-
European Journal of Pharmaceutical... Jul 2022Swallowing oral solid dosage forms is challenging in patients with dysphagia who are at risk of aspiration or choking. The most common method to facilitate drug...
Swallowing oral solid dosage forms is challenging in patients with dysphagia who are at risk of aspiration or choking. The most common method to facilitate drug administration in dysphagia patients is to mix the powdered drug with a small amount of thickened water, however little is known about the effects of this method on in vivo bioavailability of drugs. This study aimed to evaluate the impact of thickened liquids on dissolution rate and bioavailability of levetiracetam as a model drug. Powdered commercial tablets of levetiracetam, carbamazepine, atenolol and cefixime were mixed with water thickened with two commercial thickeners, modified maize starch (MS) and xanthan gam (XG), at three thickness levels: nectar, honey and pudding in test groups, and mixed with only water in the control group. At the first stage, the effects of thickened water on in vitro drug release of 4 drugs (levetiracetam, carbamazepine, atenolol and cefixime) were tested by using dialysis membrane method. Addition of both thickeners significantly reduced the release of three drugs compared to the control group, except carbamazepine. Levetiracetam which had the highest solubility was chosen as the model drug for in vivo experiments. In the second stage, New Zealand albino female rabbits (n=24) were divided into two groups as: control group (water+drug, n=6) and test group (thickened water+drug, n=18). Powdered levetiracetam tablets were mixed with water thickened with XG (n=9, 1.2%, 2.4%, 3.6%) and MS (n=9, 4%, 6%, 8%) at three thickness levels and administered to the rabbits by intragastric gavage. Blood samples were collected at 9 time points following administration. After two-weeks of wash-out, test groups were crossed over and sample collection was repeated. Blood samples were analysed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). An in vitro-in vivo correlation (IVIVC) model was developed using in vitro drug dissolution (%) and in vivo plasma concentrations of levetiracetam for control group and test groups. The peak plasma concentration (C) was lower and time to reach C (t) was relatively higher in test groups compared to control group. The lowest C was detected at the highest thickness level, however, the differences between groups were not statistically significant (p=0.117 and p=0.495 for C and t, respectively). No significant difference in total amount of levetiracetam absorbed (AUC) was found between groups (p=0.215 and p=0.183 for AUC and AUC, respectively). The comparisons according to the type of thickener also revealed that pharmacokinetic parameters did not significantly differ between groups, except for a significantly lower C when drug was mixed with MS-thickened water at nectar consistency (1.2%) compared to drug mixed with XG (4%) at the same thickness level (p=0.038). A good correlation was observed between in vitro and in vivo data, which was characterized by higher r values as the concentration of the thickening agents was increased, but not for all thickness levels studied, indicating an inability of this in vitro model to fully predict the in vivo response. These results suggest that regardless of the thickness level, the administration of levetiracetam with two commercial thickening agents commonly used in dysphagia for safe swallowing, do not affect the pharmacokinetic efficiency and thus, the bioavailability of the drug.
Topics: Animals; Atenolol; Biological Availability; Carbamazepine; Cefixime; Chromatography, Liquid; Deglutition Disorders; Diet; Food Additives; Humans; Levetiracetam; Plant Nectar; Rabbits; Starch; Tablets; Tandem Mass Spectrometry; Viscosity; Water
PubMed: 35489612
DOI: 10.1016/j.ejps.2022.106197 -
Journal of Veterinary Cardiology : the... Jun 2024A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h)...
A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h) was referred for respiratory distress and anorexia. The cat was diagnosed with pulmonary oedema secondary to obstructive hypertrophic cardiomyopathy. After stabilisation, she was discharged with furosemide (1 mg/kg q 12 h), clopidogrel (18.75 mg q 24 h), atenolol (6.25 mg q 12 h), and mirtazapine (2 mg/cat q 24 h) to increase appetite. At recheck, the cat was lethargic and presented with severe bradycardia with a junctional escape rhythm and ventriculoatrial conduction. The mirtazapine was discontinued due to its possible side-effects on cardiac rhythm. After three days, the atenolol was halved because the bradyarrhythmia was still present. After 10 days, the rhythm returned to sinus; atenolol was reintroduced twice daily with no further side-effects. The absence of a sinus rhythm with a junctional escape rhythm and P' retroconduction is compatible with a third-degree sinus block or a sinus standstill; the differentiation of these rhythm disturbances is impossible, based on the surface electrocardiogram (ECG). The sinus rhythm was restored after mirtazapine was withdrawn. However, it is not possible to rule out the role of the atenolol or the combined effect of the two drugs. The cat was affected by hypertrophic cardiomyopathy, and the role of myocardial remodelling cannot be excluded. This is the first time that a bradyarrhythmia consequent to the treatment with atenolol and mirtazapine was described in a cat.
Topics: Female; Mirtazapine; Animals; Atenolol; Cats; Cat Diseases; Cardiomyopathy, Hypertrophic; Bradycardia; Mianserin; Adrenergic beta-1 Receptor Antagonists
PubMed: 38735230
DOI: 10.1016/j.jvc.2024.03.003 -
Environmental Science & Technology Oct 2022In shallow, open-water engineered wetlands, design parameters select for a photosynthetic microbial biomat capable of robust pharmaceutical biotransformation, yet the...
In shallow, open-water engineered wetlands, design parameters select for a photosynthetic microbial biomat capable of robust pharmaceutical biotransformation, yet the contributions of specific microbial processes remain unclear. Here, we combined genome-resolved metatranscriptomics and oxygen profiling of a field-scale biomat to inform laboratory inhibition microcosms amended with a suite of pharmaceuticals. Our analyses revealed a dynamic surficial layer harboring oxic-anoxic cycling and simultaneous photosynthetic, nitrifying, and denitrifying microbial transcription spanning nine bacterial phyla, with unbinned eukaryotic scaffolds suggesting a dominance of diatoms. In the laboratory, photosynthesis, nitrification, and denitrification were broadly decoupled by incubating oxic and anoxic microcosms in the presence and absence of light and nitrogen cycling enzyme inhibitors. Through combining microcosm inhibition data with field-scale metagenomics, we inferred microbial clades responsible for biotransformation associated with membrane-bound nitrate reductase activity (emtricitabine, trimethoprim, and atenolol), nitrous oxide reduction (trimethoprim), ammonium oxidation (trimethoprim and emtricitabine), and photosynthesis (metoprolol). Monitoring of transformation products of atenolol and emtricitabine confirmed that inhibition was specific to biotransformation and highlighted the value of oscillating redox environments for the further transformation of atenolol acid. Our findings shed light on microbial processes contributing to pharmaceutical biotransformation in open-water wetlands with implications for similar nature-based treatment systems.
Topics: Ammonium Compounds; Atenolol; Biotransformation; Denitrification; Emtricitabine; Metoprolol; Nitrate Reductases; Nitrification; Nitrogen; Nitrous Oxide; Oxygen; Pharmaceutical Preparations; Photosynthesis; Trimethoprim; Water; Wetlands
PubMed: 36197061
DOI: 10.1021/acs.est.2c03566 -
European Stroke Journal Mar 2023Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially...
The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial.
BACKGROUND
Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs.
AIMS
To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs.
DESIGN
TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose.
OUTCOMES
The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv).
DISCUSSION
TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs.
FUNDING
European Union's Horizon 2020 programme.
TRIAL REGISTRATION
NCT03082014.
Topics: Humans; Amlodipine; Antihypertensive Agents; Blood Pressure; Atenolol; Losartan; Cross-Over Studies; Prospective Studies; Randomized Controlled Trials as Topic
PubMed: 37021189
DOI: 10.1177/23969873221143570 -
Clinical Journal of the American... Apr 2018There is a paucity of data available to describe drug dialyzability. Of the available information, most was obtained before implementation of modern hemodialysis... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVES
There is a paucity of data available to describe drug dialyzability. Of the available information, most was obtained before implementation of modern hemodialysis membranes. Our study characterized dialyzability of the most commonly prescribed -blockers in patients undergoing high-flux hemodialysis.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Patients on hemodialysis (=8) were recruited to an open label, pharmacokinetic, four-way crossover trial. Single doses of atenolol, metoprolol, bisoprolol, and carvedilol were administered on separate days in random order to each patient. Plasma and dialysate drug concentrations were measured, and dialyzability was determined by the recovery clearance and arterial venous difference methods.
RESULTS
Using the recovery clearance method, the dialytic clearance values for atenolol, metoprolol, bisoprolol, and carvedilol were 72, 87, 44, and 0.2 ml/min, respectively (<0.001). Applying the arterial venous difference method, the dialytic clearance values of atenolol, metoprolol, bisoprolol, and carvedilol were 167, 114, 96, and 24 ml/min, respectively (<0.001).
CONCLUSIONS
Atenolol and metoprolol are extensively cleared by hemodialysis compared with the negligible dialytic clearance of carvedilol. Contrary to estimates of dialyzability on the basis of previous literature, our data indicate that bisoprolol is also dialyzable. This finding highlights the importance of conducting dialyzability studies to definitively characterize drug dialytic clearance.
Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Atenolol; Bisoprolol; Carvedilol; Cross-Over Studies; Dialysis Solutions; Female; Humans; Male; Metoprolol; Middle Aged; Renal Dialysis
PubMed: 29519953
DOI: 10.2215/CJN.07470717 -
Brazilian Oral Research 2020This study evaluates how atenolol affects dental mineralization in offspring of female spontaneously hypertensive rats (fSHR) and normotensive Wistar rats (fW). fSHR and...
This study evaluates how atenolol affects dental mineralization in offspring of female spontaneously hypertensive rats (fSHR) and normotensive Wistar rats (fW). fSHR and fW were treated with atenolol (100 mg/Kg/day, orally) during pregnancy and lactation. Non-treated fSHR and fW were the control groups. Enamel and dentin hardness were analyzed (Knoop, 15 g load, 10s) in mandibular incisor teeth (IT) and molar teeth (MT) obtained from the male offspring of atenolol-treated and non-treated fWistar and fSHR. Data were analyzed by ANOVA, followed by Tukey post hoc test (p < 0.05). Atenolol reduced the arterial blood pressure (SBP) in fSHR, but it did not change the SBP in fW. The offspring of non-treated fSHR had lower enamel (IT and MT) and dentin (IT) hardness than the offspring of non-treated fW (p < 0.05). Atenolol increased enamel and dentin hardness in the IT obtained from the offspring of fSHR and fW (p<0.05), but the offspring of fSHR presented higher values (p < 0.05). Atenolol did not alter enamel width in the IT obtained from any of the groups, but it increased enamel and dentin hardness in the IT obtained from the offspring of fSHR and fW. Atenolol affected the IT obtained from the offspring of fSHR. Atenolol increased only enamel hardness in the MT obtained from the offspring of fW. In conclusion, maternal hypertension reduces tooth hard tissues, and treatment with atenolol increases tooth hardness in male offspring of hypertensive and normotensive female rats.
Topics: Animals; Atenolol; Dental Enamel; Dentin; Female; Hardness; Hypertension; Male; Pregnancy; Rats; Rats, Wistar
PubMed: 32785480
DOI: 10.1590/1807-3107bor-2020.vol34.0086 -
Naunyn-Schmiedeberg's Archives of... Oct 20226-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral...
6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective β-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective β- and β/β-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective β-adrenergic receptor antagonists atenolol (0.1 and 1 µM), betaxolol (1 µM), and metoprolol (1 µM) and the unselective β/β-adrenergic receptor antagonists propranolol (1 and 10 µM) and pindolol (10 µM) caused significant rightward shifts of the concentration-response curve to 6-ND (pA 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective β- and β/β-adrenergic receptor antagonists at a higher concentration (atenolol 1 µM, betaxolol 1 µM, metoprolol 1 µM, propranolol 10 µM, and pindolol 10 µM) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective β-adrenoceptor agonist RO-363, the selective β-adrenoceptor agonist salbutamol, and the selective β-adrenoceptor agonist mirabegron, up to 300 µM, had no effect on the RIEVD tone. The results demonstrate that β- and β-/β-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.
Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-2 Receptor Antagonists; Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Atenolol; Betaxolol; Dopamine; Epinephrine; Male; Metoprolol; Norepinephrine; Pindolol; Propranolol; Rats; Vas Deferens
PubMed: 35798982
DOI: 10.1007/s00210-022-02268-6 -
Military Medicine Dec 2020Anxiety disorders are among the most commonly diagnosed of psychiatric disorders. Many symptoms of posttraumatic stress disorder are also anxiety-related. Traditional...
INTRODUCTION
Anxiety disorders are among the most commonly diagnosed of psychiatric disorders. Many symptoms of posttraumatic stress disorder are also anxiety-related. Traditional medications used to treat these disorders, such as antidepressants and benzodiazepines, are often ineffective, not well-tolerated, and can be habit forming. An alternative agent is, therefore, needed. Beta-blockers are one class of medication with potential to treat anxiety-related disorders; however, current evidence remains limited and requires further characterization. To this end, this retrospective study aims to present a novel preliminary report on the use of the beta-blocker, atenolol, to potentially treat anxiety-related disorders.
MATERIALS AND METHODS
Ninety-two patients were identified from outpatient military mental health clinics in Okinawa, Japan, who had received atenolol for mental health-related symptoms. Primary measures collected were the rates of patient-reported (1) general beneficial/positive effect of atenolol, (2) adverse effects from atenolol, and (3) preference of atenolol to propranolol. Data were collected from patients who were given binary response options to report their perceived experiences for each primary measure. This study was approved by the Naval Medical Center San Diego Institutional Review Board.
RESULTS
The results showed 86% of patients reporting a positive effect and continuing to take atenolol, including 87% with a diagnosis of posttraumatic stress disorder, 100% with diagnosis of other specified trauma- and stressor-related disorder, and 81% diagnosed with anxiety disorders. In total, 90% of patients denied adverse effects or found the adverse effects tolerable. Additionally, 100% of patients who had previously taken propranolol for anxiety reported that they preferred atenolol.
CONCLUSIONS
The present preliminary observational data suggests that atenolol may be well-tolerated and effective among persons with anxiety disorders. These data also suggest that atenolol may be more effective and better tolerated than propranolol, which is the most commonly prescribed beta-blocker for these conditions; however, more rigorously controlled empirical studies are needed to further substantiate this claim. Despite an overwhelmingly high rate of positive reports from patients' self-evaluations of atenolol treatment for anxiety-related disorders, this early investigation was not placebo-controlled nor double-blinded, and formal outcome measures were not assessed due to a lack of availability. More detailed examinations are needed to further determine whether atenolol is a viable alternative or augmenting agent to propranolol, benzodiazepines, and antidepressants for anxiety disorders and trauma-related disorders.
Topics: Anxiety; Anxiety Disorders; Atenolol; Humans; Japan; Retrospective Studies
PubMed: 32728694
DOI: 10.1093/milmed/usaa170 -
Journal of Ocular Pharmacology and... Mar 2022To evaluate the effect of reducing blood pressure (BP) by atenolol and amlodipine on (1) intraocular pressure (IOP) and (2) ophthalmic artery blood flow (OAF) velocity... (Observational Study)
Observational Study
To evaluate the effect of reducing blood pressure (BP) by atenolol and amlodipine on (1) intraocular pressure (IOP) and (2) ophthalmic artery blood flow (OAF) velocity in new hypertensives. A prospective, observational cohort study conducted at a tertiary care center in India after IRB approval. New hypertensives treated with atenolol 25 mg or amlodipine 5 mg were divided into 2 groups of 30 patients each. BP, IOP by Goldmann applanation tonometry and OAF velocity by transcranial doppler sonography was performed before medication and post medication on day 1, 7, and 30. There was a significant decrease in IOP with both drugs; the effect was greater with atenolol. Atenolol: premedication IOP - 16.06 ± 2.13 mmHg and day 30-12.46 ± 1.94 (22.4%) [ < 0.001], amlodipine: premedication IOP-15.13 ± 2.55 mmHg and day 30- 13.06 ± 2.14 (13.68%) [ < 0.001]. A decrease of 0.5 mmHg in IOP with every 10 mmHg (95% CI: 0.121-0.826, value = 0.01) decrease in systolic BP was noted after oral atenolol. The OAF peak systolic velocity and mean flow velocity were equally reduced with both drugs ( < 0.001). The end-diastolic velocity, reduced only with atenolol ( = 0.049) but returned to baseline with amlodipine at 1 month. BP reduction by atenolol and amlodipine led to decreases in IOP and OAF velocity, greater with atenolol. The IOP decrease was likely due to reduced blood flow. A slight decrease in the diastolic flow of the ophthalmic artery was noted with atenolol.
Topics: Amlodipine; Atenolol; Blood Flow Velocity; Blood Pressure; Humans; Hypertension; Intraocular Pressure; Ophthalmic Artery; Prospective Studies
PubMed: 34964660
DOI: 10.1089/jop.2021.0096 -
Urologic Oncology Oct 2020Increased adrenergic innervation is observed in prostate cancer (CaP) and is associated with aggressive disease. Emerging evidence suggests that beta-adrenergic blockade...
PURPOSE
Increased adrenergic innervation is observed in prostate cancer (CaP) and is associated with aggressive disease. Emerging evidence suggests that beta-adrenergic blockade inhibits CaP progression. However, the association between type of beta-blocker use and risk of incident CaP on initial prostate biopsy has not been investigated in multiethnic populations.
MATERIALS AND METHODS
A retrospective study of racially/ethnically diverse men (64% African-American and Hispanic), who underwent initial prostate biopsy between 2006 and 2016 in a large healthcare system was performed. Oral use of beta-blocker type was assessed by reviewing active prescriptions within the 5-year period preceding initial biopsy. Patient demographics and clinical factors were collected.
RESULTS
Of 4,607 men who underwent initial prostate biopsy, 4,516 met criteria and 2,128 had a biopsy positive for CaP; 20% high-risk, 41% intermediate-risk, and 39% low or very-low risk (National Comprehensive Cancer Network classification). Overall, 15% of patients were taking a beta-blocker prior to initial biopsy, with Metoprolol, Atenolol, and Carvedilol accounting for the majority. Of beta-blocker types, Atenolol alone was associated with a 38% reduction in odds of incident CaP (P= 0.01), with a 40% and 54% reduction in risks of National Comprehensive Cancer Network intermediate and high-risk CaP (P = 0.03 and P = 0.03, respectively) compared to men not taking a beta-blocker. Furthermore, longer duration of Atenolol use (3-5 years) was associated with a 54% and 72% reduction in intermediate and high-risk disease, (P = 0.03 and P = 0.03, respectively).
CONCLUSIONS
Among beta blocker types, long-term Atenolol use is associated with a significant reduction in incident CaP risk on initial prostate biopsy for clinically-significant intermediate and high-risk disease compared to men not taking a beta-blocker.
Topics: Adrenergic beta-Antagonists; Aged; Atenolol; Carvedilol; Humans; Image-Guided Biopsy; Incidence; Male; Metoprolol; Middle Aged; Prostate; Prostatic Neoplasms; Protective Factors; Retrospective Studies; Risk Assessment; Time Factors; Ultrasonography, Interventional
PubMed: 32307329
DOI: 10.1016/j.urolonc.2020.03.024