*Tartt's Scientific Approach*

*Did You Take your Pills Today?*

Mr. Anony Mous had an unexpected heart attack last month. His doctors told him that greasy, fast foods and other cholesterol laden cuisine can no longer be consumed. No Sir, no more barbecued ribs, corned beef sandwiches and fried cheese dipped bacon/onion potato perogies for him. Dangerous rich fatty-foods foods that Anony loves, but doesn't believe that if he continues to eat may eventually kill him. That's because he has a few new pills given him by his doctors. They told him how to restrict his food intake to insure a sensible, healthy diet. But he mistakenly thinks the pills will allow him to continue to eat all of the foods that caused his problems in the first place. He erroneously believes that the pills will take care of everything! Let me start this discussion today by reminding everyone that I am not an MD, and I am not attempting to practice medicine in any form. The following article is based on * my opinions* and observations as a chemist. That being said, let's get started. As I see it, most prescription drug manufacturing companies, both Brand Name and Generic are honest, respectable and trustworthy. And no doctor, or hospital's operating competence or ethics is in question here. But some regulatory guidelines may be.

And by the way, my dear grossly overweight Mr. Mous, I know of no pill or group of pills known to contemporary science that can successfully allow a heart patient such as yourself to ingest and safely metabolize “Three large corned beef sandwiches, ten batter fried barbecued chicken wings, two large orders of fries and a 64 ounce triple malt Strawberry-Explosion milk shake at one sitting.” So unless you start to follow your doctor's orders right away, it may be bon voyage and goodbye to you sooner rather than later.

As I said, I am a Chemist, and I will be talking about prescription drugs, their manufacture, use and potencies. Also, I have included a few entries on general health related subjects.

Many people today with varied and at times multiple circulatory problems eat like Mr. Mous every day and then take their pills until…..well… But I don't think most people behave in this manner. This article is not only about circulatory problems, but other types of illnesses as well. But what if they diligently follow their doctor's orders? Can one still have difficulty? Yes, I believe one can. The main problem (as I see it) may start with your prescription drug plan. Many of these plans will no longer pay for the more expensive brand name medications that they used to cover. Many of today's prescription drug plans will substitute a generic formulation for the brand name drug you are taking. That implementation in and of itself is not the problem. It's not the generic drugs purity, or their formulation. In my opinion some problems may lie in the prescribed dosage's actual bioequivalence, and perhaps even the combined ingredient absorption coefficient. Industry competition for drug companies providing a particular product may be intense.

No matter how competent a technician or chemist is, they cannot always provide a 100% exact accurate dosage of let's say, a ten milligram tablet seven days a week, 24 hrs./day 365 days a year X billions of pills. This is because the temperature and humidity controls might fluctuate outside required guidelines. Power fluctuations even with constant voltage power supply backup can still occur. Instruments that regulate weighing, batch calculations and precise counting equipment can have problems. Unknown sources of atmospheric microbial contamination, and or any number of other unforeseen scientific malfunctions may occur at any time, not to mention human error. Any of these problems can impede or interrupt accuracy determinations. Mass production of any medicinal product including the percent purity of raw materials only multiplies the potential for problems. Current regulations reflect these difficulties. Still, I think they could be somewhat tighter.

The Food and Drug Administration guidelines state: (e.g. Check Docket No. 2003P-0531/CP1 and “Uniformity of Dosage Units” USP <905>) “The amount of the active ingredient in each of the dosage units lies within the range of 85 to 115% of the label claim and the relative standard deviation is less than or equal to 6 percent.” In other words a company can deliver to you a bottle of pills that do not actually contain an exact 10 mg dosage (or any other dosage) per pill. It only has to contain within 85 to 115% of the stated amount of active ingredient listed on the label with a standard deviation of less than or equal to 6%. I would like to see these limits preferably tightened to a 95-105% range, or at least to a 90-110% range. I'm sure this would cause some cost and compliance issues but I think it would eliminate many continuity problems when transferring people from Brand Name to a Generic program. After all, we're not exactly building “chain saws” here. As I previously stated, these are my opinions.

Note: We are not discussing “Specialty Drugs” here. They are basically used in chronic disease. Most are currently available only in Brand Name prescriptions and generally range in cost from $6,000-$350,000 per patient per year. I have no space for them in this article.

As is, this more or less than 100% accurate dosage is 100% legal. Absolute perfection in this area is not continually possible. But in plain language this means that the medicine can legally contain more or less of the medication than what is on the label and the precise amount actually prescribed by the doctor may not be present. Again, these dosages of the active ingredient must fall within the guidelines of 85-115% of the label claim and the relative standard deviation is less than or equal to 6%. Both limits (high or low) are considered to be an acceptable per pill dosage. Does this make sense? Sure it does…unless it's your blood pressure that suddenly seems to be rising ever since you began taking this new “Generic Equivalent” medication. But your prescription drug plan won't pay for the more expensive brand name drug. So what now? I mean, you don't want to have to expire over a legal discrepancy. If differences exist, and the problem is not recognized or adjusted I believe the consumer could eventually experience problems.

“Hypothetical Activity”

1. (Nonexistent company-A) What if brand name drug company-A manufactures their product near the 115% end of the legal limit. The product works very well, and the customers love it and learn to depend on its systemic medical performance. Because of the legal active ingredient concentration, over time this manufacturing procedure may make it difficult for the consumer to transition to a cheaper proposed generic drug equivalent of the same prescribed dosage. Is it possible that Nonexistent-A company's product's good results may have inadvertently (legally) “influenced” the customer? In some cases the consumer will pay the higher additional cost for it. If this happens, it appears to be perfectly legal, but is it ethical? Or is this just the everyday cost of healthy product competition and doing business as usual? After all, isn't the best product generally the most effective?
2. (Nonexistent company-B) What if generic drug company-B cannot afford to manufacture their product near the 115% legal level or perhaps are unable to afford the most expensive binders and fillers. After all, their product is cheaper than the brand name one. Because of these financial concerns and the cost of prescription drug materials they may manufacture their product nearer the lower legal limit of 85%. The inert ingredients are not supposed to increase or decrease the internal action (absorbability) of the active ingredient.

While the product is legal and more economical for the company to manufacture and its customers to afford, it appears (to me) that its continued use (at the same dosage) by the customer at or near the lower 85% concentration can cumulatively result in some slight withdrawal or ineffective symptoms (over time). This may be especially true if people are used to taking a higher priced possibly more potent (?) or bioavailable brand name drug. After using such an unadjusted medication there may be a blood titration level discrepancy. Can these types of problems be the result of bioequivalence issues? If your medicine seems to be unusually ineffective, be sure to ask your doctor about why this is happening.

As previously stated there are Inert Ingredients in the medications. Depending on the class and type of drug, there may be different binders, fillers, bioavailability additives and absorption enhancers for special applications and special drugs. Some may differ somewhat in characteristic behavior from person to person. There are digestive chelation system additives that aid in ingredient absorption. But, as previously stated, much of this specialized activity is regulated and unavailable as a generic drug. Also, your generic medication may not be as bioavailable or as readily absorbed by your body as it is naturally by some other people. Every person's digestive system is “unique” to them. Some drugs may not pass through the semi-permeable membranes as easily as some previous medicines containing specialized digestive additives. Lots of things can happen. But you shouldn't be left on your own to figure it out. That's an area better left for your doctor to explain.

Absorption problems are especially true for older individuals that internally may naturally produce less digestive acids as they age. In this case, some pills can at times be expelled almost whole and undigested in patient feces. Some of these (usually) older people are unable to break down the pills binder and filler structure to get to the medication contained in the sometimes cheaper pills for a number of reasons. I must say at this point that drug manufacturing companies cannot be held accountable for the aging processes that may eventually impair many older digestive systems. This can also happen in younger patients with digestive issues. But in some cases the composition of inert binders and fillers can influence a medication's performance and medical effectiveness in the more mature and others with compromised digestive systems. Nursing home workers have seen partially digested pills in some resident's feces. Of course, laxatives may contribute.

*Pill Disintegration/Dissolution Rates*

I will not go into too much length and “depth” into this part of our subject here. It would take a book sized volume to adequately and correctly describe all details. According to USP24 the guidelines for the disintegration rates for uncoated pills is 30 minutes and for coated pills is 45 minutes. This disintegration time length should leave only a soft palpable mass on test screen apparatus. This is not the total dissolution (dissolving) rate, or (USP <711>) which is a lot more intricate and complicated. In basket, or Paddle equipped test apparatus, simulated gastric juice solutions find that low dosage tablets (<25mg) generally require less dissolving time than high dosage tablets (>250mg). Also, enzymes may be added to certain drugs during testing to aid in dissolving pellicles (thin skin-like film) if formed.

There also may be dosage dependent kinetics that may present bioequivalence concerns. These and many other incongruent chemical variants can occur during the development of a representative “Dissolution Profile” on each drug in the comparative study system. Because the math and chemistry gets more involved from this point and I don't want this article to become difficult or boring to read I'll leave this particular part of the subject material at this level of general understanding. As in all competitive sciences, explainable differences do exist. But in these cases, I believe more therapeutic drug monitoring (TDM) is needed.

But you say “I thought these prescribed medications were equal in every way?” First of all 85% of anything is less than 115% of it. Also, is it fair to assume that these guidelines may have been (on occasion) accidentally infringed? Many of you are esteemed university educators and certainly understand these comparative arguments. Where you have people in any manufacturing process there has to be room in the specs (tolerances) for human and or equipment error. You can buy two new cars of exactly the same make. And one will out run the other. But you generally get what you're willing to pay for. Sadly, there are generally no exceptions in life to this rule. I have personally used reagents, prepared solutions and supervised Labs with guidelines similar to the ones we're discussing. I've used acceptable correction factors of 95-105% in many types of standardization work. As I said, nobody's perfect, and I'm certainly not seeking perfection, just parity.

I have seen the weights of chemicals increase before my eyes on an analytical balance when they were exposed to laboratory moisture, even when the reagents were swiftly removed from desiccation. (Drying apparatus) This can happen even in labs usually kept within regulated humidity, temperature, and atmospheric microbiological controls. Where large “batch” proportions of chemicals (pills) are produced, problems can and do still occur. There are just too many variables to list. I have personal laboratory experience in this intensely sensitive area. My experience includes helping a prominent drug manufacturing company find the source of microbial contamination in its freeze drying oven lab. I am not just arbitrarily talking about situations I've only read about. I've spent over 32 years in professional laboratory work and supervision. As I've said, I don't think that most drug manufacturing companies have any outstanding problematic or unethical practices. But I believe that there may be opportunities (like in any business) that at times may produce “questionable” results or practices. No industry is faultless. The above reasons and examples are the basis for my concern that you as a “captive” consumer of health care maintain a clear communication with your health care professionals. I've made these points clear.

*Hospitalizations*

Another area that I've been interested in briefly bringing to a general discussion is the Pneumonia/Legionnaires disease comparison. These two diseases are very similar in their diagnoses, symptoms and at times outcomes. I believe pneumonia may be mistakenly blamed for negative patient outcomes that, in fact, might have been caused by legionnaire's disease. This is not an accusation. I just want readers to be aware of the disease similarity.

One of these two diseases (Pneumonia) one might catch or develop anywhere. The other disease (Legionnaires) is a bit more selective. Unless one already has it before one is admitted, I believe a patient might be able to catch it in an unprepared hospital or nursing home. It is thought that this contagion or bacterial ”aerosolization” occurs in significant part due to contaminated heating, ventilating and air conditioning (HVAC) systems. I believe today most hospitals employ “Heating and Cooling Professionals” and may hold them responsible to their “In-house” specialists and technicians for some internal hospital air quality control. If you must enter a hospital for specialized treatment, choose that hospital carefully. You may want to mention this subject to your doctor before your initial hospitalization date.

Perhaps ask your doctor to check the hospitals records for the recent numbers of Legionnaires cases (if any). I have had some experience in researching this disease. It should be taken very seriously. Also, while you're asking the hospital these types of questions, you may want to ask them about the presence/absence of Infectious Carbapenem-Resistant Enterobacteriaceae, the new “CRE Superbug.” It currently has no cure and can make even simple infections incurable! It is mostly found in hospitals and nursing homes. And this new Bug is deadly. Speaking of bugs, there is now a Bed Bug problem in some facilities. No one deserves to get sick because they entered a negligent or particularly susceptible hospital.

*My Suggestions*

Only consider using the finest hospitals in your area. If you are prescribed a new generic drug for the replacement of your previous brand name drug please remember to monitor your physical and emotional feelings while taking the new drug carefully. Check your blood pressure frequently. At the first sign that the medication is not working as well as your previous brand name medication, tell your doctor immediately. And perhaps ask him/her if they think you should have the next higher dose of the generic drug, take an additional dose per day, or perhaps get a different medication. If he/she doesn't understand what you know from reading this article, ask them to explain to you their reason(s) for not wanting to adjust your new medication. Do you need a different drug? Perhaps it's the lack of a proper performing dosage or even your system and the inert ingredients? If they look at you with incredulity, you may want to change doctors or at least get a second opinion. It seems that a few doctors still do not like being questioned or “second guessed.” Especially by one they consider to be a” lay” patient. Well, that's just too bad. It's your health, and it's your money.

*Diet, Vitamin Supplements and Probiotics *

(Check with your doctor)

1. As a chemist I believe In order to stay healthy and help protect yourself from the daily chemical and microbial invasions we are all exposed to, I think most people should take a Daily Multi-Vitamin. It is my opinion that women should choose a nationally known reputable women's formulation. Men should choose a nationally known reputable men's formulation. I believe that Senior Citizens should take a nationally known reputable formulation specifically designed for people over the age of 50. While vitamins do not replace good sound nutrition from healthy food sources, I believe they do enhance and help to fulfill (the not always apparent) nutritional requirements.
2. I also believe that a daily probiotic like Lactobacillus Acidophilus DDS-1. (Dept. Dairy Science: Strain #1) or other proven choice forimmune system and digestive/bowel support is important. It is generally agreed that each capsule should contain in the area of at least 3 billion CFU's (colony forming units). Ask your doctor which one or which Probiotic Group (if any) may be the best choice for your needs.

“Wake Up! Pay attention to what you eat”

*Personally, I believe that too often Death starts in the Colon*- Henri W. Tartt, Chemist

“FYI”

In addition to the 40 (or more) popularly known vitamins and minerals we take in our supplements, there are hundreds (if not thousands) of micro/phytonutrients (some of which are still unknown) that we need to consume daily from fruits and vegetables. These are not generally available in meats. E.g. there are about ten well known vitamins in a strawberry, but they also contain about 700 micronutrients. Here's my favorite fruit drink recipe.

*Breakfast Drink*

One full handful of Blueberries, Two full handfuls of Red Seedless Grapes, ½ handful of Cranberries, ½ Peach, ½ small Orange (juice and pulp, not peel)) ½ Apple and ½ Pear, (save the halved, seeded fruit for the next day) One Cocktail (small) Tomato, One small cup of your favorite yogurt. Add four ice cubes. Liquefy (Blender 1-2 min.) ingredients in 10-12 ounces (or more) of your favorite cocktail blend juice. Note: Juice amounts vary according to your thickness preference. I use 11 oz. of light (Plum Smart type) Cocktail Juice. Serves 2-3. This recipe takes about 20 minutes to prepare, so be sure to allocate the time. Some people like to eat their yogurt separately as a daily treat. That's fine, just leave it out. This is a particularly heavy mixture so you will need a good, strong blender to adequately liquefy the contents. Otherwise a weak blender will just sit there and “vibrate.” (Not an advertisement – Optional - No health claims)

*Tartt's Exercise Motto*

“If you keep moving you'll keep moving. If you stop moving…..you'll stop moving”

As for exercise, I suggest you take a brisk walk (at least 30 minutes) 5-7 days per week. Run if you must, but brisk walking is better on your joints and may be just as effective. But always check with your doctor before starting any exercise program. And don't cross your legs at the knee while sitting. This may cause a “spike” in blood pressure. It's OK however, to cross them at the ankle. For some, this may be a difficult habit to break. (Ladies, some miniskirts may be problematic)

*Sleep Suggestion*

This study, that study…well,”Study Schmuddy.” In my opinion, the secret to “sleeping like baby” is thinking like a baby. In other words don't prepare for sleep. Don't think about it at all. Don't try and fall asleep or try not to do anything else. As soon as your head hits the pillow, just “crash”. Sleep is supposed to be a natural occurrence. In my view, the more you interfere or get involved with it, the more problems you invite. Forget about it. “Sleep happens.” So let it happen without your genius participation. Ask your Sleep Therapist.

*Question*: “When you feel great, do you actually look bad?”

In general, while many health care professionals are masters of making you feel they think the “world” of you, most may care, but they do not love you. Today, people are basically in love with themselves. Professionals have been trained in the methodologies of how not to care too much. This is for their and your protection. I mean, no one wants to be called into their doctor's office only to see him/her take one look at you and then “burst into tears!” However, they do need your money and your loyalty. As we saw above, Mr. Mous doesn't listen to his doctors. Mr. Mous is in the process of digging his own grave with his teeth. Will you follow suit? When it comes to food, at times it seems that collectively we are one big fat conceited group of “vacuum Cleaners.”

The fact that we as humans are members of the Animal Kingdom certainly manifests itself with the daily demonstration that everything on this planet eats everything else (living or dead) on this planet. Listen friend, we must learn to eat right and follow our doctor's orders. But we should also realize that if you feel that something's wrong with your medical program or new medication, you have to protect yourself. Today, the health dangers are so deadly and easily contagious that it is more vital than ever that you participate in your own health care. Inform, and be informed.

In part, my motivation for writing this article came not from a desire to criticize the drug manufacturing industry. And I am certainly am not inferring that our health care professionals or hospitals are in any way incompetent. But doctors and nurse practitioners are not (usually) chemist's, pharmacists or soothsayers. They rightly prescribe what they believe will work best for us. However, I do believe the area of contraindication (Drug Compatibilities) could use a bit more indiscriminate general review. While some “tweaking” may be in order, the USP guidelines, accuracy and integrity encapsulated in the FDA's efforts for quality control is still second to none in the world. But there are times when even the best efforts of the health care community can be compromised by unforeseen events or sometimes questionable practices.

*Dosing Programs*

For instance, allowing practices such as suggesting that patients dissect or cut pills into halves or sections. I think this puts some patients at a technical disadvantage. Not only are some of the instruments patients use to accomplish the cuts at times crude, (butcher knives, forks, hatchets etc.) inaccurate and unacceptable, they may result in unequally halved or even crushed pills. I'm sure this practice has resulted in missed and inaccurate doses. While efficient pill cutters are common, blades can dull and some new exotic pill shapes and configurations make it difficult to accomplish some of the cuts. Also, the amount of active ingredient contained in each and every industry produced tablet (though rare) may not be consistently homogenous throughout the entire pill. If so, this practice could make “troubleshooting” a medical issue more difficult to solve. This can contribute to inconsistent, inaccurate dosing. More therapeutic drug monitoring (TDM) may be needed.

No disrespect intended, but I believe that “One whole Pill=One Dose” (In total or in part) is a far better option. Besides, taking half doses (which some patients do) on one's own may ruin the drug's titration curve, and impede the doctor's best efforts in patient treatment. If you take your medication in this way especially without his/her authorization, you might ask the doctor what he/she thinks of this practice. In my view, while occasional drug increases do become necessary, the uncertain outcome of a patient's “Cut and Crushed Pill Adventures” could more than justify a whole rather than half an extra dose, even as little as once per day. Except in the most extreme cases I don't believe the additional dose (If needed) of medication would exceed the Maximum Therapeutic Drug Level guidelines. But these decisions are always made by the doctor.

If the “Adequately Funded” can receive better overall health care than the less fortunate, why not admit it? Why the masquerade that the “playing field” has been leveled by existing regulations? Historically, the statement “Separate but Equal” was doublespeak for “Sneaky and Evil.”

In my view, if a doctor correctly diagnosis a problem and prescribes the right medication(s) to treat that specific illness, he/she is not responsible for whether or not the medication actually works. The doctor only knows how it's supposed to work. The manufacturer of that medication must be able to demonstrate that the active ingredient in the product is 85-115% of the label claim with a relative standard deviation of less than or equal to 6%. The rest is up to your body. As previously shown, all kinds of unintentional problems can occur during drug manufacture. At times problem drugs have to be recalled. You are the products “ultimate testing machine”, and your physical and verbal input on drug performance is critical.

As most of you know, education is our best defense. I say this to everyone: Unfortunately, the tendency to ignore important health care issues and schedules is an idiosyncrasy that can and does affect people of all educational levels and backgrounds. I believe the principles and problems presented in this article are not subject or exclusive only to the United States.

*In Closing*

“Cut to The Chase”

* Tartt's Law of Sensory Discernment:*

“There is no known apparatus, device, doctor, or automated information system that can duplicate or necessarily eliminate the need for human sensory perception. Therefore, the unique human ability to taste, smell, and otherwise detect difficulties concerning their health and specific care products should be encouraged, and never discounted.” – Henri W. Tartt, Chemist

And so, it is my position that no one becomes a potential victim by just sitting around and hoping a medical issue will get better or cure itself. I believe bad things can happen if they do. If one thinks that someone else cares more for them than they care for themselves, they're probably wrong. Young or old, prince or pauper, slow or gifted, no one wants to go *First* in this class. Remember; if you think something is medically amiss in your health care program speak to your doctor about it. The life you save could be your own! And by the way, “Did You Take Your Pills Today?” Stay well.

“He who knows all the answers has not been asked all the questions” - Confucius

“Verily every man at his best is altogether vanity” – Holy Bible, Psalms 39:5

All The Best,

- Henri W. Tartt

Henri W. Tartt

Supervising Chemist &

Chief of Microbiology

City of Cleveland, Ohio (Retired)

Email:henri@henriwtartt.com