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Related Concept Videos

Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants01:18

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Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
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Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
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Pharmacodynamics in Geriatric Patients: Effects of Age01:27

Pharmacodynamics in Geriatric Patients: Effects of Age

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Age-related pharmacokinetic changes are extensively documented, but understanding age-related pharmacodynamic alterations is relatively limited. This knowledge gap can be partly attributed to the complexity of developing appropriate measures of drug responses compared to bioanalytical methods for determining drug concentrations.Most information regarding age-related differences in human pharmacodynamics originates from cross-sectional studies. However, these studies assume that observed mean...
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Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Absorption01:22

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As individuals age, their body's physiology evolves, affecting drug pharmacokinetics. The most apparent changes occur in the gastrointestinal tract, where an increase in gastric pH, a delay in gastric emptying, and a reduction in gastrointestinal motility are observed. Remarkably, these changes do not substantially modify the absorption of orally administered drugs, particularly those absorbed via passive diffusion.Transdermal drug delivery emerges as a highly viable method for older adults due...
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Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Excretion01:18

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In geriatric patients, renal physiology undergoes significant changes, including diminished renal blood flow and a lower glomerular filtration rate (GFR), leading to alterations in medication clearance. Drugs such as aminoglycoside antibiotics, lithium, and digoxin, which rely on glomerular filtration for removal from the body, particularly impact pharmacokinetics. These drugs tend to have slower clearance rates in older adults, necessitating careful dosage considerations.Evaluation of renal...
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Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism01:18

Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism

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Geriatric patients show significant variation in how their bodies process medications, which can change how effective and safe treatments are. The liver is the primary organ where drug metabolism occurs, involving two main types of chemical reactions: phase I and II. Phase I metabolism is driven by the cytochrome P450 enzyme system, which includes key types such as CYP3A, CYP2D6, and CYP2C9. Research indicates that while aging doesn't notably alter the levels or activity of these enzymes, it...
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Related Experiment Video

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Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood
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Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects.

Jack Ansell1, Sasha Bakhru2, Bryan E Laulicht3

  • 1Hofstra Northwell School of Medicine, 500 Hofstra Blvd., Hempstead, NY 11549, USA.

European Heart Journal
|September 17, 2021
PubMed
Summary
This summary is machine-generated.

Ciraparantag effectively reverses anticoagulation from apixaban and rivaroxaban in a dose-dependent manner. Specific doses achieved sustained reversal, with the drug demonstrating good tolerability in healthy elderly adults.

Keywords:
AnticoagulantAntidoteApixabanCiraparantagRivaroxaban

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Area of Science:

  • Pharmacology
  • Cardiovascular Medicine
  • Clinical Trials

Background:

  • Direct oral anticoagulants (DOACs) like apixaban and rivaroxaban are widely used.
  • Reversal agents are crucial for managing bleeding events or emergencies.
  • Ciraparantag is a novel reversal agent targeting these anticoagulants.

Purpose of the Study:

  • To assess the efficacy and safety of ciraparantag in reversing apixaban-induced anticoagulation.
  • To evaluate ciraparantag's effectiveness in reversing rivaroxaban-induced anticoagulation.
  • To determine optimal dosing for ciraparantag in elderly adults.

Main Methods:

  • Two randomized, placebo-controlled, dose-ranging trials were conducted in healthy adults aged 50-75.
  • Participants received steady-state apixaban or rivaroxaban before administration of ciraparantag or placebo.
  • Efficacy was measured by whole blood clotting time (WBCT) correction over 24 hours.

Main Results:

  • Ciraparantag demonstrated a dose-related reversal of anticoagulation for both apixaban and rivaroxaban.
  • Complete and sustained WBCT reversal was observed with specific ciraparantag doses.
  • Adverse events were mild and transient, primarily hot flashes or flushing.

Conclusions:

  • Ciraparantag effectively reverses anticoagulation from apixaban and rivaroxaban in a dose-dependent manner.
  • Sustained reversal was achieved with 60 mg for apixaban and 180 mg for rivaroxaban.
  • All tested doses of ciraparantag were well-tolerated, indicating a favorable safety profile.