Cancer begone – Cisplatin and Taxol

Hello friend!

It’s the beautiful fall season already …… nature is amazing, isn’t it? The vibrant green colors of the powerful summer foliage mellow down into the magnificently muted colors of autumn. And before you know it, the leaves are falling, giving way to the skeletal trees of winter. Come spring, the green blossoms again and the whole cycle presents itself yet again. How does nature do it? What is that amazing universal clock that tells flora and fauna exactly what to do at different times? When do plant cells know how to grow? How to give way to new cells? The moisture? The pigmentation? The seasons ……

It’s the same with life, isn’t it? Seasons of life. Spring, summer, fall and winter leading back to spring again. At times, we are in the pink of health. At other times, we are a bit under the weather. And at other times, we get hit hard and we’re really down and out. But you know what? Winter is followed by spring. The world is now waking up to the golden age of nutrition, medicine, lifestyle, positive energy, and health. Even the most dreaded diseases and conditions of the past are being challenged effectively. It’s up to us as individuals to understand that the mindset of the last century is the distant, distant past. We are now in the age of health.

Cancer has been a scary monster …. in the past. Am I saying we should underestimate cancer? Absolutely not. We most certainly have to take the responsibility of submitting ourselves to preventative and diagnostic measures. But, let’s consider we have come head to head with the fact that a loved one has been diagnosed with cancer. What next? There are options – surgery to remove cancerous tumors and localized growths, as well as radiation and chemotherapy to destroy abnormal cancer cells, both localized and diffuse.

Let’s look at chemotherapy, specifically two chemotherapeutic agents: Cisplatin and Taxol – the combination is used for gynecological cancers.

Before we get into that, back to basics. What is cancer? Cancer is an uncontrolled growth of a group of cells. During this growth, the abnormal cells compete for nutrition with normal cells, with the result that they invade and destroy adjacent normal tissue. As the abnormal cells continue to grow, they spread to other tissues of the body through blood and lymph.

Why does cancer occur? It could be due to genetic reasons or exposure to cancer-producing agents or carcinogens like tobacco smoke, chemicals, radiation and viral or bacterial infection. A genetic predisposition to cancer is fed by carcinogens resulting in abnormality in the genetic material or DNA of the cell – that’s the reason for cancer.

How do we stop cancer? How do we decelerate the abnormal cell growth? Cell growth happens in several steps. The cell skeleton or cytoskeleton is formed of microtubules, and there is DNA replication with DNA precursor nucleic acids and DNA crosslinking. The steps are catalyzed by enzymes of different kinds acting on different kinds of receptors. So, there are drugs that interfere with microtubule formation and drugs that prevent microtubule breakdown so that the cytoskeleton is made rigid essentially freezing the cell into uselessness. Taxol is a drug of the latter kind – it prevents microtubule disassembly. Then there are drugs that inhibit DNA replication either by messing with the precursors, enzymes or crosslinking. Cisplatin works by inhibiting crosslinking of DNA. There are also enzyme antagonists, as well as other anti-cancer drugs with miscellaneous mechanisms of action.

Taxol is known by its generic name paclitaxel. It was first extracted in 1967 by scientists Monroe Wall and Mansukh Wani from the bark of a plant Taxus brevifolia (Pacific yew). Satisfying the world demand that developed required a large number of trees. Later, the same compound was chemically synthesized from petrochemicals – the chemical synthesis did not yield a large enough quantity of the drug to be viable. Today, the drug is primarily made by a biotechnological process called plant cell fermentation. A line of cells from the Taxus plant is grown and fermented in large tanks to produce the drug.

Taxol forms a complex with tubulin, the building block of microtubules and prevents the breakdown of microtubules. In rapidly dividing and growing cells, microtubule formation and breakdown are essential steps of the mechanism. Another mechanism that has been seen with taxol is that it induces programmed cell death or apoptosis, by binding to a protein that would otherwise inhibit this process. Thirdly, taxol forms complexes with free-floating tubulin and prevents the formation of microtubules, the skeleton of the cells. It is used to treat cancers of the ovary, bladder, cervix, breast, head, prostate, neck and lung cancers, as well as Kaposi’s sarcoma (a cancer affecting the skin, mouth, and gastrointestinal and respiratory tracts). It is usually administered by the intravenous route.

Taxol destroys normal cells too by manifesting the above mechanisms, which is why there are side effects. However, cancer cells grow at a more rapid rate than normal cells, so taxol destroys cancer cells much more than normal cells. Side effects include brittle and thinning hair, joint pain, nausea and vomiting.

Cisplatin or cisplatinum is, as the name indicates a platinum compound. It was synthesized in the laboratory initially in the 1960s, and approved by the FDA to treat cancer in 1978. It is used to treat cancers of the connective tissue (cartilage, bone and fat), lymphoid tumors, ovarian cancer and lung cancers among others. It cross-links with DNA and prevents cell division. This activates a mechanism of programmed cell death. Cisplatin is usually administered intravenously.

Side effects of intravenous cisplatin include toxicity to kidneys and nerves, as well as hearing loss. It can cause a high degree of nausea and vomiting – which can be treated prophylactically by a combination of Emend (aprepitant), Zofran (ondansetron) and dexamethasone. Cisplatin does not cause hair loss.

There have been papers published, of localized (in situ) administration, when possible, of both cisplatin and taxol, to target cancer cells and minimize the exposure of other body organs to the drugs. This significantly reduces the side effects, thus treating the disease with minimal discomfort to the patient. The appropriateness of this method is of course determined on a case-by-case basis, depending on how localized the tumor is or the cancer cells are.

If you are reading this article, and you have been diagnosed with cancer, I’d like to say something to you. Every single human being has cancer cells in their body. Natural body mechanisms stop cancer cells from taking over and affecting body health. Sometimes however, by a combination of genetic and carcinogenic factors, cancer cells in your body take on a life of their own and overpower the normal body biochemistry. And you look back and wonder – I’ve done everything right, I haven’t smoked, I haven’t lived a life of unhealthy pleasure, I’ve never wished ill on anyone, I haven’t hurt anyone …. at least, not knowingly ….. why is this happening to me? Stop right there …… what you think and do next is critically important!

“Whatsoever things are true, whatsoever things are honest, whatsoever things are just, whatsoever things are pure, whatsoever things are lovely, whatsoever things are of good report: if there be any virtue, and if there be any praise, think on these things.” Let’s look at the science behind these words. Every thought we think releases corresponding nerve and body biochemicals. Good, uplifting thoughts release “healing” biochemicals, whereas sad, depressing, complaining thoughts release ….. let’s just say it …… “harmful” biochemicals. Think those awesome, uplifting thoughts and release “healing” biochemicals in your body to produce an environment where cancer cells cannot reside anymore.

Why do bad things happen to good people? I am not going to attempt to take on such a deep philosophical question. Different spiritual traditions can give you that answer. You will find that answer when it’s the right time. The more pertinent question is – when bad things happen, what do we do next?

How about keeping a gratitude journal? Being thankful for all the blessings in your life? For the ones who love you, your family and friends? Now, this might sound strange, but I’ve heard people being thankful for the most difficult times in their life – when they look back, they realize that it’s been the period of maximum growth of character, personality and spirituality.

And when you do have feelings of despair, anger (even if it be righteous indignation at the injustice of it all), frustration, envy or even worse ….. all those negative thoughts, write it on a piece of tissue and flush it down the drain. Replace the thoughts with the corresponding positive thoughts….. the brain can only think one thought at a time – make that a positive one ….. yes, you have the power. Is that a Pollyanna attitude? Brain and body biochemistry respond better to the irrepressibly optimistic Ms. Pollyanna than the lugubriously pessimistic Mr. Misery. Realism? Who defines realism? Realism for the one child that survived a plane crash recently is diametrically opposed to the realism of the hundreds who did not. Who is to say what your realism is?

Believe in your healing. Believe in your good health. In some awe-inspiring way, your thoughts, your neurochemicals, your biochemicals will be commanding the cancer cells from stopping their misbehavior. And ….. at some point, they will listen!

I wish you the best of health. Until next time,

Yours in good health,

Dr. Ajit Damodaran

Alendronate – for bone supremacy

Hello my friend,

Here’s a universal truth – every one of us is growing older – constantly. Every minute. Without exception. And although the effects of age show up slower in some of us than others, they do eventually appear, albeit as unwelcome guests. We’ve got to fight for our youth and health. We can’t just let entropy take over.

One of these unwelcome guests is bone fragility. Why is there a greater risk of fracture as we grow older? Here’s why. Our bone tissue is a dynamic environment. There is constant bone-building and bone breakdown. Bone formation results from the activity of cells called osteoblasts – bone-builders, and bone resorption (breakdown and re-assimilation) due to the activity of bone cells called osteoclasts – bone-breakers. Estrogen is a “female” hormone that is formed in the body of both men and women, appropriate to the age and sex of the individual. Obviously, there is more estrogen in the body of a pre-menopausal woman than a man of the same age.

In less amounts than required to create female sex-specific effects, estrogen inhibits osteoclasts, the bone-breakers, thus minimizing bone resorption. It also activates the bone-building processes. In women, estrogen is primarily made by the ovaries. In men, estrogen is mainly formed by conversion of the male hormone testosterone.

At menopause, the ovaries cease to make estrogen. The drop in estrogen levels results in increased bone resorption and decreased bone formation. This leads to reduction in bone mineral density (BMD) and increased risk of fracture. This condition is called osteoporosis. Although most common in post-menopausal women, it can occur in men too, as well as in men or women with hormonal disturbances, or due to some kinds of medicine (specific steroids called glucocorticoids).

Osteoporosis is prevented/treated with lifestyle changes like exercise, nutrition including calcium and vitamin D and medicine. Bisphosphonates are a class of medicine that have been used effectively in preventing and treating osteoporosis. Nitrogen-containing bisphosphonates are more effective than non-nitrogenous bisphosphonates. Alendronate, sold in the generic form as well as brand Fosamax is a widely used nitrogenous bisphosphonate.

When taken orally, less than one-hundredth of the dose is absorbed under fasting conditions, even less when taken with food. Half of the absorbed medicine is excreted unchanged by the kidneys, the other half is rapidly bound to exposed bone surface in the body. Once it’s absorbed by the bone, its half-life is about 10 years. What that means is that half of the alendronate is rid off by the body in 10 years, then half of the remaining half is eliminated by the body in another 10 years and so on.

Alendronate binds to the osteoclasts (the cells responsible for bone resorption, the bone-breakers), specifically inhibits an enzyme, thus blocking a protein transfer pathway within the osteoclasts. This messes with the functioning of the osteoclasts. As a result, the osteoclasts cease to do their job of bone resorption.

Bone-building continues in the presence of calcium, vitamin D and other factors. This results in increased bone density.

Are there side-effects? All drugs have side-effects. Alendronate can cause ulcers – esophageal (gullet), gastric (stomach) and duodenal (the first section of the small intestine). To reduce the incidence of ulcers, it is required that one sit or stand straight or walk for 30 minutes after ingesting the drug. Taking this medicine with a full glass of water on an empty stomach improves absorption. If dental work is done while on this medication, there is a risk of osteonecrosis (literally means bone death) of the jaw – this is rare on oral administration, more likely when alendronate is administered intravenously, mostly seen in cancer patients.

If alendronate is administered with food or a beverage other than water, absorption is reduced – this is more so with calcium, magnesium or aluminum-containing food or drugs – that includes dairy and antacids. Hormone replacement therapy along with alendronate may help with post-menopausal women.

Alendronate is usually administered in a daily dose of 10 mg or a weekly dose of 70 mg for treatment of osteoporosis. It can be administered in a daily dose as low as 5 mg or a weekly dose of 35 mg for prevention of the same. For Paget’s disease of the bone (enlarged or deformed bones – hereditary or due to a long-standing slow viral infection like measles), it’s a daily dose of 40 mg for six months.

We live in good times. Science, nutrition, lifestyle, medicine and technology give us longer and better quality lives. Are the solutions perfect? Certainly not. Does medicine lead to adverse effects. Of course. However, we can discuss options with our professionals and take the best course of action. Awesome!

My friend, until next time, do take care of yourself and your health.

Dr. Ajit Damodaran

Molecules Possessed (science fiction)

Hello friend,

Before medicinal drugs enter the marketplace, they are synthesized in a laboratory, tested in controlled environments and disease models and then, once approved by the authorities, released for medicinal use. As a student, I used to work in such a laboratory. To pass the time, I would fantasize talking to molecules (nerd alert!) – the following is a story I wrote in those days.

 

Molecules Possessed

Chin was bewilderment personified. “I’m going crazy …..”

Asked his friend Nat: “Why?”

“It’s this molecule.”

“What molecule?”

“It isn’t behaving like a molecule?”

Nat raised an amused eyebrow, “How can a molecule not behave like a molecule?”

“That is just what has me stumped. I’ll explain. See, it was four and a half years ago that I started off on this task of converting a certain chemical to another – of possible medicinal interest.”

“Hmmmmm. And?”

“And after a series of 23 reactions, I was on the brink of success. The last step was the conversion of a bicyclic compound with a side-chain to a tricyclic one.”

“Carry on.”

“After this last reaction which I carried out two days ago most meticulously, I subjected this compund to different spectroscopic determinations.”

“What are these determinations?”

“Methods of identification of a compound.”

“So you did not get the compound expected, is it?”

“That would merely be a disappointment. It wouldn’t challenge one’s sanity like this. The results we have obtained defy logic.”

“How?”

“Proton N.M.R. spectroscopy, that is one of the kinds of spectroscopy we did on the final compound, gives no signals with this compound – as if there were no hydrogen atoms attached to the carbon atoms in the molecule.”

“What of it? This molecule may not be having hydrogen atoms.”

“Impossible. All other kinds of spectroscopy we did  and the elemental analysis indicates the presence of hydrogen atoms beyond a shadow of doubt. Anyway, as the bicyclic compound I started with in the last reaction has hydrogen atoms, there is no way the product cannot have hydrogen atoms. It defies Chemistry.”

“You do have a problem there.” Pause. “I think the best you can do is get a good night’s sleep, wake up refreshed in the morning, and have a heart-to-heart talk with your molecule.”

“I’m in no mood for your wisecracks.”

“Alright. I’ll leave you alone. Relax, pal. You’ll think of an explanation in due time.”

After Nat left, Chin tried to sleep, but to no avail. Acting on an impulse, he left his room in the hostel and made his way to the laboratory.

The sample of the compound was just where he had left it – on his table. He pulled up a stool and gazed at his sample tube. The words of Nat came back to him. “Have a heart-to-heart talk with your molecule.” He smiled despite himself. How silly? Or was it? Just suppose it were possible? 

And there – like Alice in Wonderland he found himself growing smaller and smaller (no, there was no cake on the table). He slipped into the sample tube. Smaller and smaller. Curiouser and curiouser. 

He could not pinpoint any solid masses. He was in an atmosphere where there clouds of varying densities, sometimes so dense that they were almost solid masses and sometimes so rare that it almost looked as if there were only empty space there.

Chin could sense thoughts. No, they were not thoughts from his own mind. They were from somewhere around. They seemed to be addressing him.

“Hello! You’re new here, aren’t you?”

“I’ve come to meet your hydrogen atoms,” Chin found himself speaking.

“Why?”

“Why are they not giving signals?”

Laughter. All around. No sound, like human laughter. Chin could only sense it. 

“Dash it, this is frustrating.”

“Are you a scientist?”

“A student.”

“And your Ph.D. degree depends on our hydrogen atoms here?”

“I am not really worried about my degree. But that four and a half years of work should go to waste just because some hydrogen atoms want to go to sleep is…. is….” Chin could not find words to express his anguish.

“Don’t get excited. You’ll get all the signals you want.”

“Will you kindly explain what has been going on? And may I know who I am speaking to?

“You are speaking to what IS – to EXISTENCE.”

“Eh?”

“It is time your concepts were made clear. How do you define life?”

“I’m not very sure.”

“What is the structural and functional unit of the human body?”

“The cell.”

“What is the cell made of?”

“Atoms and molecules.”

“What are atoms and molecules made up of?”

“Smaller particles – protons, electrons, neutrons …”

“What is the nature of these sub-atomic particles?”

“In what sense?”

“You must be knowing about the dual nature of sub-atomic particles.”

“Yes – these ‘particles’ behave sometimes like particles and sometimes like waves of energy.”

“Okay. You know Einstein’s theory of relativity – about mass and energy being interconvertible; of mass and energy being different personifications of the same thing.”

“Yes.”

“So, in essence, your body is made of cells which are made up of atoms and molecules, which are in turn made up of subatomic particles – these particles are not strictly particles – just clouds of dense energy. Ultimately, what do we come to? Your body is made up of dense clouds of energy, as is every object in the universe, as is the universe – only the density is variant. Very, very dense energy projects itself as having mass. Therefore, EXISTENCE is ENERGY, ENERGY is EXISTENCE.”

Chin started feeling giddy. “Do you mean to say that there is no difference between a living body like mine and an inanimate object?”

“Essentially, no. But apparently, yes. What is the difference between a living human body and a dead human body? A living human body performs a multitude of functions in co-ordination. That is, there are countless molecules in the body performing in co-ordination – the body has ‘life’. When this co-ordination is lost at some stage, the body ceases to live. Yet, all the molecules continue to exist. Only the co-ordination is lost. Now, the question is – what causes this co-ordination? The answer is – a certain force.”

Chin was excited. This could be the answer eluding man through the ages. “What is this force?” he asked eagerly.

“A force. It is difficult to explain. You have not quite reached the level of intelligence required to grasp the idea. It will be something like trying to explain Einstein’s theory of relativity to a monkey.”

“Hey!” Chin turned purple with indignation.

“Suffice it to know that it’s some kind of a life-force, a different embodiment of the same energy which holds the sub-atomic particles together in proper order in an atom of a molecule. This ‘life-force’ exists in all living beings. When the life-force goes away, there is no ‘life’ as you know it.

“Okay! I’ve swallowed all this. But in what way is all this connected with my not getting proper signals in the spectrum?”

“It has all the connection. Do you know the theory of N.M.R. spectroscopy?”

“Yes. N.M.R. or Nuclear Magnetic Resonance spectroscopy is based on the principle that in the presence of an external magnetic field, nuclei of atoms absorb electromagnetic radiation of different specific frequencies to undergo transitions among specific orientations. It is this absorption of radiation that gives rise to signals.”

“Right. You see, what happened was this. Some life-force moving around in the vicinity was entrapped by the hydrogen atoms of this molecule. That is, according to your definition of life and death, these hydrogen atoms started having life – and started acting with a will of their own. They occupied the orientation of the lowest energy and refused to absorb electromagnetic radiation. With the result that you go no signals.”

Within Chin’s breast, the initial wonderment gave respectful right-of-way to exasperation, which burst out as a cry. “So, what do I do?”

“Don’t worry. You’ll get your signals tomorrow morning. This ‘life’ was only transitory. The hydrogen atoms are already ‘dead’ according to your definition.”

Chin arose from his slumber. Recollecting his nocturnal experiences, he started wondering, “Was this a dream?” It seemed likely.

Then he remembered that he had been told that he would be getting signals this morning.

Feeling like a fool, he took his sample to the instruments’ room and recorded the spectrum. Perfect. The hydrogen atoms had started giving signals. More puzzled than ever, he wondered what he would tell his Professor and colleagues. All that had happened? They would laugh at him. He was not so sure whether or not to laugh at himself.

 

Until next time, my friend, take care of yourself and your health.

Dr. Ajit Damodaran

Life is always fair!

Hello my friend,

Time for philosophical cerebrations. Logically presented, nevertheless they are just my opinions. Makes perfect sense to me ….. however, you may have a different take on the subject. Isn’t that what makes life beautiful?

To quote Napoleon Hill, “Thoughts are things.” What is the science behind that statement? Where does a thought from? It could be triggered by an event that is perceived by one of our five senses. Or, it could be triggered by a memory. Thirdly, it could be a creative thought, like they say …. from the Universe. Associated with every thought are neurotransmitters and hormones …….  natural brain and body chemicals that are released by nerve cells and other cells. Chemicals are “things”. So …… thoughts are things.

Stressful thoughts release natural chemicals like cortisol and adrenaline that, in excess, can hurt the body. Oh yes, we need cortisol and adrenaline for fight-flight-fright situations. They give us almost superhuman power to react to stressful situations. But if we get into that “hyper” mode at all times, that can create effects like lowered immunity, high blood pressure, increased abdominal fat leading to cardiovascular problems, diabetes, thyroid problems and decreased bone density.

Here’s the problem. In modern society, we live busy lives. As we live our hectic lives, our stress levels are at a constant high, at least moderately high ….. like, we have redefined what normal stress should be.

A majority of stress comes from our judging our own circumstances and others’. We believe that we deserve certain events in our lives. And we want certain events to happen to others, and certain other events not to happen to others. Why? Because we have our own perspective on what we deserve and what others deserve. When we believe we are “good” and yet these “bad” things happen to us. And when we believe someone else has been “bad” and yet “good” things happen to them.

If an individual has good fortune in any area of life, it is because of certain virtues they possess. Let’s take a simple example. Say, a person works hard and smart and becomes a billionaire (millionaire doesn’t cut it anymore, huh?). It’s basic cause and effect. The cause was good work, and the result was good rewards. In another area of life, the same person eats unwisely, does not exercise and suffers ill-health. Here, the cause was bad food and bad lifestyle and the effect was ill-health. It makes perfect sense, doesn’t it?

Let’s extend it. Say, the same person in the example above is not ever charitable. Not charitable with his money, his actions or his words. In fact, he is incredibly rude and even cruel to his employees. We are disgusted by his bad character. We start gossiping about him. Somehow, the story comes down to the fact that he is a horribly bad man and yet the Universe rewards him with good fortune. No, we got it all wrong. His good fortune results from his hard work.

On the other hand, we look at ourselves and see that we are good people. We are kind to our employees, we give to charity and so on. And yet, we are not as rich as the person above. So we come to the erroneous conclusion that our goodness is not being rewarded.

That is not the case at all. Every event in our life is perfectly fair. Every event in everyone’s life is perfectly fair. Does that give us an excuse to be not sympathetic to the troubles that our fellow humans go through? Certainly not. When we share others’ griefs, when we help people face their challenges, we are thinking charitable thoughts, we are doing charitable deeds, and that builds our own character. Good, strong character builds peace in our hearts. Scientifically, that means we develop neurochemical patterns in our brains and bodies that are beneficial to us.

I’m sure a thought must have come to your mind – yes, it’s come to my mind too. Am I saying that it is fair that a child is born in wonderful circumstances and another child is born into misfortune? I cannot make a cruel statement. I do not know the exact reason why one child was placed in the first situation and the other child in the second. Let’s send that question out to the Universe. What I am totally convinced of is that the Universe is in perfect order. We might not be able to see the order, but underlying what could be considered chaos, is a perfect world that works like clockwork. We might not know why the past was, but we can do all that we can to manifest a wonderful future.

Take the example of Oprah Winfrey. Born to a poor, teenage single mother in rural Mississippi, Oprah suffered through many struggles. In spite of her difficult beginnings, she decided to make something of herself. She started her career in a radio station. She then became a local TV co-anchor, and gradually grew to be a brilliantly successful media personality, one of the most influential people on the planet. Oprah is a role model not because of her troubled beginnings, but because she was an overcomer.

Can we assume that there is someone out there who shares Oprah’s birth day and was born in better circumstances? Is it possible that they are not as successful as Oprah? Is it possible that there is someone who was born with a silver spoon and became a total failure in life? You bet.

As we move forward into an awesome future, will there be obstacles? Absolutely. My belief is that the obstacles are the means by which we build the qualities to manifest the magnificence of our future. The heavier the weights we lift, the greater the resistance. The greater the resistance, the more the muscles build. Similarly, the heavier the obstacles in our path to our goals, the more we build mental muscle and character muscle.

The faster we move into the future, the more the obstacles. Another analogy will explain what I mean. If your car is parked in the driveway, and you put your hand out of the window, do you feel the wind? (I’m assuming a non-windy day). Take the car out on a drive through city streets at 25 miles an hour. Do you feel a gentle breeze? Yes. Take the exit onto the highway. You’re now driving at 65 mph. That’s quite a wind, isn’t it?

Obstacles and difficulties are part of the beautiful framework of the perfect Universe. However unfair it might seem, there is a purpose for every event in our lives.

What was the purpose of this philosophical treatise? Just this. When we develop an underlying belief that everything is fair in our world, we stop trying to be the manager of the world. We stop wasting our thoughts on wishing others ill. We stop frustrating ourselves with righteous indignation.

We learn to accept what we have, and we work calmly toward even better, in a spirit of inspirational dissatisfaction or divine discontent. We accept the truth of the Serenity Prayer, “God grant me the serenity to accept the things I cannot change, the courage to change the things I can, and the wisdom to know the difference.”

As we increasingly manifest this wisdom in our being, our health keeps improving. Isn’t that good?

Do take care of yourself and your health. Until next month, G’bye!

Your friend,

Dr. Ajit Damodaran

Omega-3 fatty acids

Hello friend,

As we, followed by the rest of the world, increasingly invite creature comforts into our sedentary lifestyles, there is a tendency to obesity. Associated with obesity is metabolic syndrome leading to increasing diabetes and cardiovascular disease, leading to death or at best a decreased quality of life.

Something I read quite some time ago … I think I first read of it in Deepak Chopra’s book Perfect Health …… improving health, slowing the aging process and increasing longevity by caloric restriction. There have been anecdotal reports of individuals practicing this through history. Recently, diets have been developed based on this principle, like the Okinawa diet and the CRON (calorie restriction with optimal nutrition) diet.

The following is a mechanism that is brought into play in caloric restriction. As less food is absorbed from the gastro-intestinal tract into the blood, there is less need for insulin. As a result, there is a decrease in insulin and insulin-like growth factor 1 (IGF-1). By a cascade of cellular mechanisms, this leads to an increase in the activity of a protein in the cell nucleus, called peroxisome proliferator-activated receptor (PPAR) gamma co-activator 1 (PGC-1). PGC-1 and other PPAR activators increase the activity of nuclear receptors that play a major role in the effects of caloric restriction (The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:1494-1509 (2005) © 2005 The Gerontological Society of America). They activate lipid transport and lipolysis (fat burning mechanisms). The resulting beneficial effects include decrease in blood pressure, decrease in total and bad cholesterol (LDL), decrease in triglycerides, increase in good cholesterol (HDL), decrease in blood glucose, and through all these, increased longevity.

It has now been shown that omega-3 fatty acids in our diet activate the same factors above that are activated by caloric restriction. In addition, omega-3 fatty acids decrease the levels of  hepatic sterol regulatory element binding proteins (SREBP). These proteins are genetic  transcription factors that are master regulators of lipid homeostasis. Reduction in SREBP results in a decrease in the activity of enzymes responsible for fat biosynthesis and storage. Bottom line, omega-3 fatty acids decrease fat synthesis and storage. So, it may be said that instead of starving yourself, just pop some omega-3 (read the book The Omega Diet by Dr. Artemis Simopoulos). No, please don’t take this as license to be corpulent …. the ill effects of obesity are not cancelled by omega-3 fatty acids.

Alright! What are omega-3 fatty acids? Let’s get back to basics. The macronutrients we ingest in our diet are proteins, carbohydrates and fats. (Fats are a part of a larger group of compounds called lipids. Also, lipids include sterols like cholesterol, phospholipids and others). Fats are a very concentrated form of energy. A gram of fat gives the body more than double the energy of a gram of carbohydrate or a gram of protein. Chemically, all fats are a “three-pronged” glycerol molecule linked via those three “prongs” (ester bonds) to long chain fatty acids. Each long chain fatty acid is a long chain of carbon atoms with hydrogen atoms bonded to the chain of carbon atoms. Each carbon atom (except the one forming the end of the chain) can be bonded to a maximum of two hydrogen atoms. When all the carbon atoms constituting the chain is bonded to the maximum number of hydrogen atoms they can be bonded to, it is called a saturated fatty acid. The triglyceride (that is, the glycerol linked by ester bonds to three fatty acids) is then called a saturated fat molecule. Too much saturated fat, obtained in the diet from dairy products, lard, coconut oil and cottonseed oil, is bad for the cardiovascular system. High levels can also cause breast cancer and prostate cancer. Smoking and regular alcohol ingestion increases the levels of saturated fat in the blood.

In monounsaturated fats, two of the adjoining carbons in the long chain fatty acid are not saturated with hydrogen atoms. They are each attached to only one hydrogen atom and double-bonded to each other. So, two carbon atoms saturated with hydrogen atoms would be bonded as -CH2-CH2-, whereas unsaturated double-bonded carbon atoms would be bonded as -CH=CH-. In polyunsaturated fats, there are more than one double bond in the fatty acid chain. “Omega” is the last letter of the Greek alphabet. Omega means the end. In our discussion, the omega carbon atom is the last carbon atom in the fatty acid chain. Omega-3 fatty acids are those that have a double bond at the carbon atom which is third away from the end of the fatty acid chain. Aha!

Essential fatty acids (EFAs) are those that cannot be synthesized by the human body from other components of the diet or body biochemistry. So, EFAs are required to be part of our diet. There are two groups of EFAs, the omega-3 fatty acids that we discussed above. and the omega-6 fatty acids. The latter are of course those that have a double bond at the carbon atom sixth away from the end of the fatty acid chain.

The balance of omega-3 and omega-6 fatty acids is important in the body. The ideal ratio of omega-6 to omega-3 in the diet is said to be less than 4 is to 1. In the diet of industrialized nations, the typical ratio is 10 to 1 or more. This could be cause for cardiovascular events, arthritis, cancer, depression and other mood disorders, osteoporosis and inflammation. In fact, cumulative research suggests that a lot of modern health conditions have inflammation as the underlying cause. There are signaling molecules in the body called eicosanoids, derived from omega-3 and omega-6 fatty acids. Eicosanoids from omega-6 fatty acids are pro-inflammatory, whereas those derived from omega-3 fatty acids are anti-inflammatory. To maintain equilibrium in these body processes, both omega-3 and omega-6 fatty acids are required, in the right ratio.

The important omega-3 fatty acids in our diet are eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA). Research supports the use of EPA and DHA to prevent cardiovascular disease. EPA and DHA are biosynthesized by sea-water microalgae. Fish consume these microalgae and retain large amounts of these omega-3 fatty acids in their bodies. So, consuming fish or omega-3 fatty acids extracted from fish is ….. good for health. Plant omega-3 fatty acids are not EPA or DHA, but ALA. The human body is able to convert ALA to EPA and DHA. Flaxseed is commonly used as a vegetarian alternative to fish oil.

Omega-3 fatty acids have been shown in various research studies to be beneficial against cancer as well as developmental disorders like ADHD and autism. There have also been benefits to the immune system. When given to pregnant women and lactating mothers, the babies were shown to have higher IQs. More and more scientific research gives us greater insights into the benefit of omega-3 fatty acids. We do have to be careful, though, of not slipping into one of our weaknesses in modern society. Excess! If something is good for us, well, more of it must be better. Not really.

Moderation is important. Very large doses of omega-3 can cause hemorrhagic stroke. Also, when someone has congestive cardiac failure, chronic recurrent angina or any condition where the heart is not getting enough blood flow, the normally beneficial stabilizing effect of omega-3 fatty acids is a negative because it slows down the few hyperexcited cells of the heart. This can lead to sudden cardiac death. Bleeding can be excessive in a patient who is already on aspirin and/or warfarin.

Bottom line – omega-3 fatty acids are a blessing. However, excess can be a curse. Balance, balance in everything. So ….. what should the dose be? The National Institutes of Health recommend between 650 and 900 mg daily of EPA and DHA combined, or 2.2 gm of ALA (for vegetarians). Two tablespoonsful of flaxseed contain about 3 gm of ALA.

Be well, my friend. Until next month, take care of yourself and your health.

Warm regards,

Dr. Ajit Damodaran

Celebrex – for pain and arthritis

Hello friend,

How are you? Holiday time again. Wish you a happy Easter! It’s good to be stepping into spring, isn’t it?

As we get more physically active in spring, we could possibly be exposed to injuries and ….. pain. Pain …. pain …. we’ll be talking about a prominent pain medication today …….. and toward the end of this article ….. well, we’re going to see a painful account of the state of scientific research today ……..

Let’s talk about the drug celecoxib, commonly known in the U.S. under the brand name Celebrex, and in other countries as Celebra, Cobix, Celcoxx, and Selecap. 

Celecoxib is a non-steroidal anti-inflammatory drug (NSAID – pronounced N-sed) – it is a selective COX-2 enzyme inhibitor. I’ll explain that below. Other NSAIDs, which are non-selective, are aspirin, ibuprofen (available as Advil or Motrin in the U.S., Brufen in India) and naproxen (brand name Aleve) – these are available over the counter. Where does the selectivity come from? Let’s look at the mechanism of action of these drugs.

An enzyme in the body called cyclooxygenase (COX) catalyzes the formation of lipid compounds called prostaglandins. There are different kinds of prostaglandins which have a variety of functions all over the body, including regulation of inflammation and sensitizing central nerve cells to pain, as well as contraction and relaxation of gastrointestinal muscles and secretion of stomach acid for the digestion of food.

There are three kinds of COX enzymes. COX-1 is found in most cells at a steady concentration. Prostaglandins that are responsible for the maintenance and protection of the gastrointestinal lining are dependent on COX-1 for their synthesis. COX-2 is induced at sites of inflammation. They are responsible for the synthesis of prostaglandins that cause inflammation and pain. COX-3 (a genetic variant of COX-1), has been shown to be in the brain and may be involved with prostaglandins and headaches – less is known about this enzyme.

The non-selective NSAIDs like aspirin, ibuprofen and naproxen inhibit both COX-1 and COX-2. Celecoxib selectively inhibits COX-2 thirty times more than it inhibits COX-1. Inhibition of COX-2 is beneficial – it reduces inflammation and pain; whereas inhibition of COX-1 can be a problem – it can damage the stomach lining, leading to ulcers in some patients. Selective COX-2 inhibitors, as the name indicates, selectively inhibit COX-2 and thus reduces inflammation and pain, with minimal gastric side-effects.

Prostaglandins have been shown to have a role in vasodilation (blood vessel dilation). When NSAIDs inhibit prostaglandin synthesis, the net effect on the blood vessels is to increase vascular resistance. This can lead to reduced blood perfusion through the kidney filtration apparatus in susceptible individuals. In patients with less than perfect cardiac ventricular function, this can lead to edema (fluid retention) and congestive heart failure (CHF).

COX-2 inhibitors were shown to have more of these kidney and heart side-effects than non-specific NSAIDs. A couple of COX-2 inhibitors, valdecoxib (Bextra) and rofecoxib (Vioxx), that had greater selectivity for COX-2 than celecoxib, were taken off the market because of greater cardiovascular risks than celecoxib. Although several mechanisms of action have been proposed for the greater cardiovascular toxicity of these COX-2 inhibitors, none of them is a complete explanation.

Aspirin, though an NSAID, has an antiplatelet action which prevents formation of blood clots – hence, it is used by at-risk individuals in a low dose (81 mg) daily regimen for cardiovascular health.

Celecoxib, the drug we are discussing today, is orally absorbed with a peak effect between 2 and 4 hours after ingestion. Its elimination half-life is between 6 and 12 hours – this means half of the drug in the body is eliminated in 6 to 12 hours, then half of the amount left in the body is excreted in the following 6 to 12 hours, and so on….

Celecoxib is used to treat rheumatism, osteoarthritis, acute pain and painful menstruation. Under brand name Onsenal, celecoxib is used to treat familial adenomatous polyposis (FAP), a genetic disease characterized by polyps that grow in the large intestine and/or rectum. These polyps have high levels of COX-2. By inhibiting COX-2, celecoxib decreases the growth of the polyps. Onsenal is generally used in conjunction with surgery to treat FAP.

Alright, let’s talk about ……. twenty-one research articles with fabricated data ….. wha .. aa… at? Yup! Favorable results from Celebrex, Bextra and Vioxx as well as Lyrica and Effexor for pain were made up by a prominent anesthesiologist from Springfield, Massachusetts (as reported in Scientific American, March 10, 2009 as well as Wall Street Journal, March 11, 2009 and Boston Globe, March 11, 2009).

Dr. Scott S. Reuben, Professor of Anesthesiology and Pain Medicine at Baystate Medical Center in Springfield, MA, has been influential in estimated billions of dollars of sales of COX-2 inhibitors (according to Paul White, editor, Anesthesia and Analgesia, February 20, 2009). Reuben recently admitted that he did not do any of those studies. He fabricated results, including inventing patients who never existed and forging the names of co-researchers. Scientific American calls him a medical Madoff (a reference to Bernie Madoff who recently perpetrated a 65 billion dollar investor fraud). Of course, his studies have been retracted by the medical journals they were published in.

No, it’s not all bad. Celebrex, Lyrica and Effexor are not expected to be taken off the market. None of Scott Reuben’s studies were part of the application that the manufacturers made to the US FDA or to drug authorities in other countries. They are still effective drugs.

So, why did Reuben lie? To get financial grants from the pharmaceutical companies involved. It has been reported that Reuben acted alone in the fraud.

Human beings, right? The good, the bad, the ugly….. No, we cannot develop a holier-than-thou attitude. Good does not mean perfect. None of us is perfect. However, it’s true that some imperfections in some people affect large populations of people negatively.

Let us hereby resolve to minimize our own imperfections, eh?

Until next week, do take care of yourself and your health.

Warm regards,

Dr. Ajit Damodaran

Colchicine – for gout

Hello friend,

Time has slipped by, hasn’t it …. since the last blog? Time, life …… reminds me of something that leadership teacher Dr. John Maxwell says – you cannot manage your time, you can only manage your life. Here we go ….. to the better management of life …..

As our knowledge of medical science and lifestyle increases, we live longer. As we live longer, there’s no point in living unhealthy lives, is there? A healthy lifestyle is what we intend. We watch our diet, take the right medication when necessary and live healthy, happy lives … right?

Which brings us to the management and treatment of a condition that can be painful. Gout. What is gout? High levels of uric acid in the blood along with acidic blood pH cause deposits of uric acid crystals in the cartilage of joints. This leads to painful, burning acute pain, arthritic symptoms, and with time, chronic gout including the formation of nodules called tophi that show through the skin.

Uric acid is normally present in everyone’s blood. Where does an excess of uric acid come from? Some folk may be genetically prone to it, due to aberrations in purine-pyrimidine metabolism. Purines and pyrimidines are part of amino acids (proteins are formed of amino acids), DNA, RNA, energy production in the body …. a lot of body biochemistry. Specifically, uric acid is created from the breakdown of purines. Gout is more likely in more affluent societies due to high dietary intake of proteins, fats and alcohol. “Poor man’s gout” also exists, because of ingestion of an excess of malt liquor combined with bad nutrition. Gout can also be caused from kidney failure and from lead poisoning. In the U.S., gout occurs in about 0.3 per cent of the population.

Treatment of gout. In the first century A.D., they used the extract of plants belonging to the colchicum genus to treat gout. In 1820, the active ingredient from that extract, an alkaloid named colchicine was extracted from colchicum extract  by a couple of French scientists. Research on this alkaloid showed that it inhibits deposition of uric acid crystals by inhibiting glucose oxidation to lactic acid. This is key in the treatment and prophylaxis of gout. Colchicine also prevents the mobility of white blood cells called neutrophils. This prevents inflammation. The drug is used for acute flare-ups as well as for chronic symptoms and prophylaxis between acute events.

Colchicine is used to treat familial Mediterranean fever, a genetically transmitted inflammatory disease affecting groups of people originating from areas around the Mediterranean sea.  It is also used to treat amyloidosis, a deposition of abnormal amyloid proteins in different organs, as well as to treat scleroderma, a chronic autoimmune disease where the skin or other organs harden. It can be used as preliminary treatment of pericarditis, an inflammation of the fibrous membrane around the heart.

This drug is now being investigated for anti-cancer properties. Colchicine prevents polymerization of microtubules by binding to tubulin, and thus acts as a mitotic poison (mitosis is an essential step in cell division and growth), specifically preventing the growth of cancer cells which have a greater rate of mitosis as compared to normal cells.

Molecular modifications of colchicine are being researched to develop a treatment for cancer. Why the molecular modifications? To increase the therapeutic index – higher effectiveness, lower toxicity.

Speaking of toxicity and therapeutic index, colchicine has a low therapeutic index. High toxicity. Neutropenia (reduction in blood neutrophils), gastrointestinal upset, bone marrow damage and anemia. Acute toxicity include fever, stomach upset and kidney failure.

High levels of uric acid is the primary risk factor for gout. Specifically, it’s not protein, it is a diet high in purines like meat and seafood, that lead to increased levels of uric acid. Meat and seafood consist of muscle, which has mitochondria, which has high quantities of DNA and RNA – that is the source of high purines. High amounts of vegetable protein or dairy protein, not being high in purines, do not lead to increased uric acid. A diet high in sugary soft drinks, because of high fructose corn syrup, leads to high uric acid. Drinking even one beer a day (not other alcoholic drinks) leads to elevated uric acid levels too.

Yup … like I said before … let’s eat and drink intelligently, use medicine when necessary … and live healthy.

Until next time, please do take good care of yourself and your health.

Dr. Ajit Damodaran

Pentosan polysulfate (Elmiron)

Hello friend,

The human body is an amazing integration of many, many biochemical processes. At times though, some processes go awry. And when that happens, there is less than ideal health.

A chronic inflammation of the wall of the urinary bladder has been given the name interstitial cystitis (IC). It is characterized by urgent need for urination, as frequent as every ten minutes, day and night, and sometimes severe abdominal pain. Pain usually increases as the bladder fills and decreases after voiding. There can be pelvic floor dysfunction and tension, making it difficult to start a urine stream. Other symptoms are pain with sexual intercourse, discomfort in driving and traveling.

In most cases there is no infection, as determined by urinary culture and analysis. There is also no specific diagnostic laboratory test. Most patients consult at least five physicians including psychiatrists, before IC is diagnosed. This is because it is very easy to confuse with other urinary and bladder conditions and diseases like urinary tract infection (UTI), urethral syndrome, urethritis, overactive bladder, prostatitis and so on.

Diagnosis is done by evaluating the patient’s symptoms, and cytoscopy by inserting a tube with a scope via the urinary tract into the bladder under local anesthesia. In recent years, cytoscopy is less used. Instead, exclusion of other conditions that mimic IC, a questionnaire, and a potassium sensitivity test are used. The questionnaire is the Pelvic Pain and Urgency/Frequency Patient Symptom Scale (PUF questionnaire). The potassium sensitivity test is based on the fact that intravesical potassium sensitivity can show abnormal epithelial permeability responses in patients with diseased bladder, mostly IC. Small hemorrhages called glomerulations are indicative of the beginnings of IC. More severe ulcers called Hunner’s Ulcers are a severe form of the condition.

About 90% patients of IC are women, about 10% men. Upto 12% of women may have early symptoms of IC. The prevalence of IC seems to be increasing in young and middle-aged women. Some children too have been diagnosed with this condition.

The exact reason for IC is not known – it could be allergy, immune factors or even infection. A well-accepted theory is that IC is caused by a defect in the glycosaminoglycan component of the mucin layer that protects the urothelium, the tissue layer that covers much of the urinary tract. Based on this theory, a compound synthesized in the laboratory similar in structure to glycosaminoglycan is used to treat IC.

This compound is Elmiron (pentosan polysulfate). It has been studied in placebo-controlled trials where bladder pain was significantly decreased by its administration.

When taken orally, only about 6 per cent of the dose is excreted via urine – the bioavailability is very poor. Hence, it may take several months for the effect to be seen. There have been instances where the drug has been place directly in the bladder and it is 90 per cent effective.

Oral administration has produced side effects like diarrhea, acidity and stomachache. Sleeplessness, headache, rash and hair loss have been reported. A major concern with Elmiron is it has blood thinning effects. There are cases where the administration of this drug has been stopped before surgery, to avoid the possibility of excessive bleeding.

Tricyclic antidepressants like Elavil (amitriptylene), Sinequan (doxepin) and Tofranil (imipramine) which have pain blocking effects, have been used to treat IC. Atarax (hydroxyzine), an antihistamine, has been used to treat the condition, on the assumption that histamine released by mast cells are responsible for some of the effects of IC. Tagamet (cimetidine), a specific H2-receptor histamine blocker, has been similarly used.

Recently, Elmiron has been used experimentally for a condition called Creutzfeldt-Jakob disease (CJD), a degenerative brain disease, characterized by rapidly progressing dementia, memory loss and hallucinations. These and more symptoms are due to rapid destruction of brain cells due to build-up of abnormal infectious proteins called prion proteins in the brain – this leads to a spongy appearance of the brain tissue. CJD is a transmissible spongiform encephalopathic disease, similar to mad cow disease in cattle. Elmiron has been shown to slow down the progression of CJD.

A lot more research is required to be done on interstitial cystitis, Creutzfeldt-Jakob disease and the drug Elmiron. In the meanwhile though, the drug does improve the quality of life of patients with these conditions. Isn’t that what medicine is about?

Until next week, please take good care of yourself and your health.

Dr. Ajit Damodaran

Amiodarone, antiarrhythmic agent

Hello friend!

Let’s get to the heart of  ….. the human body! It is obviously an essential organ – it pumps the blood that flows in the body, which is responsible for carrying oxygen and nutrients to all the cells of the body and transporting the waste of the cells back to the excretory processes.

It makes sense to keep the heart in working condition, in proper rhythm. Sometimes, the rhythm is affected. How? And what is the solution?

What is responsible for the rhythm of the heart? Pulses of electricity in a section of the heart initiate the process. This is something that happens at a frequency of 60 to 100 times a minute.

Alright, what’s the electricity deal? Like nerve cells, cardiac cells send messages electrochemically. Natural chemicals cause an electrical signal. There are chemical ions in the body that are electrically charged. The important ions are sodium and potassium that have one positive charge each, calcium that has two positive charges and chloride that has one negative charge. Each cell is surrounded by a cell membrane which is semi-permeable – it allows certain ions to pass through and blocks others.

In between sending electrical signals, the cell is at rest. In this state, the inside of the cell is negatively charged compared to the outside of the cell. The resting membrane potential is about -90 mV (millivolts). This means the inside of the cell is 90 mV less than the outside of the cell.

When the cell gets excited, an action potential occurs. In a nerve cell, there has to be a stimulus – a thought or a motor movement or some kind of mental or physical initiation. In a cardiac cell, the specialized conducting nature of the tissue causes it to have an action potential without any external stimulus.  The action potential is caused by a burst of electrical activity caused by a depolarizing current. This means the resting potential of -90 mV moves toward zero mV. When the depolarization of the cell reaches a threshold of about -70 mV, the cell fires an action potential and changes from negative to positive, then plateaus at around zero mV and repolarizes back to -90 mV.

The heart is a muscle with four chambers. The top two smaller chambers are the atria – the left atrium and the right atrium. The lower two chambers are the thick-walled, more muscular ones called the ventricles, left and right. How does the heart work? Two major veins called the superior vena cava and the inferior vena cava carry deoxygenated, impure blood from the upper and lower parts of the body respectively to the right atrium. The right atrium pumps this blood into the right ventricle. The blood is pumped by the right ventricle through the pulmonary artery into the lungs, where it is oxygenated. The purified, oxygenated blood is brought back via the pulmonary vein to the left atrium of the heart, which pumps it into the left ventricle. The left ventricle pumps the blood out into the rest of the body.

So, what is the sequence of events in a heartbeat? A group of cells called the sinoatrial node (SA node) on the wall of the right atrium is the natural pacemaker of the heart. An electrical impulse arises at a specific frequency from the SA node and is conducted through the heart, with a series of precisely timed depolarizations of heart cells in a four-part cycle. The atria contract, while the ventricles remain relaxed and passively full of blood. More and more blood is forced by the atria into the ventricles which keep on expanding to their muscular stretching limit. The valves between the atria and the ventricles close, following which there is a brief period of rest.  Then the ventricles contract – the deoxygenated blood from the left ventricle goes to the lungs as explained above, and the oxygenated blood from the right ventricle goes through the systemic circulation to the rest of the body. Next, the ventricles go back to resting state, and passively fill with blood.

Why would the heartbeat become irregular? It could be one of several reasons. It could be congenital. Or, it could be because of rheumatic heart disease, blood pressure or hyperthyroidism. Other reasons could be an excess of caffeine, alcohol, stress or even some cough and cold medicines sold over the counter.

Antiarrhythmics act on the heart in a variety of ways to slow the conduction so that the heart has the leisure to develop a more regular rhythm. There are different classes of antiarrhythmics based on the mechanism of action. Amiodarone is a Class III antiarrhythmic that blocks the heart’s potassium channels and thereby slows conduction.

Therapy with amiodarone should be started in a hospital under medical supervision. Severe lung problems, sometimes fatal, have arisen as a side-effect. Sometimes, the drug could worsen the heart’s arrhythmia. It may take 2 weeks or even longer for its effect to be seen.

Amiodarone is an iodine-containing medication, so the patient should not be on simultaneous radioactive iodine therapy. This medicine is not to be used during pregnancy or during breast-feeding. The drug can increase the effect of blood-thinner warfarin. It can increase the sensitivity of the skin to the sun. It can even turn the skin blue-gray in color, a condition that can persist for several months after the medication is stopped.

Other side-effects can be tiredness, constipation, loss of appetite, smell or taste changes, nausea and vomiting, dizziness, insomnia, headache, flushing and decreased sexual appetite.

The severe lung problem that amiodarone can cause, that was mentioned above, is interstitial lung disease. In this condition, a dramatically decreased diffusion capacity of the lung is seen on testing – this means that the amount of oxygen transferred from the air in the lungs to the blood is greatly reduced. This can be a deadly condition.

Amiodarone increases the effect of blood thinner warfarin and another type of anti-arrhythmic agent digoxin. Amiodarone is absorbed extensively by the fat tissue in the body, hence remains in the body for a long time. The half-life of excretion of this medicine from the body is a couple of months on an average – that means only about 50 per cent of the medicine is excreted from the body in a couple of months, then in another couple of months about 50 per cent of the remaining amount is excreted, and so on.

Yes, there are all these adverse reactions and side-effects. Yet, amiodarone is very useful in several types of arrhythmia. It is considered a “broad-spectrum” antiarrhythmic, with several effects:

• It increases the time for the repolarization of the heart after each contraction.
• It increases the time period in which the heart muscle cells are electrically stimulated in its action potential.
• It decreases the speed with which the electrical impulses move through the heart’s electrical system.
• It reduces the speed of the generation of electrical activity in the pacemaker.
• It reduces the speed of electricity through accessory pathways.
• It dilates blood vessels, resulting in decrease in blood pressure – this effect is useful in congestive cardiac failure, in which there is a weakening of the heart muscle.

As always, the medical professionals seek to balance out the benefits and the adverse effects of the drug and use it to the patient’s best advantage.

Until next week, do take care of yourself and your health ….

Dr. Ajit Damodaran

Levothyroxine (Synthroid)

Hello friend!

I hope your year has started well. Time to look at another drug. Levothyroxine, marketed under brand names Synthroid and Levoxyl, is synthetically manufactured thyroxine (also called T4). T4 is the major hormone secreted by the thyroid gland.

The thyroid hormone is made in the body by the thyroid gland, which is located in the neck. What does the hormone do? What is its role in the body? It plays an important role in metabolism. It is a catalyst in oxidative reactions. The hormone increases oxygen and energy consumption of the body - it increases the basal metabolic rate (BMR)  – BMR is the minimal calorie requirement of the body in resting state. The higher the BMR, the higher the number of calories burnt. This has resulted in a misuse of Levothyroxine for weight loss. The thyroid hormone affects body growth, temperature, heart rate and the force of contraction of the heart.

To be more accurate, thyroid hormones (plural) are secreted by the thyroid gland. The significant thyroid hormones are thyroxine (T4) and triiodothyronine (T3). Iodine is an essential part of the synthesis of the thyroid hormones. Another hormone called thyroid stimulating hormone (TSH) is synthesized and secreted by the pituitary gland in the brain. TSH stimulates the thyroid gland to release T3 and T4. The release of TSH is controlled by negative feedback - the higher the levels of T3 and T4 in the blood, the lower the TSH levels. And, the lower the T3 and T4 levels, the higher the TSH levels. TSH levels can be easily measured in the laboratory, and because of the easy correlation with T3 and T4, TSH is important to diagnose hyperthyroidism or hypothyroidism.

Hypothyroidism is a result of insufficient production of thyroid hormone by the thyroid gland. About three to five per cent of the U.S. population suffer from this condition. There have been reports that as much as ten per cent of the population may be affected if the mildest forms of subclinical hypothyroidism is included. This has a larger implication, because hypothyroidism can result in higher levels of cholesterol in the body, that could result in cardiovascular problems.

Iodine deficiency in diet can cause hypothyroidism – this can be a problem worldwide, however it is not significant in the U.S. Hypothyroidism can also be caused by thyroiditis (inflammation of the thyroid gland). How does the thyroid gland get inflamed? There are many possible reasons  ….. but it typically comes down to this: the body’s immune system …… well, it goes a little crazy. The normal role of the immune system is to develop antibodies against and attack foreign cells like bacteria and viruses. In thyroiditis, the immune system develops antibodies against the cells of the thyroid gland and attacks the thyroid gland cells in a self-destructive, autoimmune type activity.

Hashimoto’s thyroiditis or chronic lymphocytic thyroiditis results from the T-cells of the immune system attacking the thyroid. Post-partum thyroiditis affects about 5% women within one year of giving birth – the symptoms presented are first hyperthyroidism, then it gets back to normal or in about 20 per cent of those affected, it moves further into life-long hypothyroidism. Some kinds of thyroiditis can be genetically acquired. In some individuals, drugs like amiodarone (for the heart) and the anti-viral interferon can attack the thyroid cells and cause thyroiditis.

Common symptoms of hypothyroidism include fatigue, drowsiness, weight gain, increased sensitivity to cold, muscle cramps, low pulse rate, depression and constipation.

Typically the first laboratory test to evaluate hypothyroidism is measuring TSH. The higher the TSH, the greater the hypothyroidism (i.e., the lower the levels of thyroid hormone). The normal range for adults is usually in the range of 0.3 to 5 mIU/L – there are some variations between laboratories where the test is done.

The medication usually prescribed for hypothyroidism is Levothyroxine. It is available in various strengths 25 micrograms to 200 micrograms. It is usually taken on an empty stomach a half hour to one hour before breakfast, with a full glass of water. Antacids that contain calcium, aluminum or magnesium, simethicone, calcium supplements, iron, cholestyramine, colestipol, sucralfate and sodium polystyrene sulfate bind to levothyroxine and reduce the absorption from the stomach into the bloodstream. Therefore none of these listed medications should be taken less than 4 hours from levothyroxine ingestion.

Rarely, there could be temporary hair loss in the first few months of starting levothyroxine. Otherwise, it is a well-tolerated drug. Side-effects often occur if the dosage taken is too high – in this case, symptoms of hyperthyroidism are seen. These include increased sweating, increased appetite and weight loss, fever, increased pulse rate – in extreme causes even leading to a heart attack, high blood pressure and seizures. Side-effects of overdosing with levothyroxine occur 6 hours to 11 days after ingestion.

Every few months, TSH levels are tested to make sure that the dosage of medication is correctly titrated.

With that ……. I hope you have a wonderful week; wish you good health!

Dr. Ajit Damodaran