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Shaina E. Musco - One of the best experts on this subject based on the ideXlab platform.
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Dopamine-Receptor Blocking Agent-associated akathisia: a summary of current understanding and proposal for a rational approach to treatment:
Therapeutic advances in psychopharmacology, 2020Co-Authors: Shaina E. Musco, Vivian Mcallister, Ian CaudleAbstract:Dopamine-Receptor Blocking Agent-associated akathisia (DRBA-A) is an adverse effect that can significantly limit the use of these important medications for the treatment of a variety of psychiatric diseases, yet there is no unifying theory regarding its pathophysiology. This knowledge gap limits clinicians' ability to effectively manage DRBA-A and mitigate negative outcomes in an already vulnerable patient population. Based on a review of the current literature on the subject, it is hypothesized that dopaminergic and noradrenergic signaling is perturbed in DRBA-A. Accordingly, it is proposed that the optimal Agent to manage this extrapyramidal symptom should increase dopamine signaling in the affected areas of the brain and counteract compensatory noradrenergic signaling via antagonism of adrenergic or serotonergic Receptors.
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Characteristics of Patients Experiencing Extrapyramidal Symptoms or Other Movement Disorders Related to Dopamine Receptor Blocking Agent Therapy.
Journal of clinical psychopharmacology, 2019Co-Authors: Shaina E. Musco, Laura Ruekert, Jaclyn Myers, Dennis Anderson, Michael Welling, Elizabeth Ann CunninghamAbstract:Purpose/background Dopamine Receptor Blocking Agents (DRBAs), also known as antipsychotics, are medications widely used to treat a growing number of mental health diagnoses. However, their utility is limited by the potential to cause serious adverse movement reactions. Akathisia, dystonia, parkinsonism, and tardive dyskinesia (collectively known as extrapyramidal symptoms or EPSs) are associated with reduced social and occupational functioning, negative patient attitudes toward treatment, and nonadherence to pharmacotherapy. Neuroleptic malignant syndrome is a life-threatening reaction that can result from DRBA use and cause musculoskeletal dysfunction. The aim of this study is to profile patients who have developed DRBA-related movement adverse effects and identify risk factors significantly associated with each subtype of EPSs or other movement disorders (OMDs) such as neuroleptic malignant syndrome. Methods/procedures A report of all potential DRBA-related EPSs or OMDs occurrences within a large community hospital network was generated using International Classification of Diseases, Ninth Revision (ICD-9) and 10th Revision (ICD-10) billing codes. Each patient encounter was manually reviewed to confirm that a documented case of DRBA-related EPSs or OMDs had indeed occurred and subsequently determine the likely causative Agent(s). Findings/results The resultant cohort of 148 patients experiencing unique DRBA-related EPS or OMD events was analyzed. The average patient was female, middle-aged, and overweight. The most common DRBAs precipitating EPSs or OMDs were haloperidol and quetiapine. In the population studied, age was significantly associated with the subtype of EPSs experienced such that those patients with akathisia and dystonia tended to be younger, whereas those with tardive dyskinesia tended to be older. Body mass index (BMI) category was also negatively correlated with the incidence of dystonia. In addition, it was observed that exposure to specific DRBAs, classes, and routes of administration significantly affected the risk of developing different subtypes of EPSs or OMDs in the study population. Implications/conclusions To our knowledge, this is the first study to describe an association between age and BMI with the risk of akathisia and dystonia, respectively, in patients taking DRBAs. Other trends observed with age and BMI in patients developing DRBA-related EPSs support previously reported findings. Expanding the knowledge base of individual characteristics associated with the risk of developing different subtypes of EPSs or OMDs can help providers and patients anticipate and attempt to mitigate these reactions, and may ultimately improve adherence to DRBA therapy.
Bertram Pitt - One of the best experts on this subject based on the ideXlab platform.
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Aldosterone-Receptor Blocking Agents
Medical Science Symposia Series, 2002Co-Authors: Bertram PittAbstract:Study findings pertaining to aldosterone-Receptor Blocking Agents hold important implications in the care of patients with congestive heart failure (CHF). Such research is critical to the cardiovascular care of the postmenopausal population. Since its discovery in 1954, the hormone aldosterone has been a target for therapy in CHF because of its role in sodium retention and potassium excretion [1]. However, it is now clear that aldosterone is responsible for a wide array of adverse effects that contribute to the manifestation of CHF, including myocardial fibrosis, direct vascular damage, endothelial cell and baroReceptor dysfunction, and ventricular arrhythmias [1 – 6]. To control the production of aldosterone and thereby counter these effects, inhibition of angiotensin II, the peptide hormone responsible for the production and release of aldosterone, with an angiotensin-converting enzyme (ACE) inhibitor is standard treatment, based on the assumption that suppressing angiotensin II production will, in turn, suppress aldosterone production. However, increasing evidence suggests that ACE inhibitors cannot sustain suppression of aldosterone production [5,7 – 10], even when combined with an angiotensin-Receptor Blocking Agent [11]. In the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study, the ACE inhibitor enalapril combined with the angiotensin Receptor Blocking Agent candesartin in heart failure patients produced a transient reduction in serum aldosterone levels at 17 weeks. By 43 weeks, however, aldosterone levels had risen above control (Figure 1) [11].
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Angiotensin II Receptor antagonists in heart failure: Rationale and design of the evaluation of losartan in the elderly (ELITE) trial
Cardiovascular Drugs and Therapy, 1995Co-Authors: Bertram Pitt, Paul Chang, Pieter B. M. Ww. M. TimmermansAbstract:Angiotensin-converting enzyme inhibitors (ACE-I) have been proven to be effective in reducing morbidity and mortality in patients with heart failure or post-myocardial infarction left ventricular dysfunction. Despite evidence from several large-scale randomized trials, the use of ACE-I in patients with heart failure remains relatively low. In part, the failure to achieve more widespread use of ACE-I in patients with heart failure may be due to physician's perceptions of the side effects associated with ACE-I, such as angioedema, renal dysfunction, cough, and hypotension. Many of these side effects are thought to be due to ACE-I-induced bradykinin accumulation. It is possible to inhibit the effect of angiotensin II without increasing bradykinin levels using an angiotensin II type I Blocking Agent such as losartan. How effective losartan is compared with an ACE-I is uncertain, however. Some of the beneficial effects of ACE-I have been attributed to bradykinin accumulation, and therefore ACE-I might have an advantage compared with an angiotensin II type I Receptor antagonist such as losartan. On the other hand, angiotensin II may be produced by non-ACE-I-dependent mechanisms, which would suggest that an angiotensin II type I Receptor Blocking Agent would be advantageous. To determine the relative safety and efficacy of an ACE-I, which results in bradykinin accumulation and inhibitors of angiotensin II, versus an angiotensin II type I Receptor Blocking Agent, which does not result in bradykinin accumulation, we have begun the Evaluation of Losartan In The Elderly (ELITE) trial, which will compare the safety and efficacy of captopril and losartan in elderly patients with heart failure.
Elizabeth Ann Cunningham - One of the best experts on this subject based on the ideXlab platform.
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Characteristics of Patients Experiencing Extrapyramidal Symptoms or Other Movement Disorders Related to Dopamine Receptor Blocking Agent Therapy.
Journal of clinical psychopharmacology, 2019Co-Authors: Shaina E. Musco, Laura Ruekert, Jaclyn Myers, Dennis Anderson, Michael Welling, Elizabeth Ann CunninghamAbstract:Purpose/background Dopamine Receptor Blocking Agents (DRBAs), also known as antipsychotics, are medications widely used to treat a growing number of mental health diagnoses. However, their utility is limited by the potential to cause serious adverse movement reactions. Akathisia, dystonia, parkinsonism, and tardive dyskinesia (collectively known as extrapyramidal symptoms or EPSs) are associated with reduced social and occupational functioning, negative patient attitudes toward treatment, and nonadherence to pharmacotherapy. Neuroleptic malignant syndrome is a life-threatening reaction that can result from DRBA use and cause musculoskeletal dysfunction. The aim of this study is to profile patients who have developed DRBA-related movement adverse effects and identify risk factors significantly associated with each subtype of EPSs or other movement disorders (OMDs) such as neuroleptic malignant syndrome. Methods/procedures A report of all potential DRBA-related EPSs or OMDs occurrences within a large community hospital network was generated using International Classification of Diseases, Ninth Revision (ICD-9) and 10th Revision (ICD-10) billing codes. Each patient encounter was manually reviewed to confirm that a documented case of DRBA-related EPSs or OMDs had indeed occurred and subsequently determine the likely causative Agent(s). Findings/results The resultant cohort of 148 patients experiencing unique DRBA-related EPS or OMD events was analyzed. The average patient was female, middle-aged, and overweight. The most common DRBAs precipitating EPSs or OMDs were haloperidol and quetiapine. In the population studied, age was significantly associated with the subtype of EPSs experienced such that those patients with akathisia and dystonia tended to be younger, whereas those with tardive dyskinesia tended to be older. Body mass index (BMI) category was also negatively correlated with the incidence of dystonia. In addition, it was observed that exposure to specific DRBAs, classes, and routes of administration significantly affected the risk of developing different subtypes of EPSs or OMDs in the study population. Implications/conclusions To our knowledge, this is the first study to describe an association between age and BMI with the risk of akathisia and dystonia, respectively, in patients taking DRBAs. Other trends observed with age and BMI in patients developing DRBA-related EPSs support previously reported findings. Expanding the knowledge base of individual characteristics associated with the risk of developing different subtypes of EPSs or OMDs can help providers and patients anticipate and attempt to mitigate these reactions, and may ultimately improve adherence to DRBA therapy.
Lajos Baláspiri - One of the best experts on this subject based on the ideXlab platform.
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Effect of vasopressin antagonist d(CH2)5Tyr(Et)VAVP on plasma arginine vasopressin level after osmotic stimulus.
Endocrine regulations, 1991Co-Authors: Ferenc László, F. Laczi, Tamás Janáky, Lajos BaláspiriAbstract:The effect of the vasopressin antagonist d(CH2)5Tyr(Et)VAVP on the immunoreactive arginine vasopressin (AVP) level in plasma was studied in rats after osmotic stimulus. The blood samples were obtained from the eye plexus. An increased AVP level (193.2 +/- 70.0; control: 30.5 +/- 4.3 pmol/l) was detected after the administration of hypertonic NaCl solution. A much higher elevation of AVP level (1180.9 +/- 181.0 pmol/l) was observed when treatment with the antagonist was applied before the osmotic stimulus. The results indicate that this compound exerts a biological effect as a vasopressin Receptor Blocking Agent through a mechanism of competitive antagonism.
Ian Caudle - One of the best experts on this subject based on the ideXlab platform.
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Dopamine-Receptor Blocking Agent-associated akathisia: a summary of current understanding and proposal for a rational approach to treatment:
Therapeutic advances in psychopharmacology, 2020Co-Authors: Shaina E. Musco, Vivian Mcallister, Ian CaudleAbstract:Dopamine-Receptor Blocking Agent-associated akathisia (DRBA-A) is an adverse effect that can significantly limit the use of these important medications for the treatment of a variety of psychiatric diseases, yet there is no unifying theory regarding its pathophysiology. This knowledge gap limits clinicians' ability to effectively manage DRBA-A and mitigate negative outcomes in an already vulnerable patient population. Based on a review of the current literature on the subject, it is hypothesized that dopaminergic and noradrenergic signaling is perturbed in DRBA-A. Accordingly, it is proposed that the optimal Agent to manage this extrapyramidal symptom should increase dopamine signaling in the affected areas of the brain and counteract compensatory noradrenergic signaling via antagonism of adrenergic or serotonergic Receptors.
