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Table 2. 2012 AGS Beers Criteria for Potentially
Table 2. 2012 AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults Strength of Organ System/ Recommendat Quality of Recomm Therapeutic Category/Drug(s) Rationale ion Evidence endation References Anticholinergics (excludes TCAs) First-generation antihistamines Highly anticholinergic; Avoid Hydroxyzin Strong Agostini 2001 (as single agent or as part of clearance reduced with e and Boustani 2007 combination products) advanced age, and promethazi Guaiana 2010 Brompheniramine tolerance develops ne: high; Han 2001 Carbinoxamine when used as hypnotic; All others: Rudolph 2008 Chlorpheniramine increased risk of moderate Clemastine confusion, dry mouth, Cyproheptadine constipation, and other Dexbrompheniramine anticholinergic Dexchlorpheniramine effects/toxicity. Diphenhydramine (oral) Doxylamine Use of diphenhydramine in Hydroxyzine special situations such Promethazine as acute treatment of Triprolidine severe allergic reaction may be appropriate. Antiparkinson agents Not recommended for Avoid Moderate Strong Rudolph 2008 Benztropine (oral) prevention of Trihexyphenidyl extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease. Antispasmodics Highly anticholinergic, Avoid Moderate Strong Lechevallier- Belladonna alkaloids uncertain except in Michel 2005 Clidinium-chlordiazepoxide effectiveness. short-term Rudolph 2008 Dicyclomine palliative Hyoscyamine care to Propantheline decrease Scopolamine oral secretions. Antithrombotics Dipyridamole, oral short-acting* May -
Consumer Medicine Information
New Zealand Datasheet Name of Medicine DOZILE Doxylamine Succinate 25 mg Capsules Presentation Liquid filled soft gel capsules, purple, containing 25 mg doxylamine succinate. Uses Actions Doxylamine succinate is a white or creamy white powder with a characteristic odour and has solubilities of approximately 1 g/mL in water and 500 mg/mL in alcohol at 25°C. It has a pKa of 5.8 and 9.3. A 1% aqueous solution has a pH of 4.8 - 5.2. Doxylamine succinate is an ethanolamine derivative antihistamine. Because of its sedative effect, it is used for the temporary relief of sleeplessness. The drug is also used in combination with antitussives and decongestants for the temporary relief of cold and cough symptoms. It is not structurally related to the cyclic antidepressants. It is an antihistamine with hypnotic, anticholinergic, antimuscarinic and local anaesthetic effects. Duration of action is 6-8 hours. Pharmacokinetics Following oral administration of a single 25 mg dose of doxylamine succinate in healthy adults, mean peak plasma concentrations of about 100 ng/mL occur within 2- 3 hours after administration. The drug has an elimination half-life of about 10 hours in healthy adults. Absorption It is easily absorbed from the gastrointestinal tract. Following an oral dose of 25 mg the mean peak plasma level is 99 ng/mL 2.4 hours after ingestion. This level declines to 28 ng/mL at 24 hours and 10 ng/mL at 36 hours. Distribution The apparent volume of distribution is 2.5 L/kg. Metabolism The major metabolic pathways are N-demethylation, N-oxidation, hydroxylation, N- acetylation, N-desalkylation and ether cleavage. -
(12) Patent Application Publication (10) Pub. No.: US 2014/0100249 A1 Sears Et Al
US 201401.00249A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0100249 A1 Sears et al. (43) Pub. Date: Apr. 10, 2014 (54) THERAPEUTIC TREATMENT A63/37 (2006.01) A613 L/45 (2006.01) (71) Applicants: Douglas Sears, Oak Park, CA (US); A613 L/4458 (2006.01) Michael Reilly, Oak Park, CA (US) (52) U.S. Cl. CPC ............... A61K 45/06 (2013.01); A61 K3I/451 (72) Inventors: Douglas Sears, Oak Park, CA (US); (2013.01): A613 L/4458 (2013.01); A61 K Michael Reilly, Oak Park, CA (US) 3 1/137 (2013.01); A61 K31/165 (2013.01) USPC .......................................................... S14/325 (21) Appl. No.: 14/046,528 (57) ABSTRACT (22) Filed: Oct. 4, 2013 This invention discloses a treatment for a patient receiving O O medication to treat an attention deficit disorder Such as Related U.S. Application Data ADHD wherein the treatment results in a loss of appetite and (60) Provisional application No. 61/744,948, filed on Oct. impairment of the patient's attentiveness. The treatment com 9, 2012, now abandoned. bines a treatment for an attention deficit disorder with an appetite stimulant, wherein the appetite stimulant increases Publication Classification the caloric intake of a patient, which can increase the patients attentiveness. The combination treatment can be given for an (51) Int. Cl. indefinite, including, without limitation, life-long, to allow a A6 IK 45/06 (2006.01) patient to maintain normal caloric intake during treatment for A6 IK3I/65 (2006.01) an attention deficit disorder. 8aasaias: Patent Application Publication Apr. 10, 2014 Sheet 1 of 22 US 2014/010O249 A1 Figure i: improvement in Atiention with increased Caiotic intake 8aakast Patent Application Publication Apr. -
Blockade of Muscarinic Acetylcholine Receptors Facilitates Motivated Behaviour and Rescues a Model of Antipsychotic- Induced Amotivation
www.nature.com/npp ARTICLE Blockade of muscarinic acetylcholine receptors facilitates motivated behaviour and rescues a model of antipsychotic- induced amotivation Jonathan M. Hailwood 1, Christopher J. Heath2, Benjamin U. Phillips1, Trevor W. Robbins1, Lisa M. Saksida3,4 and Timothy J. Bussey1,3,4 Disruptions to motivated behaviour are a highly prevalent and severe symptom in a number of neuropsychiatric and neurodegenerative disorders. Current treatment options for these disorders have little or no effect upon motivational impairments. We assessed the contribution of muscarinic acetylcholine receptors to motivated behaviour in mice, as a novel pharmacological target for motivational impairments. Touchscreen progressive ratio (PR) performance was facilitated by the nonselective muscarinic receptor antagonist scopolamine as well as the more subtype-selective antagonists biperiden (M1) and tropicamide (M4). However, scopolamine and tropicamide also produced increases in non-specific activity levels, whereas biperiden did not. A series of control tests suggests the effects of the mAChR antagonists were sensitive to changes in reward value and not driven by changes in satiety, motor fatigue, appetite or perseveration. Subsequently, a sub-effective dose of biperiden was able to facilitate the effects of amphetamine upon PR performance, suggesting an ability to enhance dopaminergic function. Both biperiden and scopolamine were also able to reverse a haloperidol-induced deficit in PR performance, however only biperiden was able to rescue the deficit in effort-related choice (ERC) performance. Taken together, these data suggest that the M1 mAChR may be a novel target for the pharmacological enhancement of effort exertion and consequent rescue of motivational impairments. Conversely, M4 receptors may inadvertently modulate effort exertion through regulation of general locomotor activity levels. -
The Effects of Oral Administration of the Novel Muscarinic Receptor
Choi et al. BMC Urology (2020) 20:41 https://doi.org/10.1186/s12894-020-00611-8 RESEARCH ARTICLE Open Access The effects of oral administration of the novel muscarinic receptor antagonist DA- 8010 on overactive bladder in rat with bladder outlet obstruction Jin Bong Choi1, Seung Hwan Jeon2, Eun Bi Kwon3, Woong Jin Bae4, Hyuk Jin Cho2, U-Syn Ha2, Sung-Hoo Hong2, Ji Youl Lee2 and Sae Woong Kim4* Abstract Background: DA-8010 is a novel compound developed for the treatment of overactive bladder (OAB) and urinary incontinence. The aims of this study were to investigate the effects of DA-8010 on OAB in a rat model. Methods: Study animals were divided into the following five groups of seven animals each: a sham-operated control group, a control group with partial bladder outlet obstruction (BOO) (OAB group), and three DA-8010 (doses of 0.3 mg/kg/day, 1 mg/kg/day, and 3 mg/kg/day, respectively) with partial BOO groups. Oral administration of the drugs was continued for 14 days after 2 weeks of partial BOO. After 4 weeks of partial BOO, cystometrography was performed in all groups. Additionally, pro-inflammatory cytokines, Rho-kinases, and histology of the bladder were analyzed. Results: There was a significant increase in the contraction interval and a decrease in contraction pressure in the 3 mg/kg/day DA-8010 group versus those in the OAB group. Rho kinase was also significantly decreased in the DA- 8010 3 mg/kg/day dosage treatment group. The increased ratio of collagen to smooth muscle after partial BOO was significantly attenuated in the DA-8010 3 mg/kg/day dosage group. -
The Influence of a Muscarinic M1 Receptor Antagonist on Brain Choline Levels in Patients with a Psychotic Disorder and Healthy Controls
MHENS School for Mental Health and Neuroscience The influence of a muscarinic M1 receptor antagonist on brain choline levels in patients with a psychotic disorder and healthy controls. W.A.M. VingerhoetsA,B, G. BakkerA,B, O. BloemenA,C, M. CaanD, J. BooijB, T.A.M.J. van AmelsvoortA. A Department of Psychiatry & Psychology, Maastricht University, Maastricht, The Netherlands.. B Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands. C GGZ Centraal, Center for Mental Health Care, Hilversum, The Netherlands D Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands Background • The majority of the patients with a psychotic disorder report cognitive impairments in addition to positive and negative symptoms. • It is well known that the neurotransmitter acetylcholine plays an important role in cognition. • A post-mortem study of chronic schizophrenia patients demonstrated a reduction of up to 75% in the number of the acetylcholine muscarinic M1 receptors (1). • Research has shown that muscarinic cholinergic receptors play a major role in cognitive processes. Objective • To investigate in-vivo whether there are differences in baseline choline levels in the anterior cingulate cortex (ACC) and striatum between recent onset medication-free patients with a psychotic disorder and healthy control subjects. • To investigate in-vivo the influence of a muscarinic antagonist on choline levels in the ACC and striatum in recent onset medication-free patients with Figure 2. Example of a striatal spectrum. a psychotic disorder and healthy control subjects. Results Methods • No significant differences were found in baseline choline levels between the two groups in both the striatum (p=0.336) and the ACC (p=0.479). -
Comparative Effects of Cimetidine and Famotidine on the Vagally Stimulated Acid Secretion in the Isolated Mouse Whole Stomach
Comparative Effects of Cimetidine and Famotidine on the Vagally Stimulated Acid Secretion in the Isolated Mouse Whole Stomach Kazuo Watanabe1, Shingo Yano1, Masayuki Yamamoto1 and Shoko Kanaoka2 1Laboratory of Chemical Pharmacology, Department of Drug Evaluation and Toxicological Sciences, Faculty of Pharmaceutical Sciences, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263, Japan 2Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, Toyama 930-01, Japan Received July 15, 1992 Accepted December 10, 1992 ABSTRACT-We investigated the effects of cimetidine and famotidine on the acid secretory response to elec trical vagal stimulation, bethanechol and histamine in the isolated mouse whole stomach preparation. The acid secretion elicited by electrical vagal stimulation at the position of the esophagus (10 Hz, 0.3 msec, 10 V for 5 min) was reproducible by repeated stimulation in each preparation, and it was abolished by tetrodo toxin, atropine and hexamethonium. This vagally stimulated acid secretion was abolished by cimetidine (3 mM), while it was only partly inhibited by famotidine (10-100 ƒÊM). Histamine (100 ƒÊM)-induced acid secre tion was inhibited by cimetidine and famotidine, and the doses of these drugs required for complete inhibi tion were 3 mM and 10 ƒÊM, respectively. In contrast, bethanechol (10 ƒÊM)-induced acid secretion was slight ly reduced by famotidine (1-100 ƒÊM), but markedly reduced by cimetidine (3 mM). In the guinea pig ileum, millimolar concentrations of cimetidine and famotidine shifted the dose-response curve of the contractile response to acetylcholine rightward. These findings suggest that the inhibitory effect of cimetidine on the vagally stimulated or bethanechol-induced acid secretion is elicited at least partly through mechanisms different from H2-antagonism. -
Product Information
PRODUCT INFORMATION NAME OF THE MEDICINE POLARAMINE® (dexchlorpheniramine maleate) DESCRIPTION Polaramine (dexchlorpheniramine maleate) is the dextro-isomer of chlorpheniramine maleate. It is an antihistamine with anticholinergic properties Dexchlorpheniramine maleate (CAS no. 2438-32-6) is described chemically as (+)-2-[p- chloro-α-[2-(dimethylamino)ethyl]benzyl]pyridine maleate (1:1). It has the empirical formula of C16H19ClN2.C4H4O4 and the following structural formula: Dexchlorpheniramine maleate is a white, odourless, crystalline powder which in aqueous solution has a pH of between 4 and 5. It is freely soluble in water, soluble in alcohol and in chloroform, but only slightly soluble in benzene or ether. PHARMACOLOGY Pharmacodynamics Mechanism of Action: Dexchlorpheniramine, the d-isomer of the racemic compound chlorpheniramine, is two times more active than chlorpheniramine. Dexchlorpheniramine does not prevent the release of histamine, but rather, competes with free histamine for binding at the H1-receptor sites, and competitively antagonizes the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Blockade of H1-receptors also suppresses the formation of oedema, flare, and pruritus that result from histaminic activity. Since dexchlorpheniramine binds to central and peripheral H1-receptors, sedative effects are likely to occur. H1-antagonists are structurally similar to anticholinergic agents and therefore possess the potential to exhibit anticholinergic properties of varying -
Report Update 1
Drug Class Review on Newer Antihistamines Final Report Update 1 April 2006 Original Report Date: November 2004 A literature scan of this topic is done periodically The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within pharmaceutical classes. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Oregon Evidence-based Practice Center Oregon Health & Science University Mark Helfand, MD, MPH, Director Copyright © 2006 by Oregon Health & Science University Portland, Oregon 97201. All rights reserved. Note: A scan of the medical literature relating to the topic is done periodically (see http://www.ohsu.edu/ohsuedu/research/policycenter/DERP/about/methods.cfm for scanning process description). Upon review of the last scan, the Drug Effectiveness Review Project governance group elected not to proceed with another full update of this report. Some portions of the report may not be up to date. Prior version of this report can be accessed at the DERP website. Final Report Update #1 Drug Effectiveness Review Project TABLE OF CONTENTS INTRODUCTION.............................................................................................................................................................4 SCOPE AND KEY QUESTIONS.............................................................................................................................6 -
Potentially Harmful Drugs in the Elderly: Beers List
−This Clinical Resource gives subscribers additional insight related to the Recommendations published in− March 2019 ~ Resource #350301 Potentially Harmful Drugs in the Elderly: Beers List In 1991, Dr. Mark Beers and colleagues published a methods paper describing the development of a consensus list of medicines considered to be inappropriate for long-term care facility residents.12 The “Beers list” is now in its sixth permutation.1 It is intended for use by clinicians in outpatient as well as inpatient settings (but not hospice or palliative care) to improve the care of patients 65 years of age and older.1 It includes medications that should generally be avoided in all elderly, used with caution, or used with caution or avoided in certain elderly.1 There is also a list of potentially harmful drug-drug interactions in seniors, as well as a list of medications that may need to be avoided or have their dosage reduced based on renal function.1 This information is not comprehensive; medications and interactions were chosen for inclusion based on potential harm in relation to benefit in the elderly, and availability of alternatives with a more favorable risk/benefit ratio.1 The criteria no longer address drugs to avoid in patients with seizures or insomnia because these concerns are not unique to the elderly.1 Another notable deletion is H2 blockers as a concern in dementia; evidence of cognitive impairment is weak, and long-term PPIs pose risks.1 Glimepiride has been added as a drug to avoid. Some drugs have been added with cautions (dextromethorphan/quinidine, trimethoprim/sulfamethoxazole), and some have had cautions added (rivaroxaban, tramadol, SNRIs). -
A Comparative Evaluation of Lafutidine and 2 Rabeprazole in The
1 *Original research paper 2 A comparative evaluation of Lafutidine and 3 Rabeprazole in the treatment of gastritis and 4 peptic ulcer: A double-blind, randomized study 5 in Indian patients. 6 Dr. Sanjay Kumar 1, Dr. Bhupesh Dewan 2*, Deepashri Shah 2 7 8 1Global Liver and Gastroenterology Centre, Bhopal, India 2 9 Medical Department, Zuventus Healthcare Ltd., Mumbai, India 10 11 . 12 ABSTRACT 13 Aims: To assess the efficacy of lafutidine therapy versus rabeprazole in Indian patients with endoscopically and histologically proven gastritis and peptic ulcer. Study design: A double blind, double dummy, randomized, comparative study. Place and Duration of Study: Global Liver and Gastroenterology Centre, Bhopal, India, between March 2010 and October 2010. Methodology: A total of 100 patients were enrolled, including 50 with endoscopically and histologically proven gastritis and other 50 with peptic ulcer (over 5 mm in diameter). Each group was randomized to receive either lafutidine or rabeprazole tablet and their corresponding competitor placebo dummy tablet, for a period of 4 weeks. Gastritis/ulcer cure rates confirmed by endoscopic histology, symptom response and Helicobacter pylori (H. Pylori) eradication were compared among the two drugs Results: Complete cure of gastritis was observed in all the patients (100%) treated with lafutidine and 95.24% [20/21; 95% CI: 76.18 to 99.88%] patients treated with rabeprazole. Complete cure of ulcer was observed in 72.0% (18/25, 95% CI = 50.61 to 87.93%) and 79.16% (19/24, 95% CI = 57.85 to 92.87%) patients treated with lafutidine and rabeprazole respectively. There was no significant difference in gastritis/ulcer cure rate and symptom response rate between the two treatment groups at the end of the study. -
Cyproheptadine
PATIENT & CAREGIVER EDUCATION Cyproheptadine This information from Lexicomp® explains what you need to know about this medication, including what it’s used for, how to take it, its side effects, and when to call your healthcare provider. What is this drug used for? It is used to ease allergy signs. It is used to treat hives. It may be given to you for other reasons. Talk with the doctor. What do I need to tell my doctor BEFORE I take this drug? For all patients taking this drug: If you have an allergy to cyproheptadine or any other part of this drug. If you are allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had. If you have any of these health problems: Bowel block, enlarged prostate, glaucoma, trouble passing urine, or ulcers in your stomach or bowel. If you are taking certain drugs used for depression like Cyproheptadine 1/9 isocarboxazid, phenelzine, or tranylcypromine, or drugs used for Parkinson’s disease like selegiline or rasagiline. If you are taking any of these drugs: Linezolid or methylene blue. If you are 65 or older. If you are breast-feeding. Do not breast-feed while you take this drug. Children: If your child is a premature baby or is a newborn. Do not give this drug to a premature baby or a newborn. This is not a list of all drugs or health problems that interact with this drug. Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems.