Atypical antipsychotic drugs (APDs) have been hypothesized to show reduced extrapyramidal side effects (EPS) due to their rapid dissociation from the dopamine D2 receptor. However, support for this hypothesis is limited to a relatively small number of observations made across several decades and under different experimental conditions. Here we show that association rates, but not dissociation rates, correlate with EPS. We measured the kinetic binding properties of a series of typical and atypical APDs in a novel time-resolved fluorescence resonance energy transfer assay, and correlated these properties with their EPS and prolactin-elevating liabilities at therapeutic doses. EPS are robustly predicted by a rebinding model that considers the microenvironment of postsynaptic D2 receptors and integrates association and dissociation rates to calculate the net rate of reversal of receptor blockade. Thus, optimizing binding kinetics at the D2 receptor may result in APDs with improved therapeutic profile.

Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors

Sarcopenia is associated with worse recovery of physical function and dysphagia and a lower rate of home discharge in Japanese hospitalized adults undergoing convalescent rehabilitation.

https://www.thelancet.com/pdfs/journals/landia/PIIS2213-8587(14)70246-3.pdf

Renal effects of atorvastatin and rosuvastatin in patients with diabetes who have progressive renal disease (PLANET I): a randomised clinical trial.

Prescribing in older people.

Oxycodone induces overexpression of P‐glycoprotein (ABCB1) and affects paclitaxel's tissue distribution in Sprague Dawley rats

Background. A risk factor associated with stroke onset is chronic kidney disease (CKD). To prevent stroke reoccurrence, it is necessary to strictly manage blood pressure, lipids, and plasma glucose. Therefore, some cases are forced to polypharmacy, elderly patients in particular. Polypharmacy often leads to adverse drug reactions and has the potential to negatively affect the rehabilitation of stroke patients. The aim of the present study was to investigate the effects of polypharmacy using a functional independence measure (FIM). Methods. A total of 144 stroke patients with CKD were included in the present analysis. We divided stroke patients into those taking six or more drugs (polypharmacy group) and those taking less than six drugs (nonpolypharmacy group) upon admission. Patient background features, laboratory data, and FIM scores were compared. Results. FIM-Motor (FIM-M) efficiency, age, and diabetes mellitus were positively associated with polypharmacy. FIM-M efficiency in the polypharmacy group was significantly lower than in the nonpolypharmacy group. Conclusion. Polypharmacy interferes with the effect of rehabilitation in stroke patients with CKD. Pharmacists and doctors should make efforts to optimize medications to be able to respond to the outcome of each patient.

https://downloads.hindawi.com/journals/jar/2016/7957825.pdf

Impact of Polypharmacy on the Rehabilitation Outcome of Japanese Stroke Patients in the Convalescent Rehabilitation Ward.

Aim
The effect of the use of potentially inappropriate medications (PIM) on mortality and functional outcome after strokes is unclear in Japan. The aim of the present study was to establish whether treatment with PIM affects functional improvements among geriatric patients convalescing after strokes.

Methods
This retrospective longitudinal study included consecutive geriatric patients admitted and discharged from convalescent rehabilitation wards for stroke between 2010 and 2016. Demographic data, laboratory data and the Functional Independence Measure (FIM) were analyzed. We used the 2015 American Geriatrics Society Beers Criteria to screen for PIM, and the primary outcome was motor FIM gain. Multivariate regression analysis was carried out to analyze the relationship between PIM use and functional recovery.

Results
In total, 272 participants (102 men, 170 women; median age 79 years, interquartile range 72–85 years) were included in the present study. Multivariate regression analysis of motor FIM gain, adjusting for confounding factors, showed that PIM use was independently and negatively correlated with motor FIM gain. In particular, anticholinergic drugs (such as antipsychotics, antidepressants and first-generation antihistamines) were significantly increased from admission to discharge.

Conclusion
Increased PIM use during hospitalization might be a predictor of reduced functional improvement in geriatric patients after strokes. Geriatr Gerontol Int 2017; ••: ••–••.

Role of potentially inappropriate medication use in rehabilitation outcomes for geriatric patients after strokes.

Evidence is scarce regarding the polypharmacy in patients with sarcopenia. The aim of this study was to investigate the effect of deprescribing for polypharmacy on the improvement of nutritional intake and sarcopenia in older patients with sarcopenia. A retrospective cohort study was conducted with hospitalized older patients with sarcopenia undergoing rehabilitation after stroke. Study outcomes included energy intake, protein intake, handgrip strength (HG) and skeletal muscle mass index (SMI) at hospital discharge. To consider the effects of deprescribing for polypharmacy, we used multivariate analyses to examine whether the change in the number of medications during hospitalization was associated with outcomes. Of 361 patients after enrollment, 91 (mean age 81.0 years, 48.4% male) presented with sarcopenia and polypharmacy and were eligible for analysis. The change in the number of medications was independently associated with energy intake (β = −0.237, p = 0.009) and protein intake (β = −0.242, p = 0.047) at discharge, and was not statistically significantly associated with HG (β = −0.018, p = 0.768) and SMI (β = 0.083, p = 0.265) at discharge, respectively. Deprescribing was associated with improved nutritional intake in older sarcopenic patients with polypharmacy undergoing stroke rehabilitation.

https://www.mdpi.com/2072-6643/14/3/443/pdf?version=1642595990

Deprescribing Leads to Improved Energy Intake among Hospitalized Older Sarcopenic Adults with Polypharmacy after Stroke

Many patients in rehabilitation facilities are affected by polypharmacy. Polypharmacy is associated with rehabilitation outcomes and functional recovery. Consequently, a combination of rehabilitation and pharmacotherapy may improve the outcomes of older people undergoing rehabilitation. A recent report described the concept of rehabilitation pharmacotherapy. The concept envisages helping frail older people and people with disabilities to achieve the highest possible body function, activity level and quality of life. There are two key tenets of rehabilitation pharmacotherapy: "pharmacotherapy in consideration of rehabilitation" and "rehabilitation in consideration of pharmacotherapy." "Pharmacotherapy in consideration of rehabilitation" includes use of drugs to treat impairment, activity limitation and participation restriction based on the International Classification of Functioning, Disability, and Health. "Rehabilitation in consideration of pharmacotherapy" refers to tailoring of rehabilitation considering the content of pharmacotherapy. With respect to drugs and motor dysfunction, anticholinergic drugs are associated with dysphagia and fractures. Increased use of potentially inappropriate medications may adversely affect the nutritional status. With respect to activities of daily living, polypharmacy and use of potentially inappropriate medications negatively affect the improvement in motor function during rehabilitation. Potent anticholinergic drugs are more likely to impede the improvement in cognitive function. In this review, we address the concept of rehabilitation pharmacotherapy and discuss its importance from the perspective of polypharmacy, the effect of drugs on disability and disease, nutritional status and activities of daily living. Geriatr Gerontol Int 2020; 20: -.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ggi.13975

Rehabilitation pharmacotherapy: A scoping review.

Typical antipsychotics are easily expressed as adverse events such as extrapyramidal symptom (EPS). On the other hand, incidence of adverse events due to atypical antipsychotics is low. Therefore, currently, atypical antipsychotics are widely used to treat schizophrenia. However, it has been reported that there is no difference in the frequency of EPS in atypical and typical antipsychotics. This study aimed to evaluate the expression profile of EPS in atypical and typical antipsychotics treatment using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of EPS in the JADER database and calculated the reporting odds ratio (ROR) of antipsychotics potentially associated with EPS. We applied the Weibull shape parameter to time-to-event data in the JADER database. Consequently, there was little information to distinguish between the ROR of atypical and typical antipsychotics. A significant difference related to the time of onset of EPS in both antipsychotics was not recognized. However, when comparing each drug, Paliperidone, Perospirone, Blonanserin, and Aripiprazole were relatively developed as EPS in the early stage. On the other hand, Risperidone, Clozapine, Olanzapine, and Quetiapine were developed as EPS not only at an early stage but also after long-term use. In addition, this finding was suggested from the result of the cumulative incidence of EPS in each drug and of the time-to-onset analysis using Weibull distribution. These findings may contribute to future clinical practice because we revealed the expression profile of EPS in treatment with atypical and typical antipsychotics.

Evaluation of the Expression Profile of Extrapyramidal Symptoms Due to Antipsychotics by Data Mining of Japanese Adverse Drug Event Report (JADER) Database.

Eiji Kose

Papers

Impact of Polypharmacy on the Rehabilitation Outcome of Japanese Stroke Patients in the Convalescent Rehabilitation Ward.

Role of potentially inappropriate medication use in rehabilitation outcomes for geriatric patients after strokes.

Deprescribing Leads to Improved Energy Intake among Hospitalized Older Sarcopenic Adults with Polypharmacy after Stroke

Rehabilitation pharmacotherapy: A scoping review.

Evaluation of the Expression Profile of Extrapyramidal Symptoms Due to Antipsychotics by Data Mining of Japanese Adverse Drug Event Report (JADER) Database.