The Pharmacodynamics of Ethanol: Effects on Performance and Judgment
The Journal of Clinical Pharmacology, Aug 1, 1990
The objective and subjective effects produced by increasing and decreasing ethanol concentrations... more The objective and subjective effects produced by increasing and decreasing ethanol concentrations were studied in healthy volunteers on three separate occasions. A randomized, double‐blind, placebo‐controlled, four‐way crossover study was used to determine whether there is any disparity between the time course of blood ethanol concentration and its effects on either objective test performance or self rated impairment. On each study day the subjects received one of four treatments consisting of either placebo or sufficient alcohol to achieve peak estimated blood alcohol concentration (Est.BAC) of 0.07 gm/dL, 0.1 gm/dL or 0.14 gm/dL. Est.BAC determined from breath alcohol concentrations were measured 20 minutes after each “dose” until peak Est.BAC was achieved, then 1, 2, 3.5, and 4.5 hours after peak Est.BAC. Digit symbol substitution (DSS), simulated driving reaction time (SDRT), choice reaction time (CRT) and self assessment of impairment (SRI) were measured simultaneously with Est.BAC.Changes in objective performance test scores were well correlated with Est.BAC (r2 = 0.60 P < .01). Maximum impairment in test performance occurred at the same time as peak Est.BAC. Threshold Est.BAC needed to produce changes in objective test scores greater than placebo were 0.06 ± 0.01 for DSS, 0.04 ± 0.01 for SDRT, and 0.04 ± 0.02 for CRT. There was no evidence of between dose or within dose tolerance to the effects produced by various Est.BAC on any of these performance tests.Subjects' self rated degrees of impairment at various Est.BAC were influenced by whether alcohol concentrations were rising or falling. Subjective impairment ratings were greater while alcohol concentrations were increasing compared to the same Est.BAC occurring during falling alcohol concentrations. Disparities between self rated degree of impairment and decrements in test performance were greatest 1.0 hour after peak Est.BAC and maximum decrements in test performance. The delay in subjects' ability to accurately rate their impairment relative to peak Est.BAC may be a contributing factor to motorists choosing to drive while their performance is still impaired.
Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate w... more Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate,
A method for determining pindolol from human serum by high-performance liquid chromatography (HPL... more A method for determining pindolol from human serum by high-performance liquid chromatography (HPLC) is presented. Pindolol is extracted into methylene chloride from 1 mL of alkalinized serum with a recovery of 87%. The organic layer is evaporated and the residue is reconstituted in mobile phase for injection into the column. Samples are eluted from a 5-micron C18 column (250 x 4.6 mm) with acetonitrile-water containing 0.1% triethylamine, pH adjusted to 3.5 with phosphoric acid (20:80 v/v). Samples as low as 2 ng/mL have been detected.
Intranasal midazolam plasma concentration profile and its effect on anxiety associated with dental procedures
Anesthesia progress, 1996
The objectives of this study were to describe the serum concentration time profile for midazolam ... more The objectives of this study were to describe the serum concentration time profile for midazolam following intranasal administration to adult dental surgery patients and to ascertain the effect of midazolam on anxiety. Six female patients received a single 20 mg (0.32 to 0.53 mg/kg) dose of midazolam. Blood samples were collected at 5, 10, 20, 30, 45, and 60 min following dose administration. Midazolam plasma concentrations were determined by gas chromatography. Anxiety was evaluated using a 100-mm visual analogue scale. The maximum concentration of midazolam was reached 25.8 min (range 18 to 35 min) following dose administration. Maximum concentrations were variable. However, there was no relationship between the weight-adjusted dose and maximal concentration. Patients experiencing baseline anxiety exhibited a trend toward reduction in their measured anxiety score (P = 0.06). Plasma concentrations above the hypothesized minimum effective concentration for sedative effects were atta...
Quantitative effects of cetirizine and diphenhydramine on mental performance measured using an automobile driving simulator
PubMed, Jun 1, 1990
The purpose of this study was to assess the effects of cetirizine on objective measures of mental... more The purpose of this study was to assess the effects of cetirizine on objective measures of mental performance. Fifteen subjects were given single doses of cetirizine (20 mg, 10 mg, and 5 mg) diphenhydramine, 50 mg (positive control), and placebo (negative control) in this randomized, double-blinded, crossover study. An automobile driving simulator, digit symbol substitution, Trails B maze tracking and subjective feelings of drowsiness were measured at 0, 2, 4, 6, 8, and 24 hours after the dose. No differences between placebo and any of the three doses of cetirizine could be detected, however, diphenhydramine produced impaired mental performance and drowsiness. These data indicate that these doses of cetirizine produce little or no effect on cognitive function or mental performance.
The Effect of ß-Blockers on Mental Performance on Older Hypertensive Patients
Archives of internal medicine, Apr 1, 1988
• This double-blind, three-way crossover study measured the influence of β-blocker treatment on d... more • This double-blind, three-way crossover study measured the influence of β-blocker treatment on drowsiness and mental test performance in older hypertensive patients and determined if lipophilicity was a determinant of these effects. Twenty-seven hypertensive patients (mean age, 63±3 years) were studied. Patients received two weeks each of daily treatment with placebo, 100 mg of atenolol, or 150 mg of metoprolol tartrate and were evaluated on the 14th day of each treatment period, after which their next treatment period began. Mental performance was measured using Trails-A maze testing. Drowsiness was measured subjectively using a visual analogue scale, and objectively using critical fusion-frequency threshold testing. Blood pressure control was equivalent and clinically adequate in all subjects. Steady-state levels of metoprolol tartrate (235±46 ng/mL) and atenolol (453.6±56 ng/nL) achieved were those expected to produce similar β-blockade. Mental performance as measured by Trials-A testing showed better scores during β-blocker treatment compared with placebo. Trails-A scores improved as patients went from placebo to metoprolol treatment, but did not change as patients went from placebo to atenolol treatment. Critical fusion-frequency threshold measurements were lower following administration of both drugs than following that of placebo, but subjectively there was no difference in feelings of lethargy between either β-blocker and placebo. These data show greater improvement in mental testing performance to be associated with metoprolol treatment, but neither produced more lethargy than placebo in elderly patients. ( Arch Intern Med 1988;148:779-784)
The use of cannabis for the treatment of migraine has become an area of interest with the legaliz... more The use of cannabis for the treatment of migraine has become an area of interest with the legalization of medical cannabis in the USA. Understanding the mechanisms of cannabinoids, available studies, and best clinical recommendations is crucial for headache providers to best serve patients. Patients utilizing medical cannabis for migraine have reported improvement in migraine profile and common comorbidities. Reduction in prescription medication is also common, especially opioids. Side effects exist, with the majority being mild. Not enough data is available for specific dose recommendations, but THC and CBD appear to mediate these observed effects. The purpose of this article is twofold: review the limited research surrounding cannabis for migraine disease and reflect on clinical management experiences to provide recommendations that best capture the potential use of cannabis for migraine.
Pharmacist intervention and anti‐platelet medication monitoring in patients following stroke and transient ischemic attack
Journal of the American College of Clinical Pharmacy, 2021
Aspirin and clopidogrel are mainstays in secondary stroke prevention; however, some patients do n... more Aspirin and clopidogrel are mainstays in secondary stroke prevention; however, some patients do not demonstrate optimal antiplatelet effects from these therapies.
L-Methylfolate Calcium Supplementation in Adolescents and Children
Journal of Psychiatric Practice
Previous studies have shown l-methylfolate to be a safe and beneficial therapy for neuropsychiatr... more Previous studies have shown l-methylfolate to be a safe and beneficial therapy for neuropsychiatric conditions, including major depressive disorder and schizophrenia in adults. The purpose of this study was to assess safety and describe patient experience using l-methylfolate calcium in a real-world pediatric and adolescent population. A retrospective chart review of patients (7 to 20 y of age, mean age 16 y) prescribed l-methylfolate calcium at a psychiatry clinic in Amherst, NY, between January 1, 2010 and November 10, 2015 was conducted. Patients to whom l-methylfolate calcium 15 mg/d (n=139) or 7.5 mg/d (n=7) was administered were identified; 44 patients who were prescribed but to whom l-methylfolate calcium was not administered were included as a comparator population. Common neuropsychiatric diagnoses included anxiety disorders (68% in the treatment population vs. 50% in the comparator population) and mood disorders (57% in the treatment population vs. 52% in the comparator population). Antidepressants (69% vs. 55%) and mood stabilizers or antiepileptic drugs (63% vs. 57%) were frequently prescribed in combination with l-methylfolate calcium. Adverse events occurred less frequently in the treated population, possibly due to the addition of l-methylfolate calcium (10% vs. 25%, P=0.02). The most common adverse events in the treated population were impaired sleep (5 patients) and increased anxiety (3 patients). Rates of laboratory abnormalities did not differ significantly between the treated and comparator populations (P=0.13). Positive subjective treatment experiences were reported by 22.5% of treated patients and negative subjective treatment experiences were reported by 5.4% of treated patients. L-methylfolate calcium was well-tolerated in a pediatric/adolescent population and may provide benefits for patients with a range of neuropsychiatric conditions.
Work in Progress. Background: Urinary tract infection (UTI) is often considered a common cause of... more Work in Progress. Background: Urinary tract infection (UTI) is often considered a common cause of mental status changes, particularly in elderly patients and patients with a primary psychiatric condition. Additionally, the presence of genitourinary symptoms is essential to confirm diagnosis and determine the appropriate treatment course. Patients with a communication barrier may be unable to clearly convey the presence or absence of genitourinary symptoms, complicating an accurate diagnosis when mental status changes occur. Little evidence exists on diagnosing UTIs in patients who cannot communicate genitourinary symptoms; however, some guidance in long-term care facilities suggests assessing specific symptoms that do not rely on patient report. Objectives: The primary objective of this project is to provide assistance in the diagnosis and treatment of UTIs in patients who cannot communicate genitourinary symptoms through the creation of an algorithm. Secondary objectives include reducing inappropriate antibiotic use and increasing symptom documentation in this patient population. Methods: A UTI treatment algorithm for noncommunicative patients was developed using existing literature and through extensive collaboration with physicians, PhDs, and pharmacists working in the fields of emergency medicine, geriatric psychiatry, infectious diseases, microbiology, and urology. The final algorithm included comprehensive information on evaluating urinalysis (UA) results and identifying UTI symptoms, and offered guidance for antibiotic selection, dosing, and duration. Educational materials were created to enforce the most appropriate use of this algorithm, and provider education is ongoing. To limit the initial scope and allow for preintervention and postintervention data analysis, the algorithm will be utilized within the psychiatric emergency department. Adults admitted to the psychiatry service with a UA ordered and collected in the emergency department as well as an ICD-10 code representing dementia, delirium, autism spectrum disorder, or developmental delay will be included. Pregnant patients will be excluded. Outcomes: The preintervention cohort includes 56 admissions. Patients are predominantly female, with an average age of 60 years. Provider education will be completed in January, with postintervention data collection and analysis completed in February. This timeline allows for reporting on the impact of the intervention by comparing changes in UA ordering, antibiotic prescribing, and symptom documentation between preintervention and postintervention cohorts.
The ~harmacodvnamics of diphenhvdramine-induced drowsiness and chBnges in mental performance The ... more The ~harmacodvnamics of diphenhvdramine-induced drowsiness and chBnges in mental performance The time course of diphenhydramine concentrations and effects on both mental performance and subjective feelings of drowsiness were assessed in 15 healthy men. Subjects received single oral doses of diphenhydramine, 50 mg, and placebo in this double-blind crossover study. Diphenhydramine plasma concentrations and central nervous system actions were assessed for 24 hours after each treatment. Cognitive impairment was assessed with an automobile driving simulator and digit symbol substitution scores, whereas drowsiness was self-assessed on a visual analog scale. Diphenhydramine produced significant feelings of drowsiness for up to 6 hours after the dose, whereas significant mental impairment was apparent for only 2 hours. Despite the difference in duration of these effects, drowsiness and mental impairment have parallel slopes when effects are related to diphenhydramine concentrations. These data suggest that although the apparent diphenhydramine concentration thresholds to produce drowsiness are lower (30.4 to 41.5 nglrnl) than those needed to produce mental impairment (58.2 to 74.4 nglml), these effects have profiles consistent with their being manifestations of the same pharmacologic effect. (CLIN
To reduce the risks associated with the treatment of allergic disorders, physicians should unders... more To reduce the risks associated with the treatment of allergic disorders, physicians should understand the benefits and risks of drugs in the antihistamine class. The risk of central nervous system adverse effects associated with antihistamine use is significant with the use of first-generation antihistamines, which show pharmacologic activity in serotonepgic, c~adrenergic, dopaminet~ic, and muscarinic-cholinergic pathways. Adverse effects reported with the use of first-generation antihistamines most often include dlvwsiness, fatigue, and an inability to concentrate," these effects may result in decreased compliance with therapy. The second-generation antihistamines have the plvperty of low lipid solubility, which slows access across the blood-brain barrier. The low sedative profile of these new drugs may also be linked to a more p~vnounced binding to peripheral rather than brain histamine H z-receptors. The use of antihistamines with lower lipid solubility and greater specificity can provide an effective alternative for the relief of allergic symptoms, can improve compliance, and can reduce neurologic side effects. Because of the differences now recognized in the side effects of drugs of this class, an individualized approach to selection of antihistamine therapy is required.
In Reply .—We are pleased to have the opportunity to clarify a number of points from our recent a... more In Reply .—We are pleased to have the opportunity to clarify a number of points from our recent article in theArchives. 1 First, we would like to thank Dr Frohlich for his insightful editorial. 2 In his editorial, Dr Frohlich suggests that, although ours was a well-designed study, it may be argued that insufficient numbers of patients were studied. We agree that larger studies should precede any general conclusions regarding clinical management of hypertensive populations. However, to determine whether the β-blockers tested would influence indexes of mental performance and subjective lethargy measured, we had sufficient statistical power ( P =.95) based on the sample size and study design for a level of significance of P =.05. It is noteworthy to mention that similar conclusions have been simultaneously reported from two investigations of the central nervous system effects of propranolol and atenolol, which utilized a comparable study design. 3,4 Oliner and
The effect of beta-blockers on mental performance on older hypertensive patients
Archives of Internal Medicine, 1988
This double-blind, three-way crossover study measured the influence of beta-blocker treatment on ... more This double-blind, three-way crossover study measured the influence of beta-blocker treatment on drowsiness and mental test performance in older hypertensive patients and determined if lipophilicity was a determinant of these effects. Twenty-seven hypertensive patients (mean age, 63 +/- 3 years) were studied. Patients received two weeks each of daily treatment with placebo, 100 mg of atenolol, or 150 mg of metoprolol tartrate and were evaluated on the 14th day of each treatment period, after which their next treatment period began. Mental performance was measured using Trails-A maze testing. Drowsiness was measured subjectively using a visual analogue scale, and objectively using critical fusion-frequency threshold testing. Blood pressure control was equivalent and clinically adequate in all subjects. Steady-state levels of metoprolol tartrate (235.7 +/- 46 ng/mL) and atenolol (453.6 +/- 56 ng/nL) achieved were those expected to produce similar beta-blockade. Mental performance as measured by Trials-A testing showed better scores during beta-blocker treatment compared with placebo. Trails-A scores improved as patients went from placebo to metoprolol treatment, but did not change as patients went from placebo to atenolol treatment. Critical fusion-frequency threshold measurements were lower following administration of both drugs than following that of placebo, but subjectively there was no difference in feelings of lethargy between either beta-blocker and placebo. These data show greater improvement in mental testing performance to be associated with metoprolol treatment, but neither produced more lethargy than placebo in elderly patients.
characterizes the antiplatelet effects of aspirin (acetylsalicylic acid) and ibuprofen alone and ... more characterizes the antiplatelet effects of aspirin (acetylsalicylic acid) and ibuprofen alone and in combination. Methods: Ten healthy volunteers were enrolled in a single-blinded, randomized, three-way crossover study. Treatments consisted of single doses of oral aspirin (325 mg) and ibuprofen (400 mg) and concomitant administration of aspirin (325 mg) and ibuprofen (400 mg). Ex vivo whole blood platelet aggregation induced by collagen (1 µg/mL) or arachidonic acid (0.5 mmol/L) was measured by impedance aggregometry. Model development and population parameter estimation were performed using nonlinear mixed-effects modelling implemented in NONMEM. Results: Relatively complete inhibition of platelet aggregation was achieved following aspirin treatment (~77% inhibition within 2 hours), and return to baseline values occurred within 72-96 hours after dosing. In contrast, treatment with ibuprofen alone or in combination with aspirin produced transient inhibition of platelet aggregation, with complete recovery observed in 6-8 hours. The final pharmacodynamic model was based on the turnover of cyclo-oxygenase-1 (COX-1) enzyme, and incorporated irreversible inhibition by aspirin and reversible binding and antiplatelet effects of ibuprofen. The temporal response profiles from all three study arms were well described by the final model, and the parameters were estimated with good precision. The apparent turnover rate constant for COX-1 (kout) and the irreversible inhibition rate constant for aspirin (K) were estimated to be 0.0209 h-1 and 0.152 (mg/L)-1 • h-1 , with interindividual variability of 30.6% and 26.2%, respectively. Simulations were used to evaluate the influence of clinically relevant ibuprofen regimens on the antiplatelet effect of aspirin, confirming clinical reports that the antiplatelet effect of aspirin would be blocked when multiple daily doses of ibuprofen are given, even if taken after aspirin administration. Conclusions: A mechanism-based pharmacodynamic model has been developed that characterizes the antiplatelet effects of aspirin and ibuprofen, alone and concomitantly, and predicts a significant inhibition of aspirin antiplatelet effects in the presence of a typical ibuprofen dosing regimen.
The Pharmacodynamics of Ethanol: Effects on Performance and Judgment
The Journal of Clinical Pharmacology, Aug 1, 1990
The objective and subjective effects produced by increasing and decreasing ethanol concentrations... more The objective and subjective effects produced by increasing and decreasing ethanol concentrations were studied in healthy volunteers on three separate occasions. A randomized, double‐blind, placebo‐controlled, four‐way crossover study was used to determine whether there is any disparity between the time course of blood ethanol concentration and its effects on either objective test performance or self rated impairment. On each study day the subjects received one of four treatments consisting of either placebo or sufficient alcohol to achieve peak estimated blood alcohol concentration (Est.BAC) of 0.07 gm/dL, 0.1 gm/dL or 0.14 gm/dL. Est.BAC determined from breath alcohol concentrations were measured 20 minutes after each “dose” until peak Est.BAC was achieved, then 1, 2, 3.5, and 4.5 hours after peak Est.BAC. Digit symbol substitution (DSS), simulated driving reaction time (SDRT), choice reaction time (CRT) and self assessment of impairment (SRI) were measured simultaneously with Est.BAC.Changes in objective performance test scores were well correlated with Est.BAC (r2 = 0.60 P < .01). Maximum impairment in test performance occurred at the same time as peak Est.BAC. Threshold Est.BAC needed to produce changes in objective test scores greater than placebo were 0.06 ± 0.01 for DSS, 0.04 ± 0.01 for SDRT, and 0.04 ± 0.02 for CRT. There was no evidence of between dose or within dose tolerance to the effects produced by various Est.BAC on any of these performance tests.Subjects' self rated degrees of impairment at various Est.BAC were influenced by whether alcohol concentrations were rising or falling. Subjective impairment ratings were greater while alcohol concentrations were increasing compared to the same Est.BAC occurring during falling alcohol concentrations. Disparities between self rated degree of impairment and decrements in test performance were greatest 1.0 hour after peak Est.BAC and maximum decrements in test performance. The delay in subjects' ability to accurately rate their impairment relative to peak Est.BAC may be a contributing factor to motorists choosing to drive while their performance is still impaired.
Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate w... more Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate,
A method for determining pindolol from human serum by high-performance liquid chromatography (HPL... more A method for determining pindolol from human serum by high-performance liquid chromatography (HPLC) is presented. Pindolol is extracted into methylene chloride from 1 mL of alkalinized serum with a recovery of 87%. The organic layer is evaporated and the residue is reconstituted in mobile phase for injection into the column. Samples are eluted from a 5-micron C18 column (250 x 4.6 mm) with acetonitrile-water containing 0.1% triethylamine, pH adjusted to 3.5 with phosphoric acid (20:80 v/v). Samples as low as 2 ng/mL have been detected.
Intranasal midazolam plasma concentration profile and its effect on anxiety associated with dental procedures
Anesthesia progress, 1996
The objectives of this study were to describe the serum concentration time profile for midazolam ... more The objectives of this study were to describe the serum concentration time profile for midazolam following intranasal administration to adult dental surgery patients and to ascertain the effect of midazolam on anxiety. Six female patients received a single 20 mg (0.32 to 0.53 mg/kg) dose of midazolam. Blood samples were collected at 5, 10, 20, 30, 45, and 60 min following dose administration. Midazolam plasma concentrations were determined by gas chromatography. Anxiety was evaluated using a 100-mm visual analogue scale. The maximum concentration of midazolam was reached 25.8 min (range 18 to 35 min) following dose administration. Maximum concentrations were variable. However, there was no relationship between the weight-adjusted dose and maximal concentration. Patients experiencing baseline anxiety exhibited a trend toward reduction in their measured anxiety score (P = 0.06). Plasma concentrations above the hypothesized minimum effective concentration for sedative effects were atta...
Quantitative effects of cetirizine and diphenhydramine on mental performance measured using an automobile driving simulator
PubMed, Jun 1, 1990
The purpose of this study was to assess the effects of cetirizine on objective measures of mental... more The purpose of this study was to assess the effects of cetirizine on objective measures of mental performance. Fifteen subjects were given single doses of cetirizine (20 mg, 10 mg, and 5 mg) diphenhydramine, 50 mg (positive control), and placebo (negative control) in this randomized, double-blinded, crossover study. An automobile driving simulator, digit symbol substitution, Trails B maze tracking and subjective feelings of drowsiness were measured at 0, 2, 4, 6, 8, and 24 hours after the dose. No differences between placebo and any of the three doses of cetirizine could be detected, however, diphenhydramine produced impaired mental performance and drowsiness. These data indicate that these doses of cetirizine produce little or no effect on cognitive function or mental performance.
The Effect of ß-Blockers on Mental Performance on Older Hypertensive Patients
Archives of internal medicine, Apr 1, 1988
• This double-blind, three-way crossover study measured the influence of β-blocker treatment on d... more • This double-blind, three-way crossover study measured the influence of β-blocker treatment on drowsiness and mental test performance in older hypertensive patients and determined if lipophilicity was a determinant of these effects. Twenty-seven hypertensive patients (mean age, 63±3 years) were studied. Patients received two weeks each of daily treatment with placebo, 100 mg of atenolol, or 150 mg of metoprolol tartrate and were evaluated on the 14th day of each treatment period, after which their next treatment period began. Mental performance was measured using Trails-A maze testing. Drowsiness was measured subjectively using a visual analogue scale, and objectively using critical fusion-frequency threshold testing. Blood pressure control was equivalent and clinically adequate in all subjects. Steady-state levels of metoprolol tartrate (235±46 ng/mL) and atenolol (453.6±56 ng/nL) achieved were those expected to produce similar β-blockade. Mental performance as measured by Trials-A testing showed better scores during β-blocker treatment compared with placebo. Trails-A scores improved as patients went from placebo to metoprolol treatment, but did not change as patients went from placebo to atenolol treatment. Critical fusion-frequency threshold measurements were lower following administration of both drugs than following that of placebo, but subjectively there was no difference in feelings of lethargy between either β-blocker and placebo. These data show greater improvement in mental testing performance to be associated with metoprolol treatment, but neither produced more lethargy than placebo in elderly patients. ( Arch Intern Med 1988;148:779-784)
The use of cannabis for the treatment of migraine has become an area of interest with the legaliz... more The use of cannabis for the treatment of migraine has become an area of interest with the legalization of medical cannabis in the USA. Understanding the mechanisms of cannabinoids, available studies, and best clinical recommendations is crucial for headache providers to best serve patients. Patients utilizing medical cannabis for migraine have reported improvement in migraine profile and common comorbidities. Reduction in prescription medication is also common, especially opioids. Side effects exist, with the majority being mild. Not enough data is available for specific dose recommendations, but THC and CBD appear to mediate these observed effects. The purpose of this article is twofold: review the limited research surrounding cannabis for migraine disease and reflect on clinical management experiences to provide recommendations that best capture the potential use of cannabis for migraine.
Pharmacist intervention and anti‐platelet medication monitoring in patients following stroke and transient ischemic attack
Journal of the American College of Clinical Pharmacy, 2021
Aspirin and clopidogrel are mainstays in secondary stroke prevention; however, some patients do n... more Aspirin and clopidogrel are mainstays in secondary stroke prevention; however, some patients do not demonstrate optimal antiplatelet effects from these therapies.
L-Methylfolate Calcium Supplementation in Adolescents and Children
Journal of Psychiatric Practice
Previous studies have shown l-methylfolate to be a safe and beneficial therapy for neuropsychiatr... more Previous studies have shown l-methylfolate to be a safe and beneficial therapy for neuropsychiatric conditions, including major depressive disorder and schizophrenia in adults. The purpose of this study was to assess safety and describe patient experience using l-methylfolate calcium in a real-world pediatric and adolescent population. A retrospective chart review of patients (7 to 20 y of age, mean age 16 y) prescribed l-methylfolate calcium at a psychiatry clinic in Amherst, NY, between January 1, 2010 and November 10, 2015 was conducted. Patients to whom l-methylfolate calcium 15 mg/d (n=139) or 7.5 mg/d (n=7) was administered were identified; 44 patients who were prescribed but to whom l-methylfolate calcium was not administered were included as a comparator population. Common neuropsychiatric diagnoses included anxiety disorders (68% in the treatment population vs. 50% in the comparator population) and mood disorders (57% in the treatment population vs. 52% in the comparator population). Antidepressants (69% vs. 55%) and mood stabilizers or antiepileptic drugs (63% vs. 57%) were frequently prescribed in combination with l-methylfolate calcium. Adverse events occurred less frequently in the treated population, possibly due to the addition of l-methylfolate calcium (10% vs. 25%, P=0.02). The most common adverse events in the treated population were impaired sleep (5 patients) and increased anxiety (3 patients). Rates of laboratory abnormalities did not differ significantly between the treated and comparator populations (P=0.13). Positive subjective treatment experiences were reported by 22.5% of treated patients and negative subjective treatment experiences were reported by 5.4% of treated patients. L-methylfolate calcium was well-tolerated in a pediatric/adolescent population and may provide benefits for patients with a range of neuropsychiatric conditions.
Work in Progress. Background: Urinary tract infection (UTI) is often considered a common cause of... more Work in Progress. Background: Urinary tract infection (UTI) is often considered a common cause of mental status changes, particularly in elderly patients and patients with a primary psychiatric condition. Additionally, the presence of genitourinary symptoms is essential to confirm diagnosis and determine the appropriate treatment course. Patients with a communication barrier may be unable to clearly convey the presence or absence of genitourinary symptoms, complicating an accurate diagnosis when mental status changes occur. Little evidence exists on diagnosing UTIs in patients who cannot communicate genitourinary symptoms; however, some guidance in long-term care facilities suggests assessing specific symptoms that do not rely on patient report. Objectives: The primary objective of this project is to provide assistance in the diagnosis and treatment of UTIs in patients who cannot communicate genitourinary symptoms through the creation of an algorithm. Secondary objectives include reducing inappropriate antibiotic use and increasing symptom documentation in this patient population. Methods: A UTI treatment algorithm for noncommunicative patients was developed using existing literature and through extensive collaboration with physicians, PhDs, and pharmacists working in the fields of emergency medicine, geriatric psychiatry, infectious diseases, microbiology, and urology. The final algorithm included comprehensive information on evaluating urinalysis (UA) results and identifying UTI symptoms, and offered guidance for antibiotic selection, dosing, and duration. Educational materials were created to enforce the most appropriate use of this algorithm, and provider education is ongoing. To limit the initial scope and allow for preintervention and postintervention data analysis, the algorithm will be utilized within the psychiatric emergency department. Adults admitted to the psychiatry service with a UA ordered and collected in the emergency department as well as an ICD-10 code representing dementia, delirium, autism spectrum disorder, or developmental delay will be included. Pregnant patients will be excluded. Outcomes: The preintervention cohort includes 56 admissions. Patients are predominantly female, with an average age of 60 years. Provider education will be completed in January, with postintervention data collection and analysis completed in February. This timeline allows for reporting on the impact of the intervention by comparing changes in UA ordering, antibiotic prescribing, and symptom documentation between preintervention and postintervention cohorts.
The ~harmacodvnamics of diphenhvdramine-induced drowsiness and chBnges in mental performance The ... more The ~harmacodvnamics of diphenhvdramine-induced drowsiness and chBnges in mental performance The time course of diphenhydramine concentrations and effects on both mental performance and subjective feelings of drowsiness were assessed in 15 healthy men. Subjects received single oral doses of diphenhydramine, 50 mg, and placebo in this double-blind crossover study. Diphenhydramine plasma concentrations and central nervous system actions were assessed for 24 hours after each treatment. Cognitive impairment was assessed with an automobile driving simulator and digit symbol substitution scores, whereas drowsiness was self-assessed on a visual analog scale. Diphenhydramine produced significant feelings of drowsiness for up to 6 hours after the dose, whereas significant mental impairment was apparent for only 2 hours. Despite the difference in duration of these effects, drowsiness and mental impairment have parallel slopes when effects are related to diphenhydramine concentrations. These data suggest that although the apparent diphenhydramine concentration thresholds to produce drowsiness are lower (30.4 to 41.5 nglrnl) than those needed to produce mental impairment (58.2 to 74.4 nglml), these effects have profiles consistent with their being manifestations of the same pharmacologic effect. (CLIN
To reduce the risks associated with the treatment of allergic disorders, physicians should unders... more To reduce the risks associated with the treatment of allergic disorders, physicians should understand the benefits and risks of drugs in the antihistamine class. The risk of central nervous system adverse effects associated with antihistamine use is significant with the use of first-generation antihistamines, which show pharmacologic activity in serotonepgic, c~adrenergic, dopaminet~ic, and muscarinic-cholinergic pathways. Adverse effects reported with the use of first-generation antihistamines most often include dlvwsiness, fatigue, and an inability to concentrate," these effects may result in decreased compliance with therapy. The second-generation antihistamines have the plvperty of low lipid solubility, which slows access across the blood-brain barrier. The low sedative profile of these new drugs may also be linked to a more p~vnounced binding to peripheral rather than brain histamine H z-receptors. The use of antihistamines with lower lipid solubility and greater specificity can provide an effective alternative for the relief of allergic symptoms, can improve compliance, and can reduce neurologic side effects. Because of the differences now recognized in the side effects of drugs of this class, an individualized approach to selection of antihistamine therapy is required.
In Reply .—We are pleased to have the opportunity to clarify a number of points from our recent a... more In Reply .—We are pleased to have the opportunity to clarify a number of points from our recent article in theArchives. 1 First, we would like to thank Dr Frohlich for his insightful editorial. 2 In his editorial, Dr Frohlich suggests that, although ours was a well-designed study, it may be argued that insufficient numbers of patients were studied. We agree that larger studies should precede any general conclusions regarding clinical management of hypertensive populations. However, to determine whether the β-blockers tested would influence indexes of mental performance and subjective lethargy measured, we had sufficient statistical power ( P =.95) based on the sample size and study design for a level of significance of P =.05. It is noteworthy to mention that similar conclusions have been simultaneously reported from two investigations of the central nervous system effects of propranolol and atenolol, which utilized a comparable study design. 3,4 Oliner and
The effect of beta-blockers on mental performance on older hypertensive patients
Archives of Internal Medicine, 1988
This double-blind, three-way crossover study measured the influence of beta-blocker treatment on ... more This double-blind, three-way crossover study measured the influence of beta-blocker treatment on drowsiness and mental test performance in older hypertensive patients and determined if lipophilicity was a determinant of these effects. Twenty-seven hypertensive patients (mean age, 63 +/- 3 years) were studied. Patients received two weeks each of daily treatment with placebo, 100 mg of atenolol, or 150 mg of metoprolol tartrate and were evaluated on the 14th day of each treatment period, after which their next treatment period began. Mental performance was measured using Trails-A maze testing. Drowsiness was measured subjectively using a visual analogue scale, and objectively using critical fusion-frequency threshold testing. Blood pressure control was equivalent and clinically adequate in all subjects. Steady-state levels of metoprolol tartrate (235.7 +/- 46 ng/mL) and atenolol (453.6 +/- 56 ng/nL) achieved were those expected to produce similar beta-blockade. Mental performance as measured by Trials-A testing showed better scores during beta-blocker treatment compared with placebo. Trails-A scores improved as patients went from placebo to metoprolol treatment, but did not change as patients went from placebo to atenolol treatment. Critical fusion-frequency threshold measurements were lower following administration of both drugs than following that of placebo, but subjectively there was no difference in feelings of lethargy between either beta-blocker and placebo. These data show greater improvement in mental testing performance to be associated with metoprolol treatment, but neither produced more lethargy than placebo in elderly patients.
characterizes the antiplatelet effects of aspirin (acetylsalicylic acid) and ibuprofen alone and ... more characterizes the antiplatelet effects of aspirin (acetylsalicylic acid) and ibuprofen alone and in combination. Methods: Ten healthy volunteers were enrolled in a single-blinded, randomized, three-way crossover study. Treatments consisted of single doses of oral aspirin (325 mg) and ibuprofen (400 mg) and concomitant administration of aspirin (325 mg) and ibuprofen (400 mg). Ex vivo whole blood platelet aggregation induced by collagen (1 µg/mL) or arachidonic acid (0.5 mmol/L) was measured by impedance aggregometry. Model development and population parameter estimation were performed using nonlinear mixed-effects modelling implemented in NONMEM. Results: Relatively complete inhibition of platelet aggregation was achieved following aspirin treatment (~77% inhibition within 2 hours), and return to baseline values occurred within 72-96 hours after dosing. In contrast, treatment with ibuprofen alone or in combination with aspirin produced transient inhibition of platelet aggregation, with complete recovery observed in 6-8 hours. The final pharmacodynamic model was based on the turnover of cyclo-oxygenase-1 (COX-1) enzyme, and incorporated irreversible inhibition by aspirin and reversible binding and antiplatelet effects of ibuprofen. The temporal response profiles from all three study arms were well described by the final model, and the parameters were estimated with good precision. The apparent turnover rate constant for COX-1 (kout) and the irreversible inhibition rate constant for aspirin (K) were estimated to be 0.0209 h-1 and 0.152 (mg/L)-1 • h-1 , with interindividual variability of 30.6% and 26.2%, respectively. Simulations were used to evaluate the influence of clinically relevant ibuprofen regimens on the antiplatelet effect of aspirin, confirming clinical reports that the antiplatelet effect of aspirin would be blocked when multiple daily doses of ibuprofen are given, even if taken after aspirin administration. Conclusions: A mechanism-based pharmacodynamic model has been developed that characterizes the antiplatelet effects of aspirin and ibuprofen, alone and concomitantly, and predicts a significant inhibition of aspirin antiplatelet effects in the presence of a typical ibuprofen dosing regimen.
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