Use of Hypertension Drugs Leads to Hip Bone Loss in Older Men

Powerful diuretics, commonly prescribed drugs for heart failure and hypertension, can also steal calcium from the bones and cause significant bone loss in men taking them, study finds.

Between 2000 and 2002, Dr. Lionel S. Lim of Griffin Hospital, in Derby, Connecticut and colleagues tested the bone mineral density levels of 3,269 men older than age 65. Patients received follow-up examinations about 4.6 years later. The researchers collected data on medication use and found that 84 men were continuous users of loop diuretics, 181 were intermittent users and 3,004 were non-users.

At the end of the study, the researchers found that the average annual rate of decline in total hip bone mineral density was -0.78 among continuous users, -0.58 among intermittent users and -0.33 among nonusers.

“Compared with rates of hip bone loss among non-users of diuretics, adjusted rates of loss were about twofold greater among intermittent loop diuretic users and about 2.5-fold greater among continuous loop diuretic users,” wrote Dr. Lim and colleagues in the study.

These findings come to reinforce previous studies, which have found an association between the use of powerful diuretics and increased risk of fractures.

“We conclude that loop diuretic use in older men is associated with increased rates of hip bone loss. Our findings suggest that health care providers should take into account loop diuretic use when evaluating older men for risk factors for bone loss and fracture risk,” the study wrote.

The findings were similar for change at the femoral neck and trochanter, the researchers said.

The study, supported by the national Institute of Health, was published in the April 14 issue of the Archives of Internal Medicine.

Source: eFluxMedia.com

Study Finds Possible Targets for H.I.V. Drugs

Using a new type of genetic screen, researchers at Harvard Medical School have identified 273 proteins that the AIDS virus needs to survive in human cells, opening up new potential targets for drugs.

Their work, published online on Thursday by Science magazine, used RNA interference to screen thousands of protein-making genes; previously, scientists had identified only 36 human proteins that the virus uses to break into cells, hijack their machinery and start reproducing.

“This is just terrific work,” said Dr. Robert C. Gallo, director of the Institute of Human Virology at the University of Maryland and a co-discoverer of the virus. “I think it’s destined to be one of the top papers in this field for the decade.”

Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases and the government’s top AIDS expert, called the Harvard team’s work “elegant science,” but added a caution.

“It remains to be seen if any of these proteins they identified are useful clinically,” Dr. Fauci said. “This is hypothesis-generating, not hypothesis-solving. It creates a lot of work — someone has to go down each of these pathways.”

The lead author on the paper, Dr. Stephen J. Elledge, is a geneticist, and this is his first work on the human immunodeficiency virus, which causes AIDS. His previous work has been on cancer, Dr. Elledge said, trying to figure out how cells sense when their chromosomes are broken, and this paper was a collaborative effort.

“I can’t even grow H.I.V. in my lab,” Dr. Elledge said, so he had to use virus grown by Dr. Judy Lieberman, director of the medical school’s AIDS division and one of the co-authors.

Dr. Elledge’s team used a library of tens of thousands of different short interfering RNAs, bits of genetic code — each of which, when introduced into a cell, knocks out the cell’s ability to make a single protein.

Next, about 21,000 samples of cells, each crippled in its ability to produce one protein, were placed in separate wells on laboratory plates and dosed with the virus.

If the virus could not reproduce normally in a given well, it suggested that the missing protein was one of those it needed.

Of the 273 human proteins identified, only 36 had been previously found by other methods.

The virus, which is itself only a short string of genetic material inside a protective capsule, can make only 15 proteins, so it has to adopt human proteins to its own use.

The advantage of targeting human proteins is that the virus would presumably not be able to mutate to avoid drugs that block them, Dr. Elledge said. Right now, virus strains evolve resistance to antiretroviral drugs, which attack the 15 proteins made by the virus itself, like reverse transcriptase and protease. The mutations force AIDS patients to switch drug regimens — not always successfully.

The disadvantage is that blocking human proteins can, obviously, be fatal to humans. But, as Dr. Gallo pointed out, cancer therapy works that way — doctors try to block proteins that feed fast-growing tumor cells without killing too many other fast-growing cells, like those in the bone marrow.

Right now, Dr. Elledge said, only one drug that targets one of the known human proteins, a receptor called CCR5, has been developed, and it has just won approval.

The new screening technology, known as siRNA, is now used in many laboratories, so this work could theoretically have been done elsewhere, or by using older, more laborious methods.

Dr. Elledge said he benefited from working at Harvard, which could afford the expensive robotics and imaging technology needed.

“And I had lots of collaborators and very dedicated people,” he said.

To confirm that the newly identified proteins were important to the life cycle of the virus — which Dr. Elledge described as “opaque” — the team ran further tests on three of them.

Many of the proteins identified by the screen are already known to be important to cells in the immune system, which is the port of entry for H.I.V.

Dr. Abraham L. Brass, a co-author, said the screening method undoubtedly missed other proteins the virus needs, “but the majority of the ones we found are highly likely to play a role in H.I.V. propagation.”

Source: www.nytimes.com

Hypertension Drugs May Prevent and Treat Alzheimer’s, Study Finds

Drugs commonly used to treat hypertension, may be successful in preventing Alzheimer’s disease, according to a new study published in The Journal of Clinical Investigation.

In the study, researchers at the Mount Sinai School of Medicine found that geriatric patients who are being treated for high blood pressure with hypertenstion drugs may cut their risks of developing Alzheimer’s disease.

The researchers studied more than 1,500 drugs currently available to treat other disorders to determine the effectiveness of the drugs in preventing Alzheimer’s. They found that of the 55 drugs studied, seven drugs used to treat hypertension were the most effective.

Researchers found that the drugs prevented beta-amyloid production, a fragment of protein in the brain that is usually eliminated but forms a kind of plaque, or blockage, in the brain of Alzheimer’s patients.

The drugs may also prevent further deterioration in those who are already afflicted with Alzheimer's, according to the study. One drug, Valsartan, was given to Alzheimer’s diseased mice, at a three or four times lower than the normal dosage for humans, and the drug still prevented further production of this blockage in the brain.

The effectiveness of hypertension drugs in preventing this blockage in the brain may help identify future treatments that can prevent cognitive deterioration and dementia in Alzheimer’s patients, according to researchers. However, studies on human patients is necessary.

"The use of these drugs for their potential anti-Alzheimer’s disease role is still highly experimental, and at this stage we have no clinical data beyond phenomenological observation in humans" said Dr. Pasinetti, director of the Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer's disease at Mount Sinai. "We need to complete preventive and therapeutic clinical trials in the near future if we are to identify certain anti-hypertensive drugs with anti beta-amyloid antioligomeric activities, which will need to be prescribed at dosages that do not interfere with blood pressure in normotensive Alzheimer’s disease patients."

FDA: Sudden Hearing Loss Linked To Erectile Dysfunction Drugs

money.cnn.com

The U.S. Food and Drug Administration said Thursday it's approved new erectile dysfunction drug labels to more prominently display the potential risk of sudden hearing loss.

The labeling change - first reported by CNBC - applies to Pfizer Inc.'s (PFE) Viagra, Eli Lilly & Co.'s (LLY) Cialis, Levitra marketed by GlaxoSmithKline PLC (GSK), Schering-Plough Corp. (SGP) and Bayer AG (BAY). The agency said the change will also apply to Pfizer's Revatio, a drug with the same active ingredient as Viagra that's used to treat pulmonary arterial hypertension.

The FDA said it found a total of 29 reports of sudden hearing loss among patients taking the erectile dysfunction drugs. The agency said the search of its adverse-events database was prompted by a case report in medical literature of a patient with sudden hearing loss who was taking Viagra. Such adverse-event reports, which are filed to the FDA by drug companies, doctors and patients, does not mean a particular drug has caused a problem.

The FDA said hearing loss was also reported in a few patients in clinical trials of these drugs. The FDA said in most cases the sudden hearing loss occurred in one ear.

All of the drugs fall into a category of drugs known as PDE5 inhibitors.

"Though no causal relationship has been demonstrated, FDA believed that the strong temporal relationship between the use of PDE5 inhibitors and sudden hearing loss in these cases warranted revisions to the product labeling for the drug class," the FDA said in a statement posted on its Web site.

The agency noted that hearing loss is commonly reported in an aging population, especially in patients with risk factors for erectile dysfunction. "However, sudden hearing loss is an uncommon event at any age," the agency said.

Amylin drug suspected in pancreatitis cases: FDA

in.reuters.com

WASHINGTON (Reuters) - Amylin Pharmaceuticals Inc's and Eli Lilly and Co's diabetes drug Byetta may be linked to cases of acute pancreatitis in some patients, U.S. health officials said in an alert issued on Tuesday.

The U.S. Food and Drug Administration said it has reviewed 30 reports of pancreatitis in patients taking Byetta, known generically as exenatide.

"An association between Byetta and acute pancreatitis is suspected in some of these cases," an FDA alert said.

Amylin has agreed to add information about acute pancreatitis to the precautions section of Byetta's label, the FDA said.

Shares of Eli Lilly and Amylin were off 1.3 percent and 4.5 percent, respectively, in afternoon trading after the FDA alert. Shares of Alkermes Inc, the drug-delivery technology of which is being used to develop a long-acting version of Byetta, were down about 5 percent.

Officials at Amylin were not immediately available for comment. A Lilly spokeswoman had no immediate comment.

The FDA said doctors should tell patients taking Byetta to seek prompt medical care if they develop unexplained, persistent severe abdominal pain, which may or may not be accompanied by vomiting.

Byetta should be discontinued should pancreatitis be suspected, the FDA said. Should pancreatitis be confirmed, Byetta should not be restarted unless an alternative cause is identified, the agency advised.

(Additional reporting by Lewis Krauskopf and Ransdell Pierson in New York and Toni Clarke in Boston)