Chrysanthemum parthenium (L.) Berhn (feverfew) ???, ???

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Chrysanthemum parthenium (L.) Berhn (feverfew)
???, ???
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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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Intestinal Carrier Systems
P-glycoprotein (p-???) efflux transporter,
reduces drug absorption
Multidrug resistance peptides (??????, MDRs)
decreases drug absorption
Organic anion transporting polypeptide
(?????????, OATP) facilitates drug absorption
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Enteral Drug Administration
Stomach gastric emptying
Food, acidity, osmolarity (???)
Small intestine main absorption site
large surface care
carrier systems
transit time
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Drug Biotransformation
Phase I reactions cytochrome P450s
(????p540??) 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 (????) add
larger chemical groups, e.g., glucose derivatives
usually non-toxic
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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
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CYP3 about 60 of total enzymes metabolize
nearly 50 of all drugs CYP3A3, CYP3A4,
CYP3A5, and CYP3A7
CYP3A also present in the small intestine
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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.
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Decrease fluid intake bisphosphonates (???????)
irritate esophagus, aspirin damages stomach
Increased sodium intake negate antihypertensive
effects
Potent drugs with narrow therapeutic indexes
(????) or high protein binding
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Fluids for Drug Administration

• Water best, facilitates disintegration (??)
• and dissolution (??)

2. Fruit juices grapefruit (??), 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
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Grapefruit Juice
Habitual consumption inhibits CYP3A4
drug biotransformation and (OATP mediated drug
uptake)
Increase blood levels of calcium blockers, beta
blockers, statins (???, muscle pain),
tranquilizers, cyclosporine (???), warfarin
(????)
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
(??????????)
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Green and Black Teas
Tea catechins (???) significantly inhibit
sulfotransferases (???) 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
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Food-Drug Interactions
Tyramine (???) rich foods interact with
monoamine oxidase enzyme inhibitors (????????,
MAOIs for depression) sympathomimetics -
hypertension
aged cheeses, pepperoni (???), fermented
meats, fava beans (??), pickled fish, yeast
extracts, red wines, etc.
(Linezolid antibiotic ??????? is a weak MAOI
induces serotonin syndrome when used with certain
antidepressants)
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Bananas, salt substitutes, increase potassium (?)
and slow heart rate excessively when used
with angiotensin-converting enzyme inhibitors
(???????????), e.g., enalapril, or potassium
sparing diuretics e.g., spironolactone
Food rich in pyridoxine (???) B6 vitamin,
chicken, fish, pork, liver, kidney increase
conversion of levodopa (????) to dopamine
(???) thus reduce the efficacy for Parkinson
treatment
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Bitter melon (??) enhances sensitivity to
insulin, additive hypoglycemic effect with
other hypoglycemic drugs
Caffeine containing beverages intensify the
stimulating effect of Ma-huang on the heart
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Food rich in vitamin K broccoli (???),
spinach (??), kale (?????) turnip greens
(???), cauliflower (???), Brussels sprouts
(?????), can reduce the effect of warfarin
(blood clots)
soy milk, avocado (???) inhibit anticoagulation
effect of warfarin
Mango (vit A inhibits CYP2C19), alcohol (with
liver disease), potentiate warfarin
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Herb-Drug Interactions
Dong quai (Angelica sinensis, ??) Dan shen
(Salvia miltiorrhiza, ??) interact with
warfarin increase bleeding
Dong quai, inhibits platelet function by natural
coumarins (???) reduces thromboxine A2
synthesis by ferulic acid (???)
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
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Baizhi (Angelica dahurica, ??) contains
furanocoumarin
Scutellaria baicalensis (??), inhibit platelet
function
Cinchona pubescens (???) potentiates effect of
anticoagulants
Quilinggao (???), Lycium barbarum L
(???), Fenugreek (???, contain coumarins) increase
the effect of warfarin
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Ephedra sinica (Ma Haung, ??) cardiac
arrhythmias when given with cardiac glycosides,
enhance sympathomimetics, stroke, hypertension,
myocardial infarction
Hawthorn (crataegus, ??) additive effects with
digoxin (????), and potentiate cardiac
glycosides like Siberian ginseng (???)
Rhubarb (??) potassium loss enhance effects of
cardiac glycosides
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Licorice (?? Glycyrrhiza glabra) hypokalemia,
decreases inactivation of cortisol (???) by
renal 11?-hydroxysteroid dehydrogenase leading
to hypertension
Phytoestrogen (??????) containing herbs
potentiate the effects of estrogen, e.g., dong
quai, licorice
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Astragalus (??) due to immunostimulant effect
may interacts with immunosuppresssive drugs
Panax ginseng, do not use with CNS drugs,
potentiates MAOI and steroid effects
Bupleurum falcatum (??) enhances sedation
effect when taken with other CNS depressants
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Health Product-Drug Interactions
St. Johns Wort (Hypericum perforatum ???/????)
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 (??) inhibit platelet activating
factor, platelet aggregation, and thromboxane
synthetase (??????)
Fish oil (omega-3 PUFA, eicosapentanenoic
acid/EPA docosahexaenoic acid/DHA),
increases effect of warfarin
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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 (???) being
converted by alliinase (????) to allicin (??)
which inhibits platelet aggregation enhances
the effect of warfarin
Ginger (Zingiber officinale), inhibits
thromboxane synthetase
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Laxatives like senna (???), cascara sagrada
(????) and buckthorn (??) promote potassium
loss and lead to toxicity in digoxin (????)
users
Yohimbine (??? Pausinystalia yohimbe) for
erectile dysfunction, a competitive
alpha2-antagonist, can lead to hypertension
Alcohol in mouthwash and medications, interact
with metronidazole (??????), can cause
severe nausea and vomiting aldehydes (?????)
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Toxic Herbs
Slimming drug containing Guang fangii rather than
Fangji
Aristolochia fangchi (???) as anti-inflammatory,
contains aristolochic acid (AA, ????), which
is nephrotoxic and carcinogenic
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Xiao-chai-hu-tang (????) for common cold and
chronic liver disease, induces acute liver
injury and cholestasis (????)
Tripterygium wilfordii Hook (???) as
anti-inflammatory, causes severe lupus nephritis
(????)
Jin Bu Huan (???, Lycopodium serratum) herbal
sedative and analgesic, producing acute hepatitis
Dysosma pleianthum (Baijiaolian ???) contains
podophyllotoxin (????) causing
thrombocytopenia (?????) and liver damage
Podophyllum hexandrum or emodi (??)
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Pennyroyal oil (????) used as a flavoring
agent, flea repellent, menstruation induction
contains pulegone (????) which metabolized to
form toxic metabolites causing hepatic failure,
CNS and renal toxicity
Aconite (??) for neuralgia, asthma, and heart
disease, contains cardioactive alkaloids
(aconitine, ???) producing arrhythmias
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Aconitum carmichaeli (??), Coptis chinensus
(??), Datura metel L (???), Flos rhododendri
Mollis (???), Gentiana species (???)
Strychnos pierriana and S. nuxvomica (???)
Croton tiglium (??)
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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
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Welcome Dr. Chui
The End