scholarly journals A review of pharmacokinetic and pharmacodynamic interactions with antipsychotics

2016 ◽  
Vol 6 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Ruki Wijesinghe
Keyword(s):  
Drug Interactions ◽  
First Generation ◽  
Antipsychotic Drugs ◽  
Relevant Literature ◽  
Treatment Interventions ◽  
Pharmacodynamic Interactions ◽  
Common Drug ◽  
Second Generation Antipsychotics ◽  
Clinically Significant ◽  
Potential Interactions

Abstract Introduction Antipsychotics are widely used and often in combination with other drugs, thereby frequently subjected to drug-drug interactions. This review will provide a summary of potential pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions associated with antipsychotic drugs. Methods A literature search was conducted for clinically significant drug interactions with antipsychotics. Results Most common PK drug interactions take place via the cytochrome P450 (CYP) system. PK profiles of first generation antipsychotics are inadequately studied; nevertheless most common drug interactions involve changes to their metabolic processes. Interactions with second generation antipsychotics are somewhat well-established, documented, and give some guidance for therapeutic treatment interventions. PD interactions occurring at the receptor level result in additive, synergistic, or antagonistic effects. Discussion This review summarizes a collection of relevant literature of significant PK and PD interactions occurring with antipsychotics. The involvement of multiple CYP enzymes makes it more difficult to predict the extent of the interaction and clinicians should take into consideration the timeline when evaluating potential interactions.

Mechanisms of action of second generation antipsychotic drugs in schizophrenia: insights from brain imaging studies

2005 ◽  
Vol 20 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Anissa Abi-Dargham ◽  
Marc Laruelle
Keyword(s):  
First Generation ◽  
Antipsychotic Drugs ◽  
Second Generation ◽  
Dopaminergic System ◽  
Therapeutic Strategies ◽  
Therapeutic Action ◽  
Imaging Studies ◽  
High Incidence ◽  
Second Generation Antipsychotic ◽  
Clinically Significant

AbstractMultiple lines of evidence including recent imaging studies suggest that schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyperstimulation of striatal dopamine (DA) D2 receptors and understimulation of cortical DA D1 receptors. This DA endophenotype presumably emerges from the background of a more general synaptic dysconnectivity, involving alterations in N-methyl-d-aspartate (NMDA) and glutamatergic (GLU) functions. Equally important is the fact that this DA dysregulation might further impair NMDA transmission. The first generation antipsychotic (FGA) drugs are characterized by high affinity to and generally high occupancy of D2 receptors. The efficacy of FGAs is limited by a high incidence of extrapyramidal side-effects (EPS). Second generation antipsychotic (SGA) drugs display reduced EPS liability and modest but clinically significant enhanced therapeutic efficacy. Compared to FGAs, the improved therapeutic action of SGAs probably derives from a more moderate D2 receptor blockade. We will review the effects of SGAs on other neurotransmitter systems and conclude by highlighting the importance of therapeutic strategies aimed at directly increasing prefrontal DA, D1 receptor transmission or NMDA transmission to enhance the therapeutic effect of moderate D2 receptor antagonism.

scholarly journals Treatment mechanisms: traditional and new antipsychotic drugs

2000 ◽  
Vol 2 (3) ◽  
pp. 281-286
Keyword(s):  
Side Effects ◽  
Animal Studies ◽  
First Generation ◽  
Antipsychotic Drugs ◽  
Second Generation Antipsychotics ◽  
Treatment Mechanisms ◽  
1960S And 1970S ◽  
The 1960S ◽  
Efficacy Profile ◽  
Equal Efficacy

The first generation of antipsychotic drugs was discovered in the 1960s and 1970s, These agents were effective in treating psychosis, but were accompanied by significant side effects, including severe parkinsonism and akathisia. Second-generation antipsychotics were introduced in the 1990s, These drugs have at least equal efficacy to their predecessors, but far fewer side effects. Some data suggest a broader efficacy profile. Clozapine remains the only superior antipsychotic in terms of the magnitude of psychotic symptom reduction. Clinical and animal studies are consistent in suggesting that the antipsychotic component of antidopaminergic treatments is initiated by dopamine receptor blockade in the striatum and that the signal is transmitted to the neocortex through the established basal ganglia-thalamo-cortical neuronal circuits. Other neurotransmitter actions (eg, antiserotonergic) can be exerted locally, in the neocortex. Defining tissue targets of drug action may suggest additional strategies for developing new antipsychotic drugs.

scholarly journals Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

2021 ◽  
Vol 22 (17) ◽  
pp. 9582
Author(s):  
Marta Karaźniewicz-Łada ◽  
Anna K. Główka ◽  
Aniceta A. Mikulska ◽  
Franciszek K. Główka
Keyword(s):  
Drug Interactions ◽  
Effective Treatment ◽  
Mechanism Of Action ◽  
First Generation ◽  
Pharmacokinetic Parameters ◽  
Effective Management ◽  
Important Group ◽  
New Challenges ◽  
Potential Interactions ◽  
Pharmacokinetic Drug

Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug–drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.

The Association and Influencing Factors between Antipsychotics Exposure and the Risk of VTE and PE: A Systematic Review and Meta-analysis

2020 ◽  
Vol 21 (9) ◽  
pp. 930-942
Author(s):  
Luqi Dai ◽  
Qiunan Zuo ◽  
Fangying Chen ◽  
Lei Chen ◽  
Yongchun Shen
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
First Generation ◽  
Meta Analysis ◽  
Relevant Literature ◽  
Patient Characteristics ◽  
Obese People ◽  
Overweight People ◽  
Increased Risk ◽  
Second Generation Antipsychotics

Background: Different clinical studies have given inconsistent results on whether the use of antipsychotics increases the risk of thromboembolism. In this paper, we reviewed all relevant literature to provide suggestions for clinical diagnosis and treatment. Methods: PubMed, Web of Science, EMBASE, MEDLINE, Cochrane and Scopus databases were thoroughly searched up to June 2019. Two researchers independently searched the literature, extracted data. Data were analyzed by Stata 12.0 software. Results: A total of 22 studies involving 31514226 subjects were included. This meta-analysis showed that patients taking the first- or second-generation antipsychotics had a higher risk of venous thromboembolism and pulmonary embolism than those who did not, and low potency first-generation agents increased the risk of venous thromboembolism more than high potency antipsychotics, and olanzapine, clozapine, haloperidol, perphenazine and risperidone also significantly increased the risk of it. The risk of venous thrombosis in obese people was higher than that in overweight people, patients not less than 65 years old had an increased risk compared with younger patients. In addition, women taking antipsychotics had a higher risk of pulmonary embolism than men. Conclusion: The use of antipsychotics will increase the risk of venous thromboembolism and pulmonary embolism, which will be affected by the type of antipsychotics and patient characteristics.

scholarly journals Behavioral and Psychological Symptoms in Dementia (BPSD) and the Use of Antipsychotics

2021 ◽  
Vol 14 (3) ◽  
pp. 246
Author(s):  
Valeria Calsolaro ◽  
Grazia Daniela Femminella ◽  
Sara Rogani ◽  
Salvatore Esposito ◽  
Riccardo Franchi ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
First Generation ◽  
Antipsychotic Drugs ◽  
Psychological Symptoms ◽  
Rebound Effect ◽  
Safety Issues ◽  
Second Generation Antipsychotics ◽  
Therapy Interruption ◽  
Dopamine And Serotonin Receptors ◽  
Behavioral And Psychological Symptoms

Dementia affects about 47 million people worldwide, number expected to exponentially increase within 30 years. Alzheimer’s disease (AD) is the most common dementia type, accounting on its own for almost 70% of all dementia cases. Behavioral and psychological symptoms (BPSD) frequently occur during the disease progression; to treat agitation, aggressiveness, delusions and hallucinations, the use of antipsychotic drugs should be limited, due to their safety issues. In this literature review regarding the use of antipsychotics for treating BPSD in dementia, the advantages and limitation of antipsychotic drugs have been evaluated. The available medications for the management of behavioral and psychological symptoms are the antipsychotics, classed into typical and atypical, depending on their action on dopamine and serotonin receptors. First generation, or typical, antipsychotics exhibit lack of tolerability and display a broad range of side effects such as sedation, anticholinergic effects and extrapyramidal symptoms. Atypical, or second generation, antipsychotics bind more selectively to dopamine receptors and simultaneously block serotonin receptors, resulting in higher tolerability. High attention should be paid to the management of therapy interruption or switch between antipsychotics, to limit the possible rebound effect. Several switching strategies may be adopted, and clinicians should “tailor” therapies, accounting for patients’ symptoms, comorbidities, polytherapies and frailty.

Pharmacological drug interactions in the treatment of community-acquired pneumonia in hospital settings (based on electronic databases of reported drug interactions)

2021 ◽  
Vol 31 (1) ◽  
pp. 38-45
Author(s):  
O. V. Zhukova ◽  
E. S. Khoroshavina ◽  
O. V. Ruina ◽  
M. V. Khazov
Keyword(s):  
Clinical Practice ◽  
Drug Interactions ◽  
Antimicrobial Therapy ◽  
Community Acquired Pneumonia ◽  
Treatment Standards ◽  
Antibacterial Drugs ◽  
Treatment Standard ◽  
Clinically Significant ◽  
Potential Interactions ◽  
Real Clinical Practice

The article presents the results of a study of potential drug interactions in the treatment of moderate and severe community-acquired pneumonia (CAP) in hospital settings. The study was conducted by analysis of treatment standards and data from real clinical practice regarding antimicrobial therapy. Methods. The study used the lists of drug products for medical use for the treatment of CAP (according to the standards of specialized medical care for moderate and severe CAP with complications). Also, the medical records of patients (n = 165) with CAP, hospitalized in hospitals of medical organizations (Nizhny Novgorod) were used. The study period was 2 years (2015 - 2016). The study included all patients admitted to the hospital during the analyzed period. CAP was treated in accordance with treatment standards. Results. The analysis of potential interactions of drugs used for moderate and severe CAP according to the treatment standards, showed that 27 and 72 drugs can be used, respectively. 325 potential interactions are possible in hospital settings for moderate CAP and 2,485 for severe CAP. According to the treatment standard, the number of minimally clinically significant potential interactions during the pharmacotherapy of moderate CAP in hospital settings is 8, the number moderately clinically significant interactions - 19; undesirable interactions - 7. In case of severe CAP, the number of potential interactions increases and amounts to 27 minimally clinically significant, 105 moderately clinically significant, and 41 undesirable. The analysis of the results of antimicrobial therapy in real clinical practice showed 4 therapeutic duplications (prescribing 2 β-lactam antibacterial drugs simultaneously) and 2 moderately clinically significant interactions during antimicrobial therapy in hospital 1. Only 1 therapeutic duplication was noted during antimicrobial therapy in hospital 2. Therapeutic overlap has been found between β-lactam antibacterial drugs (ceftaroline fosamil and meropenem). It is advisable to prescribe no more than one в-lactam antibacterial drug and it is inappropriate to include > 3 antimicrobial drugs in an antimicrobial regimen. Conclusion. Electronic databases simplify the selection of medicines and thus ensure the safe and effective use of registered drug interactions.

Cigarette Smoking and Clinically Significant Drug Interactions

1995 ◽  
Vol 29 (11) ◽  
pp. 1139-1148 ◽  
Author(s):  
Jeffrey R Schein
Keyword(s):  
Drug Therapy ◽  
Cigarette Smoking ◽  
Drug Interactions ◽  
Oral Contraceptives ◽  
Pharmacokinetic Studies ◽  
Cytochrome P450 Enzymes ◽  
Medline Search ◽  
Pharmacodynamic Interactions ◽  
Review Articles ◽  
Clinically Significant

Objective: To review clinically significant drug interactions associated with cigarette smoking. Data Sources: Data from scientific literature were identified by using a MEDLINE search. Data were extracted, evaluated, and summarized for this review. Study Selection: Findings and experiences were selected from clinical, epidemiologic, and pharmacokinetic studies; review articles; case studies; abstracts; letters to the editor; and proceedings. Data Extraction: Data from human studies published in English were evaluated. Only interactions deemed clinically significant are included in this review. Conclusions derived from review articles on the subject of smoking and drug interactions also were used. Data Synthesis: Cigarette smoking can affect drug therapy via pharmacokinetic and pharmacodynamic mechanisms. Pharmacokinetic drug interactions are presented for theophylline, tacrine, insulin, flecainide, propoxyphene, propranolol, diazepam, and chlordiazepoxide. Pharmacodynamic interactions are described for antihypertensive and antianginal agents, antilipidemics, oral contraceptives, and histamine2-receptor antagonists. Conclusions: Cigarette smoking can reduce the efficacy of certain drugs or make drug therapy more unpredictable. Pharmacokinetic interactions may cause smokers to require a larger dosage of certain drugs through an increase in plasma clearance, a decrease in absorption, an induction of cytochrome P450 enzymes, or a combination of these factors. Pharmacodynamic interactions may increase the risk of adverse events in smokers with cardiovascular or peptic ulcer disease, and in women who smoke and use oral contraceptives. Healthcare professionals should pay special attention to patients with these profiles and should try to prevent cigarette smoking or encourage patients to discontinue this addictive habit.

Eine Stellungnahme zur Debatte über die „atypischen“ Antipsychotika

2010 ◽  
Vol 07 (01) ◽  
pp. 11-17
Author(s):  
A. Schmied ◽  
W. Kissling ◽  
J. M. Davis ◽  
S. Leucht
Keyword(s):  
Antipsychotic Drugs ◽  
Second Generation ◽  
Cost Utility ◽  
First Episode ◽  
Intervention Effectiveness ◽  
Second Generation Antipsychotics ◽  
First Episode Schizophrenia

ZusammenfassungSeit etwa zehn Jahren gibt es eine kontrovers geführte Debatte über die Antipsychotika der zweiten Generation („second generation antipsychotics“, SGA) in der Schizophreniebehandlung, die in der Publikation der sogenannten Effektivitätsstudien CATIE (Clinical Antipsychotic Trial of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) und EUFEST (European First-Episode Schizophrenia Trial) gipfelte. In der vorliegenden Übersicht fassen wir die Ergebnisse dreier aktueller systematischer Reviews zusammen, in denen die Antipsychotika der zweiten Generation (SGAs) mit Placebo, mit konventionellen Antipsychotika oder direkt miteinander verglichen wurden. Wir stellen die Metaanalysen in den Kontext anderer systematischer Reviews und beleuchten sie vor dem Hintergrund von CATIE, CUtLASS und EUFEST. Unserer Meinung nach sind viele Ergebnisse konsistent, sie werden aber von verschiedenen Experten und Interessensvertretern unterschiedlich interpretiert. Die Daten zeigen, dass SGAs keine homogene Gruppe darstellen und dass diese eher verwirrende Einteilung aufgegeben werden sollte. Unserer Meinung nach stellen die SGAs nicht den Durchbruch dar, den die Industrie gerne sehen würde. Ihre unterschiedlichen Eigenschaften erlauben aber eine bessere Ausrichtung des Behandlungsplans an den Problemen des individuellen Patienten. Diese Medikamente haben die Behandlungspalette deutlich erweitert und die meisten Psychiater, ganz zu schweigen von den Patienten, würden wohl nur sehr ungerne auf diese Präparate verzichten wollen.

Pharmakotherapie update

2020 ◽  
Vol 25 (1) ◽  
pp. 23-32
Author(s):  
Gerd Laux
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Therapeutische Maßnahmen ◽  
Second Generation Antipsychotics

Für die Therapie schizophrener Erkrankungen sind seit fast 60 Jahren Antipsychotika/Neuroleptika aufgrund ihrer antipsychotischen Wirkung von zentraler Bedeutung. Die Einteilung kann unter verschiedenen Gesichtspunkten erfolgen (chemische Struktur, neuroleptische Potenz, Rezeptorprofil), heute werden üblicherweise unterschieden typische (traditionelle, klassische, konventionelle) Antipsychotika der ersten Generation ‒ »First Generation Antipsychotics« (FGA) ‒ und sog. atypische (»neuere«) Neuroleptika bzw. Antipsychotika der zweiten Generation ‒»Second Generation Antipsychotics« (SGA). Hierzu zählen Aripiprazol, Asenapin, Cariprazin, Clozapin, Olanzapin, Quetiapin, Risperidon, Sertindol und Ziprasidon. Hierbei handelt es sich um keine homogene Gruppe – sowohl neuropharmakologisch (Wirkmechanismus), als auch hinsichtlich klinischem Wirkprofil und dem Nebenwirkungsspektrum bestehen z. T. erhebliche Unterschiede. Neben der Akut-Medikation ist eine Langzeitmedikation bzw. Rezidivprophylaxe mit Antipsychotika für die Rehabilitation vieler schizophrener Patienten im Sinne eines »Stresspuffers« von grundlegender Bedeutung. In Placebo-kontrollierten Studien trat bei Patienten, die über ein Jahr behandelt wurden, bei etwa 30% unter Neuroleptika ein Rezidiv auf, unter Placebo bei mehr als 70%. Für die Langzeitbehandlung bietet sich der Einsatz von Depot-Neuroleptika an, neu entwickelt wurden Langzeit-Depot-Injektionen mit Intervallen von bis zu 3 Monaten. Grundsätzlich ist die niedrigstmögliche (wirksame) Dosis zu verwenden. Im Zentrum der Nebenwirkungen (UAW) standen lange Zeit extrapyramidal-motorische Bewegungsstörungen (EPMS), mit der Einführung von Clozapin und anderen atypischen Antipsychotika der zweiten Generation gewannen andere Nebenwirkungen an Bedeutung. Hierzu zählen Gewichtszunahme, Störungen metabolischer Parameter und ein erhöhtes Risiko für Mortalität und zerebrovaskuläre Ereignisse bei älteren Patienten mit Demenz. Entsprechende Kontrolluntersuchungen sind erforderlich, für Clozapin gibt es aufgrund seines Agranulozytose-Risikos Sonderbestimmungen. Immer sollte ein Gesamtbehandlungsplan orientiert an der neuen S3-Praxisleitlinie Schizophrenie der DGPPN aufgestellt werden, der psychologische und milieu-/sozial-therapeutische Maßnahmen einschließt. Standard ist heute auch eine sog. Psychoedukation, für Psychopharmaka liegen bewährte Patienten-Ratgeber vor.

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