FUN2: 11:00 – 12:00 Scribe: Ryan O’Neill/Caitlin Cox
Friday, December 12, 2008 Proof: Sally Hamissou
Dr. Kim Pharmacology Page 1 of 5
I. Introduction [S1]:
a. Dr. Kim said there would be a small section of extra powerpoints uploaded soon
b. Today we will be discussing complementary and alternative medicine (CAM), with an emphasis on botanically based dietary supplements
c. A lot of medical fields are going towards “integrative medicine”
II. Learning objectives [S2]
a. Categories of complementary and alternative medicines
b. Importance of need for education in this area, a lot of your patients will want to be informed of these other options; awareness leads to acceptance and ability to advise (the more you know the more you can advise)
c. Selected botanical dietary supplements
i. Their purported efficacies
ii. Potential mechanisms (at least as far as we know)
iii. Combinations that are known to be toxic
d. Understanding of DSHEA
e. Importance of patient/doctor communication; you need feedback as a doctor
i. your patient also has a role in taking care of themselves
ii. the more you know the better you can take care of yourself
III. Perspective [S3]
a. Perspective: everything old is new again, things come back around (e.g. fashions)
i. Dietary supplements, in particular “botanicals” are as “old as the hills”, in fact much older---like 5,000 years.
ii. They pre-date you-know-who.
iii. Good stuff gets rediscovered.
IV. Definitions [S4]
a. Complementary & alternative medicine: they are different
i. Complementary – taken in addition to a medication
ii. Alternative – taken in place of other medications
1. In some cases it is not in place of, but it is the only option
b. Manipulative and body-based systems:
i. acupuncture, massage, yoga
ii. chiropractice
c. Biologically-based therapies that involve chemicals
1. Ex: St. John’s wort is a pill packed full of chemicals extracted from a flower
ii. herbal medicine (botanicals)
iii. dietary supplements – different from grounded up flowers
1. Many dietary supplements are actually botanicals, as we will see shortly.
iv. nutriceuticals – things you add to foods
d. Area of mind-body, how you can feedback into your body and make it feel better
V. Which CAM does what? [S5]
a. Acupuncture:
i. Stimulate specific brain regions that control the distal problem or pain perception
ii. Sounds mysterious, but has shown effectiveness and is as “old as the hills”
b. Music therapy:
i. Physically calms the body, non-invasive; allows the patient to cope with fears, discomfort
c. Yoga & Massage in the category of manipulative medicines
i. Also non-invasive
ii. Reduce stress, enhance circulation, improve flexibility
iii. Idea: when you are calmly doing yoga, you are not stressed about anything else
iv. This can alter your perception of pain and discomfort
d. Botanicals:
i. Can be alternative to conventional medicine
ii. Can complement conventional medication
iii. Can be the only medicine (closed off areas)
VI. Medical education & care evolving toward an integrative approach [S6]
a. Specifics of what NIH is doing toward this integrative approach: 10 years ago the Office of Alternative Medicine became National Center for Complementary & Alternative Medicine (NCCAM): budget has gone way up because they had to put more importance on this because these don’t need to be prescribed and are easily accessible.
i. Ex: Grapeseed is good for your heart & brain, but we don’t know the dosages or effective time of consumption during your lifespan is best.
ii. In plants, like Echinacea, some varieties have efficacy and some don’t. This is important because some of the vendors don’t even know this and they are grinding the flowers up and putting them into capsules.
b. Complementary to NIH and NNCAM funding research in this area: we need formal training of medical, dental and optometry students in CAM to advise your patients:
i. A lot of the universities have set up centers for Integrative Medicine already exist at major universities
1. UAB is lagging behind the mainstream of medical education
2. More and more, medical education is inclusive of CAM
c. Many hospitals nationwide offer CAM
VII. Demographics regarding CAM use [S7]
a. Who is using CAM? 80% of the world (outside of the U.S.): CAM is not complementary or alternative.
i. It’s the ONLY medicine!
b. In America:
i. Greater than 2/3 take daily supplements; most take more than just one supplement (this includes vitamins)
1. These can have synergistic effects with other medications being taken.
ii. 1/3 takes supplements instead of prescriptions.
1. Other prescriptions may have side effects, so you take something more benign.
iii. The majority take herbals do not consult their physicians because they think they are natural, and not “real medicines.”
VIII. Botanicals taken for age-related conditions. Why? [S8]
a. As scientists, we need to know that America is aging.
b. By 2050, one-third of the female population will be postmenopausal
c. What does that mean for medical consequences?
i. One-third of the female population will be at risk for heart disease, cancer, and osteoporosis.
d. By 2050, 1 in 45 Americans will be living with Alzheimer’s disease.
IX. Why do patients seek alternative treatments? [S9]
a. Tolerate the discomfort of prescription drug (side) effects
b. Allows a proactive attitude; empowers the patient;
c. Modern medicine offers “chemical” care; patient’s want and need, and will pay money for, more “natural” care.
X. The role of the patient as medicine moves toward integrative care [S10]
a. Patient must be attuned to their bodies;
b. The healthy patient must take proactive role in protecting their health (it’s a lot easier than treating the disease)
c. Patient must realize lifestyle is a consideration
i. Identify sources of and ways to reduce stress
ii. Assess relevant risk factors for diseases:
1. Obesity, smoking, diet
a. Things that you put in your mouth are huge lifestyle factors.
b. Unlike the other factors (e.g. environmental), diet is something you can do for yourself.
iii. Exercise – big factor
XI. Guidelines for medical professionals regarding CAM [S11]
a. This is out of The Journal of Academic Medicine
b. The point was made that immigration plays a major role in determining the high percentage of non-Caucasian patients who are seeing doctors.
i. A lot of these patients come from areas that rely on the only thing they know, namely, CAM remedies.
c. Be aware and respectful of cultural and ethnic bases for these remedies
XII. Regarding BOTANICALS [S12]
a. Botanicals are within the larger context of CAM
b. Botanicals are basically bags of chemicals from plants packed into pills.
c. LEARNING OBJECTIVES;
i. Health benefits of dietary supplements
1. Mechanisms of action
ii. Potential complications from dietary supplements taken with prescription drugs because they are chemicals that have effects on the cytochrome P450 system or are reliant on this system
iii. We will cover specific examples of dietary supplement:drug interactions
XIII. History lesson: Our oldest analgesics were once “botanicals.” [S13]
a. Going back to the example of good things being “as old as the hills.”
b. Pure analgesics were originally crude botanicals.
c. Morphine and heroin:
i. A long time ago the opium poppy was normal in people’s lives
ii. Many years later in 1895, Bayer coined the term “heroin.”
iii. 1973: the opioid receptor isolated
iv. 1975: the first endogenous opioid (enkephalin) was isolated and described
v. Total time to today (of first known use of morphine and heroin): over 5,000 years (this is what is meant by “over the hill”)
d. Main Point: Better analgesics have not been discovered.
i. Newer is not necessarily better, sometimes older is better.
ii. More research is needed in this area.
XIV. Another drug that started out as a crude botanical: Aspirin [S14]
a. A long time ago, Egyptians took an infusion of myrtle leaves for back pain;
b. Flash forward in time to show that at the Royal Society of London showed the analgesic properties of willow tree extract
i. 1899: Bayer: introduced acetylsalicylic acid as “aspirin”
ii. 1950: Laurence Craven (CA) first noted aspirin’s blood thinning properties
c. In the early 1970’s another British man shows that aspirin inhibits COX (cyclooxygenase)
d. Total time from the first crude use of aspirin to current: nearly 3500 years
XV. Most widely used botanicals: [S15]
a. We normally think of botanicals as just ground up flowers, but someday they may actually yield a better analgesic or painkiller.
b. Here is a list of some of the botanicals you may have heard about and the conditions they are taken for (not always effective for, though):
i. St. John’s wort - depression
ii. Echinacea – colds, flu
iii. Saw palmetto – benign prostatic hyperplasia (BPH)
iv. Cranberry – urinary tract infections
v. Ginkgo biloba – anxiety/stress
vi. Black cohosh – menopausal symptoms
vii. Grape seed extract – general well being
XVI. DSHEA, 1994 Dietary Supplement Health and Education Act [S16]
a. Because they were increasingly being used, Congress implemented the Dietary Supplement Health and Education Act of 1994. It has greatly impacted botanical use and research.
b. Because many botanicals are used in foods, the DSHEA says botanicals are dietary and do not need to be regulated up front.
c. All botanicals are now dietary supplements, even though some of them you do not actually put in food.
d. What we call, “Truthful scientific information” can be displayed on the label to promote sale, but that is tricky terminology.
e. The burden of proof of toxicity on the government, which means that up front, a company can package and sell something to you without testing whether it is toxic or not. Until there are multiple cases of people dying or getting sick from the product, the government cannot mandate doing a toxicity test.
f. You see these statements all the time:
i. “This statement has not been evaluated by the FDA.”
ii. “This product is not intended to diagnose, treat, cure, or prevent, any disease.”
XVII. Labeling under DSHEA [S17]
a. The wording: “this product promotes bone health” is allowed.
b. On the other hand, the wording: “this product prevents osteoporosis” is not allowed.
c. These products cannot state that they treat or prevent any disease, even if the product has been shown to prevent or delay disease. Because it is a dietary supplement, it cannot say that.
XVIII. Botanicals and pharmacology [S18]
a. As medical professionals, you need to know that once you extract something from a plant or seeds and put it in capsules, they are xenobiotics just like real drugs.
b. The rules of pharmacology apply in all respects to these botanicals preparations too.
i. They are subject to the same rules of uptake, metabolism and distribution
ii. Also like real prescription drugs, they can target enzymes, transporters, and receptors. Sometimes the same ones that the prescription drugs target and are where you get problems with interactions.
iii. Same pharmacogenetics aspects
XIX. How do botanicals and prescription drug interact [S19]
a. There are three possible categories for interactions:
i. They can have totally independent effects, sometimes including toxicity (independent of prescription drugs).
ii. They can enhance prescription drug action.
iii. They can inhibit.
iv. You, as medical professionals, need to be educated because there is no point for you to prescribe medication when you know or think the patient is going to go out and take or eat something bought over-the-counter thinking it is harmless. Enhancing a prescription drug might be okay if within the therapeutic window of efficacy. But if you are going to prescribe a drug that is going to disappear because of something natural that your patient takes that will cause the drug to be metabolized out of the system, that’s not good.
XX. Basis for different effects [S20]
a. How can the chemicals of a botanical enhance? By having similar chemical structures.
b. They can inhibit by also having similar structures and binding to the same target, like the estrogen receptor, locking it into conformation where it cannot function.
c. Or they can indirectly inhibit by enhancing the metabolism of the drug, so it disappears from the blood.
d. Or they can inhibit by activating metabolism of the pro-drug. Remember, that some drugs are inert chemicals when they enter the body and need to be metabolized by cytochrome P450 system to become active. If you take something that inhibits this metabolism, then the drug will not be metabolized to the active form, and therefore, will be pointless to have prescribed.
XXI. Dealing with patients and their botanical therapies [S21]
a. You need to know what people are taking.
b. Understand that “Natural” does not mean safe because interactions do occur.
c. In most cases, no clinical studies have been done on children or elderly patients to see if over-the-counter drugs have the same efficacy, so botanicals and herbals should only be taken with professional advice.
XXII. Beware of these combinations [S22]
a. Some combinations (and you should be aware of these specifics) are real no-no’s.
b. Don’t take Echinacea with Immunosuppressants.
c. Garlic and NSAIDS
d. Ginseng and NSAIDS, this combination is more controversial, but you need to ere on the side of caution, if you have read even one paper about complications.
e. Some herbals should be avoided in combination or not.
XXIII. [S23]—Skipped
XXIV. Ephedra (Ma-huang) [S24]
a. It was banned by the FDA in 2004 for abuse (overuse).
b. Now it is back on the market in a dosage range that has shown to be unharmful.
c. Sports organizations have banned it.
d. Of the 1600 reports of adverse reactions, only 20 were sentinel (severe, ending in death) events.
e. More deaths occur per year due to tylenol and aspirin overdose than has been attributed in total to ephedra. But are these analgesics being banned? No.
XXV. Ephrine family [S25]
a. Sudafed contains a very close relative to Ephedra called Phenylephrine, but it has not been banned.