The Importance of Being an Educated Consumer of Health Information

Broad Issues Critically evaluate the validity of health information Make a connection between important scientific/health issues to your personal and professional life Specific Issues Healthy diet & nutrition Physical fitness Stress & conflict management Healthy attitudes & emotions Use of drugs, vitamins, & supplements for health

The Benefit / Risk Ratio of Drug, Vitamin, & Suppplement Use

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The Benefit / Risk Ratio of Drug, Vitamin, & Supplement Use

Thesis 1: Although drugs, vitamins, and supplements have beneficial effects on society, their negative effects may outweigh their positive ones, Thesis 2: Therefore, an important aspect of a healthy lifestyle must consider both efficacy and safety.

Thesis 3: Drug, vitamin, and supplement use is highly-promoted in our society. Consequently, being able to critically analyze sources and quality of healthy studies is important to recognizing valid scientific information.

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

Conclusion: There is No Such Thing as a Free Lunch

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The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

When ever one takes a drug, vitamin , or dietary supplement, you must weigh: benefits risks

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

When ever one takes a drug, vitamin , or dietary supplement, you must weigh: Drug
Advil

Benefits
pain relief

Risks
stomach upset sedation addiction

Ratio (B/R)
high

Oxycontin

pain relief

very low

Zoloft

depression ??

lots of side effects

sedation

equal

Ambien

sleep

slightly high

Cocaine

none

stimulation addiction

very very low

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

When ever one takes a drug, vitamin , or dietary supplement, you must weigh: Drug
Marijuana

Benefits
not clearly defined nutrition

Risks
psychosis dependence none

Ratio (B/R)
not known

B vitamins

very high

Glucosamine

joint pain questionable high blood pressure anti-clotting

none expensive fatigue bleeding

equal

Altenolol Coumadin

slightly high slightly high

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

Take home message:
All drugs have varying levels of effectiveness All drugs have varying levels of risk (toxicity) For some drugs, the dose for efficacy much lower than for toxicity

For some drugs, the dose for efficacy in the same range as for toxicity

The bottom line: For drugs, vitamins, and dietary supplements there is no free lunch As a diligent consumer or patient, one must always consider the relative pros & cons. How effective is the drug? Does it actual work? Is it very safe, moderately safe, or unsafe? What are the relative effectiveness / safety ratios What are the costs relative to effectiveness

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements Digging Deeper !
How effective is the drug? Does it actual work? Quality of scientific data? Where does in come from? Manufacturing? Is it very safe, moderately safe, or unsafe?

What are the relative effectiveness / safety ratios

What are the costs relative to effectiveness

The Benefit / Risk Ratio

Estrogen Replacement Therapy of Symptoms of Menopause (HRT) Target Does it Work? Quality of Science Quality of Source Safety Efficacy/Safety Ratio bone, skin, mood etc Probably High High Moderate Mixed or uncertain

Cost

Low

The Benefit / Risk Ratio

Antidepressants
Target Does it Work? Quality of Science Quality of Source Mood Not certain High High

Safety
Efficacy/Safety Ratio Cost

Moderate
Mixed or uncertain Low

The Benefit / Risk Ratio

Ibuprofen
Target Does it Work? Quality of Science Quality of Source pain, inflammation Yes High High

Safety
Efficacy/Safety Ratio Cost

Moderate
Moderate to High Low

The Benefit / Risk Ratio

Oral Contraceptives
Target Does it Work? Quality of Science Quality of Source contraception Yes High High

Safety
Efficacy/Safety Ratio Cost

Moderate
High Low

The Benefit / Risk Ratio

Obesity Medications
Target Does it Work? Quality of Science Quality of Source Body wt Maybe High High

Safety
Efficacy/Safety Ratio Cost

Very Low
Low Moderate

The Benefit / Risk Ratio

Glucosamine
Target Does it Work? Quality of Science Quality of Source joint pain, inflammation ?? very low low to moderate

Safety
Efficacy/Safety Ratio Cost

high
High High

The Benefit / Risk Ratio

Resveratrol
Target cardio, aging, diabetes

Does it Work? Basic science = High Does it Work? Clinical Science = low Problem: ?? What to measure Quality of Science low to high mechanism unclear not known not known
The mechanisms of resveratrol's apparent effects on life extension are not fully understood, but they appear to mimic several of the biochemical effects of calorie restriction. Some studies indicates that resveratrol activates Sirtuin 1 (SIRT1) and PGC-1 and improve functioning of the mitochondria. Other research calls into question the theory connecting resveratrol, SIRT1, and calorie restriction. In addition resveratrol's ability to directly activate sirtuin 1 has been called into question.

Safety Efficacy/Safety Ratio

The Benefit / Risk Ratio

We could go on with other interesting examples..

But lets look at a couple of exceptions at two ends of the Benefit / Risk spectrum Anti-Cancer Drugs Vitamins

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

Drugs for Cancer: A Special Case
Most of them are antiproliferative & cytotoxic. They also affect rapidly dividing normal cells. This leads to toxicity which are usually severe. To greater or lesser extent the following toxicities are exhibits by all anticancer drugs.

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

Vitamins: A Special Case
In order to understand vitamins, we need to examine how they differ from drugs:

Drugs are usually synthetic or semi-synthetic cpds not normally found in the body Drugs modify normal physiological process by altering the nervous system, hormones, or enzymes Drugs have highly specific-targets and have clear dose-response relationships and kinetics

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

Vitamins: A Special Case
In order to understand vitamins, we need to examine how they differ from drugs:

Vitamins are natural substances (nutrients) found in the body in very small amounts Many vitamins act as co-factors for metabolic enzyme reactions, whereas others have hormonal-like actions, or have anti-oxidant activity They do not have clear dose-response relationships, can be stored in the body, and have long-term kinetics (biological actions are not immediate)
In general, vitamins are not drugs, but nutrients

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

Vitamins: A Special Case
In order to understand vitamins, we need to examine how they differ from drugs:

Vitamins are natural substances (nutrients) found in the body in very small amounts Many vitamins act as co-factors for metabolic enzyme reactions, whereas others have hormonal-like actions, or have anti-oxidant activity They do not have clear dose-response relationships, can be stored in the body, and have long-term kinetics (biological actions are not immediate)
In general, vitamins are not drugs, but nutrients

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

Vitamins: A Special Case For example: Caffeine (Adenosine receptor antagonist)

modulates the process of brain energy activity Stimulates alertness and energy in a dose / time dependent manner

= Caffein is DRUG Vitamin B12

is part of biochemical processes & pathways
B12 is required for proper red blood cell formation, neurological function, and DNA synthesis. A universal methyl donor for almost 100 different substrates, including DNA, RNA, hormones, proteins, and lipids. Stored in the liver for many months, deficiency rare. Used therapeutically to treat deficiency only !

= Vitamin B12 is a NUTRIENT

The Benefit / Risk Ratio of Drugs, Vitamins, & Supplements

Vitamins: A Real Example
Customer in Health Food Store: Would this Vitamin B12 supplement be good for me? Clerk in Health Food Store Probably, provides energy, but this product is a high dose, so do not take before bedtime, will keep you up all night Customer (e.g., Lasell student who studied hard in Biology) with Good Critical / Scientific Thinking Skills: Due to its role in energy metabolism, B-12 is frequently
touted as a means to boost energy and increase endurance. These claims relate to the evidence that B-12 is effective in remedying anemia caused by B-12 deficiencies. However, B-12 is not a drug that activates energy short-term energy processes (like caffeine), it participates, but does not activate red blood production, and there is no data to support the claim that increasing B-12 intake will raise your energy level in absence of nutritional deficiencies

Conclusion

Precautions
Always know what you are taking Know the effects (therapeutic efficacy) Read the warnings and cautions (safety issues) Be aware of the trade-offs between efficacy & safety Understand the differences and appropriate use of drugs vs vitamins / supplements

Medications: A Primer on How Drugs Work

In order for the body remain alive, the various organ systems must communicate with other.
The two communication systems are: Nervous system (nerves) Endocrine system (hormones)

Many drugs work by mimicking, enhancing, blocking communication (information transfer)

Medications: A Primer on How Drugs Work

In order for the body remain alive, the various organ systems must communicate with other.
Nervous system (nerves) Many drugs work by mimicking, enhancing, blocking communication (information transfer)

Stimulate to cause muscle contraction Block to cause muscle relaxation

Stimulate to increase heart rate Block to slow heart rate

Medications: A Primer on How Drugs Work

In order for the body remain alive, the various organ systems must communicate with other.
Endocrine System (hormones) Many drugs work by mimicking, enhancing, blocking communication (information transfer)

Examples: Thyroid mimic to enhance thyroid function Parathyroid hormone to increase bone strength Block testosterone to inhibit prostate cancer growth

Medications: A Primer on How Drugs Work

Some drugs act as inhibitors of cellular enzyme activity. Enzymes are necessary for metabolic actions of cells

Examples: Viagra Some anti-cancer drugs NSAIDs (Aspirin, ibuprofen, naproxen) Some antidepressants (MAO inhibitors) Statins to lower cholesterol (inhibit the enzyme HMG-CoA reductase

Medications: A Primer on How Drugs Work

Antibiotics:
Chemotherapeutic agents act by killing or weakening foreign organisms such as bacteria, worms, viruses. The main principle of action is selective toxicity, i.e. the drug must be more toxic to the parasite than to the host.

Medications: A Primer on How Drugs Work

Anti-Cancer Drugs:

Examples: Cytotoxic (kill cancer cells) by Interfering with DNA function

Antiiproliferative (slows cell division)

Medications: From the Laboratory to You

Sources of Drugs:

Synthetic: most drugs, random or rational design

Plants: aspirin, digitalis, drugs of abuse, anti-cancer Animals (extracted): hormones Minerals: potassium, magnesium etc

Medications: From the Laboratory to You

Drug Discovery & Development Process:

1. Chemistry, extraction etc

2. Biochemical / cell-based testing & screening 3. Pre-clinical animal based testing 4. Human (clinical) testing 5. FDA approval as a drug for a specific disease

Medications: From the Laboratory to You

Drug Discovery & Development Process:

1. Chemistry, extraction etc

100s to 1000s test cpds made 2. Biochemical / cell-based testing & screening Tested for specific cellular activities that may be predictive of disease targets

Medications: From the Laboratory to You

Drug Discovery & Development Process:
3. Potential drugs from #2 selected (<10) are tested in animal models (normal) and disease to determine:
activity dose safety duration of action, how to administer, metabolism, excretion

4.

Clinical trials in humans (only one drug)

Phase I: dose & safety in normal volunteers Phase II: activity in small population of disease target Phase III: activity in large population of disease target

Medications: From the Laboratory to You

Drug Discovery & Development Process:
Total time for discovery to FDA approval = 10-15 yrs
Expensive (5 billion $) High attrition: 1/100 viable drugs are approved Approval is highly specific for a disease Approved drug must be a single entity, no mixtures

Medications: Drugs for Pain

Opiates (morphine, codeine, oxycodone etc)
Mimic endogenous opioid-like neurotransmitters (endorphins) Best for internal, chronic pain, surgery Highly euphoric, reinforcing, additive, tolerance Sedation, constipation, respiratory depression

Aspirin, ibuprofen, naproxen

Inhibit COX enzymes Decrease inflammatory pain Good for headaches, muscle/joint pain, arthritis Inhibition of blood clotting, stomach irritation Acetaminophen (Tylenol): pain only, not anti-inflammatory Very safe, potential liver damage, do combine with alcohol

Medications: Drugs for High Blood Pressure

Artery Constriction Blood Volume Heart Output

Beta-Blockers (Altenolol, Metroprol)

Block the chemical neurotransmission of nerves which stimulate heart and constrict blood vessels Very safe, fatigue, depression, weight gain side effects

Diuretics (hydrochlorthiazide)
Decrease blood volume Very safe, frequent urination, potassium loss

Angiotensin Converting Enzyme Inhibitors

Decrease blood volume, relax blood vessels Moderately safe, cough

Medications: Drugs for Heart Disease Atrial Fibrillation

Digoxin Slows heart rate, does not fix abnormal rhythm Very safe Altenolol Slows heart rate, does not fix abnormal rhythm Very safe

Amiodarone Slows heart rate, may fix abnormal rhythm Can be toxic, hypothyroidism, lung fibrosis

Medications: Drugs for Heart Disease High Cholesterol

HMG-CoA reductase inhibitors (HMGs, or statins) Bile acid sequestrants Niacin (nicotinic acid) Fibric acid derivatives

Cholesterol absorption inhibitor

Combination drugs

Medications: Drugs for Heart Disease High Cholesterol

Lipoproteins

Very-low-density lipoprotein (VLDL)

Produced by the liver Transports endogenous lipids to the cells

Low-density lipoprotein (LDL) High-density lipoprotein (HDL)

Responsible for recycling of cholesterol Also known as good cholesterol

Medications: Drugs for Heart Disease High Cholesterol

Coronary Heart Disease

The risk of CHD in patients with cholesterol levels of 300 mg/dL is three to four times greater than that in patients with levels less than 200 mg/dL

Medications: Drugs for Heart Disease High Cholesterol

Coronary Heart Disease Positive Risk Factors

Age

Male 45 years or older Female 55 years or older, or women with premature menopause not on estrogen replacement therapy

Family history: history of premature CHD Current cigarette smoker Hypertension BP 140/90 or higher, or on antihypertensive medication Diabetes mellitus

Medications: Drugs for Heart Disease High Cholesterol

Treatment Guidelines

Antilipemic drugs are used as an adjunct to diet therapy Drug choice based on the specific lipid profile of the patient All reasonable non-drug means of controlling blood cholesterol levels (e.g., diet, exercise) should be tried for at least 6 months and found to fail before drug therapy is considered

Medications: Drugs for Heart Disease High Cholesterol

Antilipemics: HMG-CoA Reductase Inhibitors (HMGs, or statins)

Most potent LDL reducers

lovastatin (Mevacor) pravastatin (Pravachol) simvastatin (Zocor) atorvastatin (Lipitor) fluvastatin (Lescol)

Adverse effects

Mild, transient GI disturbances Rash Headache Myopathy (muscle pain), possibly leading to the serious condition rhabdomyolysis Elevations in liver enzymes or liver disease

Medications: Drugs for Heart Disease High Cholesterol

Bile Acid Sequestrants

cholestyramine (Questran)

colestipol hydrochloride (Colestid)

colesevelam (tablet form) Also called bile acidbinding resins and ion-exchange resins

Medications: Drugs for Heart Disease High Cholesterol

Bile Acid Sequestrants

Mechanism of action Prevent resorption of bile acids from small intestine Bile acids are necessary for absorption of cholesterol Indications Type II hyperlipoproteinemia Relief of pruritus associated with partial biliary obstruction (cholestyramine) May be used along with statins

Adverse effects

Constipation Heartburn, nausea, belching, bloating

These adverse effects tend to disappear over

Medications: Drugs for Heart Disease High Cholesterol

Niacin (Nicotinic Acid)

Vitamin B3 Lipid-lowering properties require much higher doses than when used as a vitamin Effective, inexpensive, often used in combination with other lipid-lowering drugs Mechanism of action Increases activity of lipase, which breaks down lipids Reduces the metabolism of cholesterol and triglycerides Adverse effects Flushing (due to histamine release) Pruritus GI distress

Medications: Drugs for Nervous System Depression

Uptake Inhibitors
Prozac, Lexapro, Zoloft, Paxil Active in ~50-75% patients Prolonged onset of action (weeks)

Mechanism of action Increase serotonin or norepinephrine in brain synapses

Adverse effects
Mania, agitation, headache Rapid heart rate GI distress Constipation, urinary retention, sweating, dry mouth Sedation Use with caution in elderly

Medications: Drugs for Nervous System Sleep (Hypnotics)

Benzodiazepine- Like Drugs

Ambien & Lunesta Short acting Rapid onset Valium & Ativan Longer acting Longer onset Mechanism of action Enhances activity of neurotransmitter (GABA) in the brain. Adverse effects
Sedation, memory problems Impairment of concentration DO NOT USE WITH Alcohol Tolerance, dependence, addiction Use with caution in elderly Bad dreams

Medications: Drugs for Weight Loss

The Bottom Line Part I !!

Obesity often requires long-term treatment to promote and sustain weight loss. As in other chronic conditions, such as diabetes or high blood pressure, use of prescription drugs may be appropriate for some people. While most side effects of prescription weight loss drugs are mild, serious complications have been reported. More on that below. Keep in mind that these drugs are not a cure-all for obesity. The use of weight loss drugs should be combined with physical activity and improved diet to lose and maintain weight successfully over the long term.

Medications: Drugs for Weight Loss

The Bottom Line Part II !!
The drugs used to promote weight loss have been anorexiants or appetite suppressants sibutramine (Meridia) . A drug which inhibits fat absorption orlistat (Xenical). Very few trials longer than 6 months have actually been done with any of these new drugs. These drugs are associated with adverse health effects, including an increase in heart rate and blood pressure for sibutramine and, for orlistat, a decreased absorption of fat-soluble vitamins. Ephedrine, caffeine, and fluoxetine have also been tested for weight loss but are not approved for use in the treatment of obesity. NO WONDER DRUGS ! Herbal preparations are not recommended as part of a weight loss program. These preparations have unpredictable amounts of active ingredients and unpredictable and potentially harmful effects.

Medications: Drugs for Weight Loss

Do Weight Loss Drugs Work?
Statistically significant, but modest weight loss (<5kg at 1 year).
Sibutramine: ~10 pounds Orlistat: ~ 5 pounds Most trials included lifestyle modifications as a cointervention Sibutramine & orlistat have been shown to reduce & maintain weight loss with continued therapy. Weight regain is common upon discontinuation of therapy. Long term health benefits/safety/efficacy uncertain

Medications: Drugs for Weight Loss

Herbal & Dietary Supplements Popular Pricey Poly-herbal-pharmacy Paucity of good evidence Lack of good clinical trials Mostly marketing of anedoctol evidence Possibilities for success or failure

Medications: Gastro-Intestinal Reflux (Heartburn)

Histamine H2 Antagonists
Zantac Rapid onset Mechanism of action Inhibition of stomach acid secretion

Adverse effects (not common, quite safe)

agitation, nervousness, depression, hallucinations allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue breast enlargement in both males and females breathing problems redness, blistering, peeling or loosening of the skin, including inside the mouth unusual bleeding or bruising unusually weak or tired

Medications: Gastro-Intestinal Reflux (Heartburn)

Proton Pump Inhibitors

Prilosec, Nexium Not for acute use Slow onset (several days) Mechanism of action Inhibition of stomach acid secretion

Adverse effects (not common, quite safe)

Headache Diarrhea Constipation Abdominal pain Rash EXPENSIVE Do not take more than several weeks

Medications: Arthritis

Osteoarthritis
Osteoarthritis is the most common form of arthritis, affecting millions of people around the world. Often called wear-and-tear arthritis, osteoarthritis occurs when the protective cartilage on the ends of your bones wears down over time. While osteoarthritis can damage any joint in your body, the disorder most commonly affects joints in your hands, neck, lower back, knees and hips.

Osteoarthritis gradually worsens with time, and no cure exists. But osteoarthritis treatments can slow the progression of the disease, relieve pain and improve joint function.
ANALGESICS used only for pain relief -Paracetamol (Tylenol) NSAIDs-used as an adjunct along with DMARDs to reduce the inflammation Ibuprofen Aspirin NSAIDS mainly act by inhibiting COX -1 &2 enzymes blocking COX enzyme site & thus reduces inflammation

Medications: Drugs for Nervous System Sleep Disorders (Hypnotics)

Valium-Type Drugs
Xanax, Valium, Ativan, Klonipin Slightly anxiolytic vs sedation Rapid onset

Mechanism of action Enhances activity of neurotransmitter (GABA) in the brain.

Adverse effects
Sedation, memory problems Impairment of concentration DO NOT USE WITH Alcohol Tolerance, dependence, addiction Use with caution in elderly

Medications: Arthritis Rheumatoid Arthritis

RA is characterised by the infilteration of various inflammatory cells into the joint The synovial membrane becomes highly vascularised & synovial fibroblasts proliferate & inflammatory cells release numerous CYTOKINES & GROWTH FACTORS into the joint These agents cause synovial cells to release proteolytic enzymes &Proliferating inflammatory tissue (PANNUS-tissue serving as origin of joint erosions) subsequently leads to the destruction of intra articular & peri articular structures leading to the joint deformities and dysfunction

Medications: Arthritis

Rheumatoid Arthritis
ANALGESICS used only for pain relief -Paracetamol (Tylenol)

NSAIDs-used as an adjunct along with DMARDs to reduce the inflammation Ibuprofen Aspirin NSAIDS mainly act by inhibiting COX -1 &2 enzymes blocking COX enzyme site & thus reduces inflamation

Medications: Arthritis

Rheumatoid Arthritis
Goals of Treatment Relieve pain Reduce inflammation Slow down or stop joint damage Improve a person's sense of well-being and ability to function. Current Treatment Approaches Lifestyle Medications Surgery Routine monitoring and ongoing care

Medications: Arthritis

Rheumatoid Arthritis

GOLD SODIUM THIOMALATE

HYDROXY CHLOROQUINE
AZATHIOPRINE LEFLUNOMIDE CICLOSPORINE

Medications: Arthritis Rheumatoid Arthritis

CORTICOSTEROIDS-used because of their anti inflammatory immunosuppressive property Prednisone & methyl prednisolone Act by suppressing the cytokines DMARD,s(disease modifying antirheumatic drugs)-used to slow down the progression of disease These include METHOTREXATE SULFASALAZINE-

Medications: Arthritis Rheumatoid Arthritis

BIOLOGICALRESPONSE MODIFIERS genetically engineered medications that reduce inflammation and structural damage to the joints Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) Reduce inflammation by blocking tumor necrosis factor (TNF), a cytokine or immune system protein that triggers inflammation during normal immune responses

Expensive, given by injection

Over the Counter Drugs (non-prescription)

The drug has been marketed as a prescription drug for 3 years The use of the drug has been relatively high during the time it was available as a prescription drug

Adverse drug reactions are not alarming, potential adverse effects are printed on the label, and frequency of side effects has not increased during the time it was available to the public

Over the Counter Drugs (non-prescription)

Analgesics Cold, cough, allergy, and asthma relievers: Expectorants Antitussives Antihistamines Decongestants Stimulants Sleeping aids and relaxants Dieting aids

Over the Counter Drugs (non-prescription)

Cold, cough, allergy, and asthma relievers: Coricidin HBP Cough & Cold Robitussin Cough products Sudafed Cough medicines Dimetapp DM Tylenol Cold products Vicks NyQuil and Dayquil Alka-Seltzer Plus Cold & Cough Triaminic Cough syrups

Over the Counter Drugs (non-prescription)

Cold, cough, allergy, and asthma relievers: Anti-Histamines
Blocks the action of the inflammatory mediator HISTAMINE Dry mucous membranes of nose, mouth, and upper respiratory tract Sedating: benadryl Non-Sedating: Claritin, Allegra, Zyrtec

Over the Counter Drugs (non-prescription)

Cold, cough, allergy, and asthma relievers: Decongestants
Constrict small blood vessels in the nose and respiratory tract Dry mucous membranes of nose, mouth, and upper respiratory tract Stimulation Increase heart rate & blood pressure

Over the Counter Drugs (non-prescription)

Cold, cough, allergy, and asthma relievers: Expectorants
Constrict small blood vessels in the nose and respiratory tract Dry mucous membranes of nose, mouth, and upper respiratory tract Stimulation Increase heart rate & blood pressure

Over the Counter Drugs (non-prescription)

Cold, cough, allergy, and asthma relievers: Anti-tissives
Constrict small blood vessels in the nose and respiratory tract Dry mucous membranes of nose, mouth, and upper respiratory tract Stimulation Increase heart rate & blood pressure