Pharmacodynamic interactions of antiepileptic drugs: From bench to clinical practice

2020 ◽  
Vol 104 ◽  
pp. 106939 ◽  
Author(s):  
Alberto Verrotti ◽  
Simona Lattanzi ◽  
Francesco Brigo ◽  
Gaetano Zaccara
Keyword(s):  
Clinical Practice ◽  
Antiepileptic Drugs ◽  
Pharmacodynamic Interactions

Simulating the Effects of Common Comedications and Genotypes on Alzheimer’s Cognitive Trajectory Using a Quantitative Systems Pharmacology Approach

2020 ◽  
Vol 78 (1) ◽  
pp. 413-424
Author(s):  
Hugo Geerts ◽  
Athan Spiros
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Second Generation ◽  
Standard Of Care ◽  
Systems Pharmacology ◽  
Quantitative Systems Pharmacology ◽  
Pharmacodynamic Interactions ◽  
Cognitive Trajectory

Background: Many Alzheimer’s disease patients in clinical practice are on polypharmacy for treatment of comorbidities. Objective: While pharmacokinetic interactions between drugs have been relatively well established with corresponding treatment guidelines, many medications and common genotype variants also affect central brain circuits involved in cognitive trajectory, leading to complex pharmacodynamic interactions and a large variability in clinical trials. Methods: We applied a mechanism-based and ADAS-Cog calibrated Quantitative Systems Pharmacology biophysical model of neuronal circuits relevant for cognition in Alzheimer’s disease, to standard-of-care cholinergic therapy with COMTVal158Met, 5-HTTLPR rs25531, and APOE genotypes and with benzodiazepines, antidepressants, and antipsychotics, all together 9,585 combinations. Results: The model predicts a variability of up to 14 points on ADAS-Cog at baseline (COMTVV 5-HTTLPRss APOE 4/4 combination is worst) and a four-fold range for the rate of progression. The progression rate is inversely proportional to baseline ADAS-Cog. Antidepressants, benzodiazepines, first-generation more than second generation, and most antipsychotics with the exception of aripiprazole worsen the outcome when added to standard-of-care in mild cases. Low dose second-generation benzodiazepines revert the negative effects of risperidone and olanzapine, but only in mild stages. Non APOE4 carriers with a COMTMM and 5HTTLPRLL are predicted to have the best cognitive performance at baseline but deteriorate somewhat faster over time. However, this effect is significantly modulated by comedications. Conclusion: Once these simulations are validated, the platform can in principle provide optimal treatment guidance in clinical practice at an individual patient level, identify negative pharmacodynamic interactions with novel targets and address protocol amendments in clinical trials.

Strategies to detect adverse effects of antiepileptic drugs in clinical practice

2008 ◽  
Vol 13 (1) ◽  
pp. 178-183 ◽  
Author(s):  
M. Carreño ◽  
A. Gil-Nagel ◽  
J.C. Sánchez ◽  
E. Elices ◽  
J.M. Serratosa ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Adverse Effects ◽  
Antiepileptic Drugs

Basic mechanisms of antiepileptic drugs and their pharmacokinetic/pharmacodynamic interactions: an update

2011 ◽  
Vol 63 (2) ◽  
pp. 271-292 ◽  
Author(s):  
Władysław Lasoń ◽  
Monika Dudra-Jastrzębska ◽  
Konrad Rejdak ◽  
Stanisław J. Czuczwar
Keyword(s):  
Antiepileptic Drugs ◽  
Pharmacodynamic Interactions

scholarly journals IMPACT OF ANTIEPILEPTIC DRUGS ON COGNITIVE FUNCTIONS IN CHILDREN AND ADOLESCENTS

2018 ◽  
Vol 63 (5) ◽  
pp. 130-134
Author(s):  
R. G. Gamirova ◽  
E. A. Gorobets ◽  
T. V. Ahutina ◽  
R. G. Esin
Keyword(s):  
Clinical Practice ◽  
Children And Adolescents ◽  
Antiepileptic Drugs ◽  
Cognitive Functions ◽  
Points Of View

The article presents modern points of view on the assessment of сognitive functions of the children and adolescents with epilepsy who take antiepileptic drugs (AEDs). The authors compare various AEDs which are used in modern clinical practice in Russia and abroad, their impact on cognitive functions, discuss the psychometric tools which are used in Russia to assess the dynamics of cognitive functions in this group of patients.

Treatment with antiepileptic drugs in patients with stroke. A change in clinical practice may be required

2018 ◽  
Vol 395 ◽  
pp. 4-7 ◽  
Author(s):  
Ali Jabareen ◽  
Ronen R. Leker ◽  
Sara Eyal ◽  
Dana Ekstein
Keyword(s):  
Clinical Practice ◽  
Antiepileptic Drugs
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