The addition of the 2-adrenolytic drug, yohimbine, to caffeine and ephedrine is an attractive support to obesity treatment. However, administration of three drugs influencing the cardiovascular system could have some undesirable effects, especially in obese subjects.
We tried to determine if the supporting pharmacological treatment of obese women composed of ephedrine, caffeine and yohimbine could modify the cardiovascular state at rest and during static (handgrip) or dynamic (cycloergometer) exercise. We found that loss of body mass did not differ between groups receiving only diet and groups with two or three drugs administration together with diet. We supposed that 10 days is too short a time to define real weight loss after treatment. Further study is needed to define the influence of these doses of drugs on metabolic effects and weight loss during a longer period of treatment.
However, the aim of our study was to determine if caffeine and ephedrine used together or these two drugs in combination with yohimbine were safe for the cardiovascular system. Ten days of observation is a sufficient period to detect some cardiovascular reactions. A very low caloric diet is usually associated with a decrease in adrenergic system activity. The aim of ephedrine, caffeine and yohimbine administration was to diminish this phenomenon and to increase the effect of a low caloric diet. We did not observe significant changes in most haemodynamic parameters after 10 days of diet only administration. However, the ejection fraction decreased. It is possible that this drop is one of the symptoms indicating this phenomenon.
We found that the therapy composed of ephedrine (2 25 mg) and caffeine (2 200 mg) did not modify the haemodynamic parameters at rest and during the handgrip exercise. Only during cycloergometer exercise was ejection fraction increased. This fact suggests that the combination of the drugs we used did not exert undesirable effects on the cardiovascular system. The increased in ejection fraction even has a profitable significance. It is also an indirect proof that ephedrine and caffeine in the doses we used could weakly activate the adrenergic system. For this reason the charge in the cardiovascular system in our obese subjects during static or dynamic exercise at the time of ephedrine and caffeine administration was not very large and seemed safe.We observed different reactions of the cardiovascular system when three drugs were used. Application of three drugs produced a depression of the cardiovascular system at rest, which was expressed by a decrease in stroke index and ejection fraction. This was probably the result of diastolic pressure and heart rate increase. In these circumstances, the systole of the heart is less efficient. We could speculate that these effects of yohimbine were due to an increase in noradrenaline concentration in the plasma ( Hedner et al., 1992; Tavernier et al., 1992). If this was the case, noradrenaline could increase the afterload, and thereby cardiac performance would be decreased. This could be an undesirable effect of yohimbine treatment. The same drug regimen during the handgrip test led to a decrease in ejection fraction only. Diastolic pressure, heart rate and ejection fraction tended in a similar direction during the handgrip test, but did not show significant changes between groups. We suppose that activation of the adrenergic system and following cardiovascular system during exercise is much stronger than after pharmacological stimulation. For this reason, the pharmacological influence of drugs is proportionally attenuated.
When cycloergometer exercise was performed, not only ejection fraction, but also cardiac load increased in the group receiving three drugs. The last effect was not observed during the handgrip test. However, cycloergometer exercise and handgrip are quite different types of effort. During dynamic exercise, heart rate reached higher values than during the handgrip test. Systolic pressure was inversely higher during the handgrip test. It could be speculated that, during the handgrip test, -activation predominated but during the cycloergometer exercise -activation predominated. End-diastolic index observed during dynamic exercise reached greater values than during the handgrip test. Central translocation of blood volume from the lower part of the body during exercise on the cycloergometer could have cardinal meaning. This centralization of circulation was probably in part due to the work of the leg muscles. Stroke index during cycloergometer exercise was also greater than during the handgrip test. Increased volume of heart and circulating blood, augmented heart rate together with the influence of the three drugs evoked an increase in cardiac load. The influence of yohimbine in these circumstances is very important, because we did not observe an increase in cardiac load when only two drugs were administered. This fact has significant clinical implications, because it suggests that yohimbine evokes some dangerous changes in the cardiovascular system. For this reason, this drug could only be used in some persons with caution. Our results indicate that the pharmacological support of a low caloric diet by ephedrine and caffeine during obesity treatment induces only minimal changes in the cardiovascular system, but the addition of yohimbine to this regimen may lessen the cardiac performance at rest and during the handgrip test. Using three drugs during the cycloergometer exercise leads to an increase in cardiac work. Therefore, these findings demonstrate that chronic administration of ephedrine and caffeine has no undesirable effects on cardiovascular state in obese patients. The addition of yohimbine should be treated with caution and must be excluded in particular obese individuals with cardiovascular complications.
Waluga M, Janusz M, Karpel E, Hartleb M, Nowak A. Cardiovascular effects of ephedrine, caffeine and yohimbine measured by thoracic electrical bioimpedance in obese women. Clin Physiol. 1998 Jan;18(1):69-76
Int J Mol Med. 2001 Jul;8(1):103-9. Related Articles, Links