Dr. Arthur M. Presser - President: Huntington College of Heath Assistant Professor of Pharmacy Practice - Curriculum Coordinator - Complementary & Alternative Medicine - University of Southern California School of Pharmacy
Are there herb-drug interactions? Absolutely! Are herbs evil? Absolutely not! Significant risk for patients exists primarily in 3 groups of drugs: - Immunosuppressives (cyclosporine) - Anticoagulants (warfarin) Protease inhibitors (AIDS)
Potentiation of drug via similar activity Eg. Drug diuretic and herb diuretic - Potentiation of drug via complementary activity
Lowered P-glycoprotein system (eg. Eluthero and antibiotics) Eg. Bitter melon, gymnema, fenugreek,etc. and insulin or oral hypoglycemics
Decreased effectiveness of drug via antagonistic activity Eg. CNS stimulant with CNS depressant - Reduced side effects of drug Eg. Milk Thistle and hepatotoxic drugs, Licorice and corticosteroids, Astragalus and chemotherapeutics
Proactive interaction management -- Avoid red flags: Warfarin - Interacts with just about everything - 99% protein bound, slightest change can cause problems
Use basic knowledge of herb activity to predict potential problems - Separate drugs and herbs by 2-3 hours - If patient is on a drug regimen and wants to add herb, start with low herb doses and work up - Low and Slow
Understand Phase I liver detoxification - Function is to lower harmful compounds - Xenobiotics (drugs, pesticides, hormones, bacterial toxins) Phase I - Directly neutralizes or coverts to intermediates more accessible to Phase II - P-450 enzymes (pro-oxidants) Phase II - Conjugation Binds something to toxin to make it excretable in urine or bile - Uses glutathione, sulfates, acetates, cysteine, glucuronic acid
P-450 Enzymes - Major catalyst of phase I drug biotransformation Monooxygenases Cyto= cell, chrome= color Absorb light at particular frequencies (450nm) Various isoforms (isozymes) - 16 families and 29 subfamilies - Found in smooth endoplasmic reticulum (SER) Liver cells have highly developed SER therefore large proportion of P-450 enzymes - 90% of pharmaceuticals metabolized by P-450 Isoenzymes most commonly involved in drug metabolism: 3A4, 2D6, 1A2 - Act primarily in liver, but also intestine and other cells. Primary role in 1st Pass Metabolism Process of intestinal and hepatic degradation or alteration of a drug taken by mouth, after absorption, removing some of the active substance from the blood before it enters the general circulation.
CYP families - CYP1 Drug metabolism Combustion - aromatic hydrocarbons - increased by cigarette smoke, charred food - Converts active compounds to carcinogens CYP1A2 - lowered by Kava (maybe ginkgo)
CYP3 - CYP3 A4 Drug metab (50%) Most abundant in liver - lowered by ketoconazole, progesterone, increased by acetaminophen, Drug Metab increased by St. John's Wort (most work invitro), Guggul, Garlic - lowered by goldenseal lowered by grapefruit - Narginenin, bergamottin - bioflavonoids in juice - Decr. first pass metab via CYP3A4, 1A1, 1A2 in intestine - lowered maybe by ginger, kava, oregano, sage, turmeric (1A1), chamomile, feverfew, eluthero (invitro screening)
P450 enzymes - CPY3A4, CPY3A5, CPY3A7, CPY3A3 most important isoforms for metabolizing drugs - Drugs metabolized by CPY3A4 or CPY3A3 Amlodipine, astemizole, carbamazepine, clozapine, cyclosporine, diltiazem, 17B-estradiol, ethinyl estradiol, felodipine, imipramine, midazolam, nifedipine, nisoldipine, nitrendipine, saquinavir, quinidine, triazolam, verapamil - Note: erythromycin and ketoconazole inhibit CPY3A4
P-glycoprotein - Located in apical surface of epithelial cells - Found in gut, kidney, brain, liver - ATP dependant pump that effluxes poisons out of cells - Interferes with xenobiotic absorption by pumping back into intestine lumen - Cancer cells use to reject chemotherapeutics - Bacteria use to become resistant to antibiotics
Astragalus - increases immune effects of interleukin-2 and acyclovir - May be incompatible with immunosuppressive drugs Cyclosporine - Azathioprine - Methotrexate
Bitter Melon - lowers blood sugar
Bromelain - May increase bleeding with anticoagulants - Monitor - May increase effects of antibiotics - increases efficacy of 5-fluorouracil and vincristine
Cayenne - May increase metabolism of drugs by enhancing absorption - lowers gastric mucosal damage when taken 30 min before ASA
Eleuthero - increases dig. levels (interferes with test only) - increases tolerance to chemo. (Russian studies) - increases effects of antibiotics (monomycin, kanamycin) - increases effects of adeturone (radioprotective drug) - Possible inhibition of 2C19 - Possible P-glycoprotein
Garlic - May increase bleeding times with anticoagulants 5-20 cloves = 1 ASA - lowers blood levels of protease inhibitor (Saquinavir�) - increases Indomethacin, insulin, statins Monitor - Some garlic preparations containing allicin may increase the activity of 3A4
Ginger - May increase absorption of drugs - May increase bleeding with anticoagulants (?) - May increase cholesterol lowering effects of statin drugs - Case reports of lowered effect of antacids
Ginkgo - May increase bleeding with anticoagulants - May increase activity and side effects of MAO inhibitors - Use with caution with controlled seizure disorders (case report) - May increase efficacy (potency) of haloperidol in schizophrenia - increases nifedipine plasma levels - Components of Ginkgo - Terpene lactones (ginkolides) no effect on P450 - Flavonol aglycones (kaempferol, quercetin, apigenin, myricetin, tamarixetin) lowers 1A2 and 3A. - Quercetin lowers 2C9
American Ginseng - Hypoglycemic Journal of the American College of Nutrition, Vol.23, No. 3,248-258 (2004) American and Vietnamese lowered 90 min. plasma glucose - Panax, Wild American, raised peaks - Sugar effect depends on Rb to Rg ratio
Green Tea - High in tannin, do not take with codeine or theophylline (inhib. absorption) Large amounts may increase effects and side effects of theophylline?????????? May lower effect of coronary vasodilator drugs such as dipyridamle if taken simultaneously - Synergistic with sulindac and/or tomaxifen and may reduce adverse effects May lower effects of warfarin (Case report) Blood Thinning Medications: Green tea should not be taken with warfarin, a blood-thinning medication, because the herb contains vitamin K and, thus, can render warfarin ineffective. Similarly, green tea and aspirin should not be mixed because they both prevent platelets from clotting. Using the two together, therefore, may increase your risk of bleeding.
Guggul - lowers efficacy of beta blockers and calcium channel blockers
Kava - increases actions of depressant drugs, alcohol - Contraindicated with hepatotoxic drugs and alcohol - lowers efficacy of Parkinson drugs (L-Dopa) - lowers 3A4, isolated kavalactones - No systematic studies on pharmacokinetic interactions - No unequivocal clinical evidence; In vitro studies based on theoretical considerations
Licorice - lowers efficacy, increases toxicity of diuretics - Large doses lower K - lowers efficacy and increases side effects of digoxin - Large doses lower K, Low K increases risk of digoxin toxicity - Potentiates corticosteroids - increases blood pressure (pseudoaldosteronism)
Milk Thistle - lowers hepatotoxicity of drugs APAP, haloperidol, halothane, dilantin, butyrophenones, and phenothiazines, phenytoin - lowers kidney toxicity (without reducing actions) cisplatin and doxorubicin - lowers kidney toxicity of anesthetics - Contrary to previous reports-little or no effect on 3A4 or 2D6
Pycnogenol and nifedipine (Procardia, Adalar) calcium channel blocker - Life Sciences. 2004;74:855-862 - 100mg per day, 12 week trial - Pycnogenol group needed aprox 40% less drug (P increases 0.001) - Researchers believe that Pycnogenol shifts balance of vasodilatation and vasoconstriction in the direction of vasodilatation - Lowers endothelin-1 (compound that triggers vasoconstriction) Raises 6-ketoprostiglandin F1 (compound relaxes blood vessels) - Pycnogenol improves function of the endothelium (lining of blood vessels)
St. John's Wort: Not with - Cyclosporine - Digoxin - Protease inhibitors - Warfarin - (Oral contraceptives - No reports of unwanted pregnancies but possible breakthrough bleeding)
Schizandra - lowers cardiotoxicity of adriamycin - lowers CNS stimulation of caffeine and amphetamines - lowers hepatotoxicity of drugs (including APAP) - May increase action of pentobarbital
Valerian - increases effects of CNS depressants - Minimal effect of 3A4 and no effect on 2D6 - DM (2D6) metabolized extensively to its metabolite before and after Valerian dosing. - Alprazolam (3A4) not significantly altered after Valerian dosing.
[ 14. December 2007, 04:26 PM: Message edited by: Looking ]
Posted by treepatrol (Member # 4117) on :
up
Posted by Pocono Lyme (Member # 5939) on :
Good info.
Thanks.
Posted by AliG (Member # 9734) on :
This is great! Thanks for posting. Posted by Parisa (Member # 10526) on :
Thanks!
Posted by Looking (Member # 13600) on :
Medicine Interactions - Using Medicines with Vitamins and Herbs
Check out this site -- it lists many drugs so you can just scroll down the list until you find the drug you want to know about. Click on the drug and you will see herb & vitamin interactions listed.
Warfarin for example has a long list of herbs to avoid and they give the reasons* why.
If taking Warfarin avoid:
American ginseng, Asian ginseng*, Cranberry, Dan shen, Devil's claw*, Dong quai*, Fenugreek*, Garlic*, Ginger*, Ginkgo biloba*, Horse chestnut*, Lycium barbarum*, Papain*, Quilinggao*, Quinine*, Red clover*, Reishi, Sweet clover*, Sweet woodruff*, Vitamin D*
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