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UAB receives NIH grant to proceed analysis of latest treatment for IPF

Posted in News on 25th August 2018

The College of Alabama at Birmingham has acquired a grant from the Nationwide Institutes of Well being totaling $ Eight.9 million to fund a multiyear program evaluating the position of a brand new treatment in a scientific trial for sufferers affected by idiopathic pulmonary fibrosis (IPF).

Victor Thannickal, M.D., the Ben Vaughan Branscomb Chair of Medication in Respiratory Illness and division director of Pulmonary, Allergy and Essential Care, says UAB was chosen amongst a extremely aggressive group of educational establishments to maneuver this translational program venture grant into the scientific testing part.

“UAB has one of many largest interstitial lung illness applications within the nation,” he stated. “It can be crucial that we obtain grants like this so we are able to proceed to develop higher therapies for fibrotic lung ailments.”

Whereas there at present is not any treatment for IPF, the drug GKT831 is designed to enhance on present medication that don’t enhance survival or high quality of life, and Thannickal says it might be higher tolerated than present drugs.

The part II scientific trial can be a placebo managed, double blind, randomized, parallel group research to guage the protection and efficacy of GKT831. A complete of 60 sufferers can be allotted to a 48-week remedy with the drug or matching placebo. The scientific trial is the centerpiece of this system venture grant that can be led by Steven Duncan, M.D., professor within the Division of Pulmonary, Allergy and Essential Care Medication. Different key UAB investigators in this system embody Brent Carter, M.D., Veena Antony, M.D., and Rui-Ming Liu, Ph.D.

IPF is a illness by which the gas-exchanging areas of the lungs often called alveoli develop into thickened and scarred over time. As alveoli scar, the capability of the lungs to correctly transfer oxygen into the bloodstream turns into restricted. This ends in progressive shortness of breath and ultimately results in proper coronary heart failure and dying.

Thannickal says roughly 150,000 People and 5 million individuals worldwide undergo from IPF, and 40,000 die every year. He cites that genetic dangers in addition to environmental dangers – smoking – can enhance the probability of creating the illness.

He provides that with the ability to check medication like GKT831 in each early and late part scientific trials makes UAB a singular place to advance novel therapies for IPF.

“The science that allowed us to develop this therapeutic technique was truly primarily based on a biochemical exercise I found virtually 20 years in the past,” he stated. “IPF has been my lifelong ardour, not solely to know the illness course of, however to have the ability to devise more practical therapies. Is that this going to be the reply? We do not know, however we predict it has extra promise than what’s already on the market.”

Recruiting for the trial will start as early as April 2019. UAB is the first middle, and different collaborating establishments embody the College of Michigan, College of Minnesota, Temple College and Tulane College.

Supply:

http://www.uab.edu/information/analysis/merchandise/9700-thannickal-receives-Eight-9-million-grant-to-continue-testing-of-new-drug-for-ipf

Human trial identifies frequent blood strain medicine as secure, efficient remedy for diabetes

Posted in News on 10th July 2018

Researchers on the College of Alabama at Birmingham Complete Diabetes Middle have found a secure and efficient novel remedy to cut back insulin necessities and hypoglycemic episodes in grownup topics with latest onset Sort 1 diabetes by selling the affected person’s personal beta cell operate and insulin manufacturing — the primary such discovery to focus on diabetes on this method.

The findings, revealed in the present day by Nature Medication, reveal that common oral administration of verapamil, a standard blood strain medicine first permitted for medical use in 1981, enabled sufferers to supply increased ranges of their very own insulin, limiting their want for insulin injections to stability out their blood sugar ranges.

The randomized, double-blind, placebo-controlled human trial recognized verapamil as a secure, efficient, and promising remedy — a groundbreaking discovering within the area of diabetes analysis.

“The info collected from our scientific trial offers us each indication to consider that people with Sort 1 diabetes have the promise of a remedy strategy that would scale back their exterior insulin necessities and enhance their blood sugar management and high quality of life, due to the results that verapamil has in selling the physique’s personal beta cell operate,” stated Anath Shalev, M.D., director of UAB’s Complete Diabetes Middle and principal investigator of the trial. “Whereas this analysis shouldn’t be an end-all remedy for Sort 1 diabetes, these findings are getting us nearer to disease-altering therapies that may allow people with Sort 1 diabetes to have extra management over their illness and keep a few of their physique’s personal insulin manufacturing.”

In 2014, Shalev’s UAB analysis lab found that verapamil utterly reversed Sort 1 diabetes in animal fashions and sought to check the results of the drug in human topics in a scientific trial, funded by a $ 2.1 million grant from the JDRF. Verapamil has been Meals and Drug Administration permitted and accessible for prescription for the remedy of hypertension for greater than three many years. Nonetheless, Shalev’s analysis marks the primary time that the drug has been examined for security and efficacy in treating Sort 1 diabetes.

Sort 1 diabetes happens as the results of one’s immune system attacking the beta cells within the pancreas that produce insulin to control and keep optimum blood sugar ranges. When beta cells are being destroyed, an individual’s capacity to supply insulin declines, inflicting blood sugar ranges to rise and making the individual an increasing number of depending on exterior insulin. The UAB scientific trial found that when a affected person takes verapamil, beta cell operate is preserved, enabling the physique to supply extra of its personal insulin. This lessened the scientific trial individuals’ reliance on exterior insulin, which all people with Sort 1 diabetes should have to successfully regulate their blood sugar ranges.

“At JDRF, we’re excited and inspired by the latest findings from the UAB Complete Diabetes Middle’s scientific trial. This information has the potential to alter how we take into consideration treating and in the end curing T1D,” explains Andrew Rakeman, Ph.D., assistant vp of analysis at JDRF. “We sit up for continued scientific research that can construct on and ensure these findings, increasing to further affected person populations and guiding how, when and in who verapamil may need probably the most impression in T1D.”

The verapamil scientific trial monitored 24 sufferers age 18 to 45, every over the course of 1 yr. Eleven sufferers acquired verapamil and 13 acquired placebo. All scientific trial individuals had been identified with Sort 1 diabetes inside three months of their begin within the trial and continued with their prescribed insulin pump remedy all through the length of the examine. Researchers monitored the placebo and verapamil teams’ whole every day dose of insulin, the quantity of insulin produced, the p.c change in insulin manufacturing, and their HbA1C ranges. As well as, the variety of hypoglycemic occasions that the sufferers skilled had been recorded, and the p.c of time every affected person registered in wholesome blood glucose ranges had been analyzed utilizing a steady glucose monitoring system.

“Though this can be a smaller pattern group, our trial outcomes give us promise that topics with Sort 1 diabetes have remedy choices and that we’re nearing a more practical solution to cope with this illness,” stated Fernando Ovalle, M.D., director of UAB’s Complete Diabetes Clinic and co-principal investigator of the examine. “Past verapamil permitting topics with Sort 1 diabetes the power to reside a life with much less exterior insulin dependence, these findings will impression the standard of life that they’ll have. Hopefully, by bettering total blood sugar management it’s going to additionally restrict their dangers for different comorbidities, together with coronary heart assault, blindness, kidney illness, and extra.”

Whereas this examine particularly addressed findings in grownup topics identified inside three months of the trial’s begin, Shalev notes that future long-term research are wanted to assist decide the impact of verapamil on each the pediatric Sort 1 diabetes inhabitants, and people with Sort 1 diabetes who’ve been residing with and/or identified with the illness longer than three months. Moreover, verapamil’s results on Sort 2 diabetes haven’t been examined or studied in potential managed trials; Shalev stated and future research that discover the potential for this routine to positively impression Sort 2 diabetes are due to this fact additionally wanted. Nonetheless, in mouse fashions of Sort 2 diabetes and in latest epidemiological research verapamil use has been related to decrease danger of growing Sort 2 diabetes and with higher blood sugar management.

“This trial’s outcomes affirm that we’re heading in the right direction and are getting into a brand new part of discovery because it pertains to this illness,” Shalev stated. “Diabetes impacts greater than 30 million folks in America alone, and hopefully our breakthrough will in the end result in approaches that may assist enhance the lives of all these affected by this illness.”

Supply:

http://www.uab.edu/information/analysis/merchandise/9585-human-clinical-trial-reveals-verapamil-as-an-effective-type-1-diabetes-therapy

Loperamide Diarrhea Remedy Overdose: Buying and selling One Lethal Habit For One other?

Posted in News on 6th April 2018

Final November, paramedics within the Pittsburgh suburb of Fox Chapel have been known as to the house of 29-year-old Arjun Patel, the place they discovered the younger man useless. This previous week, the health worker for Allegheny County revealed the reason for Patel’s demise: an overdose of a typical, over-the-counter diarrhea medicine containing loperamide.

Based on a doctor working at a neighborhood poison management heart, Patel’s case represents a rising and alarming pattern: loperamide abuse. Emergency doctor Dr. Michael Lynch says he has seen a rise of almost 170 p.c in calls involving loperamide overdose – and over half of these sufferers required hospitalization. Talking on a neighborhood tv information affiliate, Dr. Lynch stated, “We’re seeing individuals take 60 to 100 to a few hundred of drugs in a day.”

Loperamide is the lively ingredient in frequent, over-the-counter diarrhea drugs similar to Imodium A-D. First developed in 1969, it’s typically prescribed or utilized by individuals affected by gastroenteritis and inflammatory bowel illness in addition to occasional bouts of diarrhea. It’s included on the World Well being Group’s Listing of Important Medicines and customarily thought-about one of many most secure and handiest drugs for this function. At usually advisable doses, unwanted effects are minor and rare.

It is usually an opioid – and therein lies the basis of a rising downside.

Since these drugs don’t usually require a prescription and could be bought for round .30¢ per tablet (much less for generic variations), opioid addicts can simply receive tons of of doses, which they use merely to get “excessive.” Nevertheless, that’s solely a part of the equation. It is usually what the Washington Put up describes as “the poor man’s methadone.” As prescription opioids grow to be tougher to acquire as laws tighten, individuals battling dependancy to medication similar to morphine, heroin, and hydrocodone have found that loperamide can present reduction for withdrawal signs. Sadly, at excessive doses, loperamide could cause severe coronary heart injury and respiratory misery, affecting the central nervous system – with probably deadly penalties.

In response to this rising disaster, the FDA has requested producers of diarrhea to repackage their merchandise into single doses. The company’s present head, Dr. Scott Gottlieb, has additionally requested on-line distributors of loperamide to “take voluntary steps” in curbing abuse. If this doesn’t assist to deal with the issue, it’s doable that loperamide shall be faraway from drugstore cabinets (as was the case with pseudoephedrine, a decongestant used within the manufacture of methamphetamines) and moved behind the counter, which might require sufferers to request it from a pharmacist.

Common Remedy for Sexual Dysfunction Could Assist Forestall Colorectal Most cancers as Nicely

Posted in News on 25th March 2018

Sildenafil – initially offered by Pfizer beneath the model identify Viagra, however now obtainable in generic kind – has a variety of medical functions past the one for which it was initially developed. As well as, treating erectile dysfunction, sildenafil may be prescribed off-label for pulmonary hypertension, altitude illness, and enlarged prostate, in addition to a uncommon circulatory dysfunction often called Raynaud syndrome. Now, researchers from Augusta College and the College of South Carolina report every day dose of sildenafil may assist to cut back the chance of colorectal most cancers by as a lot as 50 %.

The research appeared this week in Most cancers Prevention Analysis. Colorectal most cancers is the third most typical type of the illness, affecting roughly four.5 % of males and simply over four % of ladies. Whereas correct weight loss plan and minimizing alcohol consumption can assist stop the illness, some people with a selected genetic mutation are at greater danger. The mutation impacts a gene often called adenomatous polyposis coli, or the “APC” gene. A standard APC gene works to suppress the formation of tumors; nonetheless, when it’s malfunctioning, a lot of polyps can develop within the decrease gastrointestinal tract, which might turn into malignant.

Within the research, scientists added sildenafil to the consuming water of laboratory mice that had been bred to be predisposed to the formation of pre-cancerous polyps. It seems that the treatment will increase the physique’s ranges of cyclic guanosine monophosphate (CGMP), which helps to control calcium in addition to the features that rely upon it. A type of features is to take care of stability within the mobile lining of the intestinal wall that protects the internal layer from dangerous pathogens. That mobile layer, often called the epithelium, performs an vital function in immune operate. When the epithelium is compromised, the outcome may be inflammatory bowel illness, celiac or Crohn’s Illness.

As well as, sildenafil prevents the manufacturing of an enzyme referred to as phosphodiesterase-5 (PDF-5), which amongst different issues, causes CGMP to interrupt down. By inhibiting PDF-5, larger quantities of CGMP are made obtainable to the cells lining the intestines, strengthening the protecting layer.

One other helpful impact of sildenafil is its capacity to assist the pure strategy of apoptosis (cell dying). Satirically, though untreated most cancers invariably kills its host, the illness itself represents an odd kind of immortality on the mobile stage; cells proceed to proliferate and refuse to die a pure dying. Dr. Darrell Browning, the lead writer of the research, explains that when sildenafil is run in small quantities, “we shrink the entire proliferating compartment in an space of our physique that immediately offers with no matter we put in our mouths and usually experiences excessive cell turnover.”

Sildenafil is just not with out unintended effects, the most typical of that are complications, flushing, indigestion and sinus issues. Nevertheless, the dose wanted to forestall colorectal most cancers is so small that the majority sufferers wouldn’t expertise these. The following research will contain human topics who’re at excessive danger for growing colorectal most cancers.

Gout treatment could assist enhance coronary heart perform in grownup sufferers

Posted in News on 27th February 2018

Researchers on the College of Cincinnati (UC) School of Medication have proven that probenecid, a drug lengthy used to deal with gout, might be able to enhance coronary heart perform in grownup sufferers who expertise coronary heart failure.

The outcomes are revealed within the Journal of the American Coronary heart Affiliation primarily based off a examine of 20 sufferers on the College of Cincinnati Medical Middle.

“We had been testing if probenecid was protected for sufferers,” says Jack Rubinstein, MD, affiliate professor within the Division of Cardiovascular Well being and Illness, and corresponding creator for the examine. “We all know that it was very more likely to be protected as a result of the medication had been taken by individuals of all ages for many years. It has a really robust security profile. We had been fairly fortunately stunned it improved the 2 principal methods in how the center features. It improves how the center contracts and the way it relaxes.”

The sufferers had been supplied probenecid as a part of a randomized, double-blind, crossover and placebo-controlled single-center medical trial. Sufferers, who averaged 57 years of age, had been enrolled throughout four-week intervals between June 2013 and April 2015.

They had been required to bear an echocardiogram, an electrocardiogram and six-minute endurance check together with different assessments, explains Rubinstein, a UC Well being heart specialist and member of the UC Coronary heart, Lung and Vascular Institute.

The examine’s first creator is Nathan Robbins, a senior analysis assistant within the UC School of Medication, who began out volunteering with Rubinstein within the laboratory inspecting the echocardiograms of animals handled with probenecid earlier than later being employed to assist recruit coronary heart failure sufferers.

“That is the primary time probenecid has been utilized in coronary heart failure sufferers and we confirmed it will increase the ejection fraction in sufferers with coronary heart failure,” says Robbins. “It was thrilling to have the ability to see this medication work from the bench to the bedside.”

Rubinstein additionally partnered with primary scientists led by Sakthivel Sadayappan, PhD, professor within the UC School of Medication and director of the center department of the UC Coronary heart, Lung and Vascular Institute. Sadayappan and his researchers examined probenecid in animal coronary heart cells and located it improved how effectively the center makes use of calcium, an necessary part in cardiac muscle contraction.

“The medication works in methods we find out about and in methods we do not find out about,” says Rubinstein. “For the previous 4 or 5 years we’ve got been determining a few of the methods the medication works. We’ve got discovered a variety of them, however there’s nonetheless lots we do not know.”

Coronary heart failure happens when the center pump will not be robust sufficient to maneuver blood all through the physique and meet the physique’s wants for oxygen, explains Rubinstein. It impacts 5.7 million individuals in the US, in line with the Facilities for Illness Management and Prevention.

“The repercussions are probably significant–if we’re capable of affirm this experiment in bigger research with longer-term comply with up–this might current a brand new approach of treating coronary heart failure for which there are restricted medical therapies accessible,” says Rubinstein.

“Left ventricular help units, pacemakers, coronary heart transplants and medicines can be found to deal with coronary heart failure sufferers, however outcomes for sufferers with coronary heart failure are nonetheless worse than outcomes for the overwhelming majority of most cancers sufferers,” says Rubinstein. “That is what we wish to successfully change.”

Different researchers within the UC School of Medication additionally aiding the examine are Mark Gilbert, MD, Mohit Kumar, James McNamara, PhD, Patrick Daly, MD, Sheryl Koch, PhD, Ginger Conway, Mohamed Effat, MD, and Jessica Woo.

The examine carried out at UC Medical Middle is expounded to Rubinstein’s work with probenecid to deal with youngsters and younger adults with hypoplastic left coronary heart syndrome. He obtained a $ 154,000 grant in June 2017 from the American Coronary heart Affiliation and Youngsters’s Coronary heart Basis to deal with this challenge with researchers at Cincinnati Youngsters’s. Hypoplastic left coronary heart syndrome is a beginning defect that impacts regular blood circulate via the center.

Supply:

http://healthnews.uc.edu/information/?/29740/