پاورپوینت کامل Herbal / Drug Interactions 81 اسلاید در PowerPoint

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پاورپوینت کامل Herbal / Drug Interactions 81 اسلاید در PowerPoint

اسلاید ۴:

اسلاید ۵:

اسلاید ۶: Steps for Detecting and Advising on Herbal/Drug InteractionsIs the patient taking any herbal supplementsDoes the herbal have efficacy for the intended useIs the product reliable (i.e.,what are they REALLY taking)Is the Rx drug one with a narrow therapeutic margin

اسلاید ۷: Evaluation of Herbal/Drug InteractionsSpeculative or Theoreticale.g. St. John’s Wort and tyramine containing foods due to MAOI effects or evening primrose oil and risk for bleeds with warfarinIn vitro effectse.g. St. John’s Wort and microsomal studies showing inhibition of CYP3A4In vivo – animal studiese.g. Kava and alcoholIn vivo – human case reportse.g. Ginkgo and warfarin bleedsIn vivo – healthy human volunteer studiese.g. indinivir and St. John’s WortIn vivo – clinical studies in patients

اسلاید ۸: Important Criteria for Evaluation of a Human Herbal/Drug Interaction ReportReputable standardized product used and carefully describedProduct used analyzed for marker compoundsSame batch used throughout studyDoses appropriateSteady state study to discern CYP inductionIs observation consistent with known mechanisms of actionIs observation consistent with literature observationsCrossover, randomized, placebo controlled human volunteer study with appropriate n

اسلاید ۹:

اسلاید ۱۰: Stevinson et al. Ann Int Med 133:420-429, 2000

اسلاید ۱۱: Spontaneous spinal hemoatoma associated with garlic Rose et al. Neurosurgery 1990;26:880-882.87 year old male2g of garlic per day for “years”presented with weakness and partial paralysisbleeding time of 11.5 min (normal = 3 min)day 3 post surgery bleed time of 5 min (after stopping garlic)Other reports: Garlic and TURP bleeding (German et al. Br J Urology 1995;76:518).Garlic and surgery bleeding (Burnham BE; Plastic Reconstr Surgery 1995;95:213).

اسلاید ۱۲: Piscitelli et al. Garlic and Saquinavir. Clin Infect Dis 2002;34:234-238. N=10 Garlic=GarliPure (Natrol)(BID)

اسلاید ۱۳: Piscitelli et al. Garlic and Saquinavir. Clin Infect Dis 2002;34:234-238. N=9 Garlic=GarliPure (Natrol)(BID)

اسلاید ۱۴: Gurley et al. Clin Pharmacol Ther 2002;72:276-287 n=12; note: used garlic oil prep (500mg TID)

اسلاید ۱۵: Markowitz et al. Clin Pharmacol Ther 2003;74:170, n=14, 3X600mg for 14d (Kwai)

اسلاید ۱۶: Garlic summaryEfficacy: Mild benefit for use in hyperlipidemia Safety: goodDrug interactions: warfarin; possibly aspirin and other antiplatelet adhesion drugs (pharmacodynamic interaction); not with HIV drugs (other 3A4 substrates) but depends on product (pharmacokinetic interaction)Product selection: Suggest enteric coated tablets standardized to about 4mg allicin yield/tabletDose: equivalent of about 4g (2-3 cloves) of fresh garlic per day i.e. 8-12 mg allicin/d

اسلاید ۱۷: Gurley et al. Clin Pharmacol Ther 2004;76:428-440.CYP 1A2

اسلاید ۱۸: Gurley et al. Clin Pharmacol Ther 2004;76:428-440.800mg BID for 30d (Wild Oats Market)(analyzed)CYP 3A4

اسلاید ۱۹: Gorski et al. Clin Pharmacol Ther 2004;75:89-100N=12 crossover, before and after 400mg QID Echinacea purpurea root extract for 8dA= Cl caffeine (CYP 1A2)B= Cl tolbutamide (CYP 2C9)

اسلاید ۲۰: Gorski et al. Clin Pharmacol Ther 2004;75:89-100N=12 crossover, before and after 400mg QID Echinacea purpurea root extract for 8dOpen circle is echinaceaA= midazolam IV (CYP 3A4)B= midazolam PO (CYP 3A4)

اسلاید ۲۱: EchinaceaSummaryEfficacy: evidence for treatment not preventionSafety: good; rare allergyDrug interactions: Pharmacodynamic: don’t give to patients taking immunosuppressive drugsPharmacokinetic: may inhibit 1A2; may inhibit intestinal 3A4 but induce hepatic; clinical significance unclearProduct selection: want standardized extract containing about 4% phenolicsDose: about 250mg QID for treatment Questions remainingWhich product Tincture Tablets Root extrract Flowering tops Pressed juice E. purpurea E. augusifolia E. pallida

اسلاید ۲۲:

اسلاید ۲۳:

اسلاید ۲۴:

اسلاید ۲۵: Bleeds associated with ginkgo use

اسلاید ۲۶: IsoformType of InhibitionKi (g/ml)CYP1A2Mixed11.20.6Competitive2.1—CYP2A6Mixed21.22.1CYP2C9Competitive9.1—CYP2D6Competitive133.1—CYP3A4Mixed17.02.5Non-linear Regression Ki Values

اسلاید ۲۷: Tolbutamide Human Study (CYP 2C9 probe)-6 Subjects (3 males, 3 females)-Subjects ingested 500mg tolbutamide and collected 6-12 hour urine (Control phase)-Followed by a 2 week wash-out period-Subjects then ingested two 60mg Ginkgo biloba extract tablets 2 times a day for 3 days-The morning of day 4 patients received a 500mg dose of tolbutamide along with the ginkgo and collected 6-12 hour total urine (Ginkgo phase)Tolbutamide dose2 week wash-out periodGinkgo biloba doseTolbutamide dose

اسلاید ۲۸: Control680 323 Ginkgo610 327

اسلاید ۲۹: Diclofenac-Ginkgo Interaction (CYP 2C9 probe)12 healthy non-smoking subjects were recruited (8 males 4 females)50 mg diclofenac potassium (immediate release) was administered every 12 hours for 14 daysOn day 8, 120 mg of Ginkgo biloba extract was added to the diclofenac regimen.On days 7 and 14 plasma collected at times (0, 0.5, 1,2,4,6,8,10, and 12 hrs)12 hour urine collectedDiclofenac 50 mg every 12 hoursGinkgo biloba 120 mg every 12 hoursDay 7 blood drawDay 14 Blood draw

اسلاید ۳۰: Control0.64 0.36Ginkgo0.61 0.33Mohutsky et al. Am J Ther 2006;13:24-31

اسلاید ۳۱: Ginkgo biloba – Diclofenac Tolbutamide Human Studies ConclusionsNo difference was observed in the metabolic ratio between the two arms of the study (tolbutamide alone and tolbutamide + Ginkgo)No difference was seen between the clearances of the two arms of the study ( diclofenac alone and diclofenac + Ginkgo)Ginkgo extract does not appear to interact with CYP2C9 substrates in humans

اسلاید ۳۲: Gurley et al. Clin Pharmacol Ther 2002;72:276-287 n=12 (CYP 3A4) ginkgo-Wild Oats Markets (24% flavone glycosides, 6% ginkgolides)(analyzed)

اسلاید ۳۳: Engelsen et al, Thromb Haemost 2002;87:1075-6. N=21, double blind, crossover. Rx=1 month with 2 week washout. Dose of warfarin did not change.

اسلاید ۳۴: Jiang et al. Br J Clin Pharmacol 2005;59:425-432.N=12 ginkgo for 7d; warfarin alone or in combination with ginkgo or ginger

اسلاید ۳۵:

اسلاید ۳۶: Ginkgo/Drug Interactions other studiesMarkowitz et al. J Clin Psycopharmacol 2003;23:576-581. No effect of multiple dosing of ginkgo on dextromethorphan (2D6) or alprozolam (3A4) pharmacokinetics. n=12Mauro et al. Am J Ther 2003;10:247-251. No effect of multiple dosing of ginkgo on digoxin (Pgp) pharmacokinetics. N=8 crossoverMohutsky et al. Am J Ther in press. No effect of multiple