The effect of activated charcoal on drug exposure following intravenous administration: A meta-analysis.

Activated charcoal both reduces primary drug absorption and enhances drug elimination. However, the two mechanisms of action overlap and are indistinguishable from each other. In order to estimate the extend of enhanced elimination, we summarized the effect of activated charcoal on intravenously administered drugs, where reduced drug exposure can be attributed to enhanced elimination. We performed a meta-analysis of randomized controlled studies evaluating the effect of orally administered activated charcoal on the systemic exposure of intravenously administered drugs. We searched the bibliographic databases PubMed, Embase and Cochrane. Meta-regression analyses of selected physiochemical drug properties on the effect sizes of activated charcoal were performed. All but one of 21 included studies used multiple-dose activated charcoal (MDAC). MDAC reduced the median half-life of the intravenously administered study drugs by 45.7% (interquartile range: 15.3%-51.3%) and area under the concentration time curve by 47.0% (interquartile range: 36.4%-50.2%). MDAC significantly improved drug elimination across nine different intravenously administered drugs, but we were unable to identify factors allowing extrapolation to other drugs. The results offer a possible and plausible rationale for the previously observed effects of single-dose activated charcoal beyond the timeframe where ingested drug is present in the gastro-intestinal tract.

Reduced Dietary Sodium Intake Increases Heart Rate. A Meta-Analysis of 63 Randomized Controlled Trials Including 72 Study Populations.

Reduced dietary sodium intake (sodium reduction) increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs) published in the period 1973-2014. Sixty-three of the RCTs including 72 study populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p < 0.00001, corresponding to 2.4% of the baseline heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction increases heart rate by as much (2.4%) as it decreases blood pressure (2.5%). This side-effect, which may cause harmful health effects, contributes to the need for a revision of the present dietary guidelines.

Normal range of human dietary sodium intake: a perspective based on 24-hour urinary sodium excretion worldwide.

BACKGROUND: The recommendation to restrict dietary sodium for management of hypertensive cardiovascular disease assumes that sodium intake exceeds physiologic need, that it can be significantly reduced, and that the reduction can be maintained over time. In contrast, neuroscientists have identified neural circuits in vertebrate animals that regulate sodium appetite within a narrow physiologic range. This study further validates our previous report that sodium intake, consistent with the neuroscience, tracks within a narrow range, consistent over time and across cultures. METHODS: Peer-reviewed publications reporting 24-hour urinary sodium excretion (UNaV) in a defined population that were not included in our 2009 publication were identified from the medical literature. These datasets were combined with those in our previous report of worldwide dietary sodium consumption. RESULTS: The new data included 129 surveys, representing 50,060 participants. The mean value and range of 24-hour UNaV in each of these datasets were within 1 SD of our previous estimate. The combined mean and normal range of sodium intake of the 129 datasets were nearly identical to that we previously reported (mean = 158.3±22.5 vs. 162.4±22.4 mmol/d). Merging the previous and new datasets (n = 190) yielded sodium consumption of 159.4±22.3 mmol/d (range = 114-210 mmol/d; 2,622-4,830mg/d). CONCLUSIONS: Human sodium intake, as defined by 24-hour UNaV, is characterized by a narrow range that is remarkably reproducible over at least 5 decades and across 45 countries. As documented here, this range is determined by physiologic needs rather than environmental factors. Future guidelines should be based on this biologically determined range.

Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride (Cochrane Review).

BACKGROUND: The question of whether reduced sodium intake is effective as a health prophylaxis initiative is unsolved. The purpose was to estimate the effects of low-sodium vs. high-sodium intake on blood pressure (BP), renin, aldosterone, catecholamines, and lipids. METHODS: Studies randomizing persons to low-sodium and high-sodium diets evaluating at least one of the above outcome parameters were included. Data were analyzed with Review Manager 5.1. RESULTS: A total of 167 studies were included. The effect of sodium reduction in: (i) Normotensives: Caucasians: systolic BP (SBP) -1.27 mm Hg (95% confidence interval (CI): -1.88, -0.66; P = 0.0001), diastolic BP (DBP) -0.05 mm Hg (95% CI: -0.51, 0.42; P = 0.85). Blacks: SBP -4.02 mm Hg (95% CI: -7.37, -0.68; P = 0.002), DBP -2.01 mm Hg (95% CI: -4.37, 0.35; P = 0.09). Asians: SBP -1.27 mm Hg (95% CI: -3.07, 0.54; P = 0.17), DBP -1.68 mm Hg (95% CI: -3.29, -0.06; P = 0.04). (ii) Hypertensives: Caucasians: SBP -5.48 mm Hg (95% CI: -6.53, -4.43; P < 0.00001), DBP -2.75 mm Hg (95% CI: -3.34, -2.17; P < 0.00001). Blacks: SBP -6.44 mm Hg (95% CI: -8.85, -4.03; P = 0.00001), DBP -2.40 mm Hg (95% CI: -4.68, -0.12; P = 0.04). Asians: SBP -10.21 mm Hg (95% CI: -16.98, -3.44; P = 0.003), DBP -2.60 mm Hg (95% CI: -4.03, -1.16; P = 0.0004). Sodium reduction resulted in significant increases in renin (P < 0.00001), aldosterone (P < 0.00001), noradrenaline (P < 0.00001), adrenaline (P < 0.0002), cholesterol (P < 0.001), and triglyceride (P < 0.0008). CONCLUSIONS: Sodium reduction resulted in a significant decrease in BP of 1% (normotensives), 3.5% (hypertensives), and a significant increase in plasma renin, plasma aldosterone, plasma adrenaline, and plasma noradrenaline, a 2.5% increase in cholesterol, and a 7% increase in triglyceride.

Therapeutic drug monitoring of antiarrhythmic drugs.

Most antiarrhythmic drugs fulfil the formal requirements for rational use of therapeutic drug monitoring, as they show highly variable plasma concentration profiles at a given dose and a direct concentration-effect relationship. Therapeutic ranges for antiarrhythmic drugs are, however, often very poorly defined. Effective drug concentrations are based on small studies or studies not designed to establish a therapeutic range, with varying dosage regimens and unstandardised sampling procedures. There are large numbers of nonresponders and considerable overlap between therapeutic and toxic concentrations. Furthermore, no study has ever shown that therapeutic drug monitoring makes a significant difference in clinical outcome. Therapeutic concentration ranges for antiarrhythmic drugs as they exist today can give an overall impression about the drug concentrations required in the majority of patients. They may also be helpful for dosage adjustment in patients with renal or hepatic failure or in patients with possible toxicological or compliance problems. Their use in optimising individual antiarrhythmic therapy, however, is very limited.