Posted by honeybee on May 31, 2006, at 11:34:44
In reply to Re: Serotonin and Heart Valve Disease, posted by honeybee on May 31, 2006, at 11:05:54
I like "Nevertheless, vigilance for the unexpected is the duty of prescribers."
http://www.psychiatrist.com/pcc/brainstorm/br5812.htm
Does Too Much Serotonin Break Your Heart?
Both drugs and diseases can increase the release of circulating serotonin. For example, some malignant carcinoid tumors secrete serotonin and can cause waves of serotonin release into the systemic circulation, which in turn can make the patient flush.6 Over time, these tumors are associated with cardiac valvular damage, especially on the right side of the heart, which presumably gets bombed with the serotonin before the serotonin moves to the lungs where metabolic enzymes chew it up.6
Recent reports indicate that similar cardiac valvular pathology is associated with fenfluramine administration.7 It is not known whether this is a chance association or whether fenfluramine causes this damage. Whether release of serotonin onto these valves by fenfluramine is the mechanism of this damage is a possibility, but it is unproven.
Fenfluramine is associated with other toxicities, both cardiovascular and CNS; that is, there is an increased incidence of primary pulmonary hypertension not only in fenfluramine users, but also in those with obesity, i.e., those most likely to take fenfluramine in the first place.8 Long-lasting depletion of serotonin from the brain due to destruction of serotonergic axon terminals is also observed in rats exposed to fenfluramine brain concentrations about 10 times higher than those in man.9 Although there have been no reports of long-lasting or permanent serotonin depletion in brains of human fenfluramine users, or any proven changes in behavior, this possibility has always been a nagging concern for the long-term safety of fenfluramine use.
Since fenfluramine also causes long-term depletion of serotonin in circulating platelets, as do the SSRIs, there is some pharmacologic overlap between these two classes of drugs. Although fenfluramine and its active metabolite are predominantly serotonin releasers, they are also reuptake inhibitors like SSRIs, in addition to being inhibitors of serotonin synthesis and perhaps directly active at some serotonin receptor subtypes.2-4,9 So far, there is no rationale or empiric observations to create any concern that the SSRIs cause cardiac problems similar to those associated with fenfluramine. Nevertheless, vigilance for the unexpected is the duty of prescribers.
In summary, there is good news and there is bad news about serotonin. The right amount in the right places is a powerful therapeutic tonic. But, too much in the wrong places can be hazardous to your health. u
poster:honeybee
thread:650450
URL: http://www.dr-bob.org/babble/20060530/msgs/650994.html