Epinephrine cardiotoxic effects

The acute cardiotoxic effects of 1,1,1-trichloroethane (reduced blood pressure and increased sensitization to epinephrine-induced arrhythmias) appear to be mediated by the compound and not its metabolites (Carlson 1973 Toraason et al. 1990, 1992) and have been associated with the ability of 1,1,1-trichloroethane to interfere with membrane-mediated processes including calcium mobilization during myocardial contraction (Herd et al. 1974 Hoffman et al. 1992 Toraason et al. 

Humans exposed at high concentrations of some halogenated hydrocarbons can develop cardiac arrhythmias. The cardiac sensitization test in dogs is considered an effective determination of potential cardiac sensitization in humans. Cardiotoxicity was observed at concentrations well below those associated with any acute toxic signs but only in the presence of greater-than-physiological doses of exogenous epinephrine. 

Topical local anesthesia is often used for eye, ear, nose, and throat procedures. Satisfactory topical local anesthesia requires an agent capable of rapid penetration across the skin or mucosa, and with limited tendency to diffuse away from the site of application. Cocaine, because of its excellent penetration and local vasoconstrictor effects, has been used extensively for ear, nose and throat (ENT) procedures. Cocaine is somewhat irritating and is therefore less popular for ophthalmic procedures. Recent concern about its potential cardiotoxicity when combined with epinephrine has led most otolaryngology surgeons to switch to a combination containing lidocaine and epinephrine. Other drugs used for topical anesthesia include lidocaine-bupivacaine combinations, tetracaine, pramoxine, dibucaine, benzocaine, and dyclonine. 

Resuscitation from bupivacaine cardiovascular toxicity is extremely difficult. However, prompt resuscitation has been successful with standard cardiopulmonary support, including the prompt correction of acidosis by hyperventilation and administration of bicarbonate as well as epinephrine, atropine, and bretylium. Local anesthetics, especially bupivacaine, also inhibit basal and epinephrine-stimulated cAMP production. This finding places greater emphasis on aggressive epinephrine therapy during bupivacaine-induced cardiotoxicity. The (SJ-isomer, levobupivacaine, appears to have a lower propensity for cardiovascular toxicity than the racemic mixture or the (R)-isomer and has recently been approved for clinical use. Ropivacaine, another newer local anesthetic, has clinical effects similar to those of bupivacaine but may be associated with a lower potential for cardiovascular toxicity. Ropivacaine is available only as the (S)-stereoisomer, which has inherently less affinity for the cardiac sodium channel. 

Cardiotoxicity of primary amines (epinephrine, norepinephrine, isoproterenol) was noted earlier, and has been recognized for nearly 100 years. The vascular toxicity of these and related compounds has also recently been recognized. The effects seem to focus on medial cells of the artery wall, rather than on adventitial or endothelial cells. Early changes include loss of medial cells, mineralization, and loss of elastic fibers. Later there is a compensatory proliferation of intimal cells. The vascular toxicity of two related compounds is particularly striking. One of these compounds, allylamine, will be discussed near the end of this chapter. The second is )S-aminoproprionitrile ()S-APN), which is the active agent in the toxic sweet pea, Lathyrus odoratus. Consumption of flour derived from this plant results in lathyrism, a condition often seen in children and young... 

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