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Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

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5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
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Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
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Local Anesthetics: Adverse Effects01:12

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While local anesthetics are generally safe and well-tolerated, they can occasionally cause adverse effects that vary in severity. Local anesthetics can induce toxicity at two distinct levels. They can either produce local effects through direct contact with the neural elements or be absorbed into the bloodstream from the injection site, leading to systemic effects.
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Antiarrhythmic Drugs: Class I Agents as Sodium Channel Blockers01:22

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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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Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
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Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists01:28

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Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...
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Major Adverse Cardiac Events with Ondansetron: A Systematic Review.

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Ondansetron does not increase the risk of major adverse cardiac events (MACE) or mortality in adults, despite concerns about its QT interval-prolonging effects. Further research is needed to optimize medication safety alerts.

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Area of Science:

  • Pharmacology
  • Cardiology
  • Clinical Pharmacy

Background:

  • Ondansetron is flagged for QT interval prolongation, a known risk factor for cardiac events.
  • Medication safety alerts frequently cite ondansetron due to this potential risk.
  • Major adverse cardiac events (MACE) associated with QT prolongation include death, cardiac arrest, and arrhythmias.

Purpose of the Study:

  • To systematically review and meta-analyze the literature on ondansetron's association with MACE.
  • To evaluate the risk of QT-prolongation-related cardiac events in adult patients receiving ondansetron compared to placebo.

Main Methods:

  • Searched Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Central for relevant randomized controlled trials (RCTs).
  • Included RCTs comparing ondansetron to placebo in adults, focusing on MACE outcomes.
  • Performed random-effects meta-analyses, applying corrections for studies with zero events.

Main Results:

  • Included 170 RCTs with 23,421 adult participants; 70% were surgical patients.
  • A total of seven MACE (all deaths) were reported across all included trials.
  • Ondansetron was not associated with an increased risk of mortality (RR: 1.03, 95% CI: 0.76-1.39) or arrhythmias.

Conclusions:

  • The current literature does not support an association between ondansetron use and increased MACE or mortality.
  • The low number of reported cardiac events limited the ability to perform definitive meta-analyses.
  • Further research is warranted to refine understanding of QT-prolonging medications and optimize medication safety alerts.