Norepinephrine cardiotoxic effects

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. 

Maprotiline and amoxapine are selective norepinephrine uptake inhibitors. They share most of the properties of the tricyclic antidepressants. Maprotiline has less sedating effect than mianserin and it is more epileptogenic than any other antidepressant. It shows considerable cardiotoxicity when taken in overdose. 

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. 

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... 

Reboxetine. Reboxetine (21) is a norepinephrine-selective reuptake inhibitor that lacks affinity for most of the monoamine receptors. It thus does not exhibit the typical side-effect profile of the tricyclics. Nevertheless, side effects include increased sweating, postural hypotension (leading to dizziness), dry mouth, constipation, blurred vision, impotence, and dysuria. Tachycardia and urinary retention have also been reported (59). There is no evidence of cardiotoxicity and sexual dysfunction seems to be rare. In contrast to some of the earlier tricyclics that are sedative, reboxetine is nonsedating and can cause insomnia (60,61).. 

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