Medication compliance in Singaporean patients with Alzheimer's disease

INTRODUCTION@#Singapore has a rapidly ageing population and an increasing prevalence of Alzheimer's disease (AD). Compliance to AD medications is associated with treatment effectiveness. We investigated compliance to acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonist and treatment persistence among patients seen at the General Memory Clinic of National University Hospital, Singapore. We also identified the reasons for non-compliance.@*METHODS@#Patients seen at the General Memory Clinic between 1 January 2013 and 31 December 2014, who were prescribed AChEIs and NMDA receptor antagonist, were included in this retrospective cohort study. Non-compliance to medications was indirectly measured by failure to renew prescription within 60 days of the last day of medication supplied by the previous prescription. The reasons for non-compliance were identified.@*RESULTS@#A total of 144 patients were included. At one year, 107 patients were compliant to AD medications, while 37 patients were non-compliant. Around 60% of the non-compliant patients discontinued the use of AD medications within the first six months, and the mean persistent treatment period among this group of patients was 10.3 ± 3.5 months. The main reason for non-compliance was patients' and caregivers' perception that memory loss was of lower priority than other coexisting illnesses. Other reasons for non-compliance included side effects of medications (18.9%), perceived ineffectiveness of treatment (16.2%), inability to attend clinic (5.4%) and high cost of medications (2.7%).@*CONCLUSION@#Our findings suggest that the reasons for medication non-compliance can be identified early. Better compliance may be achieved through a multidisciplinary approach to patient education.

Accentuation of general anaesthetic activity of ketamine by glutamate NMDA (N-methyl D-aspartate) receptor antagonist

Background: The aim of the present study was to evaluate the potentiation of general anaesthetic activity of ketamine by NMDA receptor antagonist ‘amantadine’ in wistar albino rats.Methods: The wistar albino rats of either sex were divided into three groups of five animals in each group. Group I received ketamine 80mg/kg, group II received ketamine 40mg/kg along with amantadine 40mg/kg and group III received ketamine 80mg/kg along with amantadine 40mg/kg to evaluate the potentiation of general anaesthetic effect of ketamine. The sleep latency time and the total sleeping time were measured in all the three groups.Results: The sleep latency time of group III is significantly decreased (p <0.035) and as equal to that of group II when compared to group I. The sleeping time of group III is significantly increased (p <0.001) when compared to group I.Conclusions: Amantadine - the NMDA receptor antagonist potentiates the general anaesthetic activity of ketamine.

The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.

Other N-Methyl-D-Aspartate (NMDA) Receptor Antagonists with a Rapid Onset of Action and Less Side Effect in the Treatment of Depression

Mood disorder is a common psychiatric illness with a high lifetime prevalence in the general population. Many prescribed antidepressants modulate monoamine neurotransmitters including serotonin, norepinephrine and dopamine. There has been greater focus on the major excitatory neurotransmitter in the human brain, glutamate, in the pathophysiology and treatment of major depressive disorder (MDD). Recently, ketamine, an N-methyl-D-aspartate receptor antagonist, has received attention and has been investigated for clinical trials and neurobiological studies. In this article, we will review the clinical evidence for glutamatergic dysfunction in MDD, the progress with ketamine as a rapidly acting antidepressant, and other N-methyl-D-aspartate receptor antagonist for treatment-resistant depression.

Ifenprodil for trigeminal neuralgia with resistance to carbamazepine

Ifenprodil, NMDA receptor antagonist, was very effective in the treatment of 3 patients with severe trigeminal neuralgia. <b>Patient 1</b>：A 70-year-old female had been treated for macroglobulinemia in our hospital. She had been suffered from severe trigeminal neuralgia for more than ten years. Carbamazepine given in another hospital was ineffective. We gave ifenprodil to her and it reduced her pain within 4 weeks. However, her pain relapsed after 1.5 years, so we gave pregabalin instead of ifenprodil to her. <b>Patient 2</b>：A 89-year-old male had been treated for myelodysplastic syndrome in our hospital. He also had been treated for trigeminal neuralgia in another hospital. Carbamazepine was ineffective and nerve block relieved his pain temporarily. We gave ifenprodil to him and it reduced his pain within 2 months. <b>Patient 3</b>：A 62-year-old female was referred to our hospital for the treatment of trigeminal neuralgia. She had been suffered from severe pain for about 10 years. She had taken carbamazepine with no effect. We gave ifenprodil to her and it reduced her pain within 4 weeks. Ketamin, non-selective NMDA receptor antagonist, is known to be effective in neuropathic pain, but it has various side effects. Ifenprodil, specific NMDA receptor subunit NR2B antagonist, may show better separation between efficacy and side effects.

The Trial of Continuous Intravenous Infusion of Magnesium in Patients with Postherpetic Neuralgia Refractory in Conventional Treatment: A report of 2 cases / 대한마취과학회지

Postherpetic neuralgia is one of the most troublesome diseases in pain clinics. The N-methyl-D-aspartate (NMDA) receptor antagonist, magnesium, reduces the level of neuropathic pain and hyperalgesia in patients with postherpetic neuralgia. Magnesium has been shown to exert a physiological block of the ion channel on the NMDA receptor, thereby preventing extracellular calcium ions from entering the cell and contributing to secondary neuronal changes. Accordingly, we attempted to administer a continuous intravenous infusion of magnesium, which resulted in a decrease in the VAS without side effects.

Antagonists of NMDA Receptor, Calcium Channel and Protein Kinase C Potentiate Inhibitory Action of Morphine on Responses of Rat Dorsal Horn Neuron

he present study was designed to examine whether the co-application of morphine with Ca2+ channel antagonist (Mn2+, verapamil), N-methyl-D-aspartate (NMDA) receptor antagonist (2-amino-5-phosphonopentanoic acid[AP5], Mg2+) or protein kinase C inhibitor (H-7) causes the potentiation of morphine- induced antinociceptive action by using an in vivo electrophysiological technique. A single iontophoretic application of morphine or an antagonist alone induced weak inhibition of wide dynamic range (WDR) cell responses to iontophoretically applied NMDA and C-fiber stimulation. Although there was a little difference in the potentiating effects, the antinociceptive action of morphine was potentiated when morphine was iontophoretically applied together with Mn2+, verapamil, AP5, Mg2+ or H-7. However, the potentiating action between morphine and each antagonist was not apparent, when the antinociceptive action evoked by morphine or the antagonist alone was too strong. These results suggest that the potentiating effect can be caused by the interaction between morphine and each antagonist in the spinal dorsal horn.

Therapeutic Effect of Amantadine in Traumatic Brain Injury Patients: Two Cases and Review

We reported two cases of amantadine treatment in traumatic brain injury patients and reviewed the literature of amantadine treatment of those patients. Problems with short-term memory, attention, planning, problem solving, impulsivity, disinhibition, poor motivation, and other behavioral and cognitive dificit could occur following traumatic brain injury or other types of acquired brain injury. this report described results of amantadine using in two patients with this type of symptom profile. Patients received neuropsychiatric examination as well as BPRS and Barthel index. These patients were improved, respectively from 57 point to 82 point(case 1), from 85 to 94(case 2) in Barthel index, and from 66 point to 35 point(case 1), from 55 to 32 point(case 2) in BPRS. These two patients did not reveal any other adverse effect. The rationale for using amantadine were discussed.

Morphometric Study of the Effects of Various Analgesic Compound in Experimental Arthritis Model / 대한해부학회지

Arthritis is the most common disease of joint in old age and almost all the old human are suffering from arthritis. Arthritis gives so severe pain hard to endure that it can devastate human. But we still do not know where the arthritic pain comes from and the generation mechanism of it. For the study of effects of anti-inflammatory drugs on the c-fos immunoreactive neurons, substance P-and CGRPimmunoreactive neurons in dorsal horn and DRG, cyclooxygenase (COX) inhibitors indomethacin (0.5 mg/kg), piroxicam (0.5 mg/kg), NMDA receptor antagonist MK 801 (2 mg/kg), and capsaicin (50 mg/kg) were administered to the experimental arthritis model. Male Sprague-Dawley rats were used for this study. Arthritis was induced by injection of 4% kaolin followed by 2% carrageenan into the articular capsule of left knee. Two hours, 24 hours and 7 days after injection, animals were sacrificed and processed for imunohistochemical staining for c-fos in spinal dorsal horn, for substance P (SP) and CGRP in DRG. The results were as follows; 1. The number of c-fos immunoreactive neurons were significantly decreased at 2 h after piroxicam and MK-801 administration and 1 week after indomethacin, MK-801 and capsaicin treatment in the inflamed side of dorsal horn. 2. There were the significant decrease of SP-and CGRP-immunoreactive area 2 h after indomethacin administration and 1week after capsaicin treatment in the inflamed side of dorsal horn. 3. The number of SP- and CGRP-immunoreactive neurons in DRG were decreased after drugs administration and no difference is in the degree of effectiveness between drugs. Indomethacin and piroxicam which is an inhibitors of COX, significantly reduced the expression of c-fos proteins and desensitized nociceptive primary afferents at the early time, and capsaicin, a pungent algesic substance, decreased the level of c-fos protein, SP and CGRP over a wider time in dorsal horn and DRG.

The use of Amantadine in Traumatic Brain Injury Patients

Avariety of symptoms can occur following traumatic brain injury(TBI) or other types of acquired brain injury. These symptoms can include problems with short-term memory, attention, planning, problem solving, impulsivity, disinhibition, poor motivation, and other behavioral and cognitive deficit. These symptoms may respond to certain drugs, such as dopaminergic agents. Amantadine may protect patients from secondary neuronal damage after brain injury as a effects of NMDA receptor antagonists and may improve functioning of brain-injured patients as a dopaminergic agonist. Clinically, based on current evidence, amantadine may provide a potentially effective, safe, and inexpensive option for treating the cognitive, mood and behavioral disorders of individuals with brain injury. The rationales for using amantadine are discussed, and pertinent literatures are reviewed.

Effect of NMDA Receptor Antagonist (APV)on the Toxicity Induced by Oxygen Radicals in Cultured Myocardial Cells / 체질인류학회지

Toxic effect of oxygen radicals and cardioprotective effect of N -methyl -D -aspartate (NMDA) receptor antagonists against xanthine oxidase (XO) and hypoxanthine (HX)-induced cardiotoxicity were measured in order to elucidate the mechanism of cardiotoxicity on cultured mouse myocardial cells. MTT assay was performed after myocardial cells were cultured for 12 hours at various concentrations of XO/HX alone or with D -2 -amino -5 -phosphonovaleric acid (APV) or 6 - cyano -7 -nitroquinoxaline -2,3 -dione (CNQX). In this study, XO/HX was toxic in a time -and dose -dependent manners on cultured myocardial cells, and midcytotoxicity value 50 (MTT50) was at 30 mU/ml XO and 0.1 mM HX after myocardial cells were grown for 12 hours in media containing 1 ~50 mU/ml XO and 0.1 mM HX. When cultures were treated with 30 mU/ml XO and 0.1 mM HX flus 20 80 microM APV for 12 hours, cell viability was increased remarkably, while treatment with 30 mU/ml XO and 0.1 mM HX flus 10 ~50 microM CNQX did not show any protective effect against XO/HX -induced neurotoxicity. From the above results, it is suggested that oxygen radicals are toxic on cultured mouse myocardial cells by the decrease of cell viability, and NMDA receptor antagonists such as APV are very effective in the prevention of myocardial toxicity induced by oxygen radicals.

The Effects of Intrathecal Ketamine Isomers on Formalin-Evoked Behavior and Spinal c-fos Expression in Rat / 대한마취과학회지

BACKGROUND: This study was designed to investigate the different analgesic potency and the action mechanism of the intrathecal isomers of ketamine. For these purpose, we evaluated the effect of intrathecal ketamine isomers on the behavioral response and the spinal c-fos expression in the formalin tested rats. METHOD: The subjects were divided into 2 groups(NF group, Fgroup). The NF group was designed for the purpose of the drug itself's effect on the induction of c-fos. Saline(NF/saline group), S(+) ketamine(NF/SK group), R(-) ketamine(NF/RK group) and ketamine(NF/K group) were administered intrathecally to be examined by immunocytochemical method. Same drugs were administered in the F group(F/saline, F/SK, F/RK, F/K) and formalin was injected into right hind paw of the rats after 30 minutes of intrathecal drug administration. The number of flinching was counted at intervals of 5 minutes for 60 minutes. In NF and F group, Fos immunoreactive neurons was counted after 2 hours of formalin injection and intrathecal drug injection respectively. RESULTS: In F/saline group, flinching was developed immediately after formalin injection and revealed biphasic response. The number of flinching in F/SK group, F/RK group, F/K group was significantly smaller than that of F/saline group. The number of flinching of F/SK group by comparison of F/SK vs F/RK was significantly smaller, and that of F/K group by comparison of F/RK vs F/K was significantly smaller. There was no significant difference among NF group on the total number of Fos immunoreactive neurons. In F group, Fos immunoreactive neurons increased significantly in comparison with NF group. The total number of Fos immunoreactive neurons in F/SK group, F/RK group and F/K group were significantly smaller than that of F/saline group. Of F group, the number of Fos immunoreactive neurons of F/SK was the smallest and F/K, F/RK followed increasing order. Attenuation of Fos induction by the ketamine isomers was observed in the whole spinal cord of F/SK group and F/K group but in the superficial and deep laminae of F/RK group. CONCLUSION: This study suggests that intrathecal ketamine isomers have an inhibitory effect on pathologic pain and c-fos expression in the rats and different analgesic effect which is lamina specific.