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Cardiovascular Drugs: Classification based on Therapeutic Indications01:18

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Cardiovascular diseases, encompassing a range of conditions, can significantly affect the heart's operations and the overall circulatory system. These conditions impair the heart's ability to pump blood, leading to a deficit in oxygen supply to crucial organs. Anomalies in the heart's electrical system, known as arrhythmias, can cause heartbeats to accelerate or slow down. Usually, heart rates increase during physical activity and decrease while resting or sleeping. However,...
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Heart Failure Drugs: β-Blockers01:22

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β-adrenergic antagonists, commonly known as β-blockers, block the effects of sympathetic neurotransmitters such as noradrenaline (NA) and adrenaline (ADR). They have several beneficial effects in heart failure treatment. They reduce heart rate, the force of contraction, and cardiac muscle relaxation. They also slow the atrial-ventricular conduction rate and raise the threshold for arrhythmias. The concentration of β-blockers determines their effects on bronchodilation,...
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Heart Failure Drugs: Inotropic Agents01:26

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Positive inotropic agents are commonly used as the first line of treatment for heart failure. One such agent is digoxin, derived from the genus Digitalis, which has been known for centuries but effectively utilized since 1785. However, these cardiac glycosides can have potentially toxic effects due to their mechanism of action, which involves inhibiting Na+/K+-ATPase and increasing contractility. Digoxin is absorbed orally and distributed in various tissues, including the CNS. It has a long...
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Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

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Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which...
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Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

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The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
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Myocarditis is an inflammatory condition of the myocardium requiring meticulous nursing management for optimal patient outcomes. Effective management begins with a thorough assessment of the patient's medical history, paying close attention to past infections, autoimmune disorders, travel history, and exposure to toxins or drugs. Recent viral infections and systemic diseases are particularly relevant due to their potential role in triggering myocarditis.Physical Examination and MonitoringThe...
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Cardiovascular Toxicities Associated With Ibrutinib.

Joe-Elie Salem1, Ali Manouchehri2, Marie Bretagne3

  • 1Sorbonne Université, INSERM CIC-1421, AP-HP, Regional Pharmacovigilance Center, Pitié-Salpêtrière Hospital, UNICO-GRECO.6 Cardio-Oncology Program, Department of Pharmacology, Paris, France; Departments of Medicine and Pharmacology, Cardio-Oncology program, Vanderbilt University Medical Center, Nashville, Tennessee.

Journal of the American College of Cardiology
|September 28, 2019
PubMed
Summary

Ibrutinib, a treatment for B-cell malignancies, is linked to increased cardiovascular adverse drug reactions (CV-ADR), including fatal events like arrhythmias and heart failure. Early detection and monitoring are crucial for patient safety.

Keywords:
atrial fibrillationcardiac failurecardio-oncologycardiologyibrutiniboncologyventricular tachycardia

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Area of Science:

  • Pharmacovigilance
  • Cardiovascular medicine
  • Oncology

Background:

  • Ibrutinib revolutionized B-cell malignancy treatment.
  • A clinical trial indicated increased mortality with ibrutinib, suspected to be due to cardiovascular toxicities.
  • Cardiovascular adverse drug reactions (CV-ADR) were not directly assessed in that trial.

Purpose of the Study:

  • To identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib.
  • To analyze the association between ibrutinib and CV-ADR, including fatal outcomes.

Main Methods:

  • Utilized VigiBase, an international pharmacovigilance database.
  • Performed disproportionality analysis using reporting odds ratios (ROR) and information component (IC).
  • Assessed the significance of associations using IC025 > 0.

Main Results:

  • Identified 303 ibrutinib-associated cardiovascular deaths.
  • Found significant associations between ibrutinib and supraventricular arrhythmias (ROR: 23.1), heart failure (ROR: 3.5), and CNS events (ROR: 3.7).
  • CV-ADR occurred early, with fatalities ranging from 10% to 20%.

Conclusions:

  • Severe, sometimes fatal, cardiac events are associated with ibrutinib exposure.
  • These CV-ADR must be considered in patient care and clinical trial design.
  • Supraventricular arrhythmias combined with CNS events indicate a particularly poor prognosis.