Cardiovascular system, cardiotoxic

The most serious toxic effects of cocaine involve changes in the cardiovascular system. These include cardiac arrhythmias, myocardial ischaemia and infarction, and cerebrovascular spasm, all of which can be largely explained by the facilitation of the action of catecholamines on the cardiovascular system. Another explanation of the cardiotoxicity of cocaine lies in the direct vasoconstrictive properties of its major metabolite, norcocaine. It seems likely... 

Cocaine also blocks the reuptake of norepinephrine in the PNS the combination of central and peripheral actions leads to a high probability of toxicity. The cardiovascular system is particularly sensitive to the actions of cocaine, and cardiac arrhythmias, marked increases in blood pressure, cerebral hemorrhage, myocardial ischemia, and outright heart failure are not uncommon with cocaine use. Even young, otherwise healthy individuals with normal coronary and cerebral arteries have died suddenly after cocaine use from cerebral hemorrhage or ventricular fibrillation. There have been several deaths of famous athletes attributed to cocaine cardiotoxicity. These cardiotoxic effects may be related to increased intracellular calcium levels and involve both cardiac and vascular actions of the drug. 

Based on animal research and restricted experience in overdosage (SEDA-7, 19-21), early attempts to differentiate trazodone from tricyclic antidepressants suggested that it might be relatively free of cardiotoxic effects. However, a preliminary report of a study of the effects of trazodone on the cardiovascular system in 20 subjects mentioned two patients who had ventricular dysrhythmias (7). Others have reported ventricular tachycardia (8-10), atrial fibrillation (11), and complete heart block (12). 

The application of antibodies in cardiovascular targeting in vivo originated with the experimental demonstration of the feasibility of using radiolabeled antimyosin antibody for diagnosis of acute myocardial infarction in 1976. Since then, the use of antibodies in the cardiovascular system has encompassed imaging of myocarditis,heart transplant rejection, dilated cardiomyopathy, alcohol induced cardiomyopathy,adriamycin cardiotoxicity, various other cardiomyopathies, vascular clots, atherosclerotic lesions,and even certain cancers such as soft tissue sarcomas.f Yet the best characterized and studied antibody for cardiovascular diagnostic targeting is monoclonal antimyosin Fab for its exquisite specificity... 

The cardiovascular system is more resistant to the toxic effects of local anesthetics than the nervous system. Mild circulatory depression can precede nervous system toxicity, but seizures are more likely to occur before circulatory collapse. The intravenous dose of lidocaine required to produce cardiovascular coUapse is seven times that which causes seizures. The safety margin for racemic bupivacaine is much lower. The stereospecific levorotatory isomers levobupivacaine and ropivacaine are less cardiotoxic, and have a higher safety margin than bupivacaine, but not lidocaine in the case of ropivacaine this may be at the expense of reduced anesthetic potency (14,15). Toxicity from anesthetic combinations is additive. 

The effects on the cardiovascular system of ropivacaine are similar to those of bupivacaine, although direct cardiotoxicity is less severe with ropivacaine than bupivacaine in both man and animals (SEDA-22, 143). Hypotension and bradycardia are prominent adverse effects when ropivacaine is used epidurally, particularly with concentrations of ropivacaine over 0.5% (SEDA-20, 129) (SEDA-22, 143) in one series, hypotension was observed in 30% of patients who received ropivacaine, but in only 13% of those given an equivalent dose of bupivacaine (3). 

Cocaine can have marked effects on the heart and cardiovascular system. Adverse actions may include myocardial ischemia, cardiac arrhythmias, cardiotoxicity, hypertensive effects, cerebrovascular events, and a hyperco-agulable state (24,40). By 1997 more than 250 cases of myocardial infarction related to the recreational use of cocaine had been documented in the literature (41). Although less common, aortic dissection related to use of cocaine-free base ("crackcocaine") has also been documented (42). Seizures also can be associated with cocaine use (43). 

Patients may deteriorate rapidly and progress from no symptoms to life-threatening cardiotoxicity or seizures within 1 hour. Major symptoms of tricyclic antidepressant overdose typically are manifest within 6 hours of ingestion. The principal effects of tricyclic antidepressant poisoning involve the cardiovascular system and the central nervous system and can result in arrhythmias, hypotension, coma, and seizures (see below). 

Inadvertent administration of bupivacaine can lead to fatal cardiovascular collapse that may be refractory to conventional resuscitation. A study in rats has suggested that in addition to its direct cardiotoxic effect, bupivacaine may have a toxic action on the brainstem, and that cardiovascular collapse may result from dysfunction of vital cardiorespiratory control systems (12). 

Lipid rescue as a treatment of bupivacaine overdose there is evidence with animal studies [1] that Intralipid, a commonly available intravenous lipid emulsion, is effective in treating the severe cardiotox-icity that may result secondary to local anesthetic overdose. In addition, there are human case reports of successful use of Intralipid for rescue from cardiotoxic and cardiovascular collapse from systemic bupivacaine overdose [2] as well as a widespread campaign to pub-hcize Intrahpid as an available drug for emergencies in all anesthetizing locations where bupivacaine is used. 

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