Jose de Leon, MD

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S3) ◽  
pp. 8-12 ◽  
Keyword(s):  
Genetic Variation ◽  
Adverse Drug Reactions ◽  
Antipsychotic Treatment ◽  
Inadequate Response ◽  
Drug Selection ◽  
Drug Reactions ◽  
Increased Risk ◽  
Optimal Drug ◽  
Medication Selection ◽  
Cyp 2D6

AbstractAlthough most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity.In this monograph, David A. Mrazek, MD, provides an overview of the context of genetic testing in clinical psychiatric practice. Next, Jordan W. Smoller, MD, ScD, discusses some of the practical issues related to medication selection. Finally, Jose de Leon, MD, presents a comprehensive review of antidepressant and antipsychotic treatment based on drug metabolism, and reviews the available testing methods for CYP 2D6 and 2C19 genotypes.

Jordan W. Smoller, MD, ScD

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S3) ◽  
pp. 5-7
Keyword(s):  
Genetic Variation ◽  
Adverse Drug Reactions ◽  
Antipsychotic Treatment ◽  
Inadequate Response ◽  
Drug Selection ◽  
Drug Reactions ◽  
Increased Risk ◽  
Optimal Drug ◽  
Medication Selection ◽  
Cyp 2D6

AbstractAlthough most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity.In this monograph, David A. Mrazek, MD, provides an overview of the context of genetic testing in clinical psychiatric practice. Next, Jordan W. Smoller, MD, ScD, discusses some of the practical issues related to medication selection. Finally, Jose de Leon, MD, presents a comprehensive review of antidepressant and antipsychotic treatment based on drug metabolism, and reviews the available testing methods for CYP 2D6 and 2C19 genotypes.

The Context of Genetic Testing in Clinical Psychiatric Practice

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S3) ◽  
pp. 3-4 ◽  
Author(s):  
David A. Mrazek
Keyword(s):  
Genetic Variation ◽  
Adverse Drug Reactions ◽  
Inadequate Response ◽  
Drug Selection ◽  
Drug Reactions ◽  
Metabolizing Enzymes ◽  
Drug Effectiveness ◽  
Increased Risk ◽  
Optimal Drug ◽  
Medication Selection

AbstractAlthough most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity.

scholarly journals Safety of Cholinesterase Inhibitors and NMDA Receptors Antagonists for the Treatment of Patients with Dementia

2019 ◽  
Vol 7 (4) ◽  
pp. 190-199
Author(s):  
A. P. Pereverzev ◽  
O. D. Ostroumova ◽  
O. N. Tkacheva ◽  
Y. V. Kotovskaya
Keyword(s):  
Nmda Receptor ◽  
Nmda Receptors ◽  
Adverse Drug Reactions ◽  
Cholinesterase Inhibitors ◽  
Acetylcholinesterase Inhibitors ◽  
Competitive Inhibitor ◽  
Nmda Receptor Antagonists ◽  
Drug Reactions ◽  
Receptor Antagonists ◽  
Increased Risk

For the treatment of dementia and Alzheimer’s disease, acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or the non-competitive inhibitor of N-methyl-D-aspartate receptors (NMDA receptors) memantine are currently used. The administration of these drugs can help temporarily improve or stabilize memory impairments and other cognitive functions, regress behavioral disorders, reduce the patient’s dependence on others, but at the same time can lead to the development of adverse drug reactions. The aim of this study was to analyze the information on the safety of acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the non-competitive inhibitor of NMDA receptors used to treat dementia. It was shown that stimulation of cholinergic receptors can lead to adverse drug reactions as contraction and narrowing of the pupil (miosis), an increase in lens curvature, accommodation spasm (visual impairment and an increased risk of falls), a decrease in heart rate (bradycardia) and inhibition of conduction of impulses through the conducting system heart, increased tone of the bronchi, gastrointestinal tract, gall and bladder, decreased tone of the sphincters of the digestive tract and bladder, increased secretion of exocrine and glands of the stomach, agitation, confusion. Blockade of NMDA receptors due to impairment of glutamate metabolism in the central nervous system may be the cause of neurotoxicity of NMDA receptor antagonists, and also causes dizziness, feeling of tiredness, hallucinations, drowsiness, and confusion. In case of development of adverse reactions, if possible, it is necessary to stop using the drug or reduce its dose, in case of an overdose or other need, prescribe symptomatic therapy. Information on the safety of cholinesterase inhibitors and NMDA receptor antagonists presented in the article is of practical importance for healthcare professionals, as it allows them to assess the possible risks associated with the use of drugs of these groups more accurately. In addition, the information can be used to optimize and individualize the pharmacotherapy regimens for patients with dementia, including the development of domestic protocols for the deprescribing of drugs (evidence-based practice of withdrawal, replacement or gradual dose reduction) in the elderly. 

Meperidine Misuse in a Patient with Sphincter of Oddi Dysfunction

2003 ◽  
Vol 37 (4) ◽  
pp. 534-537 ◽  
Author(s):  
Garrick P Hubbard ◽  
Kelly R Wolfe
Keyword(s):  
Pain Management ◽  
Adverse Drug Reactions ◽  
Tertiary Care ◽  
Care Facility ◽  
Sphincter Of Oddi ◽  
Drug Event ◽  
Sphincter Of Oddi Dysfunction ◽  
Drug Reactions ◽  
Increased Risk ◽  
Oddi Dysfunction

OBJECTIVE: To report a seizure occurring secondary to meperidine treatment despite normal renal and central nervous system (CNS) function, and to provide a review of meperidine's role in pain management, including its use in pancreatitis and sphincter of Oddi dysfunction. CASE SUMMARY: A 55-year-old white woman with a history of sphincter of Oddi dysfunction presented to the emergency department with severe abdominal pain. On admission to the hospital, the serum creatinine level was 0.6 mg/dL with slightly elevated aspartate aminotransferase of 56 U/L (normal range 0–31) and alanine aminotransferase of 34 U/L (0–31). The patient received repeated and escalating doses of intravenous meperidine, resulting in a generalized seizure on day 4 of hospitalization. The accumulated meperidine dose was 2125 mg. Buprenorphine was substituted in place of meperidine, and the patient had no further reported complications. She was then transferred to a tertiary-care facility for sphincter of Oddi reevaluation. An objective causality assessment revealed the adverse drug event as probable. DISCUSSION: Despite alternative opioids, meperidine continues to be used in pain management. Meperidine is different from other opioids because its active metabolite, normeperidine, is neurotoxic. Patients with renal insufficiency, liver failure, or CNS dysfunction are at increased risk for adverse drug reactions related to normeperidine accumulation. Due to normeperidine's extended half-life, however, accumulation of normeperidine can occur in any patient receiving repeated doses of meperidine. CONCLUSIONS: This case demonstrates the potential hazards that exist when using meperidine in any patient. Meperidine's inherent risks of both undertreating pain and causing adverse drug reactions should prompt clinicians and health organizations to restrict its use in pain management. This restriction should not make exceptions to meperidine's traditional use in pancreatitis or sphincter of Oddi dysfunction.

scholarly journals A Real-World, Multicenter Assessment of Drugs Requiring Weight-Based Calculations in Overweight, Adult Critically Ill Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sandra L. Kane-Gill ◽  
Nicholas P. Wytiaz ◽  
Lisa M. Thompson ◽  
Karina Muzykovsky ◽  
Mitchell S. Buckley ◽  
...  
Keyword(s):  
High Risk ◽  
Adverse Drug Reactions ◽  
Real World ◽  
Drug Reactions ◽  
Multicenter Observational Study ◽  
Increased Risk ◽  
The Us ◽  
Overweight Adult ◽  
Body Mass Indexes ◽  
Prospective Multicenter Observational Study

Prescribing appropriate doses of drugs requiring weight-based dosing is challenging in overweight patients due to a lack of data. With 68% of the US population considered overweight and these patients being at an increased risk for hospitalization, clinicians need guidance on dosing weight-based drugs. The purpose of this study was to identify “real-world” dose ranges of high-risk medications administered via continuous infusion requiring weight-based dosing and determine the reasons for dosing changes (ineffectiveness or adverse drug reactions). A prospective, multicenter, observational study was conducted in four intensive care units at three institutions. A total of 857 medication orders representing 11 different high-risk medications in 173 patients were reviewed. It was noted that dosing did not increase in proportion to weight classification. Overall, 14 adverse drug reactions occurred in nine patients with more in overweight patients (9 of 14). A total of 75% of orders were discontinued due to ineffectiveness in groups with higher body mass indexes. Ineffectiveness leads to dosing adjustments resulting in the opportunity for medication errors. Also, the frequent dosing changes further demonstrate our lack of knowledge of appropriate dosing for this population. Given the medications’ increased propensity to cause harm, institutions should aggressively monitor these medications in overweight patients.

FRAILTY AND DRUG USE

2016 ◽  
pp. 1-4
Author(s):  
K. PALMER ◽  
A. MARENGONI ◽  
P. RUSSO ◽  
F. MAMMARELLA ◽  
G. ONDER
Keyword(s):  
Older Adults ◽  
Drug Use ◽  
Adverse Drug Reactions ◽  
Poor Adherence ◽  
Drug Reactions ◽  
Adherence To Treatment ◽  
Older Population ◽  
Development Management ◽  
Increased Risk ◽  
Multiple Drugs

Older adults often have co-occurring multiple chronic and acute diseases, which progressively and steadily increase in prevalence with age (1, 2). The treatment of these diseases usually requires multiple drugs (polypharmacy); it has been estimated that more than 50% of persons aged 65 years or older receive five or more drugs concomitantly (3, 4). Drug use in the older population might raise several concerns related to an increased risk of drug-drug and drug-disease interactions, poor adherence to treatment, and increased risk of adverse drug reactions (5-7). In this chapter we will discuss what role drugs and polypharmacy play in the development, management and treatment of frailty.

What are the Characteristics of Patients Experiencing Adverse Drug Reactions to Oral Anticogulants and How Can Such Reactions be Prevented?

2020 ◽  
Vol 15 (1) ◽  
pp. 38-44 ◽  
Author(s):  
G. Spada ◽  
G.V. Vighi ◽  
S. Pagani ◽  
G.D. Vighi ◽  
M. Venegoni ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Oral Anticoagulants ◽  
Management Strategies ◽  
Real Life ◽  
Hospital Setting ◽  
Admission Diagnosis ◽  
Drug Reactions ◽  
Acute Hemorrhage ◽  
Increased Risk ◽  
Clinical Records

Introduction: Oral anticoagulants, including vitamin K inhibitors (VKAs) and direct anticoagulants (DOACs) are important for preventing and treating thromboembolic diseases. However, they are not recommended for use in all patients due to negative side effects and adverse drug reactions (ADRs). Currently, there is a paucity of information about their use in real life. Therefore, the aim of this pilot study is to report on the rate of serious ADRs in oral anticoagulant users, determine patient characteristics associated with increased risk of ADRs, and identify possible management strategies for reducing risk of ADRs within a hospital setting. Methods: Patients admitted to the Internal Medicine Department of the Vimercate Hospital were recruited between November 1, 2015 and October 31, 2016. All patients reporting an ADR associated with anticoagulant use were selected. Demographic, clinical, and observational data were extracted from electronic hospital records, in particular, by the hospital discharge letters and other clinical records. The main outcome of the study was to evaluate the incidence of anticoagulants serious adverse drug reactions conditioning hospital admission, the percentage of preventable reactions, and the determinants of those. Results and Discussion: Of the 2,064 admissions, 102 (4.9%) eligible patients were identified. Age ranged from 60-95 years (mean = 81.9, standard deviation = 6,59) and 47.1% (n=48) were female. Of the 102 cases, 68 used VKAs and 34 used DOACs. The most common admission diagnosis was heart failure following anemia or hemorrhage (56 cases), followed by acute hemorrhage (with or without anemia; 29 cases), and anemia not associated with evident hemorrhage (17cases). The majority of VKA users (n=65, 95.6%) had a high risk of major bleeding. ADRs were found to be preventable in 96% of VKA users and 68% of DOACs users. Conclusion: This study highlights the large percentage of ADRs from oral anticoagulants that can be avoided with more careful patient management. Periodic check-up of cardiac and renal function, as well as blood count, may be useful for reducing the risk of ADRs, especially in older DOACs users. Further research is needed to get new data to improve the patients monitoring system.

scholarly journals Polypharmacy and inappropriate medication use in patients with dementia: an underresearched problem

2016 ◽  
Vol 8 (1) ◽  
pp. 31-46 ◽  
Author(s):  
Carole Parsons
Keyword(s):  
Older People ◽  
Adverse Drug Reactions ◽  
Inappropriate Prescribing ◽  
Drug Reactions ◽  
Full Spectrum ◽  
People With Dementia ◽  
Increased Risk ◽  
Vulnerable Patient ◽  
The Impact ◽  
Medication Appropriateness

Multimorbidity and polypharmacy are increasingly prevalent across healthcare systems and settings as global demographic trends shift towards increased proportions of older people in populations. Numerous studies have demonstrated an association between polypharmacy and potentially inappropriate prescribing (PIP), and have reported high prevalence of PIP across settings of care in Europe and North America and, as a consequence, increased risk of adverse drug reactions, healthcare utilization, morbidity and mortality. These studies have not focused specifically on people with dementia, despite the high risk of adverse drug reactions and PIP in this patient cohort. This narrative review considers the evidence currently available in the area, including studies examining prevalence of PIP in older people with dementia, how appropriateness of prescribing is assessed, the medications most commonly implicated, the clinical consequences, and research priorities to optimize prescribing for this vulnerable patient group. Although there has been a considerable research effort to develop criteria to assess medication appropriateness in older people in recent years, the majority of tools do not focus on people with dementia. Of the limited number of tools available, most focus on the advanced stages of dementia in which life expectancy is limited. The development of tools to assess medication appropriateness in people with mild to moderate dementia or across the full spectrum of disease severity represents an important gap in the research literature and is beginning to attract research interest, with recent studies considering the medication regimen as a whole, or misprescribing, overprescribing or underprescribing of certain medications/medication classes, including anticholinergics, psychotropics, antibiotics and analgesics. Further work is required in development and validation of criteria to assess prescribing appropriateness in this vulnerable patient population, to determine prevalence of PIP in large cohorts of people with the full spectrum of dementia variants and severities, and to examine the impact of PIP on health outcomes.

scholarly journals Pharmacogenetics and Tramadol-Related Fatalities

2021 ◽  
Author(s):  
Sanaa M. Aly ◽  
Jean-Michel Gaulier ◽  
Delphine Allorge
Keyword(s):  
Genetic Variation ◽  
Adverse Drug Reactions ◽  
Drug Absorption ◽  
Blood Concentration ◽  
Drug Reactions ◽  
Therapeutic Concentration ◽  
Postmortem Blood ◽  
Concentration Levels

Tramadol (TR) is a widely prescribed pain killer because of its relatively safe profile among opioids. Nevertheless, intoxication can occur and overdose can lead to fatal outcomes. Surprisingly, in some fatalities for which death is attributable to TR alone, postmortem blood concentration levels overlap with the therapeutic concentration range. These fatal cases might be explained by pharmacokinetic and pharmacodynamic properties of TR that are known to be both enantioselective and influenced by genes. Indeed pharmacogenetics (PG) is of great importance in this issue as it has the ability to elucidate the genetic variation contributing to drug absorption, distribution, metabolism, excretion, and response so that adverse drug reactions, toxicity, and even death can be avoided. The aim of this chapter is to present this issue.

Sign in / Sign up

Export Citation Format

Share Document