Flutamide chemical structure
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Flutamide

Flutamide is an oral antiandrogen drug primarily used to treat prostate cancer. It competes with testosterone and its powerful metabolite, dihydrotestosterone (DHT) for binding to androgen receptors in the prostate gland. By doing so, it prevents them from stimulating the prostate cancer cells to grow. Flutamide has been largely replaced by a newer member of this class, bicalutamide, due to a better side-effect profile. Flutamide may also be used to treat excess androgen levels in women. It is marketed under the brand name Eulexin. more...

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Structure

Unlike the hormones with which it competes, flutamide is not a steroid; rather, it is a substituted anilide. After absorption, the molecule is quickly α-hydroxylated to its primary active form, hydroxyflutamide. Flutamide is excreted in various forms in the urine, the primary form being 2-amino-5-nitro-4-(trifluoromethyl) phenol.

Use in prostate cancer

Gonadotropin-releasing hormone (GnRH) is released by the hypothalamus in a pulsatile fashion; this causes the anterior pituitary to release leutinizing hormone (LH) and follicle-stimulating hormone (FSH). LH stimulates the testes to produce testosterone, which is metabolized to DHT by the enzyme 5α-reductase. DHT, and to a much smaller extent, testosterone, stimulate prostate cancer cells to grow. Therefore, blocking these androgens can provide powerful treatment for prostate cancer, especially metastatic disease. Normally administered are analogues of GnRH, such as leuprolide or goserilin. Although they stimulate the same receptors that GnRH does, since they are present continuously and not in a pulsatile manner, they serve to inhibit the pituitary and therefore block the whole chain. However, they initially cause a surge in activity; this is not solely a theoretical risk but may cause the cancer to flare. Flutamide was initially used at the beginning of GnRH-analogue therapy to block this surge, and it and other nonsteroidal anti-androgens continue in this use.

There have been studies to investigate the benefit of adding an anti-androgen to surgical orchiectomy or its continued use with a GnRH analogue (combined androgen blockade, CAB). Adding anti-androgens to orchiectomy showed no benefit, while a small benefit was shown with adding anti-androgens to GnRH.

Unfortunately, therapies which lower testosterone levels, such as orchiectomy or GnRH-analogue administration, also have signficant side effects. Compared to these therapies, treatment with antiandrogens exhibits "fewer hot flashes, less of an effect on libido, less muscle wasting, fewer personality changes, and less bone loss." However, antiandrogen therapy alone is less effective than surgery. Nevertheless, given the advanced age of many with prostate cancer, as well as other features, many men may choose antiandrogen therapy alone for a better quality of life.

Side effects

In addition to the effects previously mentioned, flutamide may also induce gynecomastia. Tamoxifen can partially counteract this effect. Some patients experience mild liver injury, which resolves when the drug is discontinued. It may also cause gastrointestinal side effects; one reason bicalutamide is replacing flutamide is that it appears to exhibits these to a lesser degree.

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In the best health: what four individuals learned about visiting their doctor's, asking questions, and getting a second opinion
From Black Enterprise, 1/1/05 by Keisha-Gaye Anderson

Managing your health involves more than just schedulings a yearly physical. It requires doing research, knowing your family, history and keeping up with new test a and screenings for your age and risk categories. It's also important to find a doctor with whom you feel comfortable discussing your questions and concerns. We feature bout individual of various ages who have learned the importance of being proactive about their health needs.

Camille Abrahams was no stranger to the doctor's office. Having been diagnosed with ITP (Immune Thrombocytopenic Purpura), a rare blood disease that hinders her blood's ability to clot, she knew how important it was to maintain her health and see her doctor regularly. So when she was diagnosed with osteoarthritis at 26, Abrahams was determined to get a second opinion. Her diligence paid off.

"I was a very active person and I just felt myself slowing down and I didn't know why," says Abrahams, who works for a New York-based nonprofit agency that provides technical assistance to HIV programs. Early this year, during her regular workouts at the gym, Abrahams noticed that her knuckles would swell and hurt. She also noticed other symptoms such as hair loss, chronic fatigue, skin rashes on her elbows, and sensitivity to sunlight. She sought advice from her hematologist, a specialist she had been visiting since her teens because of her blood condition. He referred her to a rheumatologist, who ran more blood tests. The result was lupus. Abrahams' white blood cell count was high and her A&A (anti-nuclear antibody) was positive. Over 90% of lupus patients have a positive A&A.

Dr. Dina Strachan, a New York-based dermatologist, says that black women should pay close attention to lupus symptoms. "Black women who suffer with lupus are much more likely to have problems or even die from [complications caused by the disorder]," she explain s. Early symptoms include scaly patches, scarring, and lesions.

Lupus is an autoimmune disease that affects various parts of the body, particularly the skin, kidneys, joints, and blood. Antibodies that usually attack foreign agents like bacteria start to attack healthy cells. The disease is approximately two to three times more prevalent in people of color and almost exclusively affects women. Abrahams was not aware that her blood condition could be considered a precursor for lupus. Since being diagnosed, she joined an online support group, Sisters with Lupus. Because stress can incite a flare-up of symptoms, Abrahams tries to keep stress to a minimum by practicing yoga. She also takes medication.

"[The] 20s is typically when people are feeling like they're healthy and invincible," says Dr. Andrea Pennington, founder of the Pennington Institute for Health and Wellness. However, young men and women should enforce good health habits as early as possible to maintain a high quality of life.

Kat Carney only visited a doctor when she absolutely had to. When back pain forced her to pay her doctor a visit seven years ago, what she learned forced her make lifestyle changes that completely transformed the way she lives today. Weighing in at 240 pounds, the former anchor for CNN Headline News was reluctant to admit there was a problem. But the doctor insisted that obesity was contributing to her back pain. "I told the nurse, 'there's something wrong with your scale,'" Carney jokes. The excess weight was not the only problem. Her inability to lose it was just one sign that something else was wrong.

Carney also noticed hair shedding from her head. Simultaneously, she was developing hirsutism, excessive growth of body hair. Her menstrual cycle was also irregular. Her doctor said that there was nothing seriously wrong, but Carney was determined to understand the problem behind her ailments. After seeing several doctors, one finally suggested that she might have Poly-cystic Ovary Syndrome, a hormonal disorder that affects approximately 10% of women of childbearing age. In PCOS sufferers, the pituitary gland sends the wrong hormonal signals to the ovaries, which in turn, will not release eggs as they would during a normal menstrual cycle. The ovaries become enlarged and develop several fluid-filled cysts, which contain mature eggs.

"Carney did the right thing by seeking more than one medical opinion," says Pennington. "As African Americans, we have to be willing to tell all the symptoms we are experiencing. It could be a signal that something bigger is going on inside that could become a big deal later on."

Women with PCOS also have higher levels of insulin, which increases their risk of developing diabetes. "When your blood sugar is elevated, it damages the lining of the coronary arteries," says Dr. Jennifer Mieres, director of nuclear cardiology at North Shore University Hospital in Manhasset, New York, and spokesperson for the GE Healthcare Women's Heart Health campaign. These elevated insulin levels also result in excess testosterone production by the ovaries, which causes excessive facial hair growth that women with PCOS often experience. Other symptoms include male pattern baldness, thinning hair, acne, oily skin, and infertility. PCOS sufferers are also at greater risk for high cholesterol and high blood pressure.

Whether obesity is a cause or result of PCOS is not clear. What is known is that weight gain is one of the main symptoms. Carney had poor eating habits that compounded her difficulty with losing weight. "My eating habits were absolutely atrocious and I got zero extracurricular physical activity," she says.

There were, and still are, no FDA-approved drugs for the treatment of PCOS. As with many sufferers of PCOS, Carney was prescribed birth control pills to regulate her hormone levels, but they caused Carney to gain weight and suffer from excessive sweating. Carney decided to research her best medication options. She found a French study about a drug called Flutamide. In the United States, the drug had been approved to treat prostate cancer. But several doctors refused to prescribe it to her for PCOS. Eventually, she found a physician who consented but insisted on monthly liver checkups and swore her off alcohol. "It ended up being the perfect medication for me," says Carney.

"Whatever physician you're working with, it's a partnership," she continues. "The doctor--patient relationship should not be adversarial."

Carney also adopted an exercise regimen that resulted in her shedding 90 pounds in 14 months. She also changed her diet by reducing her intake of refined carbohydrates and eating more fresh vegetables. Carney is now a spokesperson for NutriSystem. She also started a Website to educate women about PCOS, www.soulcysters.com, and another support Website for those struggling to control their weight, www.fitatanysize.com.

What Ben Green didn't know almost killed him. His chronic headaches weren't just stress-related. They were crucial warning signs that would have prompted him to seek medical attention sooner if he had known how close he was to death.

Green, an electronic data interchange administrator for FOX Cable Networks Group, was concerned about developing asthma, which ran in his family. He wasn't as concerned about his eating habits. He loaded up weekly at his favorite fast-food restaurant. "It was a ritual," he says. "Fried chicken, fried fish, lots of hot sauce. I ate a lot of the wrong foods."

In 2000, a particularly stressful year for Green, he began to experience severe headaches. He put off going to the doctor because he didn't have health insurance and opted to take aspirin instead. His headaches, however, became unbearable. "I started going to sleep with headaches and waking up with headaches that wouldn't go away," Green explains. In January 2001, he finally visited a clinic for a checkup.

The triage nurse took his blood pressure twice, then quickly summoned the head nurse. Green knew something was wrong. "The head nurse took my pressure and she told me I had to be hospitalized." He was admitted that same day and was assigned a doctor who checked on him every 30 minutes to make sure he remained conscious. With a blood pressure of 220 over 190, Green could have had a stroke at any moment. A healthy blood pressure is usually at or below 140 over 90.

"In general, African Americans do not seek out medical care unless something goes wrong," says Pennington. If Green had known that he fit the profile of someone who suffers from high blood pressure--African American, mid-40s, and a sedentary lifestyle with a family history of high blood pressure--he might have paid attention to his headaches earlier. Unfortunately, Green did not learn his full family history until his hospitalization.

"Very often, African Americans can have undiagnosed hypertension," says Mieres. "Hypertension is a powerful risk factor for heart disease. The 40s is usually when heart disease starts manifesting in men." Mieres advises both men and women to have an Electrocardiogram (ECG or EKG), a test that measures the electrical activity of the heart, by age 40, in addition to a routine physical exam to screen for any signs of heart disease.

Green was put on Lotrel to keep his blood pressure down and Lipitor to control his cholesterol. He brought his weight down from 265 to 235 in three months by exercising regularly and removing salt and junk food from his diet. He limits salt intake and reads food labels for sodium and sugar content. "When I go out to eat, I check the salt limits. When I order french fries, I tell them no salt."

Green was fortunate, but many African Americans are at risk for hypertension and are unaware of how serious the condition can become and what other ailments it can trigger. "African Americans have a genetic predisposition to hypertension," says Mieres. Heart disease and stroke are the No.1 and 3 killers of African American men and women. She adds, "having an elevated blood pressure destroys the lining of the vessels that supply the heart and the vessels that supply the brain. The heart has to work much harder." Preventative measures literally can be the difference between life and death.

"In the military, they make you do a physical every year," says David Dunham, a retired non-commissioned Air Force officer, who always asked to be tested specifically for diabetes. Dunham has a family history with the disease, but through 23 military physicals, the tests were always negative. Dunham was also in good physical condition, working out regularly and staying active. "I used to go to the gym, play basketball, and play softball. I was always on the go," he says. After retirement, his pattern of physical activity changed. He became more sedentary and gained 25 pounds. He also began to notice other physical changes like a continual urge to urinate, extreme thirst, and very low energy. Dunham's doctor visit revealed that he had developed Type II diabetes.

When compared with other ethnic groups, "an African American person who gains weight and has a sedentary lifestyle is twice as likely to develop diabetes," says Mieres. Type II diabetes is particularly prevalent in the African American community and Dunham's profile fit into a cluster of risk factors.

Diabetes is also a huge risk factor for heart disease. Elevated blood glucose levels destroys the lining of the heart and promotes a build up of plaque in the arteries, which blocks blood flow.

At first, Dunham's doctor prescribed oral medication. He is now taking daily insulin shots. "It was very hard. The first couple of times, I couldn't bring myself to stick myself," he says. He is also taking a low dosage of pills to keep his cholesterol and blood pressure under control. Now Dunham stays active by doing yard work for cardiovascular exercise. He takes his medicine regularly and visits his doctor every six months.

Name: Camille Abrahams

Age: 26

Health concern: lupus

Symptoms: fatigue, skin rashes, arthritis in fingers, hair loss

Degree of involvement: Abrahams was diagnosed with a blood disorder at 16 called ITP (Immune Thrombocytopenic Purpura), which caused her platelet count to be very tow and made her prone to hemorrhaging, so she was used to visiting her hematologist and other doctors regularly. Abrahams recently noticed other symptoms that led to a diagnosis of lupus.

Results: She is on medication (steroids that cause her to gain weight), goes to the gym regularly, and eats a healthy diet.

Medical Tests and Screenings For Those in their 20s

* Annual physical exam, which checks blood pressure and weight

* General blood tests: fasting blood glucose, complete blood count, and cholesterol

* Urinalysis

* Vision exam

* Rectal exam, which checks for hemorrhoids and prostate cancer

* Women should get an annual Pap smear to check for cervical cancer or other disorders, as well as a regular breast exam.

* Men should examine their testicles for lumps or other abnormalities

Name: Kat Carney

Age: 35

Health concern: Polycystic Ovary Syndrome (PCOS) Symptoms: obesity, hirsutism, hair loss, irregular menstrual cycle

Degree of involvement: Carney was reluctant to visit a doctor unless something was seriously wrong. She was forced to go because of back pain.

Results: She began a drastic fitness regimen, educated herself, and took medication. In 14 months, she lost 90 pounds and saw a reduction in all symptoms of PCOS.

Medical Tests and Screenings For Those in Their 30s

* Annual physical exam, which checks blood pressure, weight, cholesterol, and vision. Women should get a Pap smear.

* EKG to check heart rate

* Screening for diabetes and cholesterol levels

* Urinalysis

Name: Benjamin I. Green III

Age: 45

Health concerns: hypertension and high cholesterol

Symptoms: constant headaches, irritability, and tightness in the head

Degree of involvement: Green went for annual physicals and only when his headaches became unbearable.

Results: In January 2001, he was treated in the hospital for hypertension headaches only to find that his blood pressure was at the cardiac/stroke level. A change of eating habits, medication, along with exercise, has improved his health.

Medical Tests and Screenings For Those in Their 40s

* Annual blood pressure check

* Cholesterol check

* EKG

* Annual physical exam

* Bone density scan (women)

* Mammogram (women)

* Vision and blood tests

* Urinalysis

* Prostate cancer screening

* Colonoscopy (for people with a family history of colon polyps) cancer or

* Glucose screening (Type II diabetes affects many African Americans after age 40. Early screening is crucial.)

Name: David Dunham

Age: 58

Health concern: diabetes

Symptoms: thirst, frequent urination

Degree of involvement: Dunham always went for a physical each year and asked his doctor to check for diabetes because of family history.

Results: He was diagnosed with Type II diabetes two years after his retirement. He now takes prescribed medicines and daily insulin shots. Dunham also began an exercise regimen.

Medical Tests and Screenings For Those in Their 50s

* Routine physical exam

* Blood pressure reading

* Cholesterol test

* Prostate cancer screening

* Colonoscopy to check for polyps and colon cancer

* EKG to check heart rate and rhythm

HOW TO TALK TO YOUR DOCTOR

Find a good match

The doctor-patient relationship should not be adversarial. Use referrals from friends, family, and colleagues to find a doctor with whom you feel comfortable talking to and asking questions.

Know your medical history

To get a thorough analysis, come to your checkups armed with full knowledge of your personal medical history as well as your family's history.

Ask questions

Doctor's seem to have less and less time to speak in depth with patients during visits. Maximize your time by coming prepared with specific questions or specific exams you would like to request.

Get a second opinion

Don't be afraid to seek out doctors or specialists to get a second opinion or more information about a medical exam or condition.

Follow up

Always call for test results and follow up with specialists. Sometimes, follow-up exams can reveal crucial information missed the first time around.

COPYRIGHT 2005 Earl G. Graves Publishing Co., Inc.
COPYRIGHT 2005 Gale Group

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