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Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response01:15

Chronopharmacokinetics: Circadian Rhythms and Influence on Drug Response

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Circadian rhythms are cyclic changes that are crucial in plasma drug concentrations. Various standard circadian parameters, including core body temperature, heart rate, and other cardiovascular factors, directly impact disease states and the therapeutic response to drug therapy.
The time of drug administration is an important factor to consider, as it can influence the toxic dose of a drug. For example, a study conducted by Prins et al. in 1997 examined the effects of the timing of...
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The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
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Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

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Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
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Factors Affecting Drug Response: Overview01:21

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When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
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Class I antiarrhythmic drugs are used to treat various types of arrhythmias or irregular heart rhythms. These drugs block the sodium (Na+) channels in the cardiac cells, thereby affecting the movement of electrical impulses across the heart. Class I antiarrhythmic drugs are divided into three subgroups: Class IA, Class IB, and Class IC, each with distinct mechanisms of action and effects on the heart.
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The progression of a drug's impact can be analyzed by examining both the concentration-time course and the effect-time course. The concentration-time course is determined by the drug's half-life and is influenced by factors such as its pharmacokinetics, including absorption, distribution, metabolism, and elimination. The effect of the drug is often related to its concentration in the plasma and is calculated using the maximum drug effect and the plasma concentration that generates 50...
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Bempedoic Acid: for Whom and When.

Massimiliano Ruscica1, Cesare R Sirtori2, Stefano Carugo3,4

  • 1Department of Pharmacological and Biomolecular Sciences, Università Degli Studi Di Milano, Milan, Italy. massimiliano.ruscica@unimi.it.

Current Atherosclerosis Reports
|July 28, 2022
PubMed
Summary
This summary is machine-generated.

Bempedoic acid, an orally active drug, effectively lowers LDL-C and reduces inflammation. It offers an alternative to statins, with a reduced risk of muscle-related side effects due to its liver-specific activation.

Keywords:
Bempedoic acidCLEAR OUTCOMEDiabetesMyalgiahsCRP

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Area of Science:

  • Cardiovascular Pharmacology
  • Metabolic Diseases

Background:

  • Bempedoic acid is a novel, orally active, non-statin cholesterol-lowering agent.
  • It targets ATP citrate-lyase, an enzyme upstream of cholesterol biosynthesis, distinct from statin targets.

Purpose of the Study:

  • To provide clinical insights into the safety and efficacy of bempedoic acid.
  • To define the appropriate patient population for bempedoic acid prescription.

Main Methods:

  • Review of clinical data on bempedoic acid's efficacy and safety profile.
  • Analysis of bempedoic acid's mechanism of action, metabolism, and side effect profile.

Main Results:

  • Bempedoic acid (180 mg daily) achieves significant LDL-C reduction (24.5% alone, 18% with statins, 38-40% with ezetimibe).
  • It demonstrates a favorable safety profile, with no increased risk of new-onset diabetes and moderate glycemic improvement.
  • Activation in the liver, sparing skeletal muscle, minimizes risks of myalgia and myopathy.

Conclusions:

  • Bempedoic acid is a safe and effective option for lowering LDL-C, particularly for patients intolerant to statins.
  • Its unique mechanism and safety profile make it a valuable addition to the lipid-lowering therapeutic arsenal.