Lead cardiovascular system

Lead is toxic to the kidney, cardiovascular system, developiag red blood cells, and the nervous system. The toxicity of lead to the kidney is manifested by chronic nephropathy and appears to result from long-term, relatively high dose exposure to lead. It appears that the toxicity of lead to the kidney results from effects on the cells lining the proximal tubules. Lead inhibits the metaboHc activation of vitamin D in these cells, and induces the formation of dense lead—protein complexes, causing a progressive destmction of the proximal tubules (13). Lead has been impHcated in causing hypertension as a result of a direct action on vascular smooth muscle as well as the toxic effects on the kidneys (12,13). 

Lead has been shown to affect virtually every organ and/or system in the body in both humans and animals (see Figure 2-11). The most sensitive target organs of lead appear to be the nervous system (particularly in children), the hematopoietic system, and the cardiovascular system. There is evidence in... 

Figure 7.1. Vomiting Mechanisms. The afferent nervous (peripheral and central) and humoral inputs converge to the medullary area. Here the signals are examined and integrated and may lead to emesis (expulsion of gastrointestinal contents). The efferent output involves respiratory muscles, visceral organs, cardiovascular system, visceral and cutaneous vasculature. The endogenous factors are released into...

The main target organs for compound toxicity leading to either drug withdrawal or arrest of compound development as estimated in various studies [3], are classically pointing at liver, the cardiovascular system and bone marrow (hematotoxicity). Cardiovascular and hepatotoxicity were discussed in previous chapters and this chapter focuses on hematotoxicity. 

Physiological sites proposed for nitric oxide action include the immune system, where nitric oxide acts as a cytostatic agent, is tumoricidal, and can inhibit viral replication. In the cardiovascular system, nitric oxide is the biological mediator of vasodilator responses to agents such as acetylcholine and bradykinin, which act as receptors on endothelial cells to activate NOS and stimulate nitric oxide production. Diffusible nitric oxide then activates guanylate cyclase in vascular smooth muscle cells, leading to the production of cyclic guano-sine monophosphate (GMP) and vasodilation. In the brain, stimulation of A-methyl-o-aspartate receptors on... 

Ephedra (ma huang) is a popular botanical incorporated into a variety of formulations for weight loss, energy or performance enhancement, and symptomatic control of asthma. A pharmacodynamic interaction leading to a fatality has been reported with concurrent use of caffeine and ephedra (62), possibly as a result of additive adrenergic agonist effect of the ephedrine alkaloids and caffeine on the cardiovascular system and the CNS (63). Ephedra was recently withdrawn from the market (64). 

At doses up to those causing hypnosis, no significant effects on the cardiovascular system are observed in healthy patients. However, in hypovolemic states, heart failure, and other diseases that impair cardiovascular function, normal doses of sedative-hypnotics may cause cardiovascular depression, probably as a result of actions on the medullary vasomotor centers. At toxic doses, myocardial contractility and vascular tone may both be depressed by central and peripheral effects, leading to circulatory collapse. Respiratory and cardiovascular effects are more marked when sedative-hypnotics are given intravenously. 

The cardiovascular effects of local anesthetics result in part from direct effects of these drugs on the cardiac and smooth muscle membranes and from indirect effects on the autonomic nervous system. As described in Chapter 14, local anesthetics block cardiac sodium channels and thus depress abnormal cardiac pacemaker activity, excitability, and conduction. At extremely high concentrations, local anesthetics can also block calcium channels. With the notable exception of cocaine, local anesthetics also depress myocardial contractility and produce direct arteriolar dilation, leading to systemic hypotension. Cardiovascular collapse is rare, but has been reported after large doses of bupivacaine and ropivacaine have been inadvertently administered into the intravascular space. 

A third type of dose response relationship has been proposed, which is increasingly gaining acceptance, and this is the hormetic kind. This kind of dose response, for which there is experimental evidence, involves opposite effects at low doses, giving rise to a U-shaped or J-shaped curve (Fig. 2.11). That is, there may be positive or stimulatory beneficial effects at low doses. For example, some data indicate that at low doses of dioxin, the incidence of certain cancers in animals exposed is less than occurs in controls. Another example is alcohol (ethanol), for which there is evidence from a number of studies that low to moderate intake in man leads to lower levels of cardiovascular disease. Of course, high levels of intake of alcohol are well established to cause liver cirrhosis, various cancers, and also damage to the cardiovascular system. 

Because of the general ability of many of the drugs previously described to produce CNS excitation, some of the primary side effects are nervousness, restlessness, and anxiety. Because these agents also tend to stimulate the cardiovascular system, prolonged or excessive use may also lead to complications such as hypertension, arrhythmias, and even cardiac arrest. When used to treat bronchospasm, prolonged administration via inhalation may also cause some degree of bronchial irritation with some agents. 

In the cardiovascular system, there is a 10 to 20 beat per minute increase in heart rate, a 5-10 mm increase in blood pressure, and an increase in the strength of heart contractions. Nicotine increases the incidence of cardiac arrhythmia (irregular heartbeat) in susceptible people. It causes constriction of blood vessels in the skin, and causes platelets to adhere together leading to an increased possibility of blood clots. 

As indicated in Table 7.6, all hazardous chemicals in electric arc furnace dust are assumed to induce deterministic responses. The possible responses include renal toxicity, effects on the cardiovascular system, dermal or ocular effects, decrease in body weight, hepatic toxicity, and respiratory toxicity. Decrease in body weight is not a response in a particular organ but is assumed to be a health effect of concern. All deterministic responses are assumed to be induced by more than one chemical in the waste. Furthermore, some of the chemicals (barium, beryllium, chromium, and lead) are assumed to induce all responses. 

Among the many toxicants that cause convulsions are chlorinated hydrocarbons, amphetamines, lead, organophosphates, and strychnine. There are several levels of coma, the term used to describe a lowered level of consciousness. At level 0, the subject may be awakened and will respond to questions. At level 1, withdrawal from painful stimuli is observed and all reflexes function. A subject at level 2 does not withdraw from painful stimuli, although most reflexes still function. Levels 3 and 4 are characterized by the absence of reflexes at level 4, respiratory action is depressed and the cardiovascular system fails. Among the many toxicants that cause coma are narcotic analgesics, alcohols, organophosphates, carbamates, lead, hydrocarbons, hydrogen sulfide, benzodiazepines, tricyclic antidepressants, isoniazid, phenothiazines, and opiates. 

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