A Systematic Critical Review of Clinical Pharmacokinetics of Torasemide.

PURPOSE: Torasemide is a potassium-sparing loop diuretic used to treat fluid retention associated with congestive heart failure and kidney and hepatic diseases. This systematic review was conducted to combine all accessible data on the pharmacokinetics (PK) of torasemide in healthy and diseased populations, which may help clinicians avert adverse drug reactions and determine the correct dosage regimen. METHODS: Four databases were systematically searched to screen for studies associated with the PK of torasemide, and 21 studies met the eligibility criteria. The review protocol was registered in the PROSPERO database (CRD42023390178). RESULTS: A decrease in maximum plasma concentration (C max ) was observed for torasemide after administration of the prolonged-release formulation in comparison to that after administration of the immediate-release formulation, that is, 1.12 ± 0.17 versus 1.6 ± 0.2 mcg/mL. After administering an oral dose of torasemide, a 2-fold increase in the area under the concentration-time curve (AUC) was reported in patients with congestive heart failure compared with the healthy population. Moreover, the patients with renal failure (clearance < 30 mL/min) showed an increase in value of AUC 0-∞ that is, 42.9 versus 8.091 mcg.h -1 .mL -1 compared with healthy subjects. In addition, some studies have reported interactions with different drugs, in which irbesartan showed a slight increase in the AUC 0-∞ of torasemide, whereas losartan and empagliflozin did not. CONCLUSIONS: The current review summarizes all available PK parameters of torasemide that may be beneficial for avoiding drug-drug interactions in subjects with renal and hepatic dysfunction and for predicting doses in patients with different diseases.

A systematic review on the clinical pharmacokinetics of vildagliptin in healthy and disease populations.

INTRODUCTION: Vildagliptin, a dipeptidyl peptidase-4 inhibitor, is indicated to cure type 2 diabetes mellitus (T2DM). This systematic literature search aims to assess the current knowledge about the clinical pharmacokinetics (PK) of vildagliptin to provide recommendations for clinical use to prevent the harmful effects of this drug. METHODS: The PubMed, Science Direct, EBSCO, Cochrane Central Register of Controlled Trials, and Google Scholar databases were screened for articles related to the clinical PK of vildagliptin using systematic search strategies. RESULTS: The literature search identified 2118 records, among which 28 were subsumed in this systematic review that fulfilled the inclusion standards. CONCLUSIONS: This systematic review can help dose optimization among critically ill patients (e.g. renal impairment) without exposing them to the drug's toxic effects.

Clinical pharmacokinetics of cefixime: a systematic review.

Cefixime is an antibiotic from the cephalosporin class used to treat various bacterial infections. The purpose of performing this review is to thoroughly evaluate the pharmacokinetic (PK) data on cefiximeFive databases were systematically searched to identify studies on the PK of cefixime.A total of 38 articles meeting the eligibility criteria were included that provide data on concentration-time profiles or PK parameters such as peak plasma and serum concentration (Cmax), area under the curve (AUC), clearance (CL), and time to reach Cmax (tmax). A dose-dependent increase in AUC and Cmax of cefixime was depicted in healthy volunteers. The clearance of cefixime decreased according to the degree of renal insufficiency among haemodialysis patients. A significant difference in CL was found in comparing fasted and fed states. A biphasic decline in serum concentrations of cefixime was reported when it was taken without probenecid.This review compiles all the reports on the PK of cefixime in healthy and really impaired patients; the summarised information can be used to optimise cefixime dosing in different disease states. Moreover, cefixime has increased time above MIC value suggesting that it may be an effective treatment for infections caused by certain pathogens.

Introduction of typhoid vaccine in the expanded immunization program of Pakistan.

Worldwide, typhoid infects 11-20 million people each year. In Pakistan, the first extensively drug-resistant (XDR) typhoid was reported in 2016 resulting in an epidemic. To curb this battle of typhoid, the Expanded Program for Immunization (EPI) of Pakistan requested Global Alliance for Vaccines and Immunization (GAVI) for financial assistance. Hence becoming the first country to administer the vaccination against typhoid in children through EPI. To address the possible risk of endemic, it is needed that WHO and the United Nations should recommend all south Asian countries to avail of this golden opportunity provided by GAVI. Finally, the addition of typhoid vaccine in routine immunization will reduce mortalities, morbidities, health expenditure, and increase life expectancy in all low- and middle-income countries.

Bladder dysfunction and hypertension in children with Guillain-Barre syndrome.

BACKGROUND: Guillain-Barre syndrome (GBS) causes acute motor, sensory and autonomic dysfunction. There is a relative paucity of published data regarding the autonomic features of GBS. The aims of this study were to describe the incidence, management and outcome of bladder dysfunction and hypertension in GBS and to ascertain whether these features relate to muscle weakness severity. CASE-DIAGNOSIS/TREATMENT: Twenty-seven patients with a median (interquartile range) age of 5.7 (3.5-8.4) years were included, of whom 18 (67%) were male and 14 (52%) had autonomic dysfunction. One patient presented with and three subsequently developed urinary retention necessitating catheterisation for a median of 7.5 (7-14.5) days. Univariate analysis demonstrated that urinary retention was associated with weakness in all four limbs [retention: MRC muscle grade 2 (2-2.75); no retention: MRC grade 4 (3-4); p = 0.02], possibly reflecting more severe disease. Patients with hypertension (12 patients, 44%) had a longer hospital stay [median 32.5 (15.5-53.5) days; rho = 0.65; p = 0.02], and those with worse muscle weakness required more anti-hypertensive medications (upper limb rho = -0.71, p = 0.03; lower limb rho = -0.72, p = 0.03]. The majority of blood pressure treatments involved calcium channel and beta blockers. CONCLUSION: In children with GBS, bladder dysfunction and hypertension are common. The presence of severe muscle weakness may predict those at greatest risk of these complications.

Complex regional pain syndrome involving the face following snowball injury.

Complex regional pain syndrome (CRPS) is a condition of unknown etiology characterized by autonomic, sensory, and motor disturbance. CRPS usually follows an injury in the affected limb, which is often trivial in nature. CRPS involving the facial region is rare, and there have been no previous descriptions in children. We describe a 13-year-old girl with CRPS involving the face, which developed after being struck by a snowball. The clinical characteristics were similar to those of CRPS elsewhere in the body involving burning pain, hyperalgesia, and hyperesthesia. This was later accompanied by skin edema, fluctuating color, and temperature changes, as well as loss of eyebrow hair. Following detailed but inconclusive investigations, a clinical diagnosis of CRPS was made in line with Budapest diagnostic criteria. Over the next year, her condition gradually improved with ongoing comprehensive multidisciplinary input. We present this patient to alert clinicians to consider CRPS in the differential diagnosis of similar cases who present with chronic facial pain and skin changes.

Acute disseminated encephalomyelitis in conjunction with inflammatory bowel disease.

Neurological complications in paediatric patients with inflammatory bowel disease (IBD) are rare. Most previous reports involve cerebral venous thrombosis, central nervous system vasculitis, or peripheral nerve inflammation. We report a child with active inflammatory bowel disease complicated by acute disseminated encephalomyelitis (ADEM). The child presented with acute neurological deficits following an exacerbation of colitis with evidence of lesions in the central nervous system white matter on magnetic resonance imaging. Ancillary investigations did not provide evidence of systemic infection, coagulation disorders, or vasculitis. In our case the colitis improved with immunosuppressive therapy, with a similar improvement in the white matter lesions showing almost complete resolution of the MR scan changes and no evidence of infarction. This case suggests that ADEM may be another extra intestinal manifestation of inflammatory bowel disease, probably associated with an autoimmune pathogenic mechanism.

Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency.

Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in DHFR, resulting in profound enzyme deficiency. We show that cerebral folate levels, anemia, and pancytopenia of DHFR deficiency can be corrected by treatment with folinic acid. The characterization of this disorder provides evidence for the link between DHFR and metabolism of cerebral tetrahydrobiopterin, which is required for the formation of dopamine, serotonin, and norepinephrine and for the hydroxylation of aromatic amino acids. Moreover, this relationship provides insight into the role of folates in neurological conditions, including depression, Alzheimer disease, and Parkinson disease.