Docstoc

Microsoft Office Outlook Memo Style Ganoderma Extract

Document Sample
Microsoft Office Outlook Memo Style Ganoderma Extract Powered By Docstoc
					 Herbal Medicine and
Herbal-
Herbal-Drug Interactions                                                 Background Information
             Chun-
             Chun-Su Yuan, MD, PhD

  Tang Center for Herbal Medicine Research
 and Department of Anesthesia & Critical Care
        Pritzker School of Medicine
           University of Chicago
                E-mail: cyuan@uchicago.edu
            Website: http://tangcenter.uchicago.edu




Complementary and Alternative                                                 U.S. Regulatory Status of
 Medicine (CAM): Categories                                                       Herbal Products
Dietary supplements - herbs, dietary treatment
                      herbs,                                             1994 - Dietary Supplement Health and
Homeopathy                                                               Education Act (DSHEA)
                                         Books &
Acupuncture                               Classes


Oriental medicine                                                          e ba ed c es a d ood supp e e ts
                                                                         Herbal medicines and food supplements
Massage
                              Diet Products
                                                           CAM Drs Fee   sold OTC as dietary supplements
Naturopathy                      Mega Vits
                                                                         No review or approval by FDA of
Prayer and remote prayer
biofeedback                                 Herbs                        content
... …                            Out of pocket expenditures:             Notify FDA of marketing activities
                                            $27 Billion/yr
                DSHEA
        “Does Regulate Claims”
                                               FDA Modernization Act in ’97
 Manufacturers make “statements of             Make claims supported by
 nutritional support”
                                               “Authoritative statements”
                   y
 Influence on “body structure and function”       “Promote prostate h th …”
                                                - “P     t      t t heath ”
 Claim is “truthful and not misleading”         - “Maintain strong bone … ”
 Not for “diagnose, mitigate, treat, cure or   “Not-evaluated-by-
                                               “Not-evaluated-by-FDA” label
 prevent any specific disease”
 FDA to develop “GMP standards for             In case of adverse events …
 supplements”




Before and After DSHEA (1994)

 Herb use: Increased 380% from ’90-’97
                               ’90-
                                                Commonly Used Herbal
 Herb sales more than doubled since the
                                                  Medicines the U.S.
 ’94 law
 CAM expenditures $27 billion in ’97
                                                             Echinacea
Commonly Used Herbal Medicines                    Native North American plant
                                                  for wounds and infection
                                                  Has several different species
Most commonly                                     Uses
used herbs are                                        For colds and flu
European herbs                                        Best    d t the first   t
                                                      B t used at th fi t symptom
Supported by                                      Effects
history of use                                       General immune system stimulant
and research                                         A study showed it stimulates phagocytosis
                                                  Concerns
                                                                 immuno-
                                                     Diminished immuno-suppressants’ activity
                                                     Immuno-
                                                     Immuno-suppression with chronic use
                                                     Allergic reactions




      Echinacea, A Negative Study                                      Echinacea
 A NIH sponsored study                                      angustifolia,                                  pallida)
                                                 (Echinacea angustifolia, Echinacea purpurea and Echinacea pallida)

 Evaluation of Echinacea in
 experimental rhinovirus infections                    Traditional Use
                      2005:353;341-
 (Turner et al., NEJM 2005:353;341-8)
                                                       Laboratory Research
 437 volunteers randomized to 1 of 3
   hi                ti       l b
 echinacea preparations or placebo                     Clinical St d
                                                       Cli i l Study
 No significant effects on rates of
 infection, severity of symptoms or                    Safety
 viral titers
                                                       Effectiveness
 Some published comments
    Dose (160 mg) used was too low, vs. 900 mg         Acceptance
    Historical use: Root
    Different species
      Ephedra
                                                          Garlic
Uses - Respiratory conditions
Major constituent - Ephedrine                      Uses - Hypertension, high cholesterol
Effects                                            Effects
  Sympathomimetic effects
                                                      Platelet inhibition
  Increases HR and BP
                                                      Anti-
                                                      Anti-oxidant activity
Concerns                                           Concerns
  Myocardial infarction, stroke                       Potentiates other platelet inhibitors
  Catacholamine depletion
Drug abuse                                           four-
                                                   A four-year study (Koscielny et al., Atherosclerosis 1999)
  Athletic performance enhancer                       152 men and women with advanced plaque accumulation
  Recreational stimulant                              900 mg daily standardized powder and placebo
  Weight control: ephedra-containing supplements
                  ephedra-                            B-mode ultrasound to measure plaque volume at 0, 16, 36, 48 mo.
                                                      Significantly reduced plaque volume
Has been removed from the market




   Garlic and Cancer                                                            Garlic
                                                                        (Allium sativum)
J. NCI reported 40% reduction in
stomach cancer risk due to Allium                        Traditional Use
consumption
2005 USC study showed reduction in                       Laboratory Research
stomach cancer                                           Clinical St d
                                                         Cli i l Study
2005 Brit. J. Cancer documented
reduction in endometrial cancer risk                     Safety
Reported immune stimulant activity                       Effectiveness
Anti-
Anti-proliferative effects, mitotic arrest               Acceptance
and induction of apoptosis confirmed
           Ginkgo                                              Ginkgo
Uses                                                       (Ginkgo biloba)
  Cognitive impairment, dementia
  Especially Alzheimer’s disease
  Vascular disease
                                               Traditional Use
Contains                                       Laboratory Research
  Terpenoids and flavonoids
Effects                                        Clinical Study
  Vasoregulation
  On platelet-activating factor
     platelet-                                 Safety
  Scavenges free radicals
                                               Effectiveness
Concerns
  Some reports on bleeding complications       Acceptance
  Hypersensitivity




    Ginseng                                        Ginseng and Ginsenosides
 Uses
   Restore homeostasis
   Reduce stress
                                           Major constituents are
                                           ginsenosides
   Anti-
   Anti-fatigue
Contains                                   Also contains polysaccharides
   T
   Terpenoids and fl
          id    d flavonoids
                         id                and peptides
Effects                                    Most pharmacological actions are attributed
   Anti-oxidant
   Anti-                                   to ginsenosides
   Lowers blood glucose
                                           There is a wide variation in the ginsenoside
Concerns                                   content of different species of ginseng
   Ginseng abuse syndrome
   Possible interaction with warfarin
                        Ginseng                   Need to Standardize Herbal Extract
                                          etc)
     (Panax ginseng, Panax quinquefolius, etc)   #1: WI ginseng, 4-y root
                                                 #2: WI ginseng, 4-y root
                                                 #3: WI ginseng, 3-y root
    Traditional Use                                                                          Herbal product
                                                 #4: IL ginseng, 7-y root
                                                                                             often is a mixture
    Laboratory Research                                                                      Effects are difficult
                                                                                                    p
                                                                                             to compare
    Clinical Study                                                                           Standardization of
                                                                                             herbal compounds
    Safety
    Effectiveness
    Acceptance




           Kava                                                                   Kava
Uses - Anxiolytic, sedative                                                        methysticum)
                                                                            (Piper methysticum)
Contains                                                 Traditional Use
  Kavalactones
  Acting synergistically                                 Laboratory Research
Effects
  Sedation via GABA receptor
                                                         Clinical Study
  Anti-
  Anti-epileptic, neuroprotective                        Safety
  Therapeutic potential for anxiety
                                                         Effectiveness
Concerns
  Potentiates sedative effects                           Acceptance
  Liver toxicity - still available in the U.S.
      Medicinal Mushroom                         Medicinal Mushroom
Ganoderma lucidum
                                           In Japan: Asthma, hepatitis B, ulcers, high
Ling zhi, or Reishi
                                           cholesterol, high blood pressure, AIDS, kidney
“The Mushroom of Immortality”              inflammation, herpes, skin problems, weight loss, …
Uses
  Cardiovascular protection                In China: Arthritis, bronchitis, asthma, cancer,
  Anti-
  Anti-cancer                                                 ,         p     ,         ,
                                           chemo side effects, acute hepatitis, diabetes,
  Liver and kidney protection
                                           allergies, insomnia, altitude sickness, …
Contains
                                           Research data
  Terpenoids and polysaccharides
                                               Increases survival time in cancer patients on chemotherapy
Effects                                                  T-
                                               Increases T-cell counts in HIV subjects
  Immune stimulating                           Inhibits growth and invasiveness of cancer cells
  Anti-
  Anti-oxidant
Concerns                                   Phytochemistry:
                                           Phytochemistry:
  Dizziness                                    “Ganoderma – A therapeutic fungal biofactory”
  Nausea, dry mouth, abdominal upset




       Medicinal Mushroom                            Milk Thistle
   (Ganoderma lucidum, Ling zhi, Reishi)
              lucidum,                     Seeds from daisy family native to the
                                           Mediterranean
  Traditional Use                          Uses - liver disorders
                                              Cirrhosis
  Laboratory Research                         Alcoholic, viral and toxic hepatitis
                                           Contains silymarin (silybin silidianin and
                                                                      (silybin,
  Clinical Study                           silichristine, the biologically active flavonoids)

  Safety                                   Effects
                                              Protects liver cells from toxin damage
  Effectiveness                               Stimulates hepatocyte regeneration
                                           Concerns
  Acceptance                                  Generally safe
                                              Reported adverse effects - nausea and vomiting,
                                              pruritis, urticaria, allergic reactions
          Milk Thistle         St. John’s wort
                  marianum)
         (Silybum marianum)
                              Uses - Depression
Traditional Use               Effects - Inhibits
                              neurotransmitters reuptake
Laboratory Research             Serotonin
                                Norepinephrine
Clinical Study                  Dopamine
                              Effects on depression
Safety                          2002 NIH study: Both SJW and
                                Zoloft ineffective against serious
Effectiveness                   depression
                                Due to limited sensitivity
Acceptance
                              Concerns
                                Interacts with many drugs




         St. John’s wort             Valerian
     (Hypericum perforatum)   Uses
                                 Sedative, sleep aid
Traditional Use               Contains
                                 Valepotriates
Laboratory Research              Volatile oils
                                      g y g           y
                                 Acting synergistically
Clinical Study
                              Effects
                                 via GABA receptor activity
Safety
                              Concerns
Effectiveness                    Potentiates sedative effects
                                 Benzodiazepine-
                                 Benzodiazepine-like withdrawal
Acceptance                        - Discontinue gradually in dependent patients
                                  - Treat withdrawal with benzodiazepines
                         Valerian                                       An Example of
  (Valerian officinalis, Valerian angstifolia, Valerian wallichii)
                                                        wallichii)   New Drug Development
      Traditional Use                                                 Opioids for pain and diarrhea
                                                                      Agonists and antagonists
      Laboratory Research                                             Selective antagonists, e.g., MNTX
                                                                      First peripherally acting opioid
      Clinical Study                                                  antagonist

      Safety                                                                                                                  CH
                                                                                                                                   3
                                                                                                      N   CH
                                                                                                               2             +N        CH
                                                                                                                                            2

      Effectiveness                                                                              HO
                                                                                                                         HO




      Acceptance                                                                          HO
                                                                                                 O
                                                                                                               O   HO
                                                                                                                         O
                                                                                                                                            O



                                                                        Morphine               Naltrexone          Methylnaltrexone




                 Methylnaltrexone
                 - Current Status -
                                                                                   Herbal-
                                                                                   Herbal-Drug
  In April 2008, the FDA approved methylnaltrexone for
opioid-induced constipation in advanced illness patients.                          Interactions
  By early 2009, this indication has been approved by
regulatory agencies in over 30 countries.
  In early 2009, methylnaltrexone was available in 12
countries, with approximately 20 additional countries to
be launched in 2009.
          Herb-
Potential Herb-Drug Interactions
                                                                    Mechanisms of Action
 Herbs have many different constituents
 They possess pharmacological activities
                                                                              Direct effects
 Complex pharmacodynamics and
 pharmacokinetics                                                   Pharmacodynamic activities
 Lack of controlled clinical trials
                                                                   e.g., Garlic, ginkgo, ginseng - bleeding
 At least 16% of prescription medication                              Ephedra - cardiovascular effects
 users concurrently take herbs
                                                                           Ginseng - hypoglycemia
                                  herb-
 15 million Americans at risk for herb-drug
 interactions




       Mechanisms of Action                                         Mechanisms of Action
             Indirect effects - 1                                        Indirect effects - 2
                herb-
Pharmacodynamic herb-drug interactions                                      herb-
                                                            Pharmacokinetic herb-drug interactions

                Additive PD effect                               Herb affects ADME of other drugs
     Alters other drug action at effector sites                 Hepatic enzyme induction or inhibition
e.g., Kava and valerian potentiate benzodiazepine effects        Herbal PK data often not available
                                                            e.g., St. John’s wort increases metabolism of other drugs
  St. John’s wort
Herb-Drug Interactions
Herb-                                                                                   Ginseng-
                                                                              Potential Ginseng-Warfarin Interactions
Contains hypericin, hyperforin,
pseuodohypericin, and                                                           Herbs may have the potential to interact
adhyperforin, etc
                                                                                with drugs
Increases catabolism of other
d ugs
drugs                                                                           Especially those drugs that have narrow
Induces P450 enzymes                                                            therapeutic indices
  3A4 isoform
   e.g., cyclosporin, steroids,
                                                                                Such as warfarin
   alfentanyl, midazolam,
   lidocaine …                                                                                       anti-
                                                                                A commonly used oral anti-coagulant
  2C9 isoform
   e.g., warfarin, NSAID’s




                 A Case Report
 Previously maintained on stable warfarin                                                           double-
                                                                                    We conducted a double-blind,
 therapy
                                                                                              placebo-
                                                                                randomized, placebo-controlled trial
 After 2 weeks ginseng product ingestion
                                                                                to evaluate the potential interactions
                  anti-
 Decreased in the anti-coagulation effect of                                  between American ginseng and warfarin
 warfarin was observed (INR from 3.1 to 1.5)
 The effect was reversed after cessation of
 ginseng (INR returned to 3.3 in 2 weeks)
                                                             1997;54:692-
            (Janetzky K, Morreale AP. Am J Health Syst Pharm 1997;54:692-3)
                                                                  Study Flow Chart
                    Subjects                                                     Blood                      Blood        Blood        Blood                     Blood


                                                                     1st week

              non-
9 men and 11 non-pregnant women                                                  Day 1            2           3           4             5            6            7



enrolled                                                                         Warfarin      Warfarin     Warfarin


                                                                                 Blood


Age: 28.1 ± 7.0, ranges 18 - 45 yrs                                  2nd week
                                                                                 Day 1           2            3           4            5             6            7

                        exam, ECG
Screened with physical exam ECG,                                                GS/Placebo   GS/Placebo   GS/Placebo   GS/Placebo   GS/Placebo   GS/Placebo   GS/Placebo



blood chemistry, and urinalysis                                      3rd week
                                                                                 Day 1            2           3           4             5            6            7

Abstain from tobacco, drugs, and limit                                          GS/Placebo   GS/Placebo   GS/Placebo   GS/Placebo   GS/Placebo   GS/Placebo GS/Placebo



caffeine-
caffeine-containing products                                                     Blood                       Blood       Blood        Blood                     Blood


                                                                     4th week
Eat a balanced diet with consistent                                              Day 1            2            3           4            5             6           7


amount of vitamin K during the study                                            Warfarin +
                                                                                GS/Placebo
                                                                                             Warfarin +
                                                                                             GS/Placebo
                                                                                                          Warfarin +
                                                                                                          GS/Placebo
                                                                                                                       GS/Placebo   GS/Placebo   GS/Placebo GS/Placebo




  Endpoints and Data Analysis                                                                        Results
                                                                  INR generally reached peak levels on day 4
1st Endpoint: The change in peak INR
                                                                                                         2-
                                                                  Peak INR decreased significantly after 2-wk
2nd Endpoints: Changes in INR AUC; peak
                                                                  ginseng compared to placebo
warfarin plasma level; warfarin AUC
Statistical analysis:                                             Ginseng vs. placebo difference 0.19, 95% CI
 Using Wilcoxon rank-sum test
                rank-
                                                                  0.07 to 0.36, P < 0.01
 Spearman rank correlation coefficients for correlation between   INR AUC, peak warfarin level and warfarin
 INR and warfarin
                                                                  AUC significantly reduced
 Repeated measures ANOVA models were used for vitamin K
 intake
Changes in Individual Peak INR and INR AUC   Changes in Peak Warfarin and Warfarin AUC




                                                         Study Summary
        Results - continued                   Narrow therapeutic index of warfarin
                                              Crucial to keep its effect in a target range
 Peak INR and peak warfarin correlated                                            drug-
                                              The use is complicated by potential drug-drug
 Spearman rank correlation coefficient was
 S              k   l ti      ffi i t            drug-
                                              or drug-herbal interactions
      (P
 0.72 (P = 0.001)                             Our data suggest that American ginseng
                                                                 anti-
                                              reduces warfarin’s anti-coagulant effect
 Also, no difference of Vitamin K intake
 between two groups                                self-
                                              Herb self-medicating and not reporting its use
                                              Physicians should ask patients about their use
                                              of herbal medications
               Conclusions
Herbal medicine is the most frequently used
CAM modality in the U.S.
Consumers have high enthusiasm
Regulatory issues are discussed
Commonly used medicinal herbs are reviewed
Herbal-
Herbal-drug interactions are not well
characterized and outcome is difficult to predict
Some website for more information
http://tangcenter.uchicago.edu

				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:17
posted:7/18/2010
language:English
pages:14
Description: Microsoft Office Outlook Memo Style Ganoderma Extract