Transcript Slide 1

Chrysanthemum parthenium (L.) Berhn (feverfew) 小白菊, 解熱菊
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
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
Enteral Drug Administration
Stomach – gastric emptying
Food, acidity, osmolarity (滲透壓)
Small intestine – main absorption site
large surface care
carrier systems
transit time
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
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
CYP3: about 60% of total enzymes
metabolize nearly 50% of all drugs
CYP3A3, CYP3A4*, CYP3A5, and CYP3A7
CYP3A also present in the small intestine
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.
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
Fluids for Drug Administration
1. 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
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)
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
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)
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
Bitter melon (苦瓜)
enhances sensitivity to insulin, additive hypoglycemic
effect with other hypoglycemic drugs
Caffeine containing beverages
intensify the stimulating effect of
Ma-huang on the heart
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
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
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
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
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
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
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
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
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)
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
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)
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
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)
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
Welcome Dr. Chui
The End