ARE DOCTORS HAPPY WITH THEIR PROFESSION ?

Like medicine, happiness takes practice. But when it comes to happiness, some say the deck is stacked against doctors.

While physicians can legitimately point to any number of concrete problems putting the kibosh on their joy, some of their problems may lay a whole lot closer to home.

The Physician Personality

First, let's be clear. Doctors aren't the only ones struggling to find happiness. In fact, when it comes to workplace frustration, they're in good company these days. Thanks to corporate downsizing, workloads are heavier and morale lower in offices and plants around the country. Still, with the national unemployment rate hovering around 8.6%, "in most fields just having a job makes you happy with your job," says Tommy Bohannon, a divisional vice president at Merritt Hawkins.

But medicine isn't most fields. Left unchecked, physician unhappiness can lead to major problems, including disruptive behavior, burnout, medical errors, health problems, addiction, depression, and failed relationships. It can also induce doctors to leave the clinical arena: 40% of physicians responding to a 2010 survey.

Second, it's important to note that human beings are not hardwired for happiness. As O'Connor notes, "The cavemen who liked to linger contentedly around the fire were more likely to get eaten by the bears, and thus were not available to be our ancestors. Instead, those who survived to be our ancestors were alert, competitive, never satisfied, always on the move -- and we've got their genes.

That's especially true of doctors, and other high-achieving professionals. It takes ambition, perfectionism and drive to make it into -- and out of -- medical colleges and while those qualities may be very useful for achieving goals, they don't tend to foster happiness and satisfaction.

An Unforgiving Work Environment 

Transporting this Type-A personality into a workplace fraught with life-and-death decisions, litigious patients, reems of paperwork, constantly evolving technology, long hours, severe time constraints, and shifting reimbursement models simply turns up the heat.

The career they signed on for -- the one that consisted of independent private practices and personal relationships with patients -- is on its way out, according to 89% of physicians responding to theMerritt Hawkins survey. While younger doctors may happily trade the autonomy of the old model for the work-life balance and financial security of the new employment-based model, older doctors feel the rules of the game have been changed on them. To make matters worse, many have been forced to delay their retirement due to shrinking portfolios, so they unhappily toil on.

A Happiness Primer

So how's a doctor to find happiness? The same way everyone should, says one author in Medscape: work on it. Find a way to be happy in the now.

"The greatest myth of human life is the belief that I'll be happy if I just get what I want," says O'Connor. "All the research shows that as soon as we get what we want, we'll just want something else."

Instead, O'Connor counsels doctors to cultivate the essential relationships in their lives. Most people derive much of their joy and satisfaction from their family and friends: relationships that too often suffer in the face of 12-hour days and weekend call.

He also advises them to practice mindfulness, both through meditation and in their daily living. Mindful living is about taking a step back and seeing events in light of the bigger picture. The practice -- and it takes practice -- enables people to keep perspective so they can make wiser decisions based on rational thinking and intuition, rather than impulse.

But to be mindful people must learn to quiet their minds and settle down and that's something with which many doctors struggle. Dr. Aggarwal says she frequently challenges physicians to sit and do nothing for as long as they can. Few can sit still for more than a minute or two. Rather than relaxing, they try to "solve" their way through stress and burnout by doing more.

Instead, O'Connor counsels doctors to cultivate the essential relationships in their lives. Most people derive much of their joy and satisfaction from their family and friends: relationships that too often suffer in the face of 12-hour days and weekend call.

Goals Also Help

Having clear, achievable goals is important as well. For many doctors, graduating from medical school and getting into practice was a single-minded pursuit.

"The doctors who are doing well -- the ones who aren't in a burnout or stress cycle -- have an answer right off," she says. "You hear, 'I like to fish,' 'I love to camp,' 'I go bowling.' But the sad thing is many doctors don't have an answer."

It may sound trite, but for those doctors, finding a fun or fulfilling activity is itself an important goal. After all, their happiness depends on it.

Shelly M. Reese

Freelance writer, Cincinnati, Ohio

Source: Medscape

by

AKSHAYA SRIKANTH

Pharm.D Intern

Hyderabad, India

First ‘Heartless’ Man

First ‘Heartless’ Man: You Don’t Really Need A Heart, Or A Pulse

Two doctors Billy Cohn and Bud Frazier from the Texas Heart Institute successfully replaced a dying man’s heart with a device—proving that it is possible for your body to be kept alive without a heart, or a pulse. 

WATCH HERE 

In the short film ‘Heart Stop Beating’ by Jeremiah Zagar of Focus Forward Films, Zagar documents the process of the doctors—from cutting out the whole heart of 50 calves and replacing it with centrifugal pumps, to finally implanting it into their patient Craig Lewis. 
The turbine-like device, that are simple whirling rotors, developed by the doctors does not beat like a heart, rather provides a ‘continuous flow’ like a garden hose. 
After the doctors experimented on one of the calves, Abigail, Doctor Cohn told NPR: "If you listened to her chest with a stethoscope, you wouldn't hear a heartbeat. If you examined her arteries, there's no pulse. If you hooked her up to an EKG, she'd be flat-lined." 
Craig Lewis was a 55-year-old, dying from amyloidosis, which causes a build-up of abnormal proteins. The proteins clog the organs so much that they stop working, according to NPR. 
But after the operation, with the ‘machine’ as his heart's replacement, Lewis’ blood continued to spin and move through his body. 
However, when doctors put a stethoscope to his chest, no heartbeat or pulse can be heard (only a ‘humming’ sound)—which “by all criteria that we conventionally use to analyze patients”, Doctor Cohn said, he is dead. 
This is proof that “human physiology can be supported without a pulse”

Source: TAXI News
by
Akshaya Srikanth
Pharm.D Intern
Hyderabad, India

THE INDIAN GERIATRIC TALE

Geriatric medicine in India is the least known form of medicine. Becoz no one practices it, because no one gets trained in it. Presently the focus of the health administration is still on decreasing the IMR (infant mortality rate) to less than 30 per 1000 live births which right now, in India, is 54.63 per 1000 live births. It is one of the factors in determining the PQLI - Physical quality of life index in the country. PQLI is determined by the follwing

- IMR

- Life expectancy at age 1

- Literacy rate

If you notice, Life expectancy is also a determinant and presently the Life expectancy in India is 64.71 years (male: 63.9 years female: 65.57 years). That is pretty ok, so it will be a while before Geriatric medicine training is introduced into the mainstream health education. However, I am basically writing this post to string together my experiences with the elderly population.

There is no doubt most of the ailing people who are admit chronically in hospitals are about middle aged. Here I am talking about routine cases like CVE, IHD, Uncontrolled Diabetes and Hypertension and of course Cancer patients. And often instances come where there is nothing much you can do for them. I’ve come across such patients being described as ‘Gomers’ in a few Robin Cook novels. They take up hospital beds and resources that could be more effectively used otherwise. There is a solution possible for this in the form of Nursing homes and Recovery homes and such.

But there are very few such nursing homes and recovery homes in India that will take care of such patients for optimized economic disbursals. And the burden falls on mainstream hospitals. There are often scenarios played out, especially in Government run hospitals, where the doctor takes the family aside and tells them that there is nothing much they can do for their patient, so they can take him home if they wish to. There is no ‘all we can do for him is to keep him comfortable’ (as in pain relief). It’s different when a patient chooses to die in the familiarity of his home and it is different when due to lack of facilities in the hospital or due to the financial situation of the family the patient is taken home to die. Medical insurance is still in its primitive form here and government subsidies for the elderly are limited to separate Qs at railway stations and such.

This is a sore point with me becoz I lost my grandfather in exactly the same way. He was diagnosed with Carcinoma prostate and on diagnosis, his PSA levels were approximating 40 ng/ml with bone and lung mets and it was too late for any modality of treatment to be effective. He was taken to one of the better Cancer hospitals in India but after running tests and treating him for a week, the doctors promptly told my relatives to take him home, as there was nothing much they could do for him. I was 17 and a first year medical student then in the midst of exams, so I could not go visit him. But I was appalled when I learned that instead of keeping him in the hospital in pain relief, my uncle chose to bring him home. My grand father died at home, one and half months after his diagnosis amidst his family in, god - only - knows how much pain. Now after a few years of experience I realize that this should not have happened. My grandfather, 78 when he died, had been complaining of prostatism and acute body pain for 3-4 years. But as is the plight of most elderly who have to depend on their offsprings for getting them medical attention, my grandpa waited and my uncle kept dismissing it, till it was too late.

I am not sure whom to blame, the government which doesn’t make better facilities available for the elderly or my family who didn’t help him in time. 

Please note, that most of all this applies to people who are not so affording, though there are the occasional odd rich examples .It’s the norm in India for the kids to look after their parents in their old age. But there are way too many people who think of it as a burden to take care of people who have practically spent their whole life looking out for you. Its only recently that people have started saving for themselves in their retirement and old age, rather than give it all away to their kids and expecting them to fend for them in their bleak years. Also more and more old age homes are coming up in cities and many of the about-to-age populace, including my mom, have decided to live there (and die) in dignity! About my mom, its remains to be seen, as it’s a constant debate between us with me saying I won’t let her!

Examining the other side of the coin, I should mention what is being done for the elderly other than separate senior citizen Qs and concessions. The hospital, where I studied, was a tertiary Government hospital meaning that most of the difficult cases were referred there from the peripheral districts outside the city. The department of Internal medicine conducted weekly clinics for Diabetes, hypertension and Ischemic heart disease, which basically consisted of a bunch of doctors refilling prescriptions of patients and ordering tests as required. The medicines were free as were the tests. And yes, there was a geriatric clinic too, which was in conjunction with other relevant departments like surgery and orthopedics, but that was mostly prescription refilling too.

However my personal brush with elderly patients happened in two particular places. The first was in the Ophthalmology department as in intern. The most common cause of blindness in India is Cataract. In my hospital an average of 40-50 cataract extractions were done a day, and it was the interns’ responsibility to get all the relevant tests out of the way before admitting the patient. That meant giving the patient a list of tests that needed to be done and making sure they went to the right departments to get blood tests and urine tests etc done. Trust me when I say that it is one of the most challenging things to explain to an elderly, illiterate, unaccompanied lady who walks leaning on a staff and is invariably hard of hearing too, the various directions to the get her tests done. Dozens of times I have wound up taking them around for their tests and ultimately depositing them in the Ophthalmology ward, which, unfortunately, was on the fourth floor with no elevators. I suppose it was one of those times that I promised myself that my mother will never suffer a lonely older age.

The other place where I came across multitudes of geriatric patients was during my rural posting, which is a three-month long stint in one of the government run Primary Health Centers or PHCs in rural areas. Apart from the Obstetric patients who came in hordes to avail the Antenatal facilities, (India does have one of the highest populations and population growth rates in the world!), the major bulk of patients were geriatric females and occasionally males. The hypertensives and diabetics aside, they invariably came with complaints of generalized weakness, body ache and joint pains. Osteoarthritis at such a grass root clinic could hardly be treated with HRT (hormone replacement therapy). We had to resort to the NSAIDs (aspirin, Paracetamol etc) along with antacids for treating their symptoms and giving them a week’s worth of calcium supplements and Multivitamin tablets which were free of course. As per protocol, we could only prescribe a week’s worth of medication, but rest assured they returned every week.

As a Primary care physician, I could not bring myself to prescribe virtually unlimited supply of NSAIDs to any patient, over and over again, for fear of giving them Gastritis or Ulcers. Initially I tried to teach them exercises to keep the joints supple but they were more interested in the painkillers.

Then there were those who demanded injections. Not for the pain but for the weakness. It’s a habit in PHCs to give intramuscular injections of Vitamin B12 to anemic patients. The illiterate patients call them ‘Strength booster shots’ or ‘Red strength shots’ as the solution is light red in color. It’s a common for patients suffering form easy fatigability to visit such clinics and demand for ‘Strength shots’. And so used are they to them that when in shortage of Vitamin B12 injections a placebo like distilled water helps as well.

I think I have been rambling too long in this post. I will conclude by saying that much needs to be desired in the practice of Geriatric medicine in India and hope that things change soon for the better.

Source: IndianMedic

by

Akshaya Srikanth

Pharm.D Intern

Hyderabad, India

Guidelines for Oral Pharmacotherapy of Type 2 Diabetes

Diabetes mellitus is the seventh leading cause of death in the United States and affects 25.8 million Americans, with up to 27% of those 65 years and older being affected. In the United States, 11 distinct classes of oral antidiabetic agents are approved by the US Food and Drug Administration for the treatment of hyperglycemia in diabetes mellitus. There are 14% of patients with diabetes who currently take both oral agents and insulin and 58% who take oral medications only.

This report is based on a systematic review focused on head-to-head monotherapy and dual therapy. Combination therapies with more than 2 agents were not included in the review, and data on α-glucosidase inhibitors such as acarbose were excluded.

Metformin should be the initial drug for most patients with type 2 diabetes refractory to lifestyle modifications, with a second drug added if needed.
Specific recommendations in the new guidelines are:
Recommendation 1: When diet, exercise, weight loss, and other lifestyle modifications have not adequately improved hyperglycemia, clinicians should add oral pharmacologic therapy in patients with type 2 diabetes (grade: strong recommendation, high-quality evidence).

Recommendation 2: For most patients with type 2 diabetes, initial pharmacologic therapy should be monotherapy with metformin (grade: strong recommendation; high-quality evidence).

Recommendation 3: When lifestyle modifications and monotherapy with metformin fail to control hyperglycemia, clinicians should add a second drug to metformin (grade: strong recommendation; high-quality evidence).

Overall adverse effects were fewer with metformin than with sulfonylureas, and high-quality evidence showed that risk for dangerous levels of hypoglycemia was higher with sulfonylureas than with metformin or thiazolidinediones. In addition, the combination of metformin plus sulfonylureas is associated with 6-fold greater risk for hypoglycemia than the combination of metformin plus thiazolidinediones. When used as monotherapy, the risk for hypoglycemia with metformin and thiazolidinediones was similar, based on moderate-quality evidence.

Evidence was insufficient regarding any efficacy difference among various medications across subgroups of adults based on age, sex, or race.

The ACP recommended generic metformin because of its better efficacy and fewer adverse effects than most other available medications, lack of associated weight gain, and lower cost.

"Metformin is associated with an increased risk for gastrointestinal side effects. Thiazolidinediones are associated with an increased risk for heart failure, and both rosiglitazone and pioglitazone are contraindicated in patients with serious heart failure."

ACP has produced a summary of the guideline for patients: 

"AMERICAN COLLEGE OF PHYSICIANS"

STUDY HIGHLIGHTS:

• The guideline addressed the comparative effectiveness of medications for type 2 diabetes in adults 18 years and older for intermediate outcomes (hemoglobin A1c [HbA1c], lipids, weight); long-term outcomes (mortality, cardiovascular morbidity, and microvascular endpoints such as retinopathy and nephropathy); and safety across subgroups, in particular, those 65 years and older.
• The quality of randomized controlled trials was evaluated with use of Jadad criteria, and observational studies were assessed with the Guide for Conducting Comparative Effectiveness Reviews.
• Key findings were summarized for individual outcome measures to derive the final recommendations.

Intermediate outcomes:

• For HbA1c levels, 104 head-to-head comparisons were examined, and most drug agents were found to be similar in efficacy, reducing HbA1c levels by an average of 1 percentage point.
• Metformin was reported in 3 pooled studies to be more efficacious than DPP-4 inhibitors.
• All dual therapy regimens were more efficacious than monotherapy and reduced HbA1c levels by an average of 1 percentage point more than monotherapy.
• The combination of metformin with another agent was better than metformin monotherapy.
• Metformin with a sulfonylurea was more efficacious than with a DPP-4 inhibitor or thiazolidinedione.
• 79 studies with head-to-head comparisons of effect on weight were reviewed.
• Monotherapy with metformin was more effective for weight loss than with thiazolidinediones, sulfonylureas, or DPP-4 inhibitors.
• Metformin monotherapy was more effective for weight loss than combination therapy, with a mean difference of 2.2 kg.
• Metformin plus a sulfonylurea was favored vs metformin plus a thiazolidinedione.
• 74 head-to-head studies of oral therapy on lipids were examined.
• Diabetes therapies had a small to moderate effect on lipid levels: 5 to 10 mg/dL for low-density lipoprotein (LDL) cholesterol, 3 to 5 mg/dL for high-density lipoprotein (HDL) cholesterol, and 10 to 30 mg/dL for triglycerides.
• Compared with metformin monotherapy, dual therapy did not show a benefit for LDL cholesterol control.
• The combination of metformin with sulfonylurea was favored vs metformin plus a thiazolidinedione for LDL control.
• For HDL cholesterol levels, combination therapy was superior to metformin monotherapy.
• The data on triglyceride lowering were variable: metformin monotherapy was more effective than sulfonylurea monotherapy, and different combinations had slightly different effects of reductions of 10 to 25 mg/dL.

Long-term outcomes:

• The quality of evidence for long-term outcomes was poor to moderate.
• For mortality and cardiovascular morbidity, 5 randomized controlled trials and 11 observational studies showed lower all-cause mortality rates for metformin monotherapy vs sulfonylureas.
• Evidence for other comparisons was unclear or insufficient.
• Only 2 studies examined nephropathy and showed pioglitazone as superior to metformin monotherapy for reducing the albumin-to-creatinine ratio.

Comparative safety:

• No evidence showed an adverse effect of hyperglycemia for any class of medication.
• Pooled results showed a greater risk for hypoglycemia from sulfonylureas compared with metformin (OR, 4.60) and thiazolidinedione (OR, 3.88).
• Evidence was insufficient to show any difference among therapies for liver damage and macular edema.
• For congestive heart failure, 5 observational studies showed superiority of metformin vs sulfonylureas.
• The evidence across subgroups for efficacy and safety of one medication vs another was unclear and insufficient.

ACP recommendations:

• The ACP recommends oral therapy for type 2 diabetes when lifestyle modification fails to improve hyperglycemia. A goal of an HbA1c level of 7% or lower is reasonable for many, but not necessarily all, patients and should be based on individual assessment.
• The ACP recommends that clinicians prescribe monotherapy with metformin as a first-line treatment in most patients with type 2 diabetes, except when there are contraindications.
• A second oral agent is recommended when metformin and lifestyle modifications fail to control hyperglycemia.

by

AKSHAYA SRIKANTH

Pharm.D Internee

Hyderbad, India

Glucocorticoid Drugs Associated With Neuropsychiatric Illnesses, Suicide

Glucocorticoids are important neuromodulating hormones, and the authors of the current study describe the background of how glucocorticoids might affect the risk for neuropsychiatric disorders. Mood disorders are associated with dysfunction in negative feedback loops of endogenous (natural) glucocorticoids, and the risk for depression among patients with Cushing's disease is 50% to 80%. An estimated 10% of these patients experience psychosis or mania.

Estimates of the prevalence of neuropsychiatric disorders related to the exogenous administration of glucocorticoids vary widely, from less than 1% to 50%. It does appear that higher doses of glucocorticoids are more likely to promote neuropsychiatric disorders, but other details of the relationship between glucocorticoids and neuropsychiatric disorders remain unclear.

STUDY SYNOPSIS AND PERSPECTIVE

Glucocorticoid medications given in primary care settings are associated with suicidal behaviors and severe neuropsychiatric disorders, new research suggests.

In a large, population-based study of adult patients in the United Kingdom, those receiving glucocorticoids were almost 7 times more likely to commit or attempt suicide, more than 5 times more likely to develop delirium, more than 4 times more likely to develop mania, and almost twice as likely to develop depression than those with the same underlying conditions who did not receive the medications.

In addition, patients younger than 30 years were at particular risk for suicide attempts, women were more at risk for depression, and men were at especially increased risk for mania and delirium/confusion/disorientation. Higher dosages of the medications were also linked to an overall greater risk for adverse outcomes.

"Steroid-treated patients do not always know that the neuropsychiatric symptoms that they are experiencing are induced by the treatment. They may, for instance, think that they are induced by the underlying disease," lead author Laurence Fardet, MD, PhD, from the Department of Internal Medicine at Saint-Antoine Hospital in Paris, France.

"Therefore, I believe that physicians must be aware that these neuropsychiatric adverse events are frequent and potentially life-threatening in order to better inform the patient and their family, and to avoid steroids when possible," said Dr. Fardet.

With data for almost 3500 glucocorticoid-treated patients included, the investigators note that this is the largest trial to date to examine these adverse outcomes.

This study was published online February 17 in the American Journal of Psychiatry. CLICK HERE

Commonly Prescribed

Glucocorticoid medications have anti-inflammatory properties and are commonly used to treat asthma, rheumatoid arthritis, and other autoimmune diseases and to prevent transplant rejection. Although corticosteroids actually refer to both glucocorticoids and mineralocorticoids, the first 2 terms are often used interchangeably.

According to the researchers, natural glucocorticoids, which include cortisol, affect mood, behavior, and other central nervous system–related processes.

In addition, a link between synthetic glucocorticoids and depressive and manic syndromes "is relatively well documented," the investigators note.

"In view of the frequency and severity of such disturbances in various clinical populations who received prescriptions for glucocorticoids, there is a need for population-based prevalence studies," they write.

Dr. Fardet reported that he has been involved in studies examining the epidemiology of glucocorticoid-induced adverse events for about 10 years.

"While many people in the general population, about 1%, are receiving glucocorticoids at any point of time, some of their adverse events are quite unwell described in the medical literature," he said.

For this study, the investigators evaluated data from The Health Improvement Network (THIN) on all patients older than 18 years who visited UK general practices between 1990 and 2008. The study included 372,696 patients who were prescribed at least 1 glucocorticoid (mean age, 57.5 years; 59.1% women; 24% with a history of a neuropsychiatric disorder).

Cases of neuropsychiatric outcomes are coded for all patients in the THIN database.

Awareness Needed

Results showed that 786,868 courses of oral glucocorticoids were prescribed for the patient population. A total of 90 cases of attempted suicides, 19 cases of completed suicides, and 10,220 cases of severe neuropsychiatric outcomes were reported.

"The incidence of any of these outcomes was 22.2 per 100 person-years at risk for first-course treatments," report the investigators.

The adjusted hazard ratios (HRs) for the various adverse outcomes in those prescribed glucocorticoids compared with the patients who were not are shown below.

Condition	HR	95% CI
Suicidal behaviors	6.89	4.52 - 10.50
Delirium/confusion	5.14	4.54 - 5.82
Mania	4.35	3.67 - 5.16
Depression	1.83	1.72 - 1.94
Panic disorder	1.45	1.15 - 1.85

HR = hazard ratio; CI = confidence interval

Other significant risk factors for all adverse outcomes were large daily doses of the medications and a history of disorders. Interestingly, a lower risk was associated with prior treatment with glucocorticoids.

When examining specific subgroups, investigators found that women treated with the drug class were at a significantly higher risk for depression than the men who were treated, but that the men were at a higher risk for mania and delirium/confusion/disorientation.

The older the treated patient, the higher the risk was for mania, depression, and delirium/confusion/disorientation. However, younger patients who were treated (those between the ages of 18 and 30 years) were at higher risk for suicidal behaviors.

"Educating patients and their families about these adverse events and increasing primary care physicians' awareness about their occurrence should facilitate early monitoring," write the investigators.

They add that caution is needed when administering this drug type, "in particular when the reasons for prescribing are not in accordance with the consensual clinical recommendations."

CLINICAL IMPLICATIONS

Mood disorders are associated with dysfunction in negative feedback loops of endogenous glucocorticoids, and the risk for depression among patients with Cushing's disease is 50% to 80%. An estimated 10% of these patients experience psychosis or mania. Higher doses of exogenous glucocorticoids are more likely to promote neuropsychiatric disorders.

The current study by Fardet suggests that treatment with glucocorticoids can increase the risk for a number of neuropsychiatric diagnoses, along with the risk for suicide attempt or completed suicide. A history of neuropsychiatric disorders and larger daily doses of glucocorticoids predicted a higher risk for all incident outcomes, and a prior episode of glucocorticoid-induced neuropsychiatric disorder increased the risk for a subsequent episode.

Source: Medscape

by

Akshaya Srikanth

Pharm.D Resident

Hyderabad, India

DRUGS USED IN TREATMENT OF ASTHMA

Asthma is a chronic inflammatory disorder of the airways. All patients need a short-acting inhaled β2-agonist to use as needed for symptoms. Patients with mild, moderate, or severe persistent asthma need daily long-term control medication. Start treatment at a higher "step" to achieve rapid control and then "step down" to the minimum therapy needed to maintain control, or start treatment at the "step" that is appropriate to the severity of the patient's asthma and then gradually "step up" therapy until control is achieved and maintained (see chart in this section). The "step-down" approach is preferred. Increases or decreases in medication(s) may be needed over time. 

CORTICOSTEROIDS 

(eg, triamcinolone, hydrocortisone, dexamethasone, methylprednisolone, prednisolone, prednisone): Corticosteroids are steroid hormones indicated for the treatment of adrenocortical insufficiency, steroid-responsive dermatoses, inflammatory disorders, autoimmune disorders, allergic reactions, and other conditions requiring immunosuppressive effects. Corticosteroids exert their effects by binding to specific intracellular receptors and translocating into the nucleus to subsequently regulate gene expression. 

Physiologic actions of corticosteroids depend on their glucocorticoid or mineralocorticoid activity:

Glucocorticoids also play an active role on the modulation of carbohydrate, protein, and lipid metabolism. They stimulate hepatic gluconeogenesis, inhibit glucose uptake in muscle and adipose tissues to conserve glucose, and provide substrates for gluconeogenesis by mobilizing amino acids from extrahepatic tissues and stimulating lipolysis in adipose tissues. Glucocorticoids also produce potent anti-inflammatory and immunosuppressive activity through the suppression of polymorphonuclear leukocytes migration, decreased inflammatory mediator production and reduction of capillary permeability. 

Mineralocorticoids, on the other hand, play a role in the maintenance of fluid and electrolyte homeostasis. Their actions include promoting Na+ and K+ ion exchange in the distal tubule of the kidney, increasing the resorption of sodium and water and the renal excretion of K+ and H+, and stimulating the expression of sodium channels to facilitate sodium uptake from the tubular lumen.

Systemic corticosteroids with predominant glucocorticoid activity in order of decreasing potency include dexamethasone, methylprednisolone, and triamcinolone. Prednisone and prednisolone are less potent glucocorticoids with weak mineralocorticoid activity, while hydrocortisone is the least potent glucocorticoid but has increased mineralocorticoid activity compared to others in this group.

LONG-TERM CONTROL MEDICATIONS are taken daily to achieve and maintain control of persistent asthma.

Inhaled corticosteroids (eg, beclomethasone, budesonide, flunisolide, fluticasone, triamcinolone) are used in the long-term control of asthma. Systemic corticosteroids are used in long-term therapy to gain prompt control of the disease and also to manage severe persistent asthma. It is possible to prevent disease progression with their early use. Low doses are used for mild persistent asthma; medium doses are used for moderate persistent asthma; high doses are reserved for the most severe cases. To reduce the potential for adverse effects with inhalers: Use a spacer or holding chamber; rinse mouth and spit after inhalation; consider adding a long-acting inhaled β2-agonist to a low-to-medium dose of inhaled steroid rather than using a higher dose of inhaled steroid (especially for nocturnal symptoms); monitor linear growth in children; when inhaled corticosteroid doses exceed 1000mcg per day, consider supplements of calcium (1g-1.5g/day), Vitamin D (400Units/day) and estrogen replacement therapy for postmenopausal women; may reduce doses of inhaled steroids by about 25% every 2–3 months until the lowest dose required to maintain control is reached.

Cromolyn sodium and nedocromil are mild-to-moderate antiinflammatory medications. They may be used as an initial choice in addition to a bronchodilator for long-term control in children. They can also be used as preventative treatment before unavoidable exposure to known allergens and in some cases of exercise-induced asthma. They should not be used to treat acute symptoms or exacerbations.

Long-acting β2-agonists (eg, salmeterol, formoterol, sustained-release albuterol) are used with inhaled corticosteroids for long-term control of symptoms (especially nocturnal symptoms). They may also be used to prevent exercise-induced bronchospasm. They should not be used to treat acute symptoms or exacerbations.

Leukotriene antagonists (eg, zafirlukast, montelukast) may be considered alternative therapy or adjunctive therapy to low doses of inhaled corticosteroids, or cromolyn or nedocromil in mild persistent asthma. Zafirlukast may be used in children ≥5 years of age; montelukast in patients ≥12 months of age.

Theophylline, a methylxanthine, is a mild-to-moderate bronchodilator. Blood levels must be maintained within a safe but effective range.

QUICK-RELIEF MEDICATIONS are used to provide prompt treatment of acute airflow obstruction and accompanying symptoms.

Short-acting β2-agonists (eg, albuterol, levalbuterol, bitolterol, pirbuterol, terbutaline) are preferred for the relief of acute symptoms. Increase in use or use of more than one canister in one month indicates inadequate control of asthma and the need for initiating or intensifying antiinflammatory therapy. Regularly scheduled, daily use of a short-acting β2-agonist is generally not recommended; they may be considered first for preventing exercise-induced asthma.

Systemic corticosteroids (eg, methylprednisolone, prednisolone, prednisone) are used for moderate-to-severe exacerbations to speed recovery and prevent recurrence of exacerbations. The addition of a 3- to 10-day course of oral corticosteroids may be needed to reestablish control during periods of gradual deterioration or for a moderate-to-severe exacerbation. 

Anticholinergic agents (eg, ipratropium) may provide additive benefit to inhaled β2-agonists in severe exacerbations. They may also be used as an alternative bronchodilator for patients who cannot tolerate an inhaled β2-agonist.

by

AKSHAYA SRIKANTH

Pharm.D* Intern

Hyderabad, India

BREAST CANCER TREATMENT REGIMENS

BREAST CANCER TREATMENT REGIMENS
General treatment note: All trastuzumab-containing regimens require cardiac monitoring at baseline and at Months 3, 6, and 9.1
REGIMEN	DOSING
Adjuvant Therapy With Concomitant Trastuzumab
AC (doxorubicin [Adriamycin] +cyclophosphamide [Cytoxan])followed by paclitaxel (Taxol) +concurrent trastuzumab(Herceptin)	Cycles 1–4 Day 1: Doxorubicin 60mg/m2 IV + cyclophosphamide 600mg/m2 IV. Repeat cycle every 3 weeks for 4 cycles. Subsequent cycles Day 1: Paclitaxel 80mg/m2 IV once weekly for 12 weeks, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly (or trastuzumab 6mg/kg IV once every 3 weeks) to complete 1 year of treatment. OR Cycles 1–4 Day 1: Doxorubicin 60mg/m2 IV + cyclophosphamide 600mg/m2 IV. Repeat cycle every 3 weeks for 4 cycles. Subsequent cycles Day 1: Paclitaxel 175mg/m2 IV. Repeat cycle every 3 weeks for 4 cycles, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly (or trastuzumab 6mg/kg IV once every 3 weeks) to complete 1 year of treatment.
Dose-dense AC (doxorubicin +cyclophosphamide) followed bypaclitaxel + concurrent trastuzumab	Cycles 1–4 Day 1: Doxorubicin 60mg/m2 IV + cyclophosphamide 600mg/m2 IV. Repeat cycle every 2 weeks for 4 cycles. Day 2: Pegfilgrastim 6mg SC approximately 24 hrs after chemotherapy. OR Days 3–10: Filgrastim 5mcg/kg (total 300mcg or 480mcg) after chemotherapy. Subsequent cycles Day 1: Paclitaxel 175mg/m2 IV. Repeat cycle every 2 weeks for 4 cycles, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly until completion of paclitaxel. Then administertrastuzumab 6mg/kg IV once every 3 weeks to complete 1 year of treatment. Day 2: Pegfilgrastim 6mg SC approximately 24 hrs after paclitaxel. OR Days 3–10: Filgrastim 5mcg/kg (total 300mcg or 480mcg) after paclitaxel.
Docetaxel (Taxotere) +concurrent trastuzumab	Cycles 1–8 Day 1: Docetaxel 100mg/m2 IV, plus Days 1, 8 and 15: Trastuzumab 2mg/kg. Repeat cycle every 3 weeks for 8 cycles. Subsequent cycles Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 6mg/kg IV once every 3 weeks until disease progression or cumulative toxicity.
Docetaxel + concurrent trastuzumab followed by FEC (5-fluorouracil [5-FU] + epirubicin [Ellence] + cyclophosphamide)	Weeks 1–8 Day 1: Docetaxel 100mg/m2 IV. Repeat cycle every 3 weeks for 3 cycles, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly for 8 weeks. Subsequent cycles Day 1: 5-FU 600mg/m2 IV + epirubicin 60mg/m2 IV + cyclophosphamide 600mg/m2 IV. Repeat cycle every 3 weeks for 3 cycles.
Adjuvant Therapy Without Concomitant Trastuzumab
Exemestane (Aromasin)	Exemestane 25mg orally once daily; used only after 2–3 years of tamoxifen therapy for a total of 5 years hormonal therapy.
Tamoxifen	Tamoxifen 20–40mg orally daily for no longer than 5 years (doses higher than 20mg should be divided into 2 doses, AM and PM).
TAC (docetaxel + doxorubicin +cyclophosphamide)	Day 1: Doxorubicin 50mg/m2 IV, followed by cyclophosphamide 500mg/m2 IV, followed by docetaxel 75mg/m2 IV after a 1-hr interval,plus Days 4–11: Lenograstim 150mcg/m2/day or filgrastim 5mcg/kg/day. Repeat cycle every 3 weeks for 6 cycles.
AC (doxorubicin +cyclophosphamide + paclitaxel)	Cycles 1–4 Day 1: Doxorubicin 60mg/m2 IV + cyclophosphamide 600mg/m2 IV. Repeat cycle every 3 weeks for 4 cycles. Subsequent cycles Day 1: Paclitaxel 80mg/m2 IV once weekly for 12 weeks.
Dose-dense AC (doxorubicin +cyclophosphamide) followed bypaclitaxel	Cycles 1–4 Day 1: Doxorubicin 60mg/m2 IV + cyclophosphamide 600mg/m2 IV. Repeat cycle every 2 weeks. Subsequent cycles Day 1: Paclitaxel 175mg/m2 IV. Repeat cycle every 2 weeks for 4 cycles. All cycles Day 1: Check Hgb levels. Administer darbepoetin alfa 200mcg SC if Hgb <12g/dL for first cycle. Determine Hgb on Day 1 of each subsequent cycle: darbepoetin alfa 200mcg SC if Hgb 10–12g/dL, 300mcg SC if Hgb<10g/dL, withhold if Hgb >12g/dL, plus Day 2: Pegfilgrastim 6mg SC approximately 24 hrs after chemotherapy. OR Days 3–10: Filgrastim 5mcg/kg (total 300mcg or 480mcg) after chemotherapy.
TC (docetaxel +cyclophosphamide)	Day 1: Docetaxel 75mg/m2 IV + cyclophosphamide 600mg/m2 IV. Repeat cycle every 3 weeks for 4 cycles.
Neoadjuvant Therapy
Trastuzumab + paclitaxel + FEC(5-FU + epirubicin +cyclophosphamide)	Cycles 1–4 Day 1: Trastuzumab 4mg/kg IV for one dose (for first dose, administer 1 day before paclitaxel to monitor for infusion reactions), followed by trastuzumab 2mg/kg once weekly for 24 weeks total, plus Day 1: Paclitaxel 225mg/m2 continuous IV infusion over 24 hrs. Repeat cycle every 3 weeks for 4 cycles. Subsequent cycles Day 1: Epirubicin 75mg/m2 IV + cyclophosphamide 500mg/m2 IV, plus Days 1 and 3: 5-FU 500mg/m2 IV. Repeat cycle every 3 weeks for 4 cycles.
Recurrent or Metastatic Breast Cancer—Combination Therapy
Ixabepilone (Ixempra) +capecitabine (Xeloda)	Day 1: Ixabepilone 40mg/m2 IV, plus Days 1–14: Capecitabine 1,000mg/m2 orally twice daily. Repeat cycle every 3 weeks.
FEC (5-FU + epirubicin +cyclophosphamide)	Days 1 and 8: 5-FU 500mg/m2 IV + epirubicin 50mg/m2 IV +cyclophosphamide 400mg/m2 IV. Repeat cycle every 3 or 4 weeks for 6–9 cycles.
EC (epirubicin +cyclophosphamide)	Day 1: Epirubicin 75mg/m2 IV + cyclophosphamide 600mg/m2 IV. Repeat cycle every 3 weeks.
AT (doxorubicin + docetaxel)	Day 1: Doxorubicin 50mg/m2 IV + docetaxel 75mg/m2 IV. Repeat cycle every 3 weeks for max 8 cycles.
Docetaxel + capecitabine	Day 1: Docetaxel 75mg/m2 IV, plus Days 1–14: Capecitabine 1,250mg/m2 (patients ≥60 yrs: reduce to 950mg/m2) orally twice daily. Repeat cycle every 3 weeks.
GT (paclitaxel + gemcitabine [Gemzar])	Day 1: Paclitaxel 175mg/m2 IV, plus Days 1 and 8: Gemcitabine 1,250mg/m2 IV. Repeat cycle every 3 weeks.
Recurrent or Metastatic Breast Cancer—Single-Agent Therapy
Exemestane	Exemestane 25mg orally once daily.
Ixabepilone	Day 1: Ixabepilone 40mg/m2 IV. Repeat cycle every 3 weeks.
Tamoxifen	Tamoxifen 20–40mg orally daily for no longer than 5 years (doses higher than 20mg should be divided into 2 doses, AM and PM).
Pegylated liposomal encapsulated doxorubicin (PLD; Doxil)	Day 1: PLD 50mg/m2 IV. Repeat cycle every 4 weeks.
Albumin-bound paclitaxel(Abraxane)	Day 1: Albumin-bound paclitaxel 260mg/m2 IV. Repeat cycle every 3 weeks.
Capecitabine	Days 1–14: Capecitabine 1,000–1,250mg/m2 orally twice daily. Repeat cycle every 3 weeks.
Recurrent or Metastatic HER2+ Breast Cancer—First-Line Agents with Concomitant Trastuzumab
TPC (trastuzumab + paclitaxel +carboplatin [Paraplatin])	Cycle 1 Day 1: Trastuzumab 4mg/kg IV, followed by Day 2: Paclitaxel 175mg/m2 IV + carboplatin AUC=6mg/mL/min IV,followed by Days 8 and 15: Trastuzumab 2mg/kg IV. Subsequent cycles Days 1, 8 and 15: Trastuzumab 2mg/kg IV, followed by Day 2: Paclitaxel 175mg/m2 IV + carboplatin AUC=6mg/mL/min. Repeat cycle every 3 weeks. After chemotherapy, administer trastuzumab 2mg/kg IV weekly until disease progression or other discontinuation event occurs.
Paclitaxel + trastuzumab	Day 1: Paclitaxel 175mg/m2 IV. Repeat every 3 weeks for 6 cycles, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly until disease progression. OR Day 1: Paclitaxel 80mg/m2 IV once weekly. Repeat cycle every 3 weeks, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly for at least 2 cycles until disease progression.
Docetaxel + trastuzumab	Day 1: Docetaxel 100mg/m2 IV. Repeat cycle every 3 weeks for 6 cycles, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly until disease progression. OR Days 1, 8 and 15: Docetaxel 35mg/m2 IV and trastuzumab 2mg/kg IV (first dose: give trastuzumab 4mg/kg as loading dose). Repeat cycle every 4 weeks until disease progression.
Vinorelbine (Navelbine) +trastuzumab	Day 1: Vinorelbine 2mg/m2 IV once weekly for 8 weeks, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly until disease progression.
Capecitabine + trastuzumab	Days 1–14: Capecitabine 1,250mg/m2 orally twice daily. Repeat cycle every 3 weeks, plus Day 1: Trastuzumab 8mg/kg IV loading dose, followed by trastuzumab 6mg/kg IV once every 3 weeks.
Lapatinib (Tykerb) +trastuzumab for trastuzumab-exposed HER-2 positive disease	Day 1: Lapatinib 1,000mg orally once daily, plus Day 1: Trastuzumab 4mg/kg IV loading dose, followed by trastuzumab 2mg/kg IV once weekly until disease progression.

Source: NCCN Clinical Practice Guidelines in Oncology™. Breast Cancer. v 2.2011.
by
AKSHAYA SRIKANTH
Pharm.D Resident
Hyderabad, India