Cardiotoxic chemicals

Mechanisms of Cardiotoxicity Chemical compounds often affect the cardiac conducting system and thereby change cardiac rhythm and force of contraction. These effects are seen as alterations in the heart rate, conduction velocity of impulses within the heart, and contractivity. For example, alterations of pH and changes in ionic balance affect these cardiac functions. In principle, cardiac toxicity can be expressed in three different ways (1) pharmacological actions become amplified in an nonphysiological way (2) reactive metabolites of chemical compounds react covalently with vital macromolecules... 

Intentional inhalation, or huffing, of volatile organic chemicals for the purpose of inducing euphoria can bring on cardiac arrhythmia, ventricular fibrillation, myocardial infarction, cardiac arrest, and dilated cardiomyopathy, a condition in which the heart becomes enlarged and weakened, thereby limiting its ability to pump bloodJ4 15l Table 29.2 contains a list of cardiotoxic chemicals frequently, intentionally inhaled and the common sources of these chemicals. 

The most important potential complication of phenol-based peels is cardiotoxicity. Phenol is directly toxic to myocardium. Studies in rats have shown a decrease in myocardial contraction and in electrical activity following systemic exposure to phenol [i6]. Since fatal doses ranged widely in these studies, it seems that individual sensitivity of myocardium to this chemical exists. In humans neither sex/age nor previous cardiac history/blood phenol levels are accurate predictors for cardiac arrhythmia susceptibility [17]. 

With the possible exception of maprotiline, which is chemically a modified TCA with all the side effects attributable to such a molecule, all of the newer non-tricyclic drugs have fewer anticholinergic effects and are less cardiotoxic than the older tricyclics. Lofepramine is an example of a modified tricyclic that, due to the absence of a free NH2 group in the side chain, is relatively devoid of anticholinergic side effects. Thus by slightly modifying the structure of the side chain it is possible to retain the efficacy while reducing the cardiotoxicity. 

CABG coronary art y b5rpass graft CAD coronary art y disease CAP community acquired pneumonia caps capsule cardiotox cardiotoxicity CBC complete blood count CCB calcium channel blocker CF cystic fibrosis cGMP cyclic GMP, an intracellular chemical... 

A number of industrial chemicals have been linked to cardiotoxicity. Aldehydes and primary alcohols that can be metabolically oxidized to aldehydes have exhibited cardiodepressant effects. Acute exposure to ethanol has caused arrhythmia. Isopropyl alcohol (2-propanol), a widely used industrial chemical and personal care product, may cause cardiovascular depression and excessively rapid heartbeat. Some halogenated hydrocarbons, including chloroform, ethyl bromide, and trichlo-rofluoromethane, have been implicated in cardiovascular disorders, including arrhythmia. 

The selective serotonin-reuptake inhibitors (SSRI) are a new group of chemically unique antidepressant drugs that specifically inhibit serotonin reuptake (see Figure 12.3). This contrasts with the tricyclic antidepressants that nonselectively inhibit the uptake of norepinephrine, and serotonin, and block muscarinic, H histaminic and a -adrenergic receptors. Compared with tricyclic antidepressants, the SSRIs cause fewer anticholinergic effects and lower cardiotoxicity. However, the newer serotonin reuptake inhibitors should be used cautiously until their long-term effects have been evaluated. 

Phenol is cardiotoxic, and varions cardiac dysrhythmias have been noted after apphcation to the skin, or less commonly when it has been nsed for nenrolysis. Ventricular extra beats occurred during topical apphcation of phenol and croton oil in hexachlorophene soap and water for chemical peehng of a giant hairy nevus (12). Three of sixteen children treated with motor point blocks for cerebral palsy with a phenohc solution under halothane anesthesia developed cardiac dysrhythmias (13). Severe cardiac dysrhythmias followed by circulatory arrest occurred in an elderly patient with pancreatic cancer, injected with a phenohc solution to produce splanchnic neurolysis (14). The authors recommended that ethanol should replace phenol for this purpose. 

From Table 29.1, it is obvious that chemicals with many different functional groups are cardiovascular toxins. These include hydrocarbons, chlorinated hydrocarbons, ketones, pesticides, heavy metals, and others. A unifying mechanism for the action of these far different chemicals has been proposed. This mechanism is based on a consideration of oxidative stress (OS) and postulates that chemicals or their metabolites that give rise to reactive oxygen species (ROS) that are formed by electron transfer (ET) may be cardiovascular toxins. The ET-OS-ROS mechanistic perspective has been used to account for the cardiotoxicity of the chemicals listed in Table 29.3. ... 

---