Herb-drug interactionsOutlineLearning objectivesEvidence for herb-drug interactionsDrug Interaction ResolutionPK vs PDPrevalence: Canadian seniorsPrevalence: Mayo ClinicSt. John’s wort (Hypericum perforatum)St John’s wortSt. John’s wort: PK interactionsSt. John’s wortClinical strategyWarfarin-herb interactionsSlide 15Warfarin and Chinese herbsWarfarin and “G” herbsWarfarin and lipid-based agentsCase ReportSlide 20Slide 21Slide 22Garlic (Allium sativum)Slide 24Herbs and StatinsSlide 26GinkgoGinkgo and psychotropicsKava (Piper methysticum)Licorice (Glycyrrhiza glabra)Licorice: positive interactionHerbal laxativesSurgery and Dental ProceduresSlide 34Slide 35Clinical copingChecking for herb-drug interactionsDental procedures: herb side effectsHerb-drug Herb-drug interactionsinteractionsCharlotte Gyllenhaal, Ph.D.Charlotte Gyllenhaal, Ph.D.1,31,3Gail Mahady, Ph.D.Gail Mahady, Ph.D.22Departments of Medicinal Chemistry and Departments of Medicinal Chemistry and Pharmacognosy,Pharmacognosy,11 Pharmacy Practice Pharmacy Practice22Block Center for Integrative Cancer TreatmentBlock Center for Integrative Cancer Treatment336-1870, [email protected], [email protected]►Evidence for herb-drug interactionsEvidence for herb-drug interactions►Pharmacokinetic (PK) versus pharmacodynamic Pharmacokinetic (PK) versus pharmacodynamic (PD) interactions(PD) interactions►St. John’s wortSt. John’s wort►WarfarinWarfarin►MiscellaneousMiscellaneous►Herb-drug interactions and surgical/dental Herb-drug interactions and surgical/dental proceduresprocedures►Use of computer databases for clinical questionsUse of computer databases for clinical questionsLearning objectivesLearning objectives►Distinguish between pharmacokinetic and Distinguish between pharmacokinetic and pharmacodynamic interactions.pharmacodynamic interactions.►Know the principal pharmacokinetic and Know the principal pharmacokinetic and pharmacodynamic interactions of St John’s Wort, i.e. pharmacodynamic interactions of St John’s Wort, i.e. induction of CYP450 3A4, and serotonin induction of CYP450 3A4, and serotonin syndrome/photosensitivitysyndrome/photosensitivity►Know the main reasons for herb-drug interactions with Know the main reasons for herb-drug interactions with warfarin, i.e. vitamin K activity; decreased GI warfarin, i.e. vitamin K activity; decreased GI absorption or CYP450 2C9 metabolism and herbs that absorption or CYP450 2C9 metabolism and herbs that decrease platelet aggregation or thromboxane decrease platelet aggregation or thromboxane synthesis or have coumadin content. synthesis or have coumadin content. ►Know the main reasons for caution with herbs and Know the main reasons for caution with herbs and surgery or dental procedures, i.e., herbal surgery or dental procedures, i.e., herbal anticoagulants (cause bleeding), sedative or stimulant anticoagulants (cause bleeding), sedative or stimulant herbs (modify anesthesia).herbs (modify anesthesia).Evidence for herb-drug Evidence for herb-drug interactionsinteractions►Case reportsCase reportsUnderreported? 70% “don’t ask-don’t tell”Underreported? 70% “don’t ask-don’t tell”►Lab studiesLab studiesDefine mechanismsDefine mechanisms►Recent interest in CYP450 inductionRecent interest in CYP450 induction►Not necessarily borne out in trials Not necessarily borne out in trials ►Human studiesHuman studiesTrials using probe drugsTrials using probe drugsMay be too short or expensiveMay be too short or expensiveMay be done on healthy population (not always)May be done on healthy population (not always)Genetic polymorphismsGenetic polymorphismsMultiple drug/herb users, elderly patientsMultiple drug/herb users, elderly patientsDe Smet, Br J Clin Pharm 2006; 63:258-67Drug Interaction ResolutionDrug Interaction Resolution►Require dosage adjustmentsRequire dosage adjustments►Temporary or complete elimination of Temporary or complete elimination of one or the other agent to avoid serious one or the other agent to avoid serious consequencesconsequences►Close monitoring of the subjectClose monitoring of the subject►Total change of drug therapyTotal change of drug therapyPK vs PDPK vs PD►PK: absorption, distribution, metabolism, PK: absorption, distribution, metabolism, eliminationeliminationCYP450, PgPCYP450, PgPAbsorption from GI tract (laxatives)Absorption from GI tract (laxatives)►PD: pharmacological functionPD: pharmacological functionAnticoagulant drugs plus anticoagulant herbsAnticoagulant drugs plus anticoagulant herbsSedative herbs plus anesthesiaSedative herbs plus anesthesia►NegativeNegativeMostMost►Positive or synergisticPositive or synergisticPossible PD or PKPossible PD or PKDecrease side effectsDecrease side effectsPrevalence: Canadian seniorsPrevalence: Canadian seniors►Canadian seniors with osteoarthritisCanadian seniors with osteoarthritisSurvey, n = 191. Average 2.8 prescriptions, 1.9 Survey, n = 191. Average 2.8 prescriptions, 1.9 self-care productsself-care products►Potential interactions detected using standard Potential interactions detected using standard databasesdatabases214 instances, 14% possible clinical significance214 instances, 14% possible clinical significance7 herbs/supplements, associated with 5 clinically 7 herbs/supplements, associated with 5 clinically insignificant interactionsinsignificant interactions1 recommendation to stop medications (dilatiazem 1 recommendation to stop medications (dilatiazem + atrorvastatin -> statin side effects intensified)+ atrorvastatin -> statin side effects intensified)Clinically significant interactions may be rare – but Clinically significant interactions may be rare – but thus easier to forget about and harder to monitor!thus easier to forget about and harder to monitor!Putnam, Can Fam Physician 2006; 52:340-45Prevalence: Mayo ClinicPrevalence: Mayo Clinic►6 specialty areas 6 specialty areas Survey of 1795 patients; 39.6% used supplementsSurvey of 1795 patients; 39.6% used supplements►Potential interactions detected using Lexi-Potential interactions detected using Lexi-Interact (available on PDA)Interact (available on PDA)107 interactions with potential clinical significance107 interactions with potential clinical significanceGarlic, valerian, kava, ginkgo and St. John’s wort Garlic, valerian, kava, ginkgo and St. John’s wort accounted for
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