The Janus-like Association Between Proton Pump Inhibitors and Dementia

: Early pharmacoepidemiological studies suggested that Proton Pump Inhibitors (PPIs) might increase the risk of Alzheimer’s Disease (AD) and non-AD related dementias. These findings were supported by preclinical studies, specifically stressing the proamyloidogenic and indirect anticholinergic effects of PPIs. However, further large-scale pharmacoepidemiological studies showed inconsistent results on the association between PPIs and dementia. Pharmacodynamically, these findings might be related to the LXR/RXR-mediated amyloid clearance effect and anti-inflammatory action of PPIs. Further aspects that influence PPI effects on AD are related to patient-specific pharmacokinetic and pharmacogenomic characteristics. In conclusion, a personalized (individualized) medicinal approach is necessary to model and predict the potential harmful or beneficial effects of PPIs in AD and non-AD-related dementias in the future.

Anticholinergic Plant Misuse and Schizophrenia: Regarding a Case Report

Anticholinergic medication abuse is common in patients with schizophrenia. The recreational use of anticholinergic plants for their euphoria inducing and hallucinogenic properties is a rising concern in America and Eastern Europe, but rare in Portugal. Anticholinergic misuse poses a challenge to Psychiatrists treating patients with dual pathology, for its addictive potential. In managing antipsychotic medication and its side effects in this population one must have in mind the potential for abuse of anticholinergics. We present a case report of a patient with schizophrenia and abuse of anticholinergic plants, after receiving biperiden to treat extrapyramidal symptoms. Later we discuss anticholinergic effects and potential for addiction and explore ways to prevent and treat drug misuse in this context.

Irreversible effects of anticholinergic withdrawal in the elderly: a case report

Anticholinergics, such as benztropine and trihexyphenidyl, are a class of medications that have been used to treat several different conditions including antipsychotic-induced extrapyramidal side effects (EPS) that are most often associated with first-generation antipsychotics (FGAs), such as haloperidol and fluphenazine. Many other medications, including antimuscarinics, antipsychotics, and antidepressants, also have anticholinergic effects. In this report, we review the case of an 80-year-old male who experiences irreversible anticholinergic withdrawal effects following the discontinuation of trihexyphenidyl and trospium secondary to side effects. Discontinuation of anticholinergics must be approached with care as abrupt withdrawal can lead to cholinergic rebound and muscular rigidity, and in some cases can lead to acute hospitalization and an inability to return to baseline functioning, as seen in our elderly patient. Keywords: Anticholinergic withdrawal, trihexyphenidyl, trihexyphenidyl withdrawal, trospium, anticholinergic drugs, cholinergic rebound

Management of constipation in patients with schizophrenia—a case study and review of literature

Background Schizophrenia is a disorder that affects about 1% of the US population, with an extensive impact on patients’ health and their risk of later developing comorbidities from treatment. While literature on the side effect profile of antipsychotics is abundant, there are few studies on identification of anticholinergic effects on gut motility and prophylaxis development. The aim of this review is to consider antipsychotic-associated constipation in patients with schizophrenia and to discuss management of antipsychotic-induced constipation as documented in the literature. Main body We present a case of antipsychotic-induced constipation and conducted a literature review assessing the prevalence of this issue in this population. The search was done on Embase, MEDLINE, Cochrane Library, and PubMed databases. Key word searches included constipation with concurrent antipsychotic use, antipsychotics and anticholinergic effects, factors causing constipation in schizophrenia, social disparities involved with constipation, and colorectal cancer screenings. Main findings included high complication rates that may be explained by clozapine-specific side effects, negative health habits, disease, and treatment-related metabolic disorders. Co-existing negative symptoms could also be associated with health outcomes and was found to have adverse consequences on schizophrenia progression. Comorbidities of diabetes and cardiovascular complications contributed to gut hypomotility. Caregiver burden was a factor in delayed recognition of constipation as a side effect. Routine surveillance for symptoms and optimization of medications facilitates early recognition of constipation. Conclusion Overall, there is insufficient trial-based evidence to compare the effectiveness and safety of common pharmacological interventions for constipation, such as lactulose, polyethylene glycol, stool softeners, and lubricant laxatives.

Use of multiple anticholinergic medications can predispose patients to severe non-exertional hyperthermia

We present a case of a 64-year-old woman who developed severe non-exertional hyperthermia (NEHT) due to excessive anticholinergic effects from her psychiatric medications. The patient was found unresponsive in a non-air-conditioned room where the outside temperature was over 33°C. She presented with altered mental status, hypotension and an oral temperature of 42°C. Drug–drug interactions from her home medications for depression, bipolar disorder and seizures (amitriptyline, cyclobenzaprine, benztropine, topiramate, clonazepam, trazodone) were suspected. Blood cultures grew Staphylococcus hominis. The patient quickly returned to baseline with supportive care in the intensive care unit. She was treated for the Staph hominis bacteraemia with a 7-day course of vancomycin. Due to her quick recovery and lack of neurological findings, severe NEHT with associated bacteraemia was determined to have caused her presenting symptoms. This patient’s multiple anticholinergic medications increased her susceptibility to develop NEHT by inhibited sweating, this patient’s natural cooling mechanism.

Anti-Cholinergic Drug Burden Among Ambulatory Elderly Patients in a Nigerian Tertiary Healthcare Facility

Background: The use of drugs with anticholinergic effects among elderly patients is associated with adverse clinical outcomes. There is paucity of information about anticholinergic drug burden among Nigerian elderly population.Objectives: To determine the anticholinergic drug burden among elderly Nigerian patients.Methods: This was a retrospective cross-sectional study conducted among elderly patients (aged 65 and above) who visited the Family Medicine outpatients’ clinics of the Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria between July 1 and October 31, 2018. Information extracted from the case files included patient’s age, sex, diagnoses, and list of prescribed medications. Medicines with anticholinergic effects were identified and scored using the anticholinergic drug burden calculator (http://www.acbcalc.com).Results: The medical records of 400 patients were analyzed with females accounting for 60.5% of the study population. The mean age of participants was 73 ± 7.4 years with only 28 (7%) of patients having more than two co-morbid conditions. Polypharmacy was identified in 152 (38%) of the patients while 147 (36.7%) had drugs with anticholinergic effects prescribed. The anticholinergic burden was high in 60 (15%) patients. Polypharmacy was significantly associated with having more than two diagnosed conditions and high anticholinergic burden (p value of < 0 .001 and 0.013 respectively). There was significant correlation between total number of prescribed drugs and count of diagnoses (r = 0.598; p < 0 .000) and between total number of prescribed drugs and number of drugs with anticholinergic effects (r = 0 .196; p < 0 .000).Conclusion: The anticholinergic burden in this group of elderly Nigerian patients was low; majority (67%) had no exposure to drugs with anticholinergic effects with only 15% having high anticholinergic burden. Polypharmacy and multiple diagnosed conditions were positively associated with high anticholinergic burden. Based on the positive and significant correlations found in this study, a reduction in the number of prescribed medicines especially those with significant anticholinergic effects used for secondary indications may lessen the anticholinergic burden among the elderly.

Assessing Anticholinergic Effects in Older Adults

Anticholinergic medications are widely used in older adults and are a common source of adverse events in this population. Common drug classes include antiarrhythmics, antidepressants, antiemetics, first generation antihistamines, urinary incontinence antimuscarinic agents, antiparkinsonian agents, antipsychotics, antispasmodics, and skeletal muscle relaxants. These drugs have been associated with delirium, cognitive impairment, sedation, dizziness, falls, fracture, constipation, urinary retention, blurred vision, tachycardia and dry mouth. If possible, these drugs should be avoided in older adults or less toxic agents within the class should be utilized. This chapter will explore the mechanism of action of anticholinergic drugs at both the cellular and organ system level; discuss how to assess for anticholinergic drug burden; list medications with anticholinergic effects as identified in the Beer’s criteria on potentially inappropriate medication use in older adults; review anticholinergic drug–drug interactions; describe contraindications to the use of anticholinergic agents; and explore practical considerations such as the availability of these substances in nonprescription medications, their use at end of life and deprescribing.

Anticholinergic Burden among Hospitalised Older Adults with Psychiatric Illnesses- A retrospective study

Background: Drugs with anticholinergic properties are known to be associated with deleterious effects on cognition in older adults. There is a paucity of literature in this aspect in older adults with psychiatric disorders. Objective: To examine the anticholinergic cognitive burden and its predictors in hospitalised older adults having psychiatric disorders. Methods: Case records of older adults who sought inpatient care under the Geriatric Psychiatry Unit from January, 2019 to June, 2019 were reviewed. The anticholinergic burden was assessed with Anticholinergic Cognitive Burden (ACB) scale updated version, 2012. Results: Sample included 129 older adults with an almost equal number of males (53.48%) and females (46.52%) having a mean age of 67.84 (SD = 6.96) years. The diagnostic spectrum included depression (34.89%), dementia (31.01%), mania (10.85%), psychosis (13.95%), delirium (6.20%) and others (3.1%). 60.47% of the patients had more than one medical illness. 48.84% of the older adults had clinically relevant anticholinergic cognitive burden ( ACB score ≥ 3). Use of 3 or more psychotropic drugs (OR = 4.88), diagnosis of psychosis/ mania (OR = 7.62) and dementia/ delirium (neurocognitive disorders group) (OR = 5.17) increased the risk of ACB score ≥ 3. Conclusion: Nearly half of the older adults in psychiatry in-patient setting had clinically relevant anticholinergic burden, which was associated with higher use of psychotropics. Our study highlights the importance of monitoring for anticholinergic effects of psychotropics in older adults.

Heroin Adulterated with the Novel Synthetic Cannabinoid, 5F-MDMB-PINACA: A Case Series

Introduction: Heroin can be adulterated with various substances that may or may not have pharmacological effects. Here we report a case series of 8 patients who presented to the emergency department after overdose with intravenous heroin preparation adulterated with the synthetic cannabinoid methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate (5F-MDMB-PINACA). Case Series: Except for one patient, all of them presented with a typical initial opioid toxidrome consisting of central nervous system and respiratory depression along with pinpoint pupils. Naloxone was given to them, triggering severe agitation and combative behavior along with overlapping features of anticholinergic and sympathomimetic toxidrome. All patients required multiple doses of benzodiazepines. Three were successfully treated with physostigmine. Discussion: 5F-MDMB-PINACA is a synthetic cannabinoid that was added to heroin in samples obtained from patients reported in this case series. Patients demonstrated significant agitation after receiving naloxone for opioid toxidrome, presumably because of the removal of the depressant effect of opioids, which unmasked the excitatory effects of the synthetic cannabinoids. Three patients required physostigmine along with the benzodiazepines for control of their agitation, urine retention and abnormal vitals, suggesting the possibility of an anticholinergic toxidrome to have developed in these patients. Conclusion: Heroin contaminated with 5F-MDMB-PINACA exhibits variable severities of anticholinergic effects, some on presentation and others only after opiate antagonism.