Dry Eye Disease: Focus on Prescription Therapy.

Objective To review the pharmacotherapy of prescription drugs approved for treatment of chronic dry eye disease (DED). A brief background on DED management and the pharmacist's role for care is included. Data Sources Articles indexed in PubMed (National Library of Medicine), Iowa Drug Information Service, Cochrane Reviews and Trials, and Google Scholar in the past 10 years using the key words "dry eye," "dry eye and treatment," "cyclosporine," "lifitegrast," and "varenicline." Current guidelines and manufacturers' prescribing information were reviewed. Primary sources were used to locate additional resources. Study Selection/Data Extraction Sixty-five publications were reviewed, and criteria supporting the objectives identified useful resources. Data Synthesis Selected literature included practice guidelines, review articles, research articles, product prescribing information, and drug information databases. Conclusion Patient education, eliminating causative factors, improving the daily environment for eye health, and using ocular lubricants are the first steps in DED management. A therapeutic mainstay is ocular lubricants; preservative-free formulations are recommended for chronic or repeated daily use. The Food and Drug Administration approved prescription medications for chronic use for DED, cyclosporine ophthalmic emulsion and solution, lifitegrast ophthalmic solution, and varenicline nasal spray, all improve signs and symptoms but do not cure DED. The ophthalmic products all cause ocular discomfort upon instillation. As a nasal spray, varenicline does not cause ocular discomfort, but it can cause sneezing, cough, and throat and nose irritation in some patients. Pharmacists have an opportunity to provide patient education regarding lifestyle modifications to mitigate DED and provide counseling on available products. Emerging therapies may provide advances in DED treatment.

Post-traumatic Stress Disorder in Middle Age and Beyond.

OBJECTIVE: To review the clinical manifestations and treatment of post-traumatic stress disorder (PTSD) in adults and older people. DATA SOURCES: Articles indexed in PubMed, Embase, psychology databases, and the Cochrane library over the past 10 years using the key words "post-traumatic stress disorder," "stress disorders," and "post-traumatic stress disorder and treatment." STUDY SELECTION AND DATA EXTRACTION: Sixty-seven publications were reviewed and criteria supporting the primary objective were used to identify useful resources. DATA SYNTHESIS: The literature included practice guidelines; review articles; original research articles; and product prescribing information for the clinical manifestations, diagnosis, and treatment of PTSD. CONCLUSION: Psychotherapy is the first-line therapy for PTSD. Pharmacologic therapy is recommended, as second-line therapy, for adults living with PTSD who do not have access to psychotherapy or refuse psychotherapy. Pharmacologic therapy may also be considered in cases of partial, or no, response to psychotherapy. Current guidelines recommend prescribing one of 3 selective serotonin-reuptake inhibitors, either fluoxetine, paroxetine, or sertraline, or prescribing the serotonin norepinephrine reuptake inhibitor venlafaxine, for adult patients who do not have access to psychotherapy or prefer not to use psychotherapy. Unfortunately, these recommended medications have additional cautions for use in older people so may not be appropriate for many older people living with PTSD. Therapy for older people should be tailored to patient-specific symptoms, with careful consideration of the potential benefits and risks of the therapy and coexisting medical conditions of each patient.

Therapy for Open-Angle Glaucoma.

OBJECTIVE: Review the clinical manifestations and treatment of primary open-angle glaucoma (POAG). DATA SOURCES: Articles indexed in PubMed, Scopus, and Cochrane Library in the last 10 years using the key words "glaucoma," "open-angle glaucoma," and "'open-angle glaucoma' AND 'treatment.'" Primary sources were used to locate additional resources. ClinicalTrials. gov was used to locate unpublished studies. STUDY SELECTION AND DATA EXTRACTION: Eighty-one publications were reviewed and criteria supporting the primary objective were used to identify useful resources. DATA SYNTHESIS: The literature included practice guidelines, review articles, original research articles, and product prescribing information for POAG. CONCLUSION: The POAG optic neuropathies result in optic disk damage and visual field loss. Ophthalmic medication therapy retards glaucoma progression, but many older patients require multiple medications to preserve vision and quality of life. An agent from the ophthalmic prostaglandin analog class is used as initial therapy in current practice because of the convenience of once-a-day administration and lower incidence of systemic side effects and slightly increased efficacy compared with other available ophthalmic medication classes. The other ophthalmic medication classes used in clinical practice include the beta-adrenergic blocking agents, the alpha-2 adrenergic agonists, and the carbonic anhydrase inhibitors. Proper ophthalmic eye-drop administration and medication adherence are imperative for preserving vision in POAG. Selective laser trabeculoplasty is a viable alternative to ophthalmic medications either initially or if a patient experiences ocular or systemic side effects from medication therapy. A modified prostaglandin analog was approved by the Food and Drug Administration in November 2017; its role in clinical practice is still evolving.

Adolescent chronic restraint stress (aCRS) elicits robust depressive-like behavior in freely cycling, adult female rats without increasing anxiety-like behaviors.

Stress during times of rapid development is a risk factor for Major Depressive Disorder, a mood disorder that disproportionately affects women. We developed an adolescent chronic restraint stress (aCRS) protocol using female rats to address the impact of adolescent stress on female adult depressive-like behavior. Animals were divided into 4 treatment groups: not restrained:saline (NRSAL), not restrained:desipramine (NRDES), restrained:saline (RSAL), and restrained:desipramine (RDES). NRSAL and NRDES rats were housed in a separate colony room from RSAL and RDES rats. All animals were weighed and handled daily. Beginning postnatal day (PND) 34(±1), RSAL and RDES rats were restrained for 1 hour daily for 14 consecutive days. Beginning PND 55(±1), NRDES and RDES rats were given subcutaneous desipramine (5 mg/kg), which served as a positive control, daily for 14 consecutive days. During that same time period, NRSAL and RSAL rats were given subcutaneous saline daily. aCRS (RSAL and RDES) rats showed significantly attenuated weight gain compared with nonrestrained (NRSAL and NRDES) rats during the restraint period. Weight gain normalized after the final restraint session. Behavioral testing took place PND 68-69(±1), and included open field testing, the elevated plus maze, locomotor activity, and the forced swim test (FST). RSAL rats showed significantly more immobility in the FST versus all other groups, indicating depressive-like behavior. No differences between groups were observed in the other behavioral measures. These results indicate that aCRS elicits depressive-like behavioral characteristics in adult female rats without increasing anxiety-like behaviors. (PsycINFO Database Record

Fish oil and flax seed oil supplemented diets increase FFAR4 expression in the rat colon.

BACKGROUND AND OBJECTIVE: Omega-3 fatty acids, such as α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are polyunsaturated fatty acids (PUFA) that have long been associated with anti-inflammatory activity and general benefit toward human health. Over the last decade, the identification of a family of cell-surface G protein-coupled receptors that bind and are activated by free-fatty acids, including omega-3 fatty acids, suggest that many effects of PUFA are receptor-mediated. One such receptor, free-fatty acid receptor-4 (FFAR4), previously described as GPR120, has been shown to modulate anti-inflammatory and insulin-sensitizing effects in response to PUFA such as ALA and DHA. Additionally, FFAR4 stimulates secretion of the insulin secretagogue glucagon-like peptide-1 (GLP-1) from the GI tract and acts as a dietary sensor to regulate energy availability. The aim of the current study was to assess the effects of dietary omega-3 fatty acid supplementation on FFAR4 expression in the rat colon. METHODS: Sprague-Dawley rats were fed control soybean oil diets or alternatively, diets supplemented with either fish oil, which is enriched in DHA and EPA, or flaxseed oil, which is enriched in ALA, for 7 weeks. GLP-1 and blood glucose levels were monitored weekly and at the end of the study period, expression of FFAR4 and the inflammatory marker TNF-α was assessed. RESULTS: Our findings indicate that GLP-1 and blood glucose levels were unaffected by omega-3 fatty acid supplementation, however, animals that were fed fish or flaxseed oil-supplemented diets had significantly heightened colonic FFAR4 and actin expression, and reduced expression of the pro-inflammatory cytokine TNF-α compared to animals fed control diets. CONCLUSIONS: These results suggest that similar to ingestion of other fats, dietary-intake of omega-3 fatty acids can alter FFAR4 expression within the colon.

Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome.

We have previously reported that acute and chronic donepezil and nicotine administration significantly attenuate DOI-induced head twitch response (HTR) in mice. This behavior, primarily mediated by stimulation of 5-HT2A receptors, has been proposed to model tic symptoms seen in Tourette's syndrome (TS). Haloperidol, a drug widely used to treat symptoms of TS, has also been reported to reduce DOI-induced head shakes in rodents when administered acutely. These findings suggest an inhibitory interaction of these drugs with 5-HT2A receptors. To test this hypothesis, we evaluated the effects of chronic donepezil, nicotine and haloperidol on expression levels of 5-HT2A mRNA and 5-HT2A receptor density in select brain regions. Initially, we established a dose-response relationship for the acute and chronic haloperidol and DOI-induced HTR. Male ICR mice were treated twice daily with donepezil (0.1 mg/kg), nicotine (0.5 mg/kg), and once daily with haloperidol (0.4 mg/kg) for 14 days and were sacrificed 16-18 h after the last injection. These drug regimens were chosen because of their significant effects on DOI-induced HTR. Donepezil significantly increased 5-HT2A mRNA level, but not the receptor density in the striatum. In the midbrain, donepezil significantly decreased the receptor density without affecting the 5-HT2A mRNA level. In the frontal cortex, only haloperidol significantly reduced the 5-HT2A receptor density. The cortex was the only area where donepezil, nicotine and haloperidol significantly reduced the 5-HT2A receptor density. The results suggest that the anti-tic properties of donepezil, nicotine and haloperidol in this paradigm might be due to antagonism of cortical 5-HT2A receptors. Thus, further investigation of involvement of cortical 5-HT2A receptors in TS as well as evaluation of selective 5-HT2A receptor antagonists in this disorder is warranted.

Effects of donepezil on DOI-induced head twitch response in mice: implications for Tourette syndrome.

Tourette syndrome (TS) is a neurological disorder characterized by persistent motor and phonic tics. Administration of the selective 5-HT(2A/2C) agonist 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induces head twitches in mice that have been proposed to model tics seen in TS. Previous studies have demonstrated that nicotine markedly attenuates DOI-induced head twitch response (HTR). This and the reports that nicotine may have clinical efficacy in reducing symptoms of TS suggest possible involvement of the nicotinic cholinergic system in this disorder. Donepezil is an acetylcholinesterase inhibitor approved for use in mild to moderate Alzheimer's disease. The purpose of this study was to investigate whether donepezil might also reduce DOI-induced HTR, and whether its combination with nicotine might result in an additive or synergistic effect. Moreover, to elucidate the possible role of nicotinic receptors in this paradigm, the effects of mecamylamine, a nicotinic antagonist, was also evaluated. Acute and chronic administration of donepezil (0.1 mg/kg) or nicotine (0.5 mg/kg base), significantly reduced DOI-induced HTR. No additive or synergistic effects of donepezil and nicotine were observed. Acute mecamylamine administration (0.5-5.0 mg/kg) dose-dependently inhibited DOI-induced HTR. None of the mecamylamine doses blocked the inhibitory effects of donepezil or nicotine on DOI-induced HTR. These results suggest that donepezil may have therapeutic potential in treating motor tic symptoms of TS. Moreover, the action of donepezil and nicotine may be mediated through the same mechanism.