Snipping the Thread of Life

Peters, Nancy L.

doi:10.1001/archinte.1989.00390110020006

Cited by 72 publications

(2 citation statements)

References 93 publications

(5 reference statements)

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“…Other drugs, such as tricyclic antidepressants, have anticholinergic properties that are not fundamental to the primary indication and are therefore generally considered undesirable because they can produce adverse effects. Clinically significant mental status changes from these agents can range from mild cognitive impairment to delirium 6 . Patients with AD are exquisitely sensitive to the cognitive impairments induced by drugs with anticholinergic properties 7 .…”

mentioning

confidence: 99%

The Concurrent Use of Anticholinergics and Cholinesterase Inhibitors: Rare Event or Common Practice?

Carnahan

Lund

Perry

et al. 2004

J American Geriatrics Society

110

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mentioning

confidence: 99%

The Concurrent Use of Anticholinergics and Cholinesterase Inhibitors: Rare Event or Common Practice?

Carnahan

Lund

Perry

et al. 2004

J American Geriatrics Society

110

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“…Xerostomia has frequent oral consequencesrampant tooth decay, mucositis, and/or change of taste sensation. It often profoundly alters the quality of life and makes taken-for-granted functions such as speaking, chewing, swallowing solid foods, sleeping, and tolerating dentures very difficult (Baker and Ettinger, 1985;Mandel, 1987;Sreebny and Valdini, 1987;Peters, 1989).…”

Section: Introductionmentioning

confidence: 99%

Salivary Flow Induction by Buccal Permucosal Pilocarpine in Anesthetized Beagle Dogs

1992

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We tested whether permucosal delivery of pilocarpine nitrate could be used to elicit significant salivary secretion. Pilocarpine (pKa 6.6 at 37 degrees C) was applied as solutions (pHs 5.6, 6.6, 7.6; 15 mg/mL) to the buccal mucosa (2.8 cm2) of 6 anesthetized dogs. Saliva was collected continuously from cannulated submandibular and parotid ducts and blood sampled during and after drug administration. Plasma pilocarpine levels were determined by reversed-phase HPLC. Absorption rates were determined by use of data from separate zero-order intravenous infusions to the same dogs. Pilocarpine was buccally absorbed at a constant rate of 72.9 +/- 38.5 micrograms/kg/h following its application at pH 7.6. At this pH of the drug solution, the time to appearance of pilocarpine in blood plasma was 0.31 +/- 0.08 h, and the time to appearance of salivary flow was 0.86 +/- 0.32 h. A threshold dose of 32.9 +/- 7.5 micrograms/kg was required to induce secretion with the pH 7.6 drug, the steady-state submandibular flow rate was 0.14 +/- 0.11 mL/min/gland pair. Salivary flow induction was symmetrical and reached levels as high as 0.35 mL/min/submandibular gland pair without apparent tachyphylaxis. Results at pHs 5.6, 6.6, and 7.6 were consistent with the hypothesis that pilocarpine is primarily absorbed as un-ionized drug. The data indicate that transmucosal delivery of pilocarpine, avoiding "first pass" hepatic loss, may hold promise for the treatment of xerostomia.

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Pneumonia Risk, Antipsychotic Dosing, and Anticholinergic Burden in Schizophrenia

Luykx,

Correll,

Manu

et al. 2024

JAMA Psychiatry

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ImportanceAntipsychotic drugs (particularly clozapine) have been associated with pneumonia in observational studies. Despite studies of the associations between antipsychotic use and incident pneumonia, it remains unclear to what degree antipsychotic use is associated with increased risk of pneumonia, whether dose-response associations exist, and what agents are specifically associated with incident pneumonia.ObjectiveTo estimate pneumonia risk associated with specific antipsychotics and examine whether polytherapy, dosing, and receptor binding properties are associated with pneumonia in patients with schizophrenia.Design, Setting, and ParticipantsThis cohort study identified patients with schizophrenia or schizoaffective disorder (hereafter, schizophrenia) aged 16 years or older from nationwide Finnish registers from 1972 to 2014. Data on diagnoses, inpatient care, and specialized outpatient care were obtained from the Hospital Discharge Register. Information on outpatient medication dispensing was obtained from the Prescription Register. Study follow-up was from 1996 to 2017. Data were analyzed from November 4, 2022, to December 5, 2023.ExposuresUse of specific antipsychotic monotherapies; antipsychotics modeled by dosage as low (&lt;0.6 of the World Health Organization defined daily dose [DDD] per day), medium (0.6 to &lt;1.1 DDDs per day), or high dose (≥1.1 DDDs per day); antipsychotic polypharmacy; and antipsychotics categorized according to their anticholinergic burden as low, medium, and high.Main Outcomes and MeasuresThe primary outcome was hospitalization for incident pneumonia. Pneumonia risk was analyzed using adjusted, within-individual Cox proportional hazards regression models, with no antipsychotic use as the reference.ResultsThe study included 61 889 persons with schizophrenia (mean [SD] age, 46.2 [16.0] years; 31 104 men [50.3%]). During 22 years of follow-up, 8917 patients (14.4%) had 1 or more hospitalizations for pneumonia and 1137 (12.8%) died within 30 days of admission. Compared with no antipsychotic use, any antipsychotic use overall was not associated with pneumonia (adjusted hazard ratio [AHR], 1.12; 95% CI, 0.99-1.26). Monotherapy use was associated with increased pneumonia risk compared with no antipsychotic use (AHR, 1.15 [95% CI, 1.02-1.30]; P = .03) in a dose-dependent manner, but polytherapy use was not. When categorized by anticholinergic burden, only the use of antipsychotics with a high anticholinergic burden was associated with pneumonia (AHR, 1.26 [95% CI, 1.10-1.45]; P &lt; .001). Of specific drugs, high-dose quetiapine (AHR, 1.78 [95% CI, 1.22-2.60]; P = .003), high- and medium-dose clozapine (AHR, 1.44 [95% CI, 1.22-1.71]; P &lt; .001 and AHR, 1.43 [95% CI, 1.18-1.74]; P &lt; .001, respectively), and high-dose olanzapine (AHR, 1.29 [95% CI, 1.05-1.58]; P = .02) were associated with increased pneumonia risk.Conclusions and RelevanceResults of this cohort study suggest that in patients with schizophrenia, antipsychotic agents associated with pneumonia include not only clozapine (at dosages ≥180 mg/d) but also quetiapine (≥440 mg/d) and olanzapine (≥11 mg/d). Moreover, monotherapy antipsychotics and antipsychotics with high anticholinergic burden are associated with increased pneumonia risk in a dose-dependent manner. These findings call for prevention strategies aimed at patients with schizophrenia requiring high-risk antipsychotics.

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Snipping the Thread of Life

Cited by 72 publications

References 93 publications

The Concurrent Use of Anticholinergics and Cholinesterase Inhibitors: Rare Event or Common Practice?

The Concurrent Use of Anticholinergics and Cholinesterase Inhibitors: Rare Event or Common Practice?

Salivary Flow Induction by Buccal Permucosal Pilocarpine in Anesthetized Beagle Dogs

Pneumonia Risk, Antipsychotic Dosing, and Anticholinergic Burden in Schizophrenia

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