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Chrysanthemum parthenium (L.) Berhn (feverfew) 小白菊, 解熱菊

Chrysanthemum parthenium (L.) Berhn (feverfew) 小白菊, 解熱菊. Safety Use of Herbs and Medicines. 1. Sites of Absorption. 2. Carriers and Enzyme Systems. 3. Fluid and Drug Absorption. 4. Food-Drug Interactions. 5. Herb-Drug Interactions. 6. Health Product-Drug Interactions.

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Chrysanthemum parthenium (L.) Berhn (feverfew) 小白菊, 解熱菊

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  1. Chrysanthemum parthenium (L.) Berhn (feverfew) 小白菊, 解熱菊

  2. Safety Use of Herbs and Medicines 1. Sites of Absorption 2. Carriers and Enzyme Systems 3. Fluid and Drug Absorption 4. Food-Drug Interactions 5. Herb-Drug Interactions 6. Health Product-Drug Interactions

  3. Intestinal Carrier Systems P-glycoprotein (p-醣蛋白) efflux transporter, reduces drug absorption Multidrug resistance peptides (多藥物抗蛋白, MDRs) decreases drug absorption Organic anion transporting polypeptide (有機陰離子轉輸多肽, OATP) facilitates drug absorption

  4. Enteral Drug Administration Stomach – gastric emptying Food, acidity, osmolarity (滲透壓) Small intestine – main absorption site large surface care carrier systems transit time

  5. Drug Biotransformation Phase I reactions – cytochrome P450s (細胞色素p540酵素) add or remove small chemical groups more water soluble excretion, or undergo further modification sometimes bioactivated to active or toxic compounds Phase II conjugation reactions (結合作用) add larger chemical groups, e.g., glucose derivatives usually non-toxic

  6. Cytochrome P450 System Different isoenzymes: 1, 2, and 3 families and A to E subfamilies Individual members, further designated by a no. e.g., 3A4, 2D6 CYP1A2: biotransforms about 15% of medications CYP2D6: 2-6% of total enzymes but metabolizes up to 25% of medications CYP2E1: Significant in activation and inactivation of toxins, ethanol induction can lead to hepatotoxicity of paracetamol

  7. CYP3: about 60% of total enzymes metabolize nearly 50% of all drugs CYP3A3, CYP3A4*, CYP3A5, and CYP3A7 CYP3A also present in the small intestine

  8. Factors Predisposing to Drug Interactions Elderly – multiple medications, physiologic changes, endocrine dysfunction, restrictive diets, alcoholism Decrease in gastric emptying, acid secretion, intestinal motility, lean body mass ratio, drug binding proteins, renal and hepatic functions Lipid soluble drugs, e.g., benzodiazepines, are increasingly sequestered and their duration of action are prolonged.

  9. Decrease fluid intake: bisphosphonates (雙磷酸鹽類藥物) irritate esophagus, aspirin damages stomach Increased sodium intake – negate antihypertensive effects Potent drugs with narrow therapeutic indexes (治療指數) or high protein binding

  10. Fluids for Drug Administration • Water – best, facilitates disintegration (崩散) • and dissolution (溶離) 2. Fruit juices – grapefruit (西柚), orange affects carrier systems in the intestine enhance or reduce absorption alter gastric pH and osmolarity delay gastric emptying 3. Tea – caffeine, milk, better avoided 4. Milk – complex formation, antibiotics

  11. Grapefruit Juice Habitual consumption – inhibits CYP3A4* drug biotransformation and (OATP mediated drug uptake) Increase blood levels of calcium blockers, beta blockers, statins (他汀藥, muscle pain), tranquilizers, cyclosporine (環孢靈), warfarin (抗凝血制) Inhibition for over 24 hours, Citrus juice delay gastric emptying (pH & osmolarity) Orange Juice Inhibits the OATP* (P-glycoprotein intestinal transport) and absorption of levofloxacin (第四代喹諾酮類抗生素)

  12. Green and Black Teas Tea catechins (兒茶素) significantly inhibit sulfotransferases (轉磺酶) 1A1 (liver) & 1A3 (gut), increase the bioavailability of -agonists Sulfate conjugation is the major metabolic process in the elimination of -agonists More side effects of palpitation & tremor Grapefruit and Orange juices also suppress SULT1A3 but not as strong as tea

  13. Food-Drug Interactions Tyramine (亁酪素) rich foods: interact with monoamine oxidase enzyme inhibitors (單胺氧化脢抑制劑, MAOIs for depression) & sympathomimetics - hypertension aged cheeses, pepperoni (辣肉腸), fermented meats, fava beans (蠶豆), pickled fish, yeast extracts, red wines, etc. (Linezolid antibiotic “環氧酮類抗生素” is a weak MAOI induces serotonin syndrome when used with certain antidepressants)

  14. Bananas, salt substitutes, increase potassium (鉀) and slow heart rate excessively when used with angiotensin-converting enzyme inhibitors (血管收縮素轉化酶抑制劑), e.g., enalapril, or potassium sparing diuretics e.g., spironolactone Food rich in pyridoxine (比哆醇) B6 vitamin, chicken, fish, pork, liver, kidney increase conversion of levodopa (左旋多巴) to dopamine (多巴胺) thus reduce the efficacy for Parkinson treatment

  15. Bitter melon (苦瓜) enhances sensitivity to insulin, additive hypoglycemic effect withother hypoglycemic drugs Caffeine containing beverages intensify the stimulating effect of Ma-huang on the heart

  16. Food rich in vitamin K: broccoli (西蘭花), spinach (菠菜), kale (縐葉甘藍菜) turnip greens (蘿蔔葉), cauliflower (椰菜花), Brussels sprouts (球芽甘籃菜), can reduce the effect of warfarin (blood clots) soy milk, avocado (牛油果) inhibit anticoagulation effect of warfarin Mango (vit A inhibits CYP2C19), alcohol (with liver disease), potentiate warfarin

  17. Herb-Drug Interactions Dong quai (Angelica sinensis, 當歸) Dan shen (Salvia miltiorrhiza, 丹參) interact with warfarin & increase bleeding Dong quai, inhibits platelet function by natural coumarins (香豆素) & reduces thromboxine A2 synthesis by ferulic acid (阿魏酸) Dan shen, used to promote blood flow and treat CV diseases, contains coumarin, decrease elimination of warfarin, thus increases the risk of bleeding, platelet dysfunction

  18. Baizhi (Angelica dahurica, 白芷) contains furanocoumarin Scutellaria baicalensis (黃岑), inhibit platelet function Cinchona pubescens (金雞納) potentiates effect of anticoagulants Quilinggao (龜令膏), Lycium barbarum L (枸杞子), Fenugreek (胡蘆巴, contain coumarins) increase the effect of warfarin

  19. Ephedra sinica (Ma Haung, 麻黄) cardiac arrhythmias when given with cardiac glycosides, enhance sympathomimetics, stroke, hypertension, myocardial infarction Hawthorn (crataegus, 山渣) additive effects with digoxin (毛地黃素), and potentiate cardiac glycosides like Siberian ginseng (刺五加) Rhubarb (大黃) potassium loss enhance effects of cardiac glycosides

  20. Licorice (甘草 Glycyrrhiza glabra) hypokalemia, decreases inactivation of cortisol (可體松) by renal 11-hydroxysteroid dehydrogenase leading to hypertension Phytoestrogen (植物性雌激素) containing herbs potentiate the effects of estrogen, e.g., dong quai, licorice

  21. Astragalus (黃芪) due to immunostimulant effect may interacts with immunosuppresssive drugs Panax ginseng, do not use with CNS drugs, potentiates MAOI and steroid effects Bupleurum falcatum (柴胡) enhances sedation effect when taken with other CNS depressants

  22. Health Product-Drug Interactions St. John’s Wort (Hypericum perforatum 聖約翰/金絲桃草) for depression, induces CYP3A, PgP and reduces the efficacy of oral contraceptives, sildenafil, warfarin, antidepressants, anti-seizure, HIV drugs, anti-rejection medications, digoxin (induction of PgP), etc. Ginkgo biloba (銀杏) inhibit platelet activating factor, platelet aggregation, and thromboxane synthetase (血栓素合成酶) Fish oil (omega-3 PUFA, eicosapentanenoic acid/EPA & docosahexaenoic acid/DHA), increases effect of warfarin

  23. Vitamin E increases risk of bleeding with warfarin and aspirin Ginseng decreases effect of warfarin, leading to thrombosis & increases the risk of hypoglycemia with anti-diabetic drugs Garlic (Allium sativum): alliin (蒜氨酸) being converted by alliinase (蒜氨酸酶) to allicin (蒜素) which inhibits platelet aggregation & enhances the effect of warfarin Ginger (Zingiber officinale), inhibits thromboxane synthetase

  24. Laxatives like senna (番瀉葉), cascara sagrada (美鼠李皮) and buckthorn (鼠李) promote potassium loss and lead to toxicity in digoxin (毛地黃素) users Yohimbine (育享賓 Pausinystalia yohimbe) for erectile dysfunction, a competitive alpha2-antagonist, & can lead to hypertension Alcohol in mouthwash and medications, interact with metronidazole (甲硝唑抗生素), can cause severe nausea and vomiting – aldehydes (醛類化合物)

  25. Toxic Herbs Slimming drug containing Guang fangii rather than Fangji Aristolochia fangchi (廣防己) as anti-inflammatory, contains aristolochic acid (AA, 馬兜鈴酸), which is nephrotoxic and carcinogenic

  26. Xiao-chai-hu-tang (小柴胡湯) for common cold and chronic liver disease, induces acute liver injury and cholestasis (膽汁阻塞) Tripterygium wilfordii Hook (雷公藤) as anti-inflammatory, causes severe lupus nephritis (狼瘡腎炎) Jin Bu Huan (金不換, Lycopodium serratum) herbal sedative and analgesic, producing acute hepatitis Dysosma pleianthum (Baijiaolian 八角蓮) contains podophyllotoxin (鬼臼毒素) causing thrombocytopenia (血小板過低) and liver damage Podophyllum hexandrum or emodi (鬼臼)

  27. Pennyroyal oil (胡薄荷油) used as a flavoring agent, flea repellent, menstruation induction contains pulegone (胡薄荷酮) which metabolized to form toxic metabolites causing hepatic failure, CNS and renal toxicity Aconite (烏頭) for neuralgia, asthma, and heart disease, contains cardioactive alkaloids (aconitine, 烏頭鹼) producing arrhythmias

  28. Aconitum carmichaeli (川烏), Coptis chinensus (川蓮), Datura metel L (洋金花), Flos rhododendri Mollis (閙陽花), Gentiana species (龍膽草) Strychnos pierriana and S. nuxvomica (馬錢子) Croton tiglium (巴豆)

  29. Reminders 1. Inform doctors on all drug/herb uses 2. Taking drug/herb at least 1.5 hours apart if needed 3. Stop herbs if note unusual change in drug effects 4. Stop using herbs at least 2-3 weeks before operation

  30. Welcome Dr. Chui The End

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