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Adequate tissue perfusion depends on maintenance of volume status, vascular resistance, cardiac contractility, and cardiac rhythm. All of these components of the hemodynamic system are vulnerable to the effects of xenobiotics. Cardiovascular toxicity is manifested by the development of hemodynamic instability, heart failure, cardiac conduction abnormalities, or dysrhythmias. The presence of a specific pattern of cardiovascular anomalies (toxicologic syndrome or “toxidrome”) often suggests a particular class or type of xenobiotic.

In addition, an alteration in hemodynamic functioning is frequently the indirect result of metabolic abnormalities. Poisoning with a xenobiotic often leads to development of acid–base disturbances, hypoxia, or electrolyte abnormalities with secondary hemodynamic changes. In these patients, supportive care with ventilation, oxygenation, and fluid and electrolyte repletion can dramatically improve the cardiovascular status.


Maintaining cardiac contractility, heart rate and rhythm, and vascular resistance requires complex modulation of the cardiac and vascular systems. Xenobiotics cause hemodynamic abnormalities as a result of direct effects on the myocardial cells, the cardiac conduction system, or on the arteriolar smooth muscle cells. These effects are frequently mediated by interactions with cellular ion channels or cell membrane neurohormonal receptors. These complex cellular systems provide multiple sites for xenobiotics to demonstrate their toxicologic effects. Xenobiotics and xenobiotic metabolites interact with the cellular receptors, intracellular signal mechanisms, effector enzymes, or intracellular organelles.

Toxic effects of xenobiotics can be due to direct poisoning from excessive amounts of a xenobiotic that follow an overdose. Slower accumulation of the xenobiotic or active metabolites (due to alterations in metabolism) also leads to adverse effects. Additionally, the toxic effects of a xenobiotic can be altered by the characteristics of the host subject. Underlying medical conditions, presence of other xenobiotics, electrolyte abnormalities, concurrent acid–base, and hydration status contribute to the potential adverse hemodynamic effects of a xenobiotic. Even with a small concentration of a xenobiotic, hemodynamic toxicity may occur due entirely to underlying genetic differences in the cellular receptors or the intracellular signal transducers in the particular patient.

This complex interaction between the xenobiotic and patient’s physiology and genetic diversity is exemplified by the Brugada syndrome. This congenital cardiac channelopathy (Chaps. 15 and 57) predisposes to sudden cardiac death due to polymorphic ventricular tachycardia or ventricular fibrillation. Brugada syndrome is characterized by an atypical right bundle branch pattern with a characteristic cove-shaped ST segment elevation in leads V1 to V3 of the electrocardiogram (ECG) in the absence or structural heart disease, ischemia, or electrolyte disturbances).10,83 This typical type 1 Brugada ECG pattern is shown in Fig. 15-12. However, this distinctive ECG pattern can be covert30 and only unmasked by sleep, fever, bradycardia, or by xenobiotics such as vagotonic medications or class I antidysrhythmics (sodium channel blockers).4,59 The reason for this variable and dynamic response to xenobiotics is the heterogeneous genetic basis of the disorder. Mutations in ...

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