I resolve …. to keep my resolutions!

Hello friend!

Happy New Year to you and yours! On this first day of 2009, we all look forward to great achievements this year.

Let’s think back to the first day of 2008. What were our resolutions? During the course of the year, how successful were we in keeping them? If not, why not? How much of it was due to circumstances beyond our control, and how much due to lack of effort on our part? How could we have done better in 2008? How can we do better in 2009? Time to unleash an age-old tool. When rightly used, habit is a powerful tool ….. simple to use – the key is to use it consistently over a period of time.

Before we go further, let’s tie this to health. Our resolutions could be something like losing excess weight or smoking cessation. Or, it could be controlling our anger. These resolutions are directly related to our health. In addition, when we succeed in keeping our resolutions, our nerves release endorphins and “beneficial” neurotransmitters. When we don’t keep our resolutions, we tend to beat ourselves up at some level, resulting in release of stress hormones like cortisol. This can result in increase of blood pressure, increase of blood sugar, and decreased immune response.

Every habit is regulated by neurochemical patterns. Let us consider the habit of anger. How is the habit formed? What do you do when you feel angry? Take an example. Your kid does something that angers you, like leaving the cap off the toothpaste. What do you do? Do you scream? Jam it back on, muttering under your breath? Realize your kid is still learning and shrug it off? Or anything better or worse or in between?

Let us suppose you screamed (no you didn’t, we are just saying so for the sake of this example). Why do you behave the way you do in this situation? One simple answer is that you are habituated to behaving in this way. Think of the sequence of events that your body’s nervous system goes through. You see the cap off the toothpaste, your optic center gets the information, and it communicates with other parts of your brain.

Let us consider the first time this happens. Where does this reaction come from? It could be from something you witnessed. For instance, perhaps you have seen someone else scream at an irritating circumstance, say an authority figure in your childhood, or your favorite actor in the movies. The reaction to this situation is already in your head. Even supposedly spontaneous actions are already in your head (As a Man Thinketh by James Allen, DeVorss & Company, Camarillo, CA).

During one of these episodes, what happens in your nervous system to cause this reaction? The optic center speaks to your “anger” center which tells you it is okay to get angry, and your vocal cords are given the signal to emit the sound called a “scream.” Now, you have established the sequence for release of certain neurotransmitters. You had the beginnings established in your thought itself, and the entire sequence had been established in your thought. All you needed was the stimulus, the irritating circumstance, and you responded with a scream.

This happens a second time. Now you have already established the path for the release of all the necessary neurotransmitters. You go ahead and use it. And it happens a third time, and a fourth …. and so on. You see how you establish habits?

Now, how do you break an undesirable habit? You stop using that established path, and create a new path of neurotransmitters. How long does it take? Dr. Maxwell Maltz, a plastic surgeon from New York, published his book Psycho-Cybernetics in 1960 – it is still a top seller today. Beginning with studies on subjects who had plastic surgery, he showed that it took 21 days for his patients to have a new self-image after the results of the surgical procedure was evident to others. Further research showed that it took 21 days for new neural pathways to form and for the patients to see themselves as new.

What does this mean? If you want to get rid of a bad habit, give yourself a 21-day challenge. Said Mark Twain, “Habit is habit and not to be flung out of the window by any man, but coaxed downstairs a step at a time.” Consider 21 days as 21 steps. Use will-power, change your environment, get rid of anything that would tempt you to indulge in your habit, trick yourself, announce your resolution to your family, friends or colleagues, make it a wager …. if you break your resolution, you pay someone a determined amount of money – use every arrow in your quiver to stack the odds in your favor. Make sure you succeed in avoiding the bad habit for 21 days.

21 days later, you may choose to go another 21 days, but don’t look at that possibility just yet. Take it 21 days at a time. Fool your brain into thinking, “It’s only 21 days – just 21 baby steps - you can handle it!” You can use the 21-day challenge to form a new desirable habit too. Same logic.

Speaking of forming new desirable neural pathways and obliterating undesirable ones, let’s do some possibility thinking. It’s been shown that the human brain has approximately 100 billion nerve cells. The total number of inter-connections these brain cells make with one another is a ginormous number. According to brain researcher Dr. Robert Ornstein of University of California, San Francisco, the number of possible inter-connections between nerve cells is more than the number of atoms in the universe. So, are we saying that there is no limit to forming good habits and getting rid of bad habits? That we can get better and better as individuals and as a society? Are we saying that the sky is the limit in maximizing one’s potential?

Let’s dig deeper into Dr. Ornstein’s research. Bilateral specialization of the brain is what he is best known for – the concept of the right brain and the left brain. The research he did with his colleague Dr. David Galin leads to an understanding of how the left brain is focused on logical, sequential tasks whereas the right brain is holistically, aesthetically driven. The left brain provides the facts or the “text” and the right brain reads the “context” in a situation (www.robertornstein.com). Their research also shows that during deep prayer or meditation, the electrical activity between the left and right brain becomes co-ordinated, making it easier to establish new neural pathways and thus, new habits.

I hope these ideas help you with keeping your New Year resolutions, and thus feeling good about yourself. I will be thinking good thoughts about you.

Until next week, my friend, please do take care of yourself and your health ……

Dr. Ajit Damodaran

Calmly active, actively calm

Dear friend,

Merry Christmas! May you and your loved ones be showered with blessings this wonderful day, and every day ….

It is the day to write a brief article today on a topic conducive to peace and goodwill. Peace and goodwill to one’s own self, which leads to peace and goodwill to all. And good health.

A healthy spiritual life is a significant factor in good health. The organized study of the relationship between spiritual faith and healing has even been given a name, the ‘epidemiology of religion’ (Dr. Jeff Levin, author of Essentials of Complementary and Alternative Medicine – co-authored with Dr. Wayne Jonas).

Prayer and a deeper connection to the universe result in a greater orderliness of brain functioning. This results in improved cardiovascular health and decreased risk of depression. This would obviously lead to greater longevity and an improved quality of life. Okay, even from a purely self-serving viewpoint, believing in God and prayer and meditation is good for health. Dr. Larry Dossey in his book Healing Words, and Dr. Bernie Siegel in his book Love, Medicine and Miracles present some excellent case studies on prayer and healing.

Dr. Herbert Benson, Professor of Medicine at Harvard Medical School Mind-Body Medical Institute says about meditation, “The relaxation response comprises an assortment of physiological changes: a decrease below resting levels in oxygen consumption, heart rate, breathing rate and muscle tension – plus a decrease in blood pressure in some people and a shift from normal waking brain patterns to a pattern in which slower brain waves predominate.”

When the mind is in a calm, undisturbed state, brain waves called alpha waves are registered on the electroencephalogram (EEG). In meditation, one can go into states more tranquil than the alpha state. When you develop a habit of regular prayer/meditation, you carry the effects of that into your active life. You find yourself in the “zone” as you go about your daily activities. This “calmly active, actively calm” (to quote Yogananda) state of mind and body essentially carries your deep prayer into your 24-hour routine.

That does not mean walking around like a zombie. It means being calmly in control of your emotions no matter what the situation. No unnecessary release of cortisol, adrenaline and other stress hormones. Nerves of steel, blood pressure totally under control, breathing calmly…. all conducive to good health. 

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

Dr. Ajit Damodaran

Antipsychotic Seroquel

Dear friend,

The mind …… what a vast ocean of knowledge, pun intended. The mind can be so, so complicated. Controlling one’s mind is probably the most difficult task in the world. I hear Tiger Woods has tremendous mind control and focus. I know that contributes to his being probably the best golfer in the world.

The mind …..posing some philosophical questions. Where does the mind begin? Where does it end? Is it limited to the brain? Does it extend to the body? Does it extend beyond the mind and body? What about consciousness? What is consciousness? Is that chemistry? Physics? Metaphysics? No, I won’t get into all that ….. these are answers each of us finds on our own.

Alright ….. pulling myself back down to earth …. from a totally practical perspective, there are so many stimuli that are fed to the mind. Each of us has such varied responses to the same stimuli, partly dependent on our conditioning from years past. Every one of us has varying degrees of activity of different neurotransmitters in our central and peripheral nervous systems ….. some of it balanced, others unbalanced. When, for whatever reason, there is an imbalance of neurotransmitters in the brain, a combination of wise psychiatric counsel and medication can improve the quality of life.

Quetiapine (pronounced kwe-tie-a-peen) is sold under the brand name Seroquel. It is the most commonly prescribed antipsychotic drug in America. Psychosis is “osis” of the “psyche” (Greek origin) – literally, abnormal condition of the mind. Seroquel was introduced in 1997 as a treatment for schizophrenia.

In schizophrenia (from Greek “schizein” = to split, “phren” = mind), there is increased activity of neurotransmitter dopamine in one of the major dopamine pathways in the brain called mesolimbic pathway. This pathway is involved with emotions of motivation and re-inforcement. The exact mechanism of action of Seroquel is not known, but it is proposed that its primary effect is from antagonism of a type of dopamine receptor D2 and a type of serotonin receptor 5-HT2.  Dopamine and serotonin are neurotransmitters. Dopamine is involved in motor activity, cognition, motivation and reward, sleep, mood, attention and learning. Serotonin modulates sleep, sexuality, anger, aggression, body temperature, mood and appetite.

In addition, Seroquel is metabolized to the active metabolite norquetiapine. In non-human subjects (primates), norquetiapine was shown to inhibit norepinephrine transporter (NET). First of all, what is norepinephrine? Norepinephrine, also called noradrenaline, is a relative of epinephrine or adrenaline. Norepinephrine is a neurotransmitter that plays a role in attention and focus as well as depression. In fight-flight-fright situations, norepinephrine is also released as a stress hormone, but that’s a different story.

NET, that was referred to above, is a protein that helps the reuptake of the neurotransmitter norepinephrine back into its pre-synaptic storage vesicles (for a detailed description of this kind of re-uptake process, please refer to last week’s article on sertraline).

When norquetiapine inhibits NET, it prevents the re-uptake of norepinephrine. This increases the levels of norepinephrine in specific areas of the brain, which contributes to the anti-depressant effect.

Seroquel is also used in the treatment of bipolar disorder. Bipolar disorder is characterized by depressive and manic phases. Seroquel is useful in the depressive episodes. It is used alone, or in combination with lithium or Depakote (divalproex). The combination therapy is useful because lithium and Depakote are particularly useful in stabilizing mood in the manic phases of bipolar disorder.

Off-label uses of Seroquel include Tourette’s syndrome (a tic disorder characterized by involuntary movements and verbal utterances), autism, alcoholism, restless legs syndrome, obsessive-compulsive disorder and post-traumatic stress disorder (PTSD). Speaking of PTSD, check out http://dayofthedoc.blogspot.com – well-written scientific blog on November 11, 2008 (Veteran’s Day).

Seroquel has also been used as a sedative for sleep and anxiety disorders. Antagonism of the histamine H1 receptor has been proposed for the sedative effect of the drug. Yes, histamine is another neurotransmitter.

Sedation is a side-effect of Seroquel when it is not used for that purpose. Orthostatic hypotension (drop in blood pressure when you suddenly stand) is another side-effect mediated by antagonism of adrenergic alpha1 receptors. Weight gain can be a significant side-effect. There have been claims that the use of this medication can lead to diabetes. Tardive dyskinesia – uncontrollable movements of the face, tongue or other parts of the body – is a possible side-effect. Rarely, use of the drug can lead to neuroleptic malignant syndrome. This is characterized by muscle rigidity, fever, unstable blood pressure and delirium possibly leading to coma. The enzyme creatine phosphokinase (CPK) levels are raised due to high muscle activity – this enzyme is a product of muscle breakdown. If this happens, the drug is to be stopped immediately and supportive treatment given – circulatory and ventilatory, sometimes in intensive care.

Seroquel has addiction potential. “Suzie-Q” is its street name. It’s also been called “quell”. It has been snorted, injected intravenously sometimes with cocaine, and used as a “downer” to come off cocaine or amphetamine.

Let’s make a transition from the streets of society to the corridors of power in the world. Is it possible that some of the villainous leaders of history could have been psychotic? Hmmm …. could antipsychotic drugs have prevented some genocides? Who knows? Just some food for thought.

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

Dr. Ajit Damodaran

Nerve cell talk – sertraline (Zoloft)

Dear friend,

 

I’m sure you had an awesome Thanksgiving. I’m sure there was plenty of food intake. Felt really sleepy after that dinner? The turkey ….. all that tryptophan …… really? That part about the tryptophan …. a little exaggeration ….. did you know that chicken has about the same amount of tryptophan as turkey?

 

So how about the popular idea that turkey has high amounts of the amino acid tryptophan and that’s what has the soporific effect? Actually, you feel sleepy because of all the carbohydrate you ingest. What’s the mechanism? When the carbohydrates are absorbed into the blood, insulin is released. One of the effects of insulin is absorption of amino acids circulating in the blood. The amino acids that are favored in this absorption by cells are not tryptophan – which means there is a higher percentage of tryptophan left in the blood.

 

Part of the tryptophan remaining in the blood is absorbed into the brain. In the brain stem, the tryptophan is converted into a neurotransmitter called serotonin. This is a natural calming, even sedating nerve chemical. In another part of the brain, in a pea-sized organ called the pineal gland, some of the serotonin is converted into a hormone called melatonin. Melatonin is the hormone that is released by the pineal gland in response to darkness and induces sleep – it plays a role in the body’s daily circadian rhythm or biological cycle. That’s the reason for the zzzzzs.

 

Speaking of the neurotransmitter serotonin (chemical name 5-hydroxy tryptamine), it is a neurotransmitter that plays a major role in our feelings and emotions. Serotonin modulates sleep, mood, appetite, sexuality, anger, anxiety and depression. Which means that its biological formation, metabolic and transportation pathways in the body offer ways to manipulate the levels of serotonin in the brain and body, and produce beneficial therapeutic effects.

 

Research has produced several families of drugs to increase serotonin levels and thereby provide a remedy for depression. One of the most effective classes of drugs is called SSRIs (selective serotonin re-uptake inhibitors). What do they do? They prevent the reuptake of already biosynthesized serotonin into the pre-synaptic cells of the nerves. Wait a minute. What’s pre-synaptic?

 

Backing up …… Let’s define “synapse”. Synapses are junctions between nerve cells, or between nerve cells and other body cells. There are hundreds of trillions of nerve cells in the human brain. One nerve cell “talks” to other cells across these junctions. How? The “initiating” nerve cell is called the pre-synaptic cell. In the pre-synapse, docked to the membrane, there are microscopic “bags” called synaptic vesicles that store neurotransmitters. So, how exactly is the message sent across. Associated with every thought, every emotion, there is an electrical current that moves across the pre-synaptic nerve cell. The current reaches the synapse, electrically stimulates the synaptic vesicles and opens up channels in the vesicles to let calcium ions come in. These calcium ions activate certain calcium-sensitive proteins to cause the vesicles release neurotransmitters contained within them. The neurotransmitters travel across the synaptic cleft, the narrow space between the pre-synaptic and post-synaptic cells, and bind to receptor cells on the post-synaptic cells. This results in the activation of the receptor cells, following which there is an appropriate action from the post-synaptic cell. What action is that? It could be a transmission of the same message onward to other nerve cells through the similar processes. Or, let’s say the post-synaptic cell is a muscle cell – the appropriate action could be muscle movement, in combination with a whole bunch of other muscle cells.

 

Now, all the neurotransmitter molecules released by the pre-synaptic cell does not bind to the post-synaptic cell. Some of the molecules just diffuse in the synaptic cleft. Some of these diffused molecules are metabolized by enzymes to metabolites. And some of the diffused molecules are re-absorbed by the pre-synaptic cell.

 

This last process, the re-absorption …… re-uptake …… is the process that is of interest to us. A selective serotonin re-uptake inhibitor (SSRI) selectively prevents the re-uptake of serotonin by the pre-synaptic cells.

 

Sertraline (trade name Zoloft in the U.S., Lustral in the U.K., Zosert in India) is the most prescribed anti-depressant in the U.S. It is an SSRI used for treatment of major depression, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD) and social anxiety disorder (SAD). Unlabeled and investigational indications are eating disorders, generalized anxiety disorder (GAD), impulse control disorders, and treatment of mild dementia-associated agitation in non-psychotic patients.

 

Black-box warnings are required to given with anti-depressants. They can increase the risk of suicidal thinking in patients upto 24 years of age. Sertraline is not approved for use in major depressive disorder (MDD) in children, but is approved for treatment of OCD in children 6 years of age and above. It is not approved for treatment of bipolar depression.

 

This medicine should not be taken with other medicines called monoamine oxidase inhibitors (MAOI) - in fact, not even within 14 days of taking an MAOI. Why not? It leads to something called serotonin syndrome. What is that? MAOIs as well as several other drugs decrease the breakdown of serotonin, resulting in high concentrations of serotonin in the brain. Serotonin syndrome creates symptoms such as confusion, hallucinations, fever, high blood pressure, tremors and muscle twitching.

 

Possible side-effects include headache, nausea, dry mouth, upset stomach, decreased interest in sex or decreased sexual ability.

 

If sertraline administration is suddenly stopped, withdrawal symptoms include emotional instability, dizziness, headache and bad dreams. In pregnant women, the drug does cross the placenta and reach the child. Sertraline is also secreted in breast-milk.

 

A theory suggests that depression and other psychiatric complaints are a result of an imbalance of brain chemistry, popularly called chemical imbalance. Critics of this theory state that it is largely promoted by pharmaceutical companies so that they can sell more medication. Whatever be the case, there are situations where depression is effectively treated by using anti-depressants like sertraline, resulting in improvement in the quality of life. It is upto the medical professionals treating the patient to determine whether the depression can be treated by psychological counseling and change of lifestyle including setting and working toward goals in various aspects of life, or whether the condition requires drug therapy.

 

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

 

Dr. Ajit Damodaran

 

 

Happy Thanksgiving!

Hello friend,

I wish you a wonderful Thanksgiving with your family and friends.

See you next week, stay well!

Dr. Ajit Damodaran

Advair – for asthma and COPD

Hello friend!

Greetings! Let’s talk about breath. Can you think of anything more important to life than breath? What if you find it difficult to breathe? That’s what happens with conditions like asthma and chronic obstructive pulmonary disease (COPD). 

Advair is the brand name of an inhaler combination of two drugs, fluticasone (a steroid derivative – a very mild dose, don’t worry) and salmeterol (a beta-2 agonist), used for control of asthma, COPD and chronic bronchitis. It is available all over the world under different brand names – for example, it is available as Seretide in the United Kingdom, and as ForAir in India.

What is asthma? It is a chronic disease of the respiratory system. It’s when the immune system of the body becomes overprotective. It starts looking at simple things like dust and pollen as the enemy (remember the movie Conspiracy Theory starring Mel Gibson? – our body starts behaving like Mel Gibson’s character). The airways get constricted, and there is release of mucus along with inflammation. As a result, there is difficulty breathing, and in acute episodes, wheezing, shortness of breath and cough.

The mechanism of constriction of the airways in the lungs is blockage of the beta-2-adrenergic receptors of the smooth muscle by an immune system component, Immunoglobulin E.  This is accompanied by inflammation. Until recently, the main theory advanced has been that immune cells called helper T cells were the main culprits creating the inflammation response.

Recently, a couple of Boston researchers advanced another theory – the main players may not be helper T cells, but natural killer T cells (http://www.news.harvard.edu/gazette/2006/03.16/01-asthma.html). Natural killer T cells are also immune system cells. Of course, a lot more research has to be done before establishing in detail the role of natural killer T cells. There is a possibility that this discovery may be the beginning of even more advances in the medicinal treatment of asthma.

Genetic and environmental factors are involved. Children seem to suffer from asthma more in developed countries. A hypothesis that has been suggested is that due to increased hygiene and aggressive use of antibiotics in children, certain beneficial bacteria in the gastro-intestinal tract of children are wiped out. This modifies the immune system, resulting in asthma. Emotional stress can also cause asthma, the suggested mechanism involving the immune system. Environmental factors such as automobile and industrial pollution, cigarette smoke and extensive exposure to cold air act as triggers to evoke an asthma attack, especially when there is a predisposition due to genetics or a compromised immune response.

The practice of yoga has been reported to reduce asthma. A journal report (Thorax 2002 Feb;57(2):110-5) -Sahaja yoga in the management of moderate to severe asthma: a randomised controlled trial, by Manocha et al from the Natural Therapies Unit, Royal Hospital for Women, NSW, Australia draws the following conclusion: “This randomised controlled trial has shown that the practice of Sahaja yoga does have limited beneficial effects on some objective and subjective measures of the impact of asthma. Further work is required to understand the mechanism underlying the observed effects and to establish whether elements of this intervention may be clinically valuable in patients with severe asthma”. Yoga is known to reduce stress. Since it is known that stress is a contributor to asthma, could the reduction in stress be one of the mechanisms by which yoga controls asthma?

COPD. Very similar to asthma, except that the constriction of the airways is not easily reversible, and progressively gets worse with age. With time, the lung tissue gets destroyed and causes emphysema. The cause of COPD is partly genetic, coupled with cigarette smoke, pollution, occupational air hazards, frequent lung infection and a diet that includes a lot of cured meat. Even a history of cigarette smoking that leads to long-term inflammation in the lungs can spark an auto-immune response leading to COPD, many years after cessation of the smoking habit. In later stages, COPD can lead to pulmonary high blood pressure and cor pulmonale (right ventricular dilation and hypertrophy in the heart).

Fluticasone, the steroid component of Advair, reduces inflammation in the airways. In the inhaled form, it is directly delivered to the lungs where the inflammation has occurred, and is not significantly delivered to the rest of the body, resulting in fewer steroid side-effects.

Salmeterol is a long-acting beta-2 agonist or LABA. It acts on the beta-2 adrenergic receptor, thus relaxing the muscles around the airways to prevent wheezing and shortness of breath.

For the long-term treatment of asthma and COPD, Advair is inhaled by mouth twice daily.

Advair is not to be used for acute symptoms of asthma or COPD. For these, your doctor will have prescribed a short-acting beta-2 agonist. Also, do not use Advair if you have a severe allergy to milk proteins. This medication has not been approved for use during pregnancy or while breast-feeding.

Common side-effects are upper respiratory infections, thrush in the mouth and throat, headache, hoarseness and voice changes, bronchitis, cough and nausea/vomiting. In children with asthma, Advair may cause infections in the ear, nose and throat. Make sure you rinse your mouth with water after each dose, and spit the water out.

Now for some controversy. Salpeter at al at the Santa Clara Valley Medical Center published an article in 2006 (“Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths” Ann Intern Med 144 (12): 904–12). The authors say in a press release: “These agents can improve symptoms through bronchodilation at the same time as increasing underlying inflammation and bronchial hyper-responsiveness, thus worsening asthma control without any warning of increased symptoms. Three common asthma inhalers containing the drugs salmeterol or formoterol may be causing four out of five US asthma-related deaths per year and should be taken off the market”. Essentially, they are saying that symptoms are the body’s way of asking for help. When we mask the symptoms, the disease continues to worsen, but the lack of symptoms prevent us from realizing it – and that can and has lead to death.

Here’s a response to the above opinion: “Salpeter and colleagues … assert that salmeterol may be responsible for 4000 of the 5000 asthma-related deaths that occur in the United States annually. However, when salmeterol was introduced in 1994, more than 5000 asthma-related deaths occurred per year. Since the peak of asthma deaths in 1996, salmeterol sales have increased about 5-fold, while overall asthma mortality rates have decreased by about 25%, despite a continued increase in asthma diagnoses. In fact, according to the most recent data from the National Center for Health Statistics, U.S. asthma mortality rates peaked in 1996 (with 5667 deaths) and have decreased steadily since. The last available data, from 2004, indicate that 3780 deaths occurred. Thus, the suggestion that a vast majority of asthma deaths could be attributable to LABA use is inconsistent with the facts.” – Harold Nelson and Paul Dorinsky, 2006, Annals of Internal Medicine, 145 (9), 706.

Dr. Salpeter’s response to the above letter: “It is true that the asthma death rate increased after salmeterol was introduced, then peaked and is now starting to decline despite continued use of the long-acting beta-agonists. This trend in death rates can best be explained by examining the ratio of beta-agonist use to inhaled corticosteroids… In the recent past, inhaled corticosteroid use has increased steadily while long-acting beta-agonist use has begun to stabilize and short-acting beta-agonist use has declined… Using this estimate, we can imagine that if long-acting beta-agonists were withdrawn from the market while maintaining high inhaled corticosteroid use, the death rate in the United States could be reduced significantly …” 2006, Annals of Internal Medicine, 145 (9), 708-710.

As a result of published research, beginning 2005, the Advair label has a warning that the drug might increase the chance of asthma attacks that can result in death.

Here’s the bottom line. The benefits of using Advair far outweigh the risk, even of death. The incidence of death is about one in a 1000. On the other hand, the use of Advair improves the quality of life, and saves lives by allowing patients to breathe better and longer.

Until next week, breathe deeply. Live well. Please take care of yourself and your health.

Dr. Ajit Damodaran

Drinking water

Hello friend,

I’m writing this on Veteran’s Day, November 11 – over the decades, our veterans have sacrificed much to protect our way of life. If you are a veteran, thank you, thank you! And if you’re not, just as I’m not, please make sure you thank at least one veteran today.

Thus far, I’ve been writing articles on drugs. How about water? Kind of important for health, isn’t it? Well, in 2004, about half of the world’s population had no access to safe drinking water. One of the Millennium Development Goals of the United Nations, in collaboration with several international organizations including the Rotary Club, is to halve, by 2015, the proportion of people without sustainable access to safe drinking water and basic sanitation. So, we’re hoping that by 2015, about 75% of the world will have access to safe drinking water.

What kind of water is good for drinking? The Environmental Protection Agency (EPA) of the U.S. has a list of contaminants – these are microorganisms, different kinds of chemicals and radioactive contaminants – that have been assigned maximum contaminant levels (MCL) which are enforced by law, and maximum contaminant level goals (MCLG) which are not enforced by law. The MCLG is that level below which there is no known or expected risk to health. What’s the difference between MCL and MCLG again? Let’s take an example. The MCLG for coliform bacteria including fecal coliform and E. coli (which is a measure of fecal contamination) is 0 per cent. The MCL is 5 per cent. How is that percentage arrived at? More than 5.0% samples total coliform-positive in a month. (For water systems that collect fewer than 40 routine samples per month, no more than one sample can be total coliform-positive per month.) Every sample that has total coliform must be analyzed for either fecal coliforms or E. coli. If there are two consecutive total coliform-positive samples, and one is also positive for E.coli fecal coliforms, that water has an MCL violation.

In plain English, the ideal situation is there should be never any contamination. Zero. However, for practical purposes, there can be a very slight contamination, as explained above. For more details, please read www.epa.gov/safewater/contaminants/index.html. To find out the quality of drinking water where you live (in the U.S.), please contact your local government to send you a Consumer Confidence Report (CCR) – they should be automatically sending it to you once a year. You can also check the EPA website at www.epa.safewater/ccr/whereyoulive.html to get the same information. You may be surprised to know that many a time, the contaminant levels exceed the MCLs.

There have been recent press reports about traces of medicine that we consume are being found in drinking water supply. An MSNBC.com report in September 2008 is titled Drugs in water affect 46 million in U.S.  The article goes on to say “The drug residues detected in water supplies are generally flushed into sewers and waterways through human excretion. Many of the pharmaceuticals are known to slip through sewage and drinking water treatment plants.” Disgusting? You bet. But America still has better water supply than most places in the world.

What’s the solution to the problem? As far as water for drinking, we make sure that it is filtered. Get one of the top filters recommended by www.consumerreports.org (pay attention specifically to what contaminants are filtered by your filter of choice and what contaminants you have in your water supply) and if you’d like, boil the water as a second step. As far as water for other purposes at home, the contamination is not significant. However, if you’d rather, there are filters available to purify the entire water supply into your home.

Bottled water? As we live our present lifestyle as movers and shakers (yup, talkin’ about you), we consume bottled water. The U.S. alone consumed more than 9,000 million gallons of bottled water in 2007, double that in the year 2000 (in excess of 4,500 million gallons that year).

Guess what? Bottled water is less regulated than tap water. It is regulated by the Food and Drug Administration which requires that bottled water be as safe as tap water. However, whereas the EPA requires that government-certified labs test tap water daily, the FDA requires only once-a-year testing. The EPA has set controls on bacteria, the FDA has not. Need more such facts? Go to www.nrdc.org/water/drinking/bw/exesum.asp (that’s the website of Natural Resources Defense Council).

With all this information, what bottled water should we drink? The website www.bottledwater.org/public/statistics_main.htm provides you that info – that’s the website of the International Bottled Water Association (IBWA). Any member of that association provides you with bottled water with contaminants, if any, below FDA standards. I got this information and some more above from the book The Seven Pillars of Health, by Dr. Don Colbert, MD (published by Siloam).

How much water should we drink? A rule of thumb does say eight 8-ounce glasses of water a day. Or, total water intake in ounces should be half of our body weight in pounds (that includes the water we get from fruit and vegetables – if we are getting the right number of portions, that would be about a quart of water – so, considering an average body weight, the actual amount of water we should drink would probably be about eight 8 ounce glasses of water a day). But of course, it does vary with body weight, the climate, active or sedentary lifestyle and so on. Another suggestion that has been offered is to drink enough water where you urinate every three to five hours, and the urine is colorless to light yellow. This much we do know, generally we tend to drink a lot less of water than we should. I do need to let you know, any major change in your water intake or dietary habits must be undertaken only in consultation with your physician.

Drinking water does mean drinking water – not coffee, tea, caffeinated drinks and so on. Caffeine is a diuretic, commonly called a fluid medication – it makes the body get rid of more water through urine than the volume consumed.

Why is drinking enough water important? Here are several reasons why. Our body is primarily aqueous. The brain and the muscles are 75 per cent water, the bones are 22 per cent. Water carries oxygen and nutrients to every cell of the body. Blood is an aqueous medium of blood constituents. Water also gets rid of waste from the body. It cushions joints and protects vital organs. It’s great for skin health too.

What if you don’t drink enough water? Dehydration. Headaches, low blood pressure, dizziness, fainting, muscle cramps …. in extreme cases, delirium, unconsciousness, leading to death. About age 50 onward, we don’t feel as thirsty as we used to when the body loses water. With the result that there’s increased possibility of dehydration. When senior citizens have pneumonia, if it is accompanied by dehydration, there is a theory that the body is not able to create enough fluid to get rid of microorganisms in the phlegm. Nursing homes and caregivers to senior citizens do have to keep this in mind and make sure that their wards get adequate water, with the understanding that they have diminished thirst sensation and may not always ask for water.

Even if we don’t have symptoms of dehydration, being mildly dehydrated is also not ideal for health. We do have to make sure we drink enough water to be healthy. Just a visual, if it helps – with enough water, we look like healthy grapes, without enough water we look like shriveled, dry raisins – or prunes. Oooh – graphic, huh?

Improving health, comfort and appearance by drinking pure water? Perfect! That’s just the beginning, of course. The foods we eat, the lifestyle we lead and even the thoughts we think, the emotions we feel …. over time, all have effects on the water-holding capacity of the plasma proteins and subsequently the ability of plasma to nourish different tissues and organs – Dr. R.D. Kulkarni, MD, my research adviser when I did my Masters’ Degree in Pharmacy at the University of Mumbai, India, explains these concepts in his book Principles of Pharmacology in Ayurved, (Ayurved, literally the science of life in Sanskrit, is the traditional system of medicine in India). Dr. Kulkarni is a doctor of modern medicine, formerly Post-Doctoral Fellow in Medicine at the Johns Hopkins Hospital in Baltimore, Professor of Pharmacology retired from the University of Mumbai, who used his logical powers of modern pharmacology to evaluate the ancient medicinal tradition of India.

Take care of yourself and your health. We’ll meet again next week!

Dr. Ajit Damodaran

The Flu Vaccine – Saving Lives

Hello friend!

Smallpox was eradicated in 1979. Polio is almost eradicated, thanks to the WHO, the UNICEF and the Rotary Club. How was this accomplished? Answer in one word – vaccination.

So anytime you hear anyone speak passionately against vaccination, remember smallpox and polio. If it were not for vaccination, a lot more people would be paralyzed or ….. dead. Historically, vaccination originated in China and India a couple of millenniums (would that be “millennia”?) ago.

How does vaccination work?

Let’s consider influenza or the flu. It is caused by a virus. The virus attacks the body and causes flu symptoms. How? It latches on to membrane cells of the nose, throat and lungs, and uses up the cell constituents to grow and reproduce, killing the host cells in the process. This causes runny nose, coughing, sneezing, headache, fever – all the flu symptoms are caused by the body trying to get rid of the waste cells and the virus. If someone already has asthma or emphysema, the symptoms obviously get worse. In the weak or the elderly, flu can lead to death. Yes, there are about 36,000 deaths every year due to the flu and associated infections and causes, in the U.S. alone.

When the virus attacks the body, the body’s immune system rises to the occasion and fights the virus. It creates antibodies against the virus. However, the virus creates the symptoms of the disease too. If the virus is killed and then injected intramuscularly as a flu vaccine, it creates the same antibody response without evoking the symptoms of flu. The vaccine can also be given intranasally – it’s available under the brand name FluMist. It contains attenuated or weakened live flu virus (LAIV = Live Attenuated Influenza Vaccine). Although the viruses are live, they cannot give you the flu, although they can give you mild symptoms like runny nose, nasal congestion, headache, sore throat and chills. The viruses are cold-adapted, meaning they can cause mild infection only in the cool temperatures of the nose, not the warmer temperatures of the lungs. The intranasal vaccine is given only to healthy individuals between 2 and 49 years of age, who are not pregnant.

How effective is the flu vaccine? The flu virus strains keep on changing genetically by a couple of mechanisms. So the vaccine that is developed this year is 70 to 90% effective in healthy individuals, and less so in unhealthy and elderly individuals, but will be less effective next year. So the vaccine has to be reformulated next year, and every year to keep up with the genetic changes, that scientists try to predict to the best of their ability. Typically, the flu vaccine is tri-valent. It is effective against the 2 strains of influenza A viruses and one strain of influenza B virus likely to be the most dominant that year. There is approximately a six-month lag time between the time the prediction is made and the flu vaccine is available. The process is co-ordinated by the World Health Organization.

Even though the trivalent vaccine is created to be specifically effective against 3 strains of influenza virus, it is also partially effective against related strains of the viruses genetically close to the three. Also, an indirect advantage of getting vaccinated is to reduce the chances of being a carrier of the virus to elderly or unhealthy kith and kin, and to the community in general. This is the reason why health care professionals are encouraged to get flu vaccination annually.

Research in the field of genetics continues to make the vaccine more effective over time. Kudos to my friends doing that research.

Possible side effects of the flu vaccine are headache, mild fever, discomfort at the site of injection, and muscle ache. They shouldn’t last long. Please contact your doctor if they do. Rarely, the body responds rather intensely to the viral antigen, resulting in the Guillain-Barre syndrome – it’s an auto-immune reaction of the body, resulting in paralysis in the lower limbs spreading to the upper limbs. If this happens, immediate treatment with intravenous immunoglobulins and plasma filtration is required.

The vaccine is manufactured in chicken eggs. If you are allergic to eggs, please be aware that you might be allergic to the i.m. vaccine too.

A controversy that has received press is the long-term effect of a preservative called thimerosal, an organo-mercury compound that is used in flu vaccine. There have been questions as to whether thimerosal causes autism in children. The Institute of Medicine panel of 2004 could not find any evidence of the same. However, the American Academy of Pediatrics (AAP) decided to err on the side of safety and continue not using thimerosal in vaccines for children. In fact, in 1999 the AAP and the Centers for Disease Control (CDC) recommended the phasing out of thimerosal from vaccines for children, and that has been done for most vaccines.

As we understand the positives and negatives of this precautionary measure against the flu, the positives overwhelmingly trump the negatives. Personally, methinks the greatest positive is that, even if we are healty enough not to get the flu, getting the flu-shot reduces the chances of our carrying the virus to folks less healthy than us. What price can we put on that? And if there is ever a time that our body defenses are down, be it due to physical or emotional factors, does it not make more sense to have beefed up the body’s defenses?

Is health not better than disease? And for 36,000 people each year, is life not better than death? This year, you could be saving the life of someone you love.

Please go get the flu shot. The earliest you can get it in North America is in September. But you can get the flu shot in later months too. Typically flu season peaks around January or later, although it can hit as early as October too. For some reason, it happens during the cold season.

Please take care of yourself and your health.

Dr. Ajit Damodaran

Warfarin – blood thinner

Hello friend,

Thank you for reading. I am really enjoying writing my weekly blog. As I write, and as I receive responses to my writing, my understanding of the basics of pharmacology of each medication is strengthened. Win-win situation, eh?

This week, I’ll be writing on rat poison and blood thinner. What a combination!

Warfarin was first synthesized in the laboratories of the University of Wisconsin at Madison. The Wisconsin Alumni Research Foundation (WARF) funded the research – hence the name warfarin, derived from WARF. It was originally introduced as a rodent killer in the late 1940s. Because of the blood thinning properties of warfarin, it caused hemorrhage in rodents leading to death. In the 1950s, the therapeutic anticoagulant activities of this compound in humans were discovered and begun to be used. Warfarin prevents thrombosis and embolism.

What is thrombosis? It’s a blood clot that prevents the regular flow of blood. How does that happen? Suppose there is an injury to a blood vessel. The natural defenses of the body come into play. The platelets in the blood and fibrin combine to form a clot so as to prevent blood loss. Of course, there can be degrees of clot formation. What if the body gets into high gear and forms a really big clot? Could it be so large that it blocks much of the diameter of the blood vessel? What if it breaks free and travels through the blood stream and lodges itself into another part of the blood stream? (this is called an embolism). And, why would such a large clot be formed? It could be an infection or an injury in a blood vessel, genetic or auto-immune reasons that make the body over-react to such stimulus, it could be that the blood is moving slowly, say when you sit in a confined space for a long period of time without much movement, or it could be a combination of these factors.

A couple of the more devastating effects of thrombosis/embolism is a heart attack or a stroke. How do we prevent it? That’s where warfarin helps.

Warfarin is the generic name of the drug. It is marketed in the generic form, as well as under the brand names Coumadin and Jantoven. It is used to treat or prevent blood clots in the veins (venous thrombosis) or lungs (pulmonary embolism) or following heart valve replacement, to name a few conditions.

What is the mechanism of action? It inhibits an enzyme called vitamin K epoxide reductase. This is an enzyme that plays a significant role in activating certain clotting factors in the blood. Warfarin is called a vitamin K antagonist.

When warfarin is used as a drug, it is very important to regularly monitor its effects and adjust the dose accordingly. This is done by measuring INR (international normalized ratio), a blood test that measures the clotting efficacy of the blood. Genetics plays a role in the response of the individual to warfarin. Also, warfarin interacts with other drugs like antibiotics and thyroid medication,  as well as with some kinds of food, especially those with high vitamin K, like spinach, kale and collards. It interacts with herbs like ginseng, St. John’s wort, gingko biloba as also garlic and ginger.

The primary side-effect is excessive bleeding and bruising. When the INR rises, there could be bleeding from the gums, in the stools or bleeding from the nose. It’s important to avoid engaging in sports and other activities that might cause injury and bleeding, and to be gentle while brushing one’s teeth and shaving.

A less common but severe complication can occur especially when initiating warfarin treatment. A natural anti-coagulant factor that occurs in the body is protein C. Warfarin reduces the levels of protein C faster than it reduces the coagulant factors. In individuals that have a genetic problem with originally lower levels of protein C, the sudden reduction of protein C causes a paradoxical coagulation, resulting in massive thrombosis – this can lead to skin necrosis (literally skin death) and gangrene. To avoid this, another anticoagulant heparin can be given intravenously along with the beginning of warfarin therapy.

There have been some reports of increased osteoporosis-related fracture in patients on warfarin therapy. This could be due to reduction in bone minerals or vitamin K deficiency from long-term use of warfarin.

Rarely, there can be severe pain and darkening of toes, typically the big toe, to the point of what’s been called the purple toe syndrome. This is due to cholesterol particles breaking loose from atherosclerotic plaque and migrating (cholesterol embolism) to the blood vessels of the feet.

Despite the side-effects and the need for regular monitoring, warfarin is a very useful drug. If someone has had a heart attack, it is used to reduce the risk of stroke and further heart problems.

I hope the information was useful. Until next week, please take care of yourself and your health …..

Dr. Ajit Damodaran

Lisinopril – for blood pressure

Hello, my friend,

In South America, there is a venomous pit viper called jararaca. Medicine from a snake? Absolutely!

In 1970, experiments were published about a peptide (a small protein) called bradykinin potentiating factor (BPF) derived in Brazil from the venom of the snake Bothrops jararaca (that’s the scientific name). BPF inhibits an enzyme found in our body called angiotensin converting enzyme (ACE). When ACE is inhibited, there is a reduction in blood pressure.

In the mid-1970s, a drug called captopril was synthesized from BPF. That was the first medication for high blood pressure in the class ACE inhibitors.

What is blood pressure (BP)? Why is it important? BP is the force that’s created against the walls of arteries as blood is transported through the body. Too much pressure can damage the arterial walls. When you take BP, it appears as two numbers. The higher number is the systolic pressure, which is the measure of the pressure when the heart pumps blood into the arteries. The lower number is the diastolic pressure, the pressure when the heart rests between beats. For an adult, the normal blood pressure is 120/80 or less. With an excited emotional state or activity, BP does rise temporarily, but it comes back to resting state.

When the BP stays consistently high, the condition is called hypertension. Over a period of time, that can lead to heart problems, kidney problems, damage of the retina in the eye, or stroke. As BP increases slowly with time, we don’t feel any symptoms. The first symptom could be death. This is why hypertension has been called the silent killer. Routine visits to the doctor now become even more important, don’t they? Catch it early, and control it.

Essential hypertension is when there appears to be no root cause – however, there are risk factors – men  are more likely to have it than women, and blacks more than whites in America. More salt in the diet, not enough potassium, calcium or magnesium in the diet, stress, obesity, diabetes, chronic uncontrolled alcohol intake, and lack of physical activity are all risk factors.

Secondary hypertension is when it is because of another condition, often kidney disease.

One of the primary mechanisms by which our body controls blood pressure is a physiological process called the renin angiotensin system. How does that work?

Certain kidney cells produce and store an enzyme called renin. This enzyme is released when there is a fall in blood pressure, or reduced sodium levels in the blood, when we are faced with a fight-flight-fright situation that activates our sympathetic nervous system, or the kidney is exposed to hormone-like substances called prostaglandins or medicinal drugs called beta-agonists.

Renin acts on a substance produced by the liver, called angiotensinogen, which circulates in the blood. The product is a peptide called angiotensin I. An enzyme called angiotensin converting enzyme (ACE) cleaves angiotensin I to produce the peptide hormone angiotensin II. Most of this last reaction happens in the capillaries of our lungs.

Angiotensin II (AII) is a very powerful agent to increase blood pressure. It does so by constricting blood vessels, and by activating the adrenal gland to release aldosterone. Aldosterone causes the kidney to reabsorb more sodium and water as a result of which there is increase in the volume of blood. This causes an increase in blood pressure. AII increases BP by a couple more mechanisms. It causes the medulla to increase cardiac output, and stimulates the hypothalamus to increase our thirst and to stimulate antidiuretic hormone (ADH) which gets the kidney to reabsorb even more water. As a result of these two mechanisms, our blood volume increases even more, causing an increase in BP.

It stands to reason that by controlling the effects of angiotensin II, we can decrease blood pressure, doesn’t it? What if we were to inhibit the enzyme that catalyzes the conversion of angiotensin I to angiotensin II? That would result in less production of AII.

That’s exactly what an ACE inhibitor does. An ACE inhibitor is a competitive inhibitor of ACE. Being structurally similar to angiotensin I, the ACE inhibitor links to ACE molecules, not leaving enough ACE to act on Angiotensin I. This means less Angiotensin II is formed.

As we saw earlier, captopril was the first in this class of anti-hypertensive drugs. The second drug was enalapril. The third, that was introduced in the early 1990s, was lisinopril (brand names in the U.S. are Prinivil and Zestril).

Lisinopril is different from other ACE inhibitors in that it does not have to be converted by the liver into another entity to activate it. It is water-soluble, penetrates body tissue very well, stays in the body for a long time (as a result, it can be given as a once-daily dose) and is excreted unchanged in the urine. Lisinopril can be used with other medicine to treat congestive heart disease or to improve survival in patients after a heart attack.

This medicine may cause dizziness or even fainting when you first start using it. Make sure you don’t drive or use any heavy machinery before you know how your body reacts to this medicine. Inform your doctor immediately if you have difficulty breathing, tightness in the chest, or swelling of face or lips, or rash/hives. Also tell your doctor immediately if you have unusual heartbeat, nausea or diarrhea, change in amount of urine, unusual joint pain or muscle pain. Drink plenty of water if engaging in activities that cause perspiration. Rarely, it can lower your resistance to infection – avoid close contact with people who have colds or other infections. If you take anti-diabetic medications, lisinopril may affect your blood sugar – please do monitor your blood sugar carefully. This drug should not be used by pregnant women. It’s unknown if it’s secreted in breast milk. It’s better not to take it while breast-feeding.

Cough is a fairly common side-effect with lisinopril and other ACE inhibitors. If it gets bothersome, tell your doctor.

Control of high blood pressure is very important to prevent heart, brain, eye, kidney and other problems as we grow older. When there is a slight consistent increase in blood pressure, your doctor will probably ask you to enforce lifestyle changes – like getting regular exercise, dietary changes like more plant-based food, less sodium, enough potassium (typically at least 3,500 mg. per day) less fat, reduction in calorie intake, controlling cholesterol through diet and medication, and so on. Deep breathing exercises like in yoga, connecting emotionally to loved ones at a deeper level, having a pet like a dog or a cat to get some unconditional love, lots of good humor and laughter, and prayer …… all of this induces a feeling of well-being and helps in good cardiovascular health.

However, if all of that is not enough, and if medication is necessary, a diuretic medication and an ACE inhibitor can be the first line of medication.

Whatever it takes, my friend, whatever it takes! Until we meet next week …. please do make your health a high priority!

Take care …. of yourself and your health ….

Dr. Ajit Damodaran