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Nutraceuticals: Potential Roles And Potential Risks For Pain Management As originally published in World Institute of Pain, Pain Practice, Volume 2, Number 2, 2002
By: Dr. Adam Kaye, PharmD, Alan Kaye, A. Hegazi, R. Sabar, B. Deaton, J. Powell and R. Hofbauer |
Abstract: Over the past 2 decades, the world health market has been flooded with over the counter herbal products, also known as nutraceuticals. Although many of these products are neither recommended nor prescribed by conventional medical practitioners, an increasing number of people are taking these products on a daily basis. A recent survey at Texas Tech University School of Medicine in Lubbock, Texas concluded that 32% of patients scheduled for elective surgery or pain procedures were taking one or more herbal supplements; however, 70% did not disclose these during a routine anesthetic assessment.1 Pain physicians are also increasingly needed in the care of these patients. As many of these agents carry a potential to cause bleeding problems, we have reviewed here briefly, the basic mechanisms of coagulation and correlated the role of commonly used herbs known to possess side effects, which can cause excessive bleeding. In addition, we have reviewed a number of potential useful herbal derived agents for pain management.
THE HEMOSTATIC MECHANISM
The cessation of bleeding from a damaged blood vessel depends on 3 processes, primary hemostasis, coagulation, and fibrinolysis. Primary hemostasis is a local process and takes place within seconds of vascular injury and involves the interaction between platelets and injured vascular intima. In a process called platelet activation, platelets spread along the surface of the denuded blood vessel and adhere to the subendothelial collagen layer via glycoprotein receptors and the von Willebrand factor.2 The activation process causes the platelets to change shape and undergo a release reaction, extruding the contents of their granules, and releasing multiple compounds into the blood, including ADP, serotonin, clotting factors V, VIII, fibrinogen and many other chemical mediators, important to primary hemostasis and the subsequent coagulation process. With sufficient stimulus, the platelets synthesize thromboxane A2 (TXA2), which stimulates further ADP release and also has potent vasoconstrictor actions. ADP increases platelet activation and leads to the aggregation of platelets to each other via fibrinogen strands. Finally, the platelets expose a new phospholipid on the surface called platelet factor 3, which changes the surface charge of the platelet and creates a "procoagulant" activity. The interaction of clotting factors will follow on the phospholipid surface of the activated platelet and result in the formation of fibrin, reinforcing the friable platelet plug.3 Endothelial cells secrete prostacyclin (PGI2), which has actions opposite those of TXA2. PGI2 inhibits platelet activation, secretion, and aggregation, and prostacyclin is a potent vasodilator. Any imbalance in the production of the 2 prostaglandins, thromboxane or prostacyclin, can lead to a defect in primary hemostasis or to abnormal coagulation. Besides prostacyclin, intact endothelial cells release ADPase, which degrades surplus ADP, decreasing platelet activation and platelet aggregation at the periphery of the platelet plug.BASIC PRINCIPLES OF THE COAGULATION MECHANISM
Coagulation involves the interaction of many plasma proteins, called clotting factors, which interact in various reaction sequences to produce insoluble fibrin clot.4 Most of the clotting factors circulate in an inactive form, called a procoagulant molecules or zymogens. During the process of coagulation, a portion of this protein molecule is cleaved off and the remaining protein becomes an active cleavage enzyme, called a serine protease. The "activated clotting factor," designated by a small "a" after the Roman numeral of the factor, cleaves off a portion of the next procoagulant clotting factor, which "activates"that factor in succession.In a chain reaction-like fashion, one factor "activates" another, until fibrinogen (factor I) is cleaved to form fibrin. All of the plasma zymogens, except von Willebrand factor (vWF), are synthesized in the liver. The synthesis of factors II, VII, IX, and X is dependent on vitamin K. Factor VIII circulates as part of a factor VIII-vWF complex. The major role of vWF is to promote adhesion of platelets to subendothelial surfaces.5
Commonly used herbs known to potentially cause excessive bleeding by modulation of the coagulation pathway include garlic, ginger, gingko biloba, ginseng (see Table 1):
Dr. Adam Kaye, PharmD, is a California Licensed Pharmacist and a Clinical Associate Professor of Pharmacy Practice at University of the Pacific's Thomas J. Long School of Pharmacy. He has also been employed by a national pharmacy company since 1992 and has served as a Pharmacy Manager since 1997.
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