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CAM in UME at DALHOUSIE 2006 CAM BASICS Jana Sawynok, PhD Dept. Pharmacology, Dalhousie University [email protected] (902)494-2596 What is CAM? COMPLEMENTARY and ALTERNATIVE MEDICINE (CAM) Health-related systems, treatments, practices, and products which do not currently have widespread acceptance within Canadian health care systems. e.g. herbal remedies, chiropractic, massage therapy acupuncture, homeopathy, naturopathy meditation, relaxation, visualization (see Typologies) Why teach CAM? - widespread use by patients - lack of discussion about CAM use - knowledge lacking amongst medical students, physicians - both groups want more CAM in UME
• Physicians must know about and educate patients about potential
adverse effects including drug interactions
• Some CAM therapies improve health outcomes, and patients should
not be denied the option of these potentially helpful therapies
INTEGRATIVE MEDICINE Healing-oriented medicine that takes into account the whole person; Emphasizes the therapeutic relationship, and makes use of all appropriate therapies (conventional, CAM). Overview of session
A.
Utilization of CAM prevalence, who uses CAM and why
sources of information methodological issues central themes for CAM
Natural health products (NHPs)*, acupuncture*, chiropractic*, bodywork, naturopathy*, homeopathy*, mind-body work*, energy therapies (identified by NWG)
____________________________________________________________ CAM BASICS (2 hrs) Presentation by Dr. J. Sawynok, PhD; Dept. Pharmacology Appendix I Table of contents of recommended CAM resources Timeline of events relevant to CAM development CAM PRACTICE (2 hrs) Presentations by invited CAM practitioners; with Q and As (Naturopath, Chiropracteur) Dal Faculty, Dr. E. Gold, MD, CCFP, FCFP; Dept. Family Medicine currently President CCMA (Canadian Complementary Medical Assocn) ___________________________________________________________ Note: This is an initial step towards attaining goals identified in Appendix I. Typologies
____________________________________________________________ 1. Biologically based therapies use substances found in nature, such as herbs, special diets, or vitamins (doses outside use in conventional medicine) e.g. dietary supplements, herbal products
____________________________________________________________ 2. Manipulative and body-based therapies are based on manipulation or movement of one or more body parts
____________________________________________________________ 3. Mind-body interventions use a variety of techniques designed to enhance the mind’s ability to affect bodily function and symptoms e.g. relaxation, meditation, guided imagery, hypnosis, cognitive behavioural therapy, expressive therapies
____________________________________________________________ 4. Energy therapies involve the use of energy fields and biofields (as reflected in meridians, chakras) e.g. acupuncture, homeopathy Qi gong, Reiki, therapeutic touch energy psychotherapies (e.g. TFT, EFT)
____________________________________________________________ 5. Alternative medical systems are built upon complete systems of theory and practice. Often, these systems have evolved apart from, and earlier than, the conventional medical approach used in the US e.g. naturopathy, homeopathy Traditional Chinese Medicine (TCM), Ayurvedic Medicine
____________________________________________________________ www.nccam.nih.gov
B. Utilization of CAM
Trends in Alternative Medicine Use in the United States, 1990-1997. Results of a follow-up National survey Eisenberg et al (1998) JAMA 280:1569 Telephone based survey of 1539 adults in 1990, 2055 in 1997. 1993 NEJM study reported: 34% used CAM; 72% did not disclose; out-of-pocket expenditures comparable to hospitalization. ____________________________________________________________
_________________________________________________________________________________________________________ Back problems
____________________________________________________________________________________ Allergies
____________________________________________________________________________________ Fatigue
____________________________________________________________________________________ Arthritis
____________________________________________________________________________________ Neck problems
____________________________________________________________________________________ High blood pressure
____________________________________________________________________________________ Sprains/strains
____________________________________________________________________________________ Insomnia
____________________________________________________________________________________ Lung problems
____________________________________________________________________________________ Skin problems
____________________________________________________________________________________ Digestive problems
____________________________________________________________________________________ Depression
____________________________________________________________________________________ Anxiety
____________________________________________________________________________________
Why patients use CAM Significant predictors of CAM use (Astin, 1998): (1) Education
Holistic philosophy (body/mind/spirit) or cultural creative (interest in environment, personal growth)
(3) Health status (particularly chronic conditions)
(the more health problems, the more likelihood of use)
Why patients use alternative medicine Other factors involved in CAM use (nccam website): (4)
Thought CAM with conventional medicine would help
Conventional medical professional suggested it
____________________________________________________________ Note: Reasons identified vary according to nature of survey C. Evidence
Textbooks: [Note: Table of contents listed in Appendix II]
INTEGRATIVE MEDICINE David Rakel (2003) Saunders
INTEGRATIVE MEDICINE. PRINCIPLES FOR PRACTICE Kligler and Lee (2004) McGraw Hill
HERBAL-DRUG INTERACTIONS AND ADVERSE EFFECTS An Evidence-Based Quick Reference Guide Richard Philip (2004) McGraw Hill
Websites: nccam.nih.gov National Centre for Complementary and Alternative Medicine Databases: PubMed, Cochrane Library
Evidence Based Medicine: I
Series of case studies (observational trials)
Limitation of model: Provides information of effectiveness over a population, BUT does not provide information on the outcome in an individual Central themes for CAM: (1)
Emphasizes the INDIVIDUAL (involves individualized interventions; lesion vs suseptibility theory of disease)
(problems understood as interconnections between systems; emotions, stress contribute to health)
(body has innate ability to heal itself, need to remove impediments to healing)
reconceptualization of body (ENERGY systems)
(role of meridians, chi or qi, in pathogenesis and healing)Note: CAM is amenable to investigation using evidence-based principles, provided careful design features are used. 1. Different study questions require different methodologies/analysis 2. Results of observational studies can inform the design of trials 3. Existing procedures are robust for alternative therapies and complementary systems 4. Complex systems can be studied as “gestalts” Levin et al. Quantitative Methods in Research on CAM: Methodological Manifesto. Med Care (1997) 35:1079-1094 D. Specific Practices
Main modalities identified by the NWG on CAMinUME as requiring exposure in the medical curriculum ________________________________________________________ Natural Health Products (NHPs)
Acupuncture/Traditional Chinese Medicine
Homeopathy Mind-body practices Therapeutic bodywork Energy therapies Expressive therapies _________________________________________________________
Acupuncture __________________________________________ • originated in China over 5000 years ago
• health is determined by a balanced flow of Qi
• Qi courses along 14 major meridian systems
• over 1000 acupuncture points in meridian system
• needles inserted into acupoints (manual, electrical stimulation;
also pressure, lasers, heat via moxibustion)
• Western interest in acupuncture developed during 1970s (endorphin mechanism; NIH reviewed efficacy; FDA reclassified acupuncture needles from “experimental” to “medical device”)
• different forms of acupuncture exist (Chinese, Korean,
THE WEB THAT HAS NO WEAVER. UNDERSTANDING CHINESE MEDICINE (2000) Ted Kaptchuk CLINICAL ACUPUNCTURE (2001) Stux, Hammerschlag CONTEMPORARY CHINESE MEDICINE and ACUPUNCTURE (2002) Monod Cassidy
Science of Acupuncture ____________________________________________________________ Meridian system does not correspond to conventional structures, BUT it has been “visualized” in a number of ways, and plausible mechanisms have been invoked. ____________________________________________________________ (1) Conductivity mapping reveals acupoints have higher electrical conductivity than non-points Reveals differences (highs/lows) along a meridian system, and singular points and separatrices in surface mapping. Organizing centres (play role in development, morphogenesis) have high electrical conductivity, and high density of gap junctions; has led to Morphogenetic Singularity Theory, in which meridian system originates from a network of organizing centres. Brain imaging reveals that stimulation of acupoints evokes activity in corresponding areas fMRI study reveals that needle stimulation of UB67 (lateral foot; used to treat eye disorders) leads to activation of visual cortex. [Cho et al (1998) PNAS USA 95:2670] fMRI study reveals laser acupuncture of GB43 (between 4th and 5th toe; used for hearing problems) leads to activation of cortical and subcortical sites involved in processing sound and language [Siedentopf et al (2005) Lasers in Medical Science 20:68] (3) Endorphins (endogenous opioids) mediate aspects of analgesia and antiemetic effects of acupuncture Studies in animals and/or humans reveal that naloxone (opioid receptor antagonist) can block acupuncture analgesia, and antiemetic effects.
Does Acupuncture Work? ____________________________________________________________ Conclusive data for P6 (PC6, pericardium meridian) for nausea of chemotherapy, pregnancy, surgery (PONV)
good paradigm, as P6 is a standard point; the outcome is clear; short time course is evaluated
____________________________________________________________ •
Systematic review:Vickers (1996) J R Soc Med 89:303
27/29 studies provide positive evidence for P6 (manual, electrical stimulation, acupressure or via Seabands)
Meta-analysis:Lee and Done (1999) Anesth Analg 88:1362
19 trials; Acupuncture of P6 equivalent to antiemetic drugs in preventing PONV (post-op nausea and vomiting) Recent high quality trial: Gan et al (2004) Anesth Analg 99:1070 Compared electroacupuncture stimulation of P6 (A), ondansetron (O), sham control (P) (placement of electrodes) (25 per group, breast surgery; PONV outcomes at 2 and 24 hrs) complete response (no N,V, or rescue medication) * more effective than drug, lower cost *
Acupuncture and Pain ____________________________________________________ Issues in acupuncture research: •
adequacy of blinding (hollow-headed needle, laser on or off)(non-acupoint shams can produce effects)
role of placebo (needle is exotic, slightly invasive, produces mild pain, balance of energy appealing concept)
adequacy of treatment (choice and number of sites, number of treatments, standard vs individual sites)
____________________________________________________________ Recent high quality trials with placebo: He et al (2004) Effect of acupuncture on chronic neck pain in sedentary female workers: a 6-month and 3-year follow-up study. Pain 109:299
AP for 3-4 weeks provides significant benefit during treatment, and long-term benefits remaining at 3 years De Hoyas et al (2004) Randomized trial of long term effect of acupuncture for shoulder pain. Pain 112:289
AP for 7 weeks leads to reduction in pain compared to
placebo at 7 weeks, 3 months and 6 months
“Pragmatic trial” concept: Vickers et al (2004) Health Technol Assess 8:1-50 401 patients with chronic headache, mainly migraine, in Eng/Wales 12 AP treatments over 3 mo, vs usual care, outcomes 3 and 12 mo
AP lower than controls at 12 mo (22 fewer headache days)
15% less drugs, 25% fewer GP visits, 15% fewer sick days
Acupuncture and Osteoarthritis _________________________________________ Berman et al (2004) Ann Intern Med 141:901-910 Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial
Large trial (570 patients); acupuncture (8wk+taper) vs sham
and educational controls; adequate duration (26 wks) Outcomes: • significant WOMAC decreases at 8wk and 26 wk • effect size similar to NSAIDs, acetaminophen • useful as adjunctive therapy
See also: (1) Witt et al (2005) Lancet 366:136 N=150; acupuncture for 8 weeks vs minimal acup vs wait list
AP for 8 weeks vs minimal AP vs wait list
Reveals sham AP has effect compared to wait list,
(2) Pariente et al (2005) NeuroImage 25:1161 Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture
Belief that acupuncture is being given leads to
activation of neuronal substrates of pain which are
similar to those activated by real acupuncture
Homeopathy ____________________________________________________________
• founded late 18th century by Samuel Hahnemann (1755-1843) “Like
• remedies from plants, animals and minerals
• differs from herbal remedies, as involves extractions AND dilutions
• US FDA recognizes homeopathic remedies as drugs, regulates
manufacturing, labeling and dispensing (DIN-HM) Homeopathic Pharmacopoeia
• widely used in Europe (used 20-40% physicians)
• 3000 medical doctors and licensed health care providers practice
__________________________________________________________
Ten most common diagnoses of patients seeking care using Homeopathic Medicine compared with physicians using Conventional Medicine Homeopathic Medicine (n=1177) Conventional Medicine (n=11614) Arch Fam Med (1998) 7:537-540
______________________________________________________________________
Like cures like (Law of Similars)
(homois “similar” – pathos “suffering”)
The more a remedy is diluted, the greater its potency (Law of Infinitesimal Dose) - X, C and M potency; 10X, 100X, 1000X - ultra-low dose (microdose) therapy - after 24X potency, no molecular trace remains
(raises the question of plausibility; see below)
Illness is specific to individual e.g.1: migraine has >20 symptom patterns and remedies e.g. 2: cold with tears, eye irritation, thin, clear nasal discharge treated with onion extracts; cold with thick, yellow nasal discharge and loss of thirst treated with purple cone flower Mechanism:
• Activates self-regulatory mechanisms that are protective • NMR (nuclear magnetic resonance) imaging of remedies reveals some distinct readings (electromagnetic frequency
• Mechanism not well understood, but remedies activate endogenous energy systems (vibrational medicine) See: ENERGY MEDICINE. THE SCIENTIFIC BASIS. Oschman JL (2000) Edinburgh, Churchill Livingstone
Does Homeopathy work? • History of use (>200 years); widespread use in Europe • Accounts of patients and doctors support practice _________________________________________________________________ Lancet (1997) 350:834 Are the clinical effects of homeopathy placebo effects? A meta analysis of placebo controlled trials
Results of meta-analysis (119 trials) are not compatible
with the hypothesis that the clinical effects of homeopathy
Lancet (2004) 366:726-732 Are the clinical effects of homeopathy placebo effects? Comparative study of placebo-controlled trials of homeopathy and allopathy
Compared 110 homeopathic trials with 110 matched
conventional medicine trials. Weak evidence for specific
effect of homeopathic remedies, but strong evidence for
specific effects on conventional interventions. Findings
compatible with clinical effects of homeopathy being due
_______________________________________________________
E. Implications for practice
CASE EXAMPLE 1 ____________________________________________________ John’s herbal dilemma Canadian J CME (Jan 2004) 117-124 Complementary medicine: What you should know ____________________________________________________ John, 67, had a myocardial infarction and was placed on ramipril, metoprolol, acetylsalicylic acid (ASA) and pravastatin. A few weeks later, after an uneventful recovery, he was feeling quite tired, had difficulty with erections, and had memory loss. He believed this came from the medications and he decided to stop his pills. He then visited a naturopath who suggested he take St. John’s Wort, garlic, and ginko biloba. He returns to see you and his blood pressure is 160/95 mmHg. He is feeling much better since stopping the medications and taking herbal remedies. He would like to continue taking them, but also wants to stay on the ASA. What would you say and do? ____________________________________________________________ TREATING JOHN: John could benefit from blood pressure control and medicine to prevent another heart attack. However, he felt unwell, and so discontinued all his medications. Perhaps John is depressed. Educate him about the risks and benefits of conventional therapy. Negotiate that he take some of the medications, and perhaps drop the beta blocker, and see if the erectile dysfunction and tiredness wane. He cannot take ginko and ASA together because of the risk of spontaneous bleeds. Explain the risk benefit of both treatments and let him decide which to take. Staying on the St. John’s Wort may help with his depression. Give John a number of follow up visits, making sure he is making well-informed choices.
CASE EXAMPLE 2 ____________________________________________________ Mike’s case
Canadian J Diagnosis (Mar 2004) 81-84 Needling the facts: An evidence-based review of acupuncture ____________________________________________________ Mike, a 35-year-old tennis player, was experiencing lateral epicondyle pain for approximately three months. His initial treatment consisted of naproxen (500 mg twice daily, for two weeks), and conventional physical therapy for two months. These treatments were unsuccessful in alleviating his pain. Mike was then referred for cortisone injections. The diagnosis of lateral epicondylitis was confirmed on examination. The patient was given the option of cortisone injections or acupuncture. After potential adverse effects were discussed, he expressed concerns with the cortisone injections, and opted for acupuncture. Treatment consisted of five electroacupuncture sessions within three weeks (once or twice weekly). After the treatments, Mike’s epicondylar pain abated, and he was able to play tennis at the same level as prior to pain onset. He has yet to seek further treatment. ____________________________________________________________ Appendix I CAM Learning objectives ____________________________________________________ From: National Working Group on Complementary and Alternative Medicine (CAM) in Undergraduate Medical Education (UME) project, a national initiative to teach CAM in UME in Canada, led by Dr. Marja Verhoef (University of Calgary), with representatives from most medical schools in Canada (Nov 2003 report). ____________________________________________________ KNOWLEDGE K1 Definitions,
classification schemes, prominent practices
List/describe CAM therapies used in certain prominent conditions
Identify safety issues, interactions with conventional medicine
Identify reliable sources for evidence, evaluate evidence
Understand regulation and credentialing of common CAM practitioners in student’s province
Discuss CAM in a professional manner (history, listening respectfully, informing)
Locate, understand, evaluate and communicate information regarding safety and efficacy of CAM therapies
Communicate effectively with CAM practitioners
Describe beliefs regarding CAM, identify how these may affect practice
Demonstrate respect for beliefs and choices of those who use CAM
Appendix II Contents of some recommended CAM resources ____________________________________________________ INTEGRATIVE MEDICINE (2003) Ed. D. Rakel; Saunders Part I: Integrative Medicine Ch 1 Philosophy of integrative medicine Part II: Integrative Approach to Disease Ch 3 Depression
Ch 7 Migraine/Tension Head Ch 8 Peripheral Neuropathy
Ch 10 Parkinson’s Disease Ch 11 Otitis Media
Ch 13 Upper Resp Infection Ch 14 HIV Disease
Ch 36 Recurring Abdominal Ch 37 Fibromyalgia
Ch 48 Benign Prostatic Hyp Ch 49 Urolithiasis
Part III: Disease Prevention Ch 65 Prevention of Breast Cancer
Ch 76 Preventing Age-Related Macular Degen
Ch 79 Prevention of Urinary Tract Infect
Part IV: Tools for Your Practice Ch 81 Food Allergy
Ch 82 Elim Diet and Food Hypersensitivities
Appx II (cont’d)
Ch 93 Journaling
Ch 99 Strain/Counterstrain Manipulations
Ch 101 Acupuncture for Nausea/Vomiting Ch 102 Spiritual Assessment and Care Ch 103 Therapeutic Homeopathy
____________________________________________________________________________ __ INTEGRATIVE MEDICINE. Principles for Practice (2004) B. Kligler, R. Lee; McGraw-Hill PART 1: Basic Principles Ch 1 Integrative Medicine: Basic Principles Ch 2 Psychosocial Determinants of Health and Illness: Reintegrating Mind, Body and Spirit Ch 3 Mind-Body Medicine
Ch 4 A New Definition of Patient Centered-Care
PART II: Therapeutic Modalities Ch 5 Botanical Medicine: Overview
Ch 6 Issues Concerning the Safety of Herbs
Ch 11 Movement/Body-Centred Therapies Ch 12 Homeopathy Ch 13 Physical Activity and Exercise
Ch 16 Selected Issues in Environmental Medicine
PART III: Integrative Approaches (IA) to Specific Conditions Ch 17 IA (*) to Allergy
Ch 29 IA to Rheumatology Part IV: Integrative Approaches Through the Life Cycle Ch 30 IA to the Care of Children Part V: Legal and Ethical Issues Ch 36 Legal and Ethical Issues in Integrative Medicine Part VI: Selected Cases in Integrative Medicine Ch 37 Selected Cases in Integrative Medicine * Note: IA indicates Integrative Approach Appx II (cont’d)
______________________________________________________________________ HERBAL-DRUG INTERACTIONS AND ADVERSE EFFECTS. An Evidence-Based Quick Reference Guide (2004) R.B. Philip, McGraw Hill SECTION 1: Overview and General Principles SECTION 2: Alphabetical Listing of Herb and Nutriceutical Monographs (contains 262 pages listing 2-3 pages each for individual agents, with sections on Sources/ Description/Use, Pharmacology, Adverse Effects/Interactions, References for each agent) Appendix I Documented and Potential Interactions Between Botanicals/Nutriceuticals and Anticoagulant/Platelet-inhibiting Drugs Appendix II Confirmed and Theoretical Interactions (Potentiative or Additive) Between Herbs/Nutriceuticals and Psychotropic/Other Centrally Acting Drugs Appendix III Herbs/Botanicals That May Cause Hepatotoxicity Appendix IV Herbs and Foods That May Contain Phytoestrogens and/or Phytoprogestins Appendix V Herbal Preparations That May Cause Adverse Reactions When Used Systemically, Topically for skin Conditions, or in Cosmetics Appendix VI Botanicals That May Alter Drug Biotransformations Appendix VII Botanicals that can Affect Cardiovascular Function / Lower Serum Lipids Appendix VIII Herbal Remedies and Nutriceuticals With Anti-inflammatory and Antirheumatic Properties Appendix IX Members of the Compositae (Daisy or Asteraceae) Family, Including Wild and Garden Flowers Appendix X Herbal and Other Alternative Remedies Purported to Have Hypoglycemic or Antidiabetic Properties Appendix XI Herbs and the Kidney: Diuretic and Nephrotoxic Herbs Appendix XII Herbs/Botanicals and Cancer (Herbs Shown to be Carcinogenic in Laboratory Studies/ Herbs Shown to be Antineoplastic in Laboratory Studies) Appendix XIII Psoralen-containing Botanicals Capable of Causing Phytophotodermatitis Appendix XIV Some Useful Websites Appendix III Selected readings ______________________________________________ PHILOSOPHY OF INTEGRATIVE MEDICINE. Rakel and Weil (2003) Chapter 1 of INTEGRATIVE MEDICINE listed in Appendix II.
TRENDS IN ALTERNATIVE MEDICINE USE IN THE UNITED STATES, 1990-1997. Results of a Follow-up National Survey Eisenberg et al (1998) JAMA 280:1569
WHY PATIENTS USE ALTERNATIVE MEDICINE. Results of a National Survey. Astin (1998) JAMA 279:1548 DIVERSITY, THE INDIVIDUAL, AND PROOF OF EFFICACY: COMPLEMENTARY AND ALTERNATIVE MEDICINE IN MEDICAL EDUCATION. Park (2002) Am J Public Health 92:1568
PSYCHONEUROIMMUNOLOGY: INTERACTI0NS BETWEEN THE NERVOUS SYSTEM AND THE IMMUNE SYSTEM Ader et al (1995) Lancet 345:99-103 EMOTIONS AND DISEASE: FROM BALANCE OF HUMORS TO BALANCE OF MOLECULES Sternberg (1997) Nature Medicine 3:264-267
MIND-BODY MEDICINE: STATE OF THE SCIENCE, IMPLICATIONS FOR PRACTICE. Astin et al (2003) J Am Board Fam Pract 16:131-147 This REVIEW considers the effectiveness of mind-body therapies (relaxation, meditation, guided imagery, hypnosis, biofeedback, cognitive behavioral therapy, psychoeducational approaches) in diverse medical conditions.
THE BALANCE WITHIN. THE SCIENCE CONNECTING HEALTH AND EMOTIONS (2001) Esther Sternberg, MD This BOOK addresses the connections between the immune system and the brain, providing a construct for how stress and emotions contribute to health. It has an interesting historical section.
FROM DOCTOR TO HEALER. THE TRANSFORMATIVE JOURNEY (1998) Robbie Davis-Floyd and Gloria St. John, Rutgers University Press This BOOK explores multiple health paradigms, from biomedical to humanistic to holistic. It also contains interviews with physicians who use holistic approaches, and addresses the issue of paradigm shift. Appendix IV Timeline of events relevant to CAM development ______________________________________________
CAM teaching in Medical Schools in Canada
Mainstream medical journals publish CAM articles
(New Eng J Med, J Am Med Assoc or JAMA)
NCCAM (National Centre for Complementary and Alternative Medicine) evolves from OAM
Eisenberg review of CAM use (NEJM)
(or Psychoneuroimmunoendocrinology, PNIE) Nervous system-immune-endocrine system connections Neuropeptides identified in these systems
Endogenous opioids implicated in acupuncture
Opiate receptor, and endorphins discovered
China invades Tibet, Dalai Lama goes into exile
RCTs developed; “Powerful placebo” acknowledged
Journal of Cardiac Failure Vol. 12 No. 3 2006Aldosterone Antagonism Improves Endothelial-DependentVasorelaxation in Heart Failure via Upregulation ofEndothelial Nitric Oxide Synthase ProductionHOANG M. THAI, MD, BAO Q. DO, MD, TRUNG D. TRAN, MD, MOHAMED A. GABALLA, PhD,Background: Altering the renin-angiotensin aldosterone system improve mortality in heart failure (HF)in part through an impro
NAME OF THE MEDICINAL PRODUCT Actos ▼ tablets. 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 15 mg, 30 mg or 45 mg of pioglitazone as hydrochloride. For a full list of excipients, see 6.1. 3. PHARMACEUTICAL Tablet. The tablets are white to off-white, round, convex and marked ‘15’ on one face and ‘ACTOS’ on the other face. The tablets are whi