESULTS: Currently, first-line treatment for OAB is behavioral therapy that uses lifestyle modifications, bladder-control techniques, and psychotherapy. Second-line therapy includes antimuscarinic agents or beta 3 adrenergic agonists, and studies have shown that combination therapy with antimuscarinics and beta 3 adrenergic agonists provides even greater efficacy than monotherapy. Third-line therapies discussed include onabotulinumtoxinA, posterior tibial nerve stimulation, and sacral neuromodulation. OnabotulinumtoxinA has been FDA-approved as a nonpharmaceutical treatment option for refractory OAB with minimal side effects restricted to the urinary tract. Posterior tibial nerve modulation and sacral neuromodulation are successful in treating refractory OAB, but the costs and complication rates make them high-risk procedures. Therefore, surgical intervention should be a last resort. Estrogen therapy is effective in alleviating urinary incontinence in postmenopausal women, consistent with the association between estrogen deficiency and genitourinary syndrome. Potassium channel activators, voltage-gated calcium channel blockers, and phosphodiesterase inhibitors look to be promising options for the future of OAB management. As new therapies are developed, individuals with OAB can better personalize their treatment to maximize their quality of life and cost-effective care.

Novel Designer Benzodiazepines: Comprehensive Review of Evolving Clinical and Adverse Effects.

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals. Clonazolam, or 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-α]-[1,4]-benzodiazepine, is a triazolo-analog of clonazepam. It is reported to be over twice as potent as alprazolam. Deschloroetizolam (2-Ethyl-9-methyl-4-phenyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine) is part of the thienodiazepine drug class, which, like benzodiazepines, stimulates GABA-A receptors. Meclonazepam ((3S)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one) is a designer benzodiazepine with additional anti-parasitic effects. Although it has proven to be an efficacious therapy for schistosomiasis, its sedative side effects have prevented it from being marketed as a therapeutic agent. The use of DBZs has been a subject of multiple recent clinical studies, likely related to increasing presence and availability on the internet drug market and lack of regulation. Many studies have aimed to identify the prevalence of DBZs and their effects on those using them. This review discussed these designer benzodiazepines and the dangers and adverse effects that the clinician should know.