A study was conducted to see whether liraglutide helped with improving excessive daytime sleepiness for those with Type II diabetes who were also obese. This included 158 obese adults with a body mass of over 30kg/m2 and Type II diabetes who had begun liraglutide therapy at the start of the study. A significant amount of data was collected, including data from the Epworth Sleeping Scale (ESS), anthropometric parameters, glucose-control, and metabolic parameters. This data was collected at baseline and at both one month and three months after baseline.
The results showed major reductions in ESS score with the study participants at both months 1 and 3 (-1.3±2 p <0.001 and -1.5 ± 3.0 p<-.001, respectively). Significant reductions were also seen after 3 months in body weight, BMI, waist and neck circumferences, HbA1c, mean blood glucose, fasting blood glucose, triglycerides, and total cholesterol levels.
Overall, 3 months of liraglutide treatment proved effective in reducing excessive daytime sleepiness in obese participants with Type II diabetes. More research is required to see if liraglutide could improve other abnormal sleep pattern disorders and obstructive sleep aponea. I am wondering if liraglutide does one day prove to be effective in improving these disorders, would it be able to be indicated for patients without diabetes or obesity but with sleep disorders?
BMC Endocr Disord. 2015 Dec 4;15:78
A study was performed on C57BL/6J and APP/PSI mice to determine how NO2 affected neuronal function. This was done because air pollution has been connected with higher risks of cognitive impairment and neurodegenerative diseases. NO2 is a typical primary air pollutant and a contributor to aerosols. In this study, the mice were exposed to NO2 inhalation. This showed that this inhalation led to spatial learning and memory deterioration, aggravated amyloid β42 (Aβ42) accumulation, and induced pathological abnormalities and cognitive defects associated with Alzheimer’s disease.
The data showed that cyclooxygenase-2 (COX-2)-mediated arachidonic acid metabolism of prostaglandin E2 (PGE2) played a key role in these results. It was found that increasing endocannabinoid 2-arachidonoylglycerol (2-AG) by inhibiting monoacylglycerol lipase (MAGL) prevented the production of PGE2, Aβ42 accumulation, and neurodegeneration. This showed that MAGL inhibitors could be a potential drug therapy for treating NO2-induced cognitive impairment.
The questions I have are how would we know when to recommend this therapy and what are the side effects of it? Could it be used to treat Alzheimer’s Disease? Is this even a safe method for treating impaired neuronal function?
Sci Rep. 2016 Mar 01;doi:10.1038/srep22429
A study was done to evaluate sleep and mood disorders for patients with irritating ocular disease. This study was conducted in six eye clinics with 503 outpatients who had been diagnosed with irritating ocular surface diseases. 301 patients had dry eye disease (DED), and 202 of the participants had other ocular surface diseases.
For the 146 participants with severe dry eye disease, the mean Pittsburgh Sleep Quality Index (PSQI) was 6.4 ± 3.2, and the mean Hospital Anxiety and Depression Scale (HADS) score was 11.1 ± 5.7. For the 155 with mild DED, the mean PSQI was 5.5 ± 3.3 and the mean HADS score was 9.8 ± 4.0. For the 124 with chronic conjuctivitis, the PSQI was 5.5 ± 3.1 and the HADS score was 9.5 ± 6.6, and for the 78 with allergic conjuctivitis, the PSQI was 5.0 ± 3.3 and the HADS score was 8.9 ± 5.3.
These results showed that there were statistically significant differences among all of the four aforementioned groups for PSQI (p<0.05). It was determined the PSQI and HADDS scores were correlated significantly with how severe the participants’ DED was (p<0.05). Sleep quality is much worse in patients with DED compared to those with other irritating ocular surface disorders. The more severe the dry eye disease, the worse the sleep quality. I am curious about what medications can be prescribed to people with this disorder to help them get better sleep.
Sci Rep. 2016 Mar 01;doi:10.1038/srep22480
Glutathione (GSH) deficiency is one of the first negative effects of Parkinson’s Disease (PD). This deficiency has been linked to causing oxidative stress, mitochondrial dysfunction, impaired autophagy, and cell death. This information led to the hypothesis that GSH supplementation may be able to help alleviate Parkinson’s symptoms or to help slow down its progression.
A study was done to test the effectiveness of GSH supplementation as a drug therapy for PD. 15 participants with midstage PD were included in this study, and its more specific objective was to evaluate whether intranasal GSH, (in)GSH, is capable of increasing CNS GSH concentrations. This was determined by a magnetic resonance spectroscopy scan done on each of the participants. After baseline GSH levels were measured, each participant self administered 200 mg (in)GSH while they were in the scanner. After this, serial GSH levels were obtained in these participants over the course of an hour.
There was statistically significant evidence that (in)GSH increased brain GSH relative to the base amount (p<0.001). There was no increase in GSH 8 minutes after the (in) GSH was administered, but the levels were higher than baseline at all the other time points. This was the first study to show that intranasal GSH elevates brain GSH levels.
Apparently, GSH supplementation increases GSH brain levels for at least one hour for people with Parkinson’s. I am curious to see what further studies will be done to determine if this increase could last for longer. As of now, I do not know how reliable GSH supplementation is as a treatment for Parkinson’s disease because it is not efficient to have to take any medication every hour. I also am wondering if any studies will be done to see the effect of GSH supplementation on the other symptoms of Parkinson’s disease.
NPJ Parkinsons Dis. 2016 Feb 25;doi:10.1038/npjparkd.2016.2
Vitamin B12 is crucial for brain development and function. This is because vitamin B12’s active metabolites are important cofactors for two reactions. One reaction involves the metabolite methylcobalamin (MeCbl), and it is folate dependent methylation of HCY to methionine by methionine synthase in the cytoplasm. The other metabolite, adenosylcobalamin (AdoCbl), is used as a cofactor for the conversion of methylmalonylCoA to succinylCoA by methylmalonyl CoA mutase in mitochondria. Despite us knowing this, vitamin B12’s role in the brain across the lifespan has not been investigated until this study.
In this study, the levels of five vitamin B12 species in postmortem human frontal cortexes of 43 control subjects were measured. These cortexes ranged from those of 19 week old fetuses to those of 80 year old individuals. Of the subjects, twelve of them were autistic and nine of them were schizophrenic.
The results of this study showed that total B12 levels were significantly lower in the front cortexes of the older control subjects 60 years and older. This reflected over a ten fold age dependent decline in the B12 metabolite MeCbl. Levels of another B12 metabolite, cyanocobalamin (CNCbl) were much higher in fetal brain samples, further showing that vitamin B12 levels decrease with age. The levels of MeCbl and AdoCbl in autistic and schizophrenic subjects were more than three fold lower than the controls that were the same age as these subjects, but who did not have autism or schizophrenia.
This study is interesting to me because it makes me wonder whether taking vitamin B12 supplements would help with aging, or improve the mental state of those with autism or schizophrenia. I feel that it may be beneficial for pharmacists to recommend these supplements to patients with autism or schizophrenia. However, it is important that if they do begin doing this that they counsel these patients or their caregivers on the common side effects of taking vitamin B12 supplements. Some of these side effects include joint pain, dizziness, headache, and nasopharyngitis.
PLoS ONE. 2016;11(1): 1-19.
A study was done on rats to test the effectiveness of acetylcholinesterase inhibitors for smoking cessation therapy. This involved training rats to self administer 0.03 mg/kg per 0.59 mL doses of nicotine intravenously on a fixed-ratio-5 schedule of reinforcement. This means the rats were given positive reinforcement every 5 times they administered the nicotine themselves during this training. Once they were self-administering nicotine consistently, they were given one of two acetylcholinesterase inhibitors, 3.0 mg/kg of donepezil or 5.0 mg/kg of galantamine. They were given one of the two medications once daily for ten days, each day right before their daily nicotine self-administration sessions. Each day these medications were given to the rats, the rats’ self-administration of nicotine clearly decreased based on observation. Researchers knew this was not due to malaise-like adverse effects of the drugs because repeated administration of the drugs did not affect sucrose self-administration or food intake for the rats.
A study was also done on humans to test whether acetylcholinesterase inhibitors were effective for smoking cessation. For one week, a group of smokers were given either 8.0 mg of galantamine or a placebo daily. For the second week, without a break in between the two weeks, the same individuals were given 16.0 mg of the same medication or the placebo daily. This helped prove galantamine plays a role in smoking cessation therapy because the smoking rate and smoking satisfaction of those taking it decreased over these two weeks compared to those taking the placebo. Overall, I found this article very interesting, and I am curious to see if this class of medications actually begins to be used for smoking cessation therapy. I am also wondering if individuals will need to be on as strong of doses as those who are taking the same class medications for disease states such as Alzheimer’s.
Transl. Psychiatry. 2016;713(6):1-8.
Schizophrenic patients on antipsychotic medications tend to experience the adverse effect of dyslipidemia. At this time, no effective treatments have been established to treat this adverse effect. As a result, data was pooled from two randomized, placebo-controlled trials. 201 schizophrenic patients that experience antipsychotic-induced dyslipidemia were either given 1000 mg of metformin to take each day for 24 weeks, or a placebo.
After the 24 week period, the mean difference in the LDL values between individuals receiving metformin and those receiving the placebo treatment decreased by 1.02 mmol/L. Only 25.3% of patient in the metformin group had LDL levels greater than or equal to 3.37 mmol/L, while 64.8% of those in the placebo group had LDL levels greater than or equal to that. It is evident that metformin is effective in reversing antipsychotic-induced dyslipidemia. This study also showed that metformin helped people on antipsychotics lose weight, lowered their total cholesterol and triglyceride levels, and increased their HDL levels. Additionally, insulin resistance can be induced by antipsychotics, and metformin would help with this as well.
After reading about this study, I am wondering whether automatically putting schizophrenic patients on metformin as well as antipsychotics should become the normal protocol. Should this happen, or should we as pharmacists monitor their cholesterol and insulin levels while they are on antipsychotics and only suggest they begin metformin if they exhibit any of the aforementioned adverse effects? If we do put these patients on metformin, how should we counsel and monitor them?
Mol. Psychiatry. 2016 Jan 26;doi:10.1038/mp.2015.221.
This article discusses a clinical pharmacist, Dr. Keliana O’Mara, who works in the neonatal ICU at the University of Florida Health Shands Hospital. She is the only pharmacist in this unit, and her role there is incredibly important.
One of the sickest patients that O’Mara had to work with was a baby girl who was born at 28 weeks gestation. This baby had a congenital diaphragmatic hernia and cardiac defect. Because her diaphragm did not develop completely, her abdominal contents were pushed into her chest cavity, and as a result she only had the functionality of 1.5 of her lungs.
O’Mara did a significant amount to save this baby’s life while the baby was in the neonatal ICU. She was in charge of the pain and sedation management for the infant as she went in and out of several surgeries for developmental defects. After all of the infant’s surgeries, O’Mara realized that the infant had developed a fungus in her blood. As a pharmacist, she was able to notice that the antifungal that the infant was to be started on would most likely not work because the infant had been on it previously, and the fungus in the infant’s blood was most likely resistant to the medication as a result. O’Mara was able to collaborate with the primary physician and get the medication changed to a broader spectrum antifungal medication. This was beneficial because a later culture showed that the fungus in the infant’s blood would have indeed been resistant to the original medication.
Another role that O’Mara has in the neonatal ICU is to help implement better treatment methods there. For example, by looking at 2 years of vancomycin dosing data, O’Mara realized that half of the infants in the NICU never reached a therapeutic level of this antibiotic in their blood. As a result, she got permission to begin individualized pharmacokinetic/pharmacodynamic dosing for vancomycin. This is when a pharmacist evaluates serial blood concentrations of a drug after patients receive the first dose. The pharmacist then creates an appropriate dosing regiment personalized for each patient based on these values. Doing this for vancomycin ultimately led to a quicker clearance of bacterial infections in infants in this NICU, and therefore a shorter amount of time that they needed to be on the antibiotic.
Pharmacists who work in the neonatal ICU are additionally crucial because of how small the doses are for babies. Pharmacists must make sure that an infant is never getting too much medication and that mixtures of medications are always made properly. Adding more fluid to a dose to dilute it is not possible for a 500 mg infant because this could lead to fluid overload in the baby. As a result, pharmacists working in this unit have to be extra precise and careful. They also need to make sure the team they are working with understands the latest drug data. It is their job to show physicians when a medication should not be used in an infant, for example if scientific data shows that the treatment and placebo yields the same response from a drug.
I overall found this article very interesting. It is incredible how different one’s experience can be as a pharmacist just by working in one unit of a hospital over another. It also is crazy to think how easy and life threatening it can be to mess up one small part of an infant’s medication regimen. It is clear that a pharmacist is crucial in the NICU of every hospital, and it amazes me how much of an impact one pharmacist can have on saving someone’s life and allowing a premature baby to one day make it home.
Pharmacy Today. 2015;Health-System Edition:2-3.