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Drugs & Aging May 2015Inappropriate medications are often used in older adults despite their unfavourable risk-to-benefit profile. Although many of the medications in the American Geriatrics...
BACKGROUND
Inappropriate medications are often used in older adults despite their unfavourable risk-to-benefit profile. Although many of the medications in the American Geriatrics Society (AGS) Beers list are potentially inappropriate because of their anticholinergic properties, little is known regarding the nature and extent of potentially inappropriate anticholinergic medication use in older adults.
OBJECTIVES
To determine the prevalence of, and factors associated with, potentially inappropriate anticholinergic medication use in the older population.
METHODS
A retrospective, cross-sectional study was conducted, involving older adults (aged 65 years and older), using 2009-2010 Medical Expenditure Panel Survey (MEPS) data. The 2012 AGS Beers Criteria were used to define potentially inappropriate anticholinergic medications on the basis of the list of medications to avoid using in older adults irrespective of the diagnosis. Descriptive analyses were used to examine the nature and extent of potentially inappropriate anticholinergic medication use. Multivariable logistic regression within the conceptual framework of the Andersen Behavioral Model was used to identify the factors associated with potentially inappropriate anticholinergic use in older adults.
RESULTS
According to the MEPS, there were 78.60 million older adults in the USA; an estimated 7.51 million (9.56 %) of these older adults used potentially inappropriate anticholinergic medications in 2009-2010. The most frequently used potentially inappropriate anticholinergics were cyclobenzaprine, promethazine, amitriptyline, hydroxyzine and dicyclomine. Multivariable regression analyses revealed that female sex, residing in the South and the presence of anxiety disorder increased the likelihood of receiving potentially inappropriate anticholinergic medications, whereas older adults aged 75-84 or ≥ 85 years, and those with over 15 years of education, had a decreased likelihood of receiving potentially inappropriate anticholinergic medications.
CONCLUSION
The study found that approximately one in ten older adults used potentially inappropriate anticholinergic medications. Several predisposing, enabling and need factors were associated with the use of potentially inappropriate anticholinergic medications. Concerted efforts are needed to optimize potentially inappropriate anticholinergic medication use in older adults.
Topics: Aged; Aged, 80 and over; Behavior; Cholinergic Antagonists; Cross-Sectional Studies; Educational Status; Female; Geography; Health Services Needs and Demand; Health Status; Humans; Inappropriate Prescribing; Male; Models, Statistical; Prevalence; Retrospective Studies; Sex Factors; Socioeconomic Factors; United States
PubMed: 25832970
DOI: 10.1007/s40266-015-0257-x -
Saudi Pharmaceutical Journal : SPJ :... Mar 2020, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, has been used for the treatment of several respiratory-related...
, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, has been used for the treatment of several respiratory-related disorders. The present study was designed to evaluate the bronchodilatory and antimicrobial activities of leaves crude extract (Of.Cr). Ex-vivo experiments were conducted on guinea-pig trachea provided with physiological oxygenated buffer solution using emkaBath setup. The crude extract was analyzed by gas chromatography-mass spectrometry. Of.Cr, showed the presence of terpenes, fragrance components, saponins, and higher fatty acids. Of.Cr when tested on contracted tracheal chains with carbamylcholine (CCh, 1 µM) and high K (80 mM) produced relaxation by showing higher potency against CCh with incomplete inhibition of high K. Dicyclomine, used as a positive control, also showed selectively higher potency to inhibit CCh when compared with its effect against K. In the anticholinergic curves, Of.Cr at 1 mg/mL deflected CCh-induced concentration-response curves (CRCs) competitively to the right like dicyclomine (0.03 µM) and atropine whereas a higher dose of Of.Cr (3 mg/mL) produced a non-parallel shift in the CCh curves like a higher dose of dicyclomine (0.1 µM). In the calcium channel inhibitory assay, Of.Cr at 3 & 5 mg/mL, deflected CRCs of Ca to the right like verapamil, used as positive control. Of.Cr, at concentrations (1-3 mg/mL) increases cAMP levels in isolated tracheal homogenates, similar to positive control phosphodiesterase inhibitor (papaverine). When tested for antibacterial activity against standard and clinical strains, Of.Cr was found more active (MIC 475 µg/ml) against S. aureus (NCTC 6571), while the maximum inhibition (MIC 625 µg/ml) was observed by the extract when tested against MRSA. These results determine the mechanistic pathways of the observed bronchodilatory effect of with a combination of anticholinergic and dual inhibition of phosphodiesterase and voltage-gated Ca channels.
PubMed: 32194329
DOI: 10.1016/j.jsps.2020.01.007 -
Journal of Ethnopharmacology Mar 2018Cyperus species are famous for their traditional uses and very commonly used for their anti-spasmodic and anti-diarrheal activities. Cyperus niveus Retz. is used in...
ETHNOPHARMACOLOGICAL RELEVANCE
Cyperus species are famous for their traditional uses and very commonly used for their anti-spasmodic and anti-diarrheal activities. Cyperus niveus Retz. is used in local traditional system of medicine in Pakistan to treat diarrhea and emesis.
AIM OF THE STUDY
The aim of the study was to validate the traditional uses and to provide the possible mechanisms for the medicinal use of Cyperus niveus Retz. as anti-spasmodic, anti-diarrheal and anti emetic.
MATERIALS AND METHODS
The in-vivo studies of anti-diarrheal, charcoal meal GI transit test and anti-emetic activities were conducted in rats, mice and chicks respectively, while isolated tissues of rabbit's jejunum and rat's ileum were used for in-vitro experiments. Phytochemical analysis was also undertaken.
RESULTS
The phytochemical study of hydro-ethanolic extract of Cyperus niveus Retz. showed the presence of flavonoids, phenols, alkaloids, tannins, saponins and glycosides. Cn. Cr caused significant inhibition of castor oil-induced diarrhea in rats (300,500 & 700mg/kg) using loperamide (10mg/kg, p.o) as standard. Cn. Cr also significantly decreased the motility in charcoal meal GI transit test at 100-200mg/kg in mice, using atropine (3.0mg/kg) as positive control. In jejunum tissue, Cn. Cr relaxed carbachol(1µM) and K(80mM)-induced contractions, similar to the effect of dicyclomine. Pre-incubation of isolated rat ileum tissues with Cn. Cr (0.1mg/mL) caused the corresponding shift of CCh concentration response curve (CRC) to right without decrease in max. response whereas at the concentration of 0.3mg/mL caused the rightward nonparallel shift with max. response suppression, similar to dicyclomine. Antimuscarinic effect was further confirmed when prior administration of Cn. Cr (0.1, 0.3 and 1mg/mL) caused concentration dependent inhibition of induced contractions of carbachol, comparable to atropine (1µM). To confirm the Ca channel blocking (CCB), the rabbit jejunum was pre-incubated with Cn. Cr (0.3 & 1.0mg/mL), produced a shift in CRCs of calcium toward right with decrease in the maximum response at next concentration, similar to that of dicyclomine. The organic fraction of Cyperus niveus Retz. (Cn. Dcm) showed Ca antagonist and anticholinergic activities with higher potency against K(80mM) induced contractions, like verapamil, while aqueous fraction (Cn. Aq) relaxed only carbachol(1µM) induced contractions with no prominent effect on K (80mM)-contractions even at the higher concentration of 10mg/mL, similar to atropine. Cn. Cr also showed significant anti-emetic effect in Chick emesis model using chlorpromazine as standard.
CONCLUSION
This study shows the presence of antidiarrheal and spasmolytic activities in Cyperus niveus Retz. extract, mediated by dual blocking mechanisms of muscarinic receptors and Ca channels. The results further indicate the presence of anti-emetic activity in Cn. Cr, which may be because of its anti-muscarinic potential. This study provides the scientific bases to the traditional use of Cn. Cr in diarrhea and emesis.
Topics: Animals; Antidiarrheals; Antiemetics; Calcium Channel Blockers; Castor Oil; Chickens; Copper Sulfate; Cyperus; Diarrhea; Female; Flavonoids; Folklore; Gastrointestinal Transit; Ileum; Jejunum; Male; Medicine, Traditional; Mice, Inbred BALB C; Muscarinic Antagonists; Pakistan; Parasympatholytics; Phenols; Phytotherapy; Plant Extracts; Rabbits; Rats, Sprague-Dawley; Vomiting
PubMed: 29122673
DOI: 10.1016/j.jep.2017.11.006 -
Scientific Reports Sep 2019Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera)...
Memory loss is one of the most tragic symptoms of Alzheimer's disease. Our laboratory has recently demonstrated that 'i-Extract' of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naïve mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.
Topics: Animals; Blotting, Western; Dendrites; Dicyclomine; Female; Male; Memory; Mice; Mice, Transgenic; Nerve Regeneration; Neuroprotective Agents; Pilocarpine; Plant Extracts; Receptor, Muscarinic M1; Reverse Transcriptase Polymerase Chain Reaction; Scopolamine; Withania
PubMed: 31570736
DOI: 10.1038/s41598-019-48238-6 -
Behavioral Neuroscience Feb 2016Extensive research has shown the involvement of the central cholinergic system in the acquisition and consolidation of tasks involving conditioned fear responses, such...
Extensive research has shown the involvement of the central cholinergic system in the acquisition and consolidation of tasks involving conditioned fear responses, such as those observed in contextual fear conditioning (CFC), tone fear conditioning (TFC) and inhibitory avoidance (IA). However, there are few data concerning the role of this system in the memory retrieval process. Therefore, the present study aimed to compare the effects of the administration of an M1 antagonist on retrieval during these tasks. For each behavioral procedure, groups of male Wistar rats were trained. Twenty-four hr later, they were treated with different doses of dicyclomine (16, 32, or 64 mg/kg, i.p.) or with saline 30 min before the test session. The results showed that dicyclomine at doses of 16 and 32 mg/kg impaired CFC without interfering with IA performance. Moreover, only 64 mg/kg impaired TFC. These data suggest that M1 muscarinic receptors contribute to memory retrieval in CFC and TFC but are not essential for retrieval in IA.
Topics: Analysis of Variance; Animals; Avoidance Learning; Conditioning, Classical; Dicyclomine; Dose-Response Relationship, Drug; Emotions; Fear; Freezing Reaction, Cataleptic; Male; Mental Recall; Muscarinic Antagonists; Rats; Rats, Wistar
PubMed: 26619084
DOI: 10.1037/bne0000113 -
Journal of Ethnopharmacology Dec 2016Seeds of Sisymbrium irio Linn has been used traditionally in different regions of Pakistan for the treatment of gastrointestinal, airways and vascular system ailments....
Anti-cholinergic and Ca-antagonist mechanisms explain the pharmacological basis for folkloric use of Sisymbrium irio Linn. in gastrointestinal, airways and vascular system ailments.
ETHNOPHARMACOLOGICAL RELEVANCE
Seeds of Sisymbrium irio Linn has been used traditionally in different regions of Pakistan for the treatment of gastrointestinal, airways and vascular system ailments. To insight the pharmacological basis, in vitro study was conducted in order to validate its folkloric uses.
MATERIAL AND METHODS
70% aqueous-methanolic extract of seeds from S. irio (Si.MEs) was tested on isolated rabbit aorta, jejunum and trachea strip hanged in tissue bath having physiological solutions aerated with carbogen and their responses were measured and recorded via Power Lab.
RESULTS
The Si.MEs exhibited the transient spasmogenic effect (0.01-1.0mg/mL) on spontaneous jejunum contractions, followed by the spasmolytic effect. The addition of atropine resulted in blocking in spasmogenic effect while the spasmolytic effect was originated, suggesting the presence of an antimuscarinic effect. Likewise verapamil, Si.MEs (0.03-5mg/mL) repressed the high concentration K(80mM)-induced contraction and also drifted the Ca concentration-response curves toward right (0.3-3.0mg/mL), possibly signifying the Ca channel blockade. Furthermore, Si.MEs exhibited nonspecific relaxant effect on carbachol (1µM)- and high concentration K(80mM)-induced tracheal contractions in a way comparable to dicyclomine, suggesting the coexistence of Ca-antagonistic and/or antimuscarinic properties. Additionally, Si.MEs also relaxed the phenylephrine(1µM)- and high concentration K(80mM)-induced aortic contraction (0.01-3mg/mL), suggesting blockade of Ca channel. Moreover, oral administration of Si.MEs, as high as 6g per kg, did not produce lethality among the treated groups of mice.
CONCLUSIONS
Aqueous-methanolic extract of seeds from S. irio (Si.MEs) exhibited the bronchodilator and gut modulator (spasmogenic and spasmolytic) activities, probably through dual blockade of muscarinic receptors and Ca channels, whereas, vasodilator effect may be due to Ca channels blockade.
Topics: Animals; Aorta; Brassicaceae; Bronchodilator Agents; Calcium Channel Blockers; Cholinergic Antagonists; Dose-Response Relationship, Drug; Ethnobotany; Ethnopharmacology; Female; Folklore; Gastrointestinal Agents; Gastrointestinal Motility; In Vitro Techniques; Jejunum; Male; Methanol; Mice; Muscle Contraction; Phytotherapy; Plant Extracts; Plants, Medicinal; Rabbits; Seeds; Solvents; Trachea; Vasoconstriction; Vasodilator Agents
PubMed: 27693774
DOI: 10.1016/j.jep.2016.09.028 -
Neurochemistry International Jun 2018We demonstrated that activation of protein kinase Cδ (PKCδ) and inactivation of the glutathione peroxidase-1 (GPx-1)-dependent systems are critical for methamphetamine...
We demonstrated that activation of protein kinase Cδ (PKCδ) and inactivation of the glutathione peroxidase-1 (GPx-1)-dependent systems are critical for methamphetamine (MA)-induced recognition memory impairment. We also demonstrated that exposure to far-infrared rays (FIR) causes induction of the glutathione (GSH)-dependent system, including induction of the GPx-1 gene. Here, we investigated whether exposure to FIR rays affects MA-induced recognition memory impairment and whether it modulates PKC, cholinergic receptors, and the GSH-dependent system. Because the PKC activator bryostatin-1 mainly induces PKCα, PKCε, and PKCδ, we assessed expression of these proteins after MA treatment. MA treatment selectively increased PKCδ expression and its phosphorylation. Exposure to FIR rays significantly attenuated MA-induced increases in PKCδ phosphorylation. Importantly, bryostatin-1 potentiated MA-induced phosphorylation of PKCδ. MA treatment significantly decreased M1, M3, and M4 muscarinic acetylcholine receptors (mAChRs) and β2 nicotinic acetylcholine receptor expression. Of these, the decrease was most pronounced in M1 mAChR. Exposure to FIR significantly attenuated MA-induced decreases in the M1 mAChR and phospho-ERK, while it facilitated Nrf2-dependent GSH induction. Dicyclomine, an M1 mAChR antagonist, and l-buthionine-(S, R)-sulfoximine (BSO), an inhibitor of GSH synthesis, counteracted against the protective potentials mediated by FIR. More importantly, the memory-enhancing potential of FIR rays was significantly counteracted by bryostatin-1, dicyclomine, and BSO. Our results suggest that exposure to FIR rays attenuates MA-induced impairment in recognition memory via up-regulation of M1 mAChR, Nrf2-dependent GSH induction, and ERK phosphorylation by inhibiting PKCδ phosphorylation by bryostatin-1.
Topics: Animals; Glutathione Peroxidase; Memory Disorders; Methamphetamine; Mice, Knockout; NF-E2-Related Factor 2; Protein Kinase C-delta; Receptor, Muscarinic M1; Up-Regulation; Glutathione Peroxidase GPX1
PubMed: 29572053
DOI: 10.1016/j.neuint.2018.03.009 -
Journal of Pharmaceutical Sciences Sep 2023
Erratum to Factors Effecting the Morphology of Eudragit S-100 Based Microsponges Bearing Dicyclomine for Colonic Delivery Journal of Pharmaceutical Sciences volume 100 Issue 4 (2011) 1545-1552.
PubMed: 37453528
DOI: 10.1016/j.xphs.2023.07.011 -
Asian Journal of Psychiatry Aug 2019Prescription drug suicide merits study to guide the development of strategies to reduce suicide risk. We examined prescription drug suicide specifically in non-abusers...
BACKGROUND
Prescription drug suicide merits study to guide the development of strategies to reduce suicide risk. We examined prescription drug suicide specifically in non-abusers of prescription drugs; this is a relatively unexplored subject.
METHODS
Six-year data on prescription drug suicide in non-abusers were extracted from the records of the Department of Forensic Medicine at the All India Institute of Medical Sciences, New Delhi. These records contained information obtained from the scene of the suicide, from interviews with relatives of the deceased, and from forensic toxicological analyses at two laboratories.
RESULTS
There were 27 (8%) cases of prescription drug suicide in non-abusers out of 338 cases of suicidal poisoning. The mean age of this sample was 26 years. The sample was 74% male. Nearly half of the cases (44%) were students. A combination of dextropropoxyphene with dicyclomine, with or without paracetamol, was used by 41% of cases. Overdose was achieved through the ingestion of 10-40 (median, 30) tablets or by the injection of 2-3 (median, 2) vials of medication. In 52% of cases, it appeared that the drugs had been procured over the counter.
CONCLUSIONS
It is reassuring that the absolute number of prescription drug suicides in non-abusers was small; the findings, however, are important because they could serve as a baseline for assessing time trends in future studies. For the present, we suggest that prescription drugs of potential abuse, especially those containing opioids and antispasmodics, should be prescribed and dispensed judiciously, especially to youth.
Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Forensic Medicine; Humans; India; Male; Parasympatholytics; Physicians; Prescription Drugs; Retrospective Studies; Students; Suicide; Universities; Young Adult
PubMed: 31374376
DOI: 10.1016/j.ajp.2019.07.039 -
European Journal of Pharmaceutical... Oct 2018Spray-dried chitosan microparticles have been widely exploited as vehicles for mucosal drug delivery. Despite their advantages as pharmaceutical formulations, one of the...
Spray-dried chitosan microparticles have been widely exploited as vehicles for mucosal drug delivery. Despite their advantages as pharmaceutical formulations, one of the major challenges is achieving sustained drug release, which would diminish toxicity and dosage frequency. The aim of this study was to formulate mucoadhesive glutaraldehyde cross-linked chitosan microparticles loaded with doxylamine succinate and pyridoxine hydrochloride as potential nasal drug delivery systems with sustained release. Microparticle models were formulated via spray-drying technique, using glutaraldehyde in different concentrations (0.1-1.0 mg/mL) as a cross-linking agent for chitosan. The obtained particles were with spherical shape, smooth surface and median diameter of 4 μm. The drug entrapment efficiency was high (80.47%-94.25%), indicating a tendency to decrease at higher glutaraldehyde concentrations. FTIR data demonstrated that there were no chemical interactions between glutaraldehyde and the drugs. The in vitro studies showed that the cross-linking process substantially limited particles swelling. The cross-linked particles exhibited sustained drug release characteristics at pH 6.8 over a period of 5 h with an initial burst-effect in the first 30 min. Drug release followed Korsmeyer-Peppas kinetics. Although a decrease of the particles mucoadhesive properties was observed after modification, all cross-linked formulations demonstrated high in vitro adsorption of mucin. The proposed models of mucoadhesive microsphere with sustained drug release are a perspective ground for further development of a novel delivery system for nasal administration of doxylamine and pyridoxine.
Topics: Adhesiveness; Administration, Intranasal; Antiemetics; Chemistry, Pharmaceutical; Chitosan; Cross-Linking Reagents; Delayed-Action Preparations; Dicyclomine; Doxylamine; Drug Carriers; Drug Combinations; Drug Compounding; Drug Liberation; Feasibility Studies; Gastric Mucins; Glutaral; Kinetics; Microspheres; Pyridoxine; Solubility
PubMed: 30077710
DOI: 10.1016/j.ejps.2018.07.059