So just what IS restless leg syndrome? I've always thought it was just stress manifesting itself in the middle of the night and a brief stroll around the bedroom or a good stretch and it goes away. Apparently, it's way more prevalent in the U.S. and several new drugs for treatment have recently been approved by the FDA. Now for a medical definition:
Restless legs syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs and an uncontrollable urge to move when at rest in an effort to relieve these feelings. RLS sensations are often described by people as burning, creeping, tugging, or like insects crawling inside the legs. Often called paresthesias (abnormal sensations) or dysesthesias (unpleasant abnormal sensations), the sensations range in severity from uncomfortable to irritating to painful.
The most distinctive or unusual aspect of the condition is that lying down and trying to relax activates the symptoms. As a result, most people with RLS have difficulty falling asleep and staying asleep. Left untreated, the condition causes exhaustion and daytime fatigue. Many people with RLS report that their job, personal relations, and activities of daily living are strongly affected as a result of their exhaustion. They are often unable to concentrate, have impaired memory, or fail to accomplish daily tasks.
Current treatment involves dopamine agonist treatment. One such drug is Requip, drug name ropinirole. In 2005, requip became the only drug approved by the U.S. Food and Drug Administration specifically for the treatment of moderate to severe RLS. The drug was first approved in 1997 for patients with Parkinson’s disease. Requip stimulates D2 and D3 type dopamine receptors, to stimulate motor neuron firing (activity-or signaling). The specific mechanism of action for the indication of both Parkinson's and RLS are unknown.
The side effects of ropinirole are interesting to say the least. It has been reported that dopamine receptor agonists stimulate compulsive gambling ( NEUROLOGY 2007;68:301–303). Three subjects were followed from either never gambled or 1-2 visits to a casino to visiting a casino 3-4 times a week and losing up to several hundred thousand dollars. One possible mechanism of action is the stimulation of D3 receptors, the highest concentration of which is found in the mesolimbic pathways [in the brain, centers for controlling the following functions] implicated in motivation, emotion, and reward behaviors, which could lead to the development of pathologic
gambling.
I can understand the "reward" part of the gamble--USC 2nd half football games the last 2 years have paid rents. Just goes to show how pharmacological manipulation of brain function can have drastic effects.
Wednesday, September 19, 2007
Coming tomorrow....Dopamine agonists and getting down on some ACTION!
a tease:
Compulsive gambling with extreme losses -- in two cases, greater than $100,000 -- by people without a prior history of gambling problems has been linked to a class of drugs commonly used to treat the neurological disorder restless legs syndrome (RLS). A new Mayo Clinic study is the first to describe this compulsive gambling in RLS patients who are being treated with medications that stimulate dopamine receptors in the brain.
Mechanism of action and my interpretation tomorrow (later today).....
Compulsive gambling with extreme losses -- in two cases, greater than $100,000 -- by people without a prior history of gambling problems has been linked to a class of drugs commonly used to treat the neurological disorder restless legs syndrome (RLS). A new Mayo Clinic study is the first to describe this compulsive gambling in RLS patients who are being treated with medications that stimulate dopamine receptors in the brain.
Mechanism of action and my interpretation tomorrow (later today).....
Wednesday, May 23, 2007
Researchers are reporting a potential "cure" for hepatitis C,
Use of the drug peginterferon, either alone or in combination with the drug ribavirin, reduced levels of the virus to undetectable levels for up to seven years, the researchers said.
"This paper strongly suggests, for the first time, that hepatitis C is a curable disease," said lead researcher Dr. Mitchell Shiffman, a professor at Virginia Commonwealth University School of Medicine and chief of hepatology and medical director of the school's Liver Transplant Program. "After treatment, 99.6 percent of the patients remained virus undetectable for over five years," he added.
In the study, 997 patients with hepatitis C or with both hepatitis C and
HIV' were treated with either Pegasys (peginterferon alfa-2a) alone or in tandem with ribavirin. Shiffman's team then monitored blood levels of hepatitis C once a year for an average of 4.1 years, and as long as seven years.
The researchers found that 99 percent of patients with hepatitis C who were treated successfully with peginterferon alone, or in combination with ribavirin, had no detectable virus up to seven years later.
"This is the first long-term study that confirms what we believed for many years that these individuals are truly cured of hepatitis C," Shiffman said.
The remaining eight patients tested positive for hepatitis C at an average of two years after treatment. There was no pattern to the patients as far as age, gender or hepatitis C genotype. It isn't known whether these patients had a relapse or were re-infected with the virus, the researchers noted.
The findings were to be presented Monday at the 38th annual Digestive Disease Week conference, in Washington, D.C.
Hepatitis C is a blood-borne infectious disease of the liver and is one of the most important causes of chronic liver disease in the United States. An estimated 4.1 million Americans have been infected with hepatitis C, and 3.2 million are chronically infected. The number of new infections each year declined from an average of 240,000 in the 1980s to about 26,000 in 2004, the latest year for which statistics are available. The number of hepatitis C-related deaths could increase to 38,000 a year by the year 2010, surpassing annual HIV deaths, according to the U.S. Centers for Disease Control and Prevention.
The virus is usually spread through contact with infected blood and blood products. Blood transfusions and the use of shared, unsterilized, or poorly sterilized needles, syringes and injection equipment have been the main routes of transmission in the United States, according to the National Institutes of Health.
Most people who have hepatitis C don't know they have it, Shiffman said. "Of those who have been diagnosed, only about 25 percent have received treatment, because of the side effects of treatment," he said. "The reason why you should treat it is because you can cure hepatitis C, and we finally have the data to definitively document it."
Dr. Eugene Schiff, chief of the division of hepatology and professor of medicine at the University of Miami Miller School of Medicine, agrees that most cases of hepatitis C can be cured.
"In contrast to hepatitis B or HIV, this virus can be totally eradicated and cured," he said.
But, many patients find the side effects of treatment off-putting. Those side effects can include fever and chills, Shiff said. "You feel pretty lousy. After treatment starts, you feel worse the day after your shot, but it tapers off over the course of the week," he said. "Along with that anxiety, irritability and depression can develop. And we are quick to use antidepressants to allow these people to stay on the medication."
Additional side effects include a drop in the production of white blood cells and anemia. Often patients are giving additional drugs to combat these conditions, Shiff said.
Treatments can go on for as many as 72 weeks, depending on the reaction to therapy Shiff said. "Some people are reluctant to get treatment, because they heard that the treatment isn't so pleasant," he said. "But they should come out and get treatment."
Schiff noted that new antiviral drugs to treat hepatitis C are being tested. "It is hoped that these new antivirals will be more effective and have less severe side effects and may even be used without peginterferon alfa-2a or ribavirin," he said.
UMMM--Going to have to call BS on this one. The authors must be in dire need of NIH funding to be making such bold observations. The fact IS, that >60% of patients of HCV infection are already resistant to both therapies. This data is not anything new in the HCV field. The "new" drugs that are being investigated beyond PEG-interferon and nucleoside polymerase inhibitors are very promising however. TLR agonists are coming of age as potent immune stimulators as well as combination cytokine therapy.
"This paper strongly suggests, for the first time, that hepatitis C is a curable disease," said lead researcher Dr. Mitchell Shiffman, a professor at Virginia Commonwealth University School of Medicine and chief of hepatology and medical director of the school's Liver Transplant Program. "After treatment, 99.6 percent of the patients remained virus undetectable for over five years," he added.
In the study, 997 patients with hepatitis C or with both hepatitis C and
HIV' were treated with either Pegasys (peginterferon alfa-2a) alone or in tandem with ribavirin. Shiffman's team then monitored blood levels of hepatitis C once a year for an average of 4.1 years, and as long as seven years.
The researchers found that 99 percent of patients with hepatitis C who were treated successfully with peginterferon alone, or in combination with ribavirin, had no detectable virus up to seven years later.
"This is the first long-term study that confirms what we believed for many years that these individuals are truly cured of hepatitis C," Shiffman said.
The remaining eight patients tested positive for hepatitis C at an average of two years after treatment. There was no pattern to the patients as far as age, gender or hepatitis C genotype. It isn't known whether these patients had a relapse or were re-infected with the virus, the researchers noted.
The findings were to be presented Monday at the 38th annual Digestive Disease Week conference, in Washington, D.C.
Hepatitis C is a blood-borne infectious disease of the liver and is one of the most important causes of chronic liver disease in the United States. An estimated 4.1 million Americans have been infected with hepatitis C, and 3.2 million are chronically infected. The number of new infections each year declined from an average of 240,000 in the 1980s to about 26,000 in 2004, the latest year for which statistics are available. The number of hepatitis C-related deaths could increase to 38,000 a year by the year 2010, surpassing annual HIV deaths, according to the U.S. Centers for Disease Control and Prevention.
The virus is usually spread through contact with infected blood and blood products. Blood transfusions and the use of shared, unsterilized, or poorly sterilized needles, syringes and injection equipment have been the main routes of transmission in the United States, according to the National Institutes of Health.
Most people who have hepatitis C don't know they have it, Shiffman said. "Of those who have been diagnosed, only about 25 percent have received treatment, because of the side effects of treatment," he said. "The reason why you should treat it is because you can cure hepatitis C, and we finally have the data to definitively document it."
Dr. Eugene Schiff, chief of the division of hepatology and professor of medicine at the University of Miami Miller School of Medicine, agrees that most cases of hepatitis C can be cured.
"In contrast to hepatitis B or HIV, this virus can be totally eradicated and cured," he said.
But, many patients find the side effects of treatment off-putting. Those side effects can include fever and chills, Shiff said. "You feel pretty lousy. After treatment starts, you feel worse the day after your shot, but it tapers off over the course of the week," he said. "Along with that anxiety, irritability and depression can develop. And we are quick to use antidepressants to allow these people to stay on the medication."
Additional side effects include a drop in the production of white blood cells and anemia. Often patients are giving additional drugs to combat these conditions, Shiff said.
Treatments can go on for as many as 72 weeks, depending on the reaction to therapy Shiff said. "Some people are reluctant to get treatment, because they heard that the treatment isn't so pleasant," he said. "But they should come out and get treatment."
Schiff noted that new antiviral drugs to treat hepatitis C are being tested. "It is hoped that these new antivirals will be more effective and have less severe side effects and may even be used without peginterferon alfa-2a or ribavirin," he said.
UMMM--Going to have to call BS on this one. The authors must be in dire need of NIH funding to be making such bold observations. The fact IS, that >60% of patients of HCV infection are already resistant to both therapies. This data is not anything new in the HCV field. The "new" drugs that are being investigated beyond PEG-interferon and nucleoside polymerase inhibitors are very promising however. TLR agonists are coming of age as potent immune stimulators as well as combination cytokine therapy.
Monday, May 21, 2007
FDA Issues Safety Alert on Diabetes Drug
Diabetes Drug Avandia Raises Risk of Heart Attack, Study Suggests; FDA Issues Safety Alert
The widely prescribed diabetes drug Avandia is linked to a greater risk of heart attack and possibly death, a new scientific analysis revealed, and the U.S. government issued a safety alert Monday.
The Food and Drug Administration urged diabetics taking the pill to talk to their doctors, but stopped short of forcing a sharper warning label on the drug sold by GlaxoSmithKline PLC of London.
More than 6 million people worldwide have taken the drug since it came on the market eight years ago. Pooled results of dozens of studies revealed a 43 percent higher risk of heart attack, according to the review published by the New England Journal of Medicine.
Experts said the overall risk was small and cautioned people not to stop taking the drug on their own but to talk to their doctors.
The company downplayed the report of heart risks, saying the analysis by Dr. Steven Nissen and statistician Kathy Wolski at the Cleveland Clinic is not definitive scientific proof. In a conference call Monday, Dr. Lawson McCartney who leads Glaxo's diabetes drug development, said the company is not seeing "anything like" the problems reported in the medical journal.
"We remain very confident in the safety and of course in the efficacy of Avandia as an important diabetic medicine," McCartney said.
The government will take no immediate action on a label change or other measures regarding the drug, said Dr. Robert J. Meyer of the FDA's Center for Drug Evaluation and Research.
Some data suggests "that there is a potentially significant increase in the risk" but there also is risk if patients switch drugs or do not keep their blood-sugar under control, an FDA statement says.
FDA officials acknowledged that Glaxo submitted information last August indicating some increased risk from the drug but that other studies were contradictory. However, several members of Congress expressed alarm and said they would hold hearings on the safety issues.
Avandia is used to treat Type 2 diabetes, the most common form of the disease, which is linked to obesity and afflicts 18 million Americans and 200 million people worldwide. This form of diabetes occurs when the body does not make enough insulin or cannot effectively use what it manages to produce.
Avandia helps sensitize the body to insulin and was considered a breakthrough medication for blood-sugar control.
Worried patients should not quit Avandia on their own and should discuss concerns with their doctors, wrote Drs. Bruce Psaty and Curt Furberg in an editorial in the New England Journal. Psaty is with the University of Washington in Seattle and Furberg is with Wake Forest University.
However, to the extent that the new analysis shows valid risks, the drug "represents a major failure of the drug-use and drug-approval processes in the United States," they said.
When the drug was approved, "evidence was at best mixed" on its benefit, wrote the two doctors. Both have been frequent critics of the FDA's failure to spot dangers in the drug approval process and its conduct in the case involving Vioxx. The popular arthritis medicine sold by Merck & Co. was taken off the market in 2004 when heart problems came to light after it had been taken by millions of people
Several experts said Avandia was another example of the FDA failing to detect a safety problem early enough.
Glaxo's shares trading in the United States fell $3.85, or 6.6 percent, to $53.89 in afternoon trading.
The report on the diabetes drug's risks follow Glaxo's $2.5 million settlement of a lawsuit filed by former New York Attorney General Eliot Spitzer over the release of data on the safety and effectiveness of its drugs. Spitzer, now New York governor, accused Glaxo of fraudulently withholding some results of studies that had examined the safety of prescribing the antidepressant Paxil to children.
The widely prescribed diabetes drug Avandia is linked to a greater risk of heart attack and possibly death, a new scientific analysis revealed, and the U.S. government issued a safety alert Monday.
The Food and Drug Administration urged diabetics taking the pill to talk to their doctors, but stopped short of forcing a sharper warning label on the drug sold by GlaxoSmithKline PLC of London.
More than 6 million people worldwide have taken the drug since it came on the market eight years ago. Pooled results of dozens of studies revealed a 43 percent higher risk of heart attack, according to the review published by the New England Journal of Medicine.
Experts said the overall risk was small and cautioned people not to stop taking the drug on their own but to talk to their doctors.
The company downplayed the report of heart risks, saying the analysis by Dr. Steven Nissen and statistician Kathy Wolski at the Cleveland Clinic is not definitive scientific proof. In a conference call Monday, Dr. Lawson McCartney who leads Glaxo's diabetes drug development, said the company is not seeing "anything like" the problems reported in the medical journal.
"We remain very confident in the safety and of course in the efficacy of Avandia as an important diabetic medicine," McCartney said.
The government will take no immediate action on a label change or other measures regarding the drug, said Dr. Robert J. Meyer of the FDA's Center for Drug Evaluation and Research.
Some data suggests "that there is a potentially significant increase in the risk" but there also is risk if patients switch drugs or do not keep their blood-sugar under control, an FDA statement says.
FDA officials acknowledged that Glaxo submitted information last August indicating some increased risk from the drug but that other studies were contradictory. However, several members of Congress expressed alarm and said they would hold hearings on the safety issues.
Avandia is used to treat Type 2 diabetes, the most common form of the disease, which is linked to obesity and afflicts 18 million Americans and 200 million people worldwide. This form of diabetes occurs when the body does not make enough insulin or cannot effectively use what it manages to produce.
Avandia helps sensitize the body to insulin and was considered a breakthrough medication for blood-sugar control.
Worried patients should not quit Avandia on their own and should discuss concerns with their doctors, wrote Drs. Bruce Psaty and Curt Furberg in an editorial in the New England Journal. Psaty is with the University of Washington in Seattle and Furberg is with Wake Forest University.
However, to the extent that the new analysis shows valid risks, the drug "represents a major failure of the drug-use and drug-approval processes in the United States," they said.
When the drug was approved, "evidence was at best mixed" on its benefit, wrote the two doctors. Both have been frequent critics of the FDA's failure to spot dangers in the drug approval process and its conduct in the case involving Vioxx. The popular arthritis medicine sold by Merck & Co. was taken off the market in 2004 when heart problems came to light after it had been taken by millions of people
Several experts said Avandia was another example of the FDA failing to detect a safety problem early enough.
Glaxo's shares trading in the United States fell $3.85, or 6.6 percent, to $53.89 in afternoon trading.
The report on the diabetes drug's risks follow Glaxo's $2.5 million settlement of a lawsuit filed by former New York Attorney General Eliot Spitzer over the release of data on the safety and effectiveness of its drugs. Spitzer, now New York governor, accused Glaxo of fraudulently withholding some results of studies that had examined the safety of prescribing the antidepressant Paxil to children.
Wednesday, May 16, 2007
Thursday, April 5, 2007
US aims to tighten rules on direct-to-consumer drug ads
With a new Congress controlled by the Democratic Party, the US biotech industry might be facing tighter restrictions on direct-to-consumer (DTC) advertising. This spring, Congress is set to debate measures that include a two-year moratorium on advertising for newly approved products and higher user fees for extra Food and Drug Administration (FDA) staff to monitor television, print and radio advertisements.
The US and New Zealand are the only countries that allow DTC drug advertising, and such ads pumped $4.5 billion into the US media economy in 2006, up from $2.8 billion in 2002, according to the drug and biotech industries.
However, over the past several years—and after the spectacular safety failure in 2004 of a heavily advertised and top-selling drug, the COX-2 inhibitor Vioxx (rofecoxib)—calls have grown louder for more government control.
"The ads have limited educational value and may oversell the benefits of drugs in ways that might conflict with promoting...health," says Dominick Frosch, assistant professor of medicine at the University of California, Los Angeles (UCLA). In the January/February issue of the Annals of Family Medicine, Frosch and colleagues published an analysis of television drug ads, concluding that 95% of analyzed ads appealed to emotion and none mentioned lifestyle changes as an alternative to a pill.
The US and New Zealand are the only countries that allow DTC drug advertising, and such ads pumped $4.5 billion into the US media economy in 2006, up from $2.8 billion in 2002, according to the drug and biotech industries.
However, over the past several years—and after the spectacular safety failure in 2004 of a heavily advertised and top-selling drug, the COX-2 inhibitor Vioxx (rofecoxib)—calls have grown louder for more government control.
"The ads have limited educational value and may oversell the benefits of drugs in ways that might conflict with promoting...health," says Dominick Frosch, assistant professor of medicine at the University of California, Los Angeles (UCLA). In the January/February issue of the Annals of Family Medicine, Frosch and colleagues published an analysis of television drug ads, concluding that 95% of analyzed ads appealed to emotion and none mentioned lifestyle changes as an alternative to a pill.
Riding a bike in the desert: Flomax
Every male mammal will eventually present with symptoms of an enlarged prostate. Non cancerous prostate enlargement is termed benign prostatic hyperplasia (BPH) and is a common chronic disease, with the incidence of BPH increasing with age.
This enlargement causes partial blockage of the urethra which impedes urinary output and and may lead to obstructive and irritative symptoms. It is caused by enlarged cells and cells that grow to compensate the enlarged cells within the prostate. The growing cells are called smooth muscle cells and have specific receptors on their cell surface that can regulate their rigidness, such that when these receptors are inhibited, they relax. This results in increased flow.
Flomax blocks these receptors and causes increased urinary flow by relaxing enlarged/proliferating smooth muscle cells within the prostate.
This enlargement causes partial blockage of the urethra which impedes urinary output and and may lead to obstructive and irritative symptoms. It is caused by enlarged cells and cells that grow to compensate the enlarged cells within the prostate. The growing cells are called smooth muscle cells and have specific receptors on their cell surface that can regulate their rigidness, such that when these receptors are inhibited, they relax. This results in increased flow.
Flomax blocks these receptors and causes increased urinary flow by relaxing enlarged/proliferating smooth muscle cells within the prostate.
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