Clinical Pharmacology An Integrative East-West Perspective

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Clinical Pharmacology An Integrative East-West Perspective Malcolm Taw, MD UCLA Center for East West Medicine Department of Medicine David Geffen School of Medicine, UCLA

N Engl J Med. 2000 Dec 21;343(25):1833-8.

Ephedra Brief Overview & History Ephedra (Ma Huang Chinese herbal name) - popular ingredient in dietary supplements used for weight loss & increasing energy Adverse events reported with high profile case of young Baltimore Orioles pitcher s death in February 2003 Was banned from market in April 2004 by FDA due to safety concerns Ban lifted (on products containing less than 10 mg of ephedra) in April 2005 after judge ruled that dietary supplements considered as food not drugs according to the DSHEA (Dietary Supplement Health and Education Act) of 1994.

Under the Dietary Supplement Health and Education Act (DSHEA), the FDA bears the burden of proof to show that a dietary supplement presents a significant or unreasonable risk to prevent it from being marketed; in contrast, for drugs that have similar pharmacologic properties to ephedra, manufacturers bear the burden of proof of showing that the drug is safe and effective before it can be marketed.

N Engl J Med. 2000 Dec 21;343(25):1835.

N Engl J Med. 2000 Dec 21;343(25):1835.

N Engl J Med. 2000 Dec 21;343(25):1836.

Example of Severe Cardiovascular/CNS Adverse Events N Engl J Med. 2000 Dec 21;343(25):1835-6.

Chinese Medical Pharmacology

Ma Huang (Ephedra) Chinese Medical Use Bensky D, Gamble A. Chinese Herbal Medicine: Materia Medica. Eastland Press. 1986. p 38.

Chen J. Chinese Medical Herbology and Pharmacology, Art of Medicine Press. 2001. p 39

Katzung, BG. Basic & Clinical Pharmacology. Lange Medical Publications. 2004. p. 86

Yin & Yang Theory Two extremes brought into dynamic balance Black/White, Hot/Cold, Day/Night

Yin & Yang Theory (Modern Western Medicine) Hot/Cold (Physiologic temperature = 98.6 deg F) Acid/Base (Physiologic balance ph = 7.4) Sympathetic/Parasympathetic Electrolyte disorders Oxygen/CO2 Hyper/Hypothyroidism

Hot & Cold (Physiologic Effects) Cold Vasoconstriction, bradycardia Decreased blood flow to the skin Shivering Piloerection Heat Vasodilation, tachycardia Increased blood flow to the skin Sweating

Yin & Yang Theory (Clinical Signs & Symptoms) Yang (Heat) Yang Heat Red face Thirst Likes cold drinks Scanty-dark urine Constipation Red tongue Full pulse Yin Cold Pale face No thirst Likes hot drinks Profuse-pale urine Loose stools Pale tongue Empty pulse Yin (Cold) Yang Excess ----- Yin Deficiency -- Balance -- Yang Deficiency -----Yin Excess

Balance of Yin & Yang Yang Heat Sympathetic Yin Cold Cholinergic

Imbalance of Yin & Yang (from Yang Excess) Yang Excess Increased Heat Sympathetic Overdrive Yin Cold Cholinergic

Imbalance of Yin & Yang (from Deficiency of Yin) Yang Heat Sympathetics Deficiency of Yin Decreased Cold Decreased Cholinergic Activity

Yin & Yang Heat Patterns (Traditional Chinese Medicine) Yin Deficiency Yang Excess Face Mouth Thirst Heat sensation Sweating Mind Sleep Bowels Tongue Pulse Treatment Malar flush Whole face red Dry mouth Mouth/tongue ulcers Desire to drink sips of cold H20 Desire to drink cold H20 Afternoon/evening All day Nightsweats Sweats all day Vague anxiety, fidgeting Very restless, agitated Wakes up frequently Dream disturbed, very restless Dry stools Constipation Red, peeled, thin Red with yellow coating Floating-Empty, rapid Full-Rapid-Overflowing Nourish Yin, Clear Empty-Heat Clear Heat Extreme Heat Wind Pattern

Yin & Yang Patterns (Correlation with Western Medical Pharmacology) Sympathetic Overdrive - Tachycardia - Anxiety - High blood pressure - Aggressiveness - Hyperthermia - Constipation - Profuse sweating - Urinary retention - Insomnia Anti-cholinergic activity - Tachycardia - Cutaneous flushing - Dry eyes - Delirium - Dry mouth - Dry stools - Decreased sweating - Urinary retention Dry as a bone, red as a beet, mad as a hatter, blind as a bat

Example of Severe Cardiovascular/CNS Adverse Events N Engl J Med. 2000 Dec 21;343(25):1835-6.

Western Clinical Pharmacology Katzung, BG. Basic & Clinical Pharmacology. Lange Medical Publications. 2004. p. 323

Katzung, BG. Basic & Clinical Pharmacology. Lange Medical Publications. 2004. p. 126

Katzung, BG. Basic & Clinical Pharmacology. Lange Medical Publications. 2004. p. 128

Katzung, BG. Basic & Clinical Pharmacology. Lange Medical Publications. 2004. p. 129

Katzung, BG. Basic & Clinical Pharmacology. Lange Medical Publications. 2004. p. 326

Summary Herbs, such as Ephedra (Ma Huang), are often used inappropriately and should be used only according to the intended purposes from a traditional Chinese medical perspective Regulation of herbs is important based on a correct understanding of their original use A proper understanding of herbs allows true integration of Chinese and Western medications/herbs that will maximize therapeutic efficacy while minimizing potential herb-drug interactions as well as adverse events/reactions