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Decreased pulse rate01:14

Decreased pulse rate

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Bradycardia is a medical condition in which the heart rate is slower than normal. It occurs when the heart's natural pacemaker, the sinus node, generates slower electrical impulses than the standard rhythm. In adults, bradycardia is diagnosed when the pulse rate falls below 60 beats per minute, indicating a deviation from the normal heart rate range.
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Increased pulse rate01:17

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Tachycardia is a condition marked by an abnormally fast or irregular heart rate, surpassing the typical resting rate. In adults, tachycardia is characterized by a pulse rate ranging from 100 to 180 beats per minute. The increased heart rate can result in inadequate blood flow to various body parts, ultimately diminishing the oxygen supply to organs and tissues.
Many factors can elevate the risk of developing tachycardia. These include advanced age, a family history of arrhythmias, and an...
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Factors Affecting Renal Clearance: Drug's Physicochemical Properties and Plasma Levels01:31

Factors Affecting Renal Clearance: Drug's Physicochemical Properties and Plasma Levels

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Renal clearance of a drug is influenced by various factors, including its physicochemical properties and plasma levels. These factors play a significant role in determining how efficiently the kidneys eliminate a drug.
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Drug Elimination: Non-Renal Routes01:23

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The liver plays a pivotal role in eliminating drugs and their metabolites, primarily through a process known as biliary excretion. This process involves the hepatocytes, the primary cells in the liver that generate bile. A range of transporters actively expels polar drugs or hydrophilic drug metabolites into the bile, which transports the drugs and metabolites into the small intestine. From here, they are eventually expelled from the body through feces. In some instances, the original drug or a...
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Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant

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In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
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Drug Elimination by Renal Route: Tubular Reabsorption01:22

Drug Elimination by Renal Route: Tubular Reabsorption

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During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the...
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Loop diuretics decrease the renal elimination rate and increase the plasma levels of trimethylamine-N-oxide.

G Latkovskis1,2,3, E Makarova4, M Mazule2

  • 1Institute of Cardiology and Regenerative Medicine, University of Latvia, Riga, Latvia.

British Journal of Clinical Pharmacology
|August 3, 2018
PubMed
Summary

Loop diuretics and mineralocorticoid receptor antagonists increase trimethylamine-N-oxide (TMAO) levels by reducing its excretion. Loop diuretic use is a key confounder in TMAO cardiovascular risk studies.

Keywords:
biomarkerscardiovascular pharmacologyloop diureticstrimethylamine-N-oxide

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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Biochemistry

Background:

  • Trimethylamine-N-oxide (TMAO) is an emerging biomarker for cardiovascular disease (CVD) risk.
  • Understanding factors influencing TMAO levels, such as medications, is crucial for accurate risk assessment.

Purpose of the Study:

  • To investigate the association between common cardiovascular medications and plasma TMAO levels in patients with CVD.
  • To validate these associations in a preclinical mouse model.

Main Methods:

  • Observational, cross-sectional study of 300 CVD patients (excluding diabetes) with detailed drug history.
  • Animal study involving CD1 mice to assess TMAO pharmacokinetics with specific drugs.

Main Results:

  • Loop diuretics and mineralocorticoid receptor antagonists were significantly associated with higher plasma TMAO levels.
  • In mice, furosemide and torasemide administration altered TMAO pharmacokinetics, decreasing urinary excretion and increasing tissue concentrations.
  • Probenecid did not affect plasma TMAO, suggesting the interaction is not mediated by organic anion transporters.

Conclusions:

  • Loop diuretics elevate plasma TMAO by reducing its urinary excretion rate.
  • The use of loop diuretics must be considered a potential confounding factor in studies evaluating TMAO as a cardiovascular risk marker.