Comprehensive review of cardiovascular toxicity of drugs and related agents PMC

Alcohol doesn’t just affect us in the short-term with reduced inhibitions, blackouts and hangovers. It can also leave a lasting effect on the body, especially our brain, immune system and heart. It’s also important to know that the ways in which alcohol affects your heart will vary from person to person, depending on your age and other conditions you may have. Marie Vopršalová is the senior lecturer in Toxicology at the department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Czech Republic.

Therefore, people with heart disease or risk factors should stop drinking or limit their alcohol intake to reduce their risk of a heart attack. Ethanol-induced changes may be related to oxidative what are sugar alcohols or nonoxidative pathways of ethanol metabolism. More than one mechanism may be activated and may lead to the multitude of ethanol-induced changes in cellular proteins and cell function.

Aldosterone/cortisol activity in a mineralocorticoid sensitive kidney tubule cell under physiological conditions (A), or after inhibition by glycyrrhetinic acid (B). Through DNA binding (4), the expression of Na+ channels and Na+/K+‐ATPase (5) is upregulated. When glycyrrhetinic acid is present in plasma, it can penetrate into cells (6), where it has a high affinity for the enzyme (7). As a consequence of enzyme inhibition, cortisol is not inactivated and binds to MR (8) and the same cascade (part A, 4–5) occurs without the need for aldosterone. BThioridazine is considered to possess a higher risk than haloperidol; torsade de pointes can develop with low doses, but in overdose torsade de pointes is infrequent.

  1. The earliest recorded death caused by mercury is the one of Qin Shi Huang, an Emperor of China (260–210 BC).
  2. Some workshop participants expressed disagreement regarding the urgency
    of concern with consumption of energy drinks, with one audience member
    remarking that he has not seen “in the real clinical
    world” the adverse effects being studied in the lab.
  3. For many years, mercury was used in a wide variety of human activities, and now, exposure to this metal from both natural and artificial sources is significantly increasing.
  4. Further follow-up is needed to determine the exact profile and outcomes of related cardiac side effects.

Cytotoxics, such as anthracyclines, or other biological agents have been implicated in causing clinically significant cardiac dysfunction. Many targeted agents have been introduced in clinical practice and rare, but serious, complications have been described. Further follow-up is needed to determine the exact profile and outcomes of related cardiac side effects.

In more severe intoxications, atrial and also ventricular tachydysrhythmias could appear, likely due to the delayed afterdepolarization leading to increased automaticity and/or ectopic activity. The treatment of these dysrhythmias is not simple and mortality is still a serious issue. There are several treatment approaches that depend on the symptoms.4, 304 Activated charcoal is used to avoid further absorption of the cardiac glycoside and interrupt the enterohepatic circulation. Atropine is preferred for bradycardia or AV blocks and temporal pacing can also be used.305 The digoxin‐specific antibody fragments are very important in the treatment of moderate or severe intoxication. Correction of possible hypokalemia should be performed as soon as possible and ventricular dysrhythmias may require additional symptomatic treatment.

The implication for nursing practice is the need for critical care nurses to screen, assess, and educate patients who take opioids. In collaboration with healthcare providers, critical care nurses can assess heart structure and function with results of studies such as electrocardiography and continuous ambulatory ECG monitoring to screen for dysrhythmias and disorders of myocardial repolarization, such as prolonged QT intervals. 3Greenfield and colleagues (2005) studied the effects of alcohol at meal time in a group of nonsmoking, healthy postmenopausal women.

Cardiac Manifestations of Adoptive Cell Transfer

These data highlight how gender may be an important modifier of the alcohol threshold level and can shape the alcohol benefit–risk relationship. This category includes primarily substances isolated from ephedra, their synthetic congeners (amphetamines, Fig. 1), and cathinone derivatives (Fig. 3). They possess a methyl group on the α‐carbon that increases their ability to cross‐membranes and that also largely contributes to their psychoactive proprieties. Therefore, amphetamines also increase the cytosolic content of monoamines in part through inhibition of their metabolism. In general, their effect on serotonin is lower with the exception of 3,4‐methylendioxymetamphetamine (MDMA),40 which will be discussed separately. Concerning their adrenergic activity, most of them are considered to be pure indirect sympathomimetics, but natural ephedrine (1R,2S‐ephedrine) also has significant direct agonistic activity on β1‐ and β2‐adrenergic receptors.

Human Studies on the Effect of Caffeine on Arrhythmias and Other

High levels of triglycerides in the blood have therefore been linked to atherosclerosis, heart disease, and stroke. In the cardiovascular system, acute inorganic mercury exposition in vivo promotes reduction of myocardial force development [30] and inhibited myosin ATPase activity [31]. Numerous studies have also revealed that mercury generates oxygen free radicals mainly by activation of NAPHoxidase [35, 36].

Alcohol Consumption: Categories, Measurement, and Patterns

Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system. The associations between drinking and CV diseases such as hypertension, coronary heart disease, stroke, peripheral arterial disease, and cardiomyopathy have been studied extensively and are outlined in this review. Β2‐agonists, when inhaled at therapeutic doses to treat bronchoconstriction, are considered to be relatively safe from the cardiovascular point of view; however, their selectivity is not absolute and in higher doses they also bind to β1‐receptors.

Nevertheless, the drug may impose cardiac risk particularly in the ischemic myocardium. Taken together, these data show that chronic low doses of mercury have an important and deleterious effect on vascular function by reducing NO bioavailability. The degree of severity of mercury exposure is comparable to traditional cardiovascular risk factors, such as hypertension diabetes or hypercholesterolemia. Therefore, mercury could be considered an important risk factor for cardiovascular disease that could play a role in the development of cardiovascular events. The association between mercury exposure and an increased risk of developing cardiovascular and neurological diseases is apparent.

As part of SHADE-ONE, Higgins also measured percent flow-mediated
dilatation at 50 minutes as well as at baseline and 90 minutes and found
that it decreased over time and was lowest at 90 minutes. According to
Higgins, most people’s caffeine levels peak between 45 and 60
minutes after consumption. He found it interesting that with this energy
drink, which he noted has other important ingredients in addition to
caffeine, the maximal effect was observed at 90 minutes. The finding
suggests to Higgins that there may be something about energy drinks that
makes them “different beasts” than coffee and other modes
of caffeine delivery. For example, maybe there is something in them that
affects the pharmacokinetics or dynamics of caffeine by interacting with
the caffeine and thereby having more deleterious effects on ECF.

Endothelial cell function (ECF) serves an important role in mediating the
vascular effects of caffeine exposure, according to John Higgins. 3 Greenfield and colleagues (2005) studied the effects of alcohol at meal time in a group of nonsmoking, healthy postmenopausal women. Each woman was given either no alcohol or 15 g of alcohol (1 standard drink) with either a low-carbohydrate or a high-carbohydrate, high-fat meal. The researchers found that the alcohol-drinking subjects (particularly those who were insulin sensitive) had higher insulin levels and a slower rise in glucose levels after a low-carb meal. They recommended confirming these results in younger women and in men, particularly since their subjects had been older women, who have more significant cardiovascular risk. In humans, endothelial function is assessed by measuring the widening (i.e., dilation) of the brachial artery under different conditions.

Oxidative Stress and Apoptosis: Linked Mechanisms

Thimerosal is metabolized in the human body and degraded into ethylmercury and thiosalicylate. The chemical difference between these compounds is an important determinant of their toxicity [42, 43]. Organic mercury compounds, also called organometallic, result from a covalent bond between mercury and the carbon [8] atom of an organic functional group such as a methyl, ethyl, or phenyl group.

What are the acute exposure effects?

Biogenesis of miRNAs starts in the nucleus of the cell where miRNA genes are transcribed by RNA polymerase into primary miRNAs. The miRNA of the RISC complex binds to the target messenger RNAs preventing translation. After myocardial infarction, for example, miRNA levels increase signaling-reduced systolic function when the left ventricle ejection fraction is less than 50%. Microvesicles shed from the cell, such as exomes, export the miRNAs and transport them to other locations, sober living insurance coverage and payment options in effect constituting intercellular communication and thereby regulating genetic function and protein generation. In drug toxicity as well as oncology, miRNAs are becoming useful tools in making diagnoses and offer new therapeutic approaches. Exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction [111–113] and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase.

Cardiomyopathy is a known risk factor for heart failure, which is a condition where the heart muscle is weakened and cannot pump enough blood to supply the rest of the body. Heart failure causes people to become fatigued much more easily and they often lose their ability to perform rigorous activity and exercise. Holiday heart syndrome can happen if you don’t abstinence violation effect springerlink typically drink alcohol, but then have a few at a holiday party or if you binge drink. This can cause you to develop an irregular heartbeat, called atrial fibrillation, which can increase your risk of stroke, heart attack and heart failure. Some of the potential cellular changes related to ethanol consumption reviewed above are illustrated in figure 5.

Leave a Comment