Schizophrenia is a prevalent and disabling disorder, commonly treated with medications such as clozapine and olanzapine. However, long-term side effects and limitations of these drugs, coupled with treatment resistanc...Schizophrenia is a prevalent and disabling disorder, commonly treated with medications such as clozapine and olanzapine. However, long-term side effects and limitations of these drugs, coupled with treatment resistance in a significant proportion of patients, necessitate alternative strategies. Furthermore, individuals with schizophrenia are at an increased risk of developing kidney and liver diseases, which may be influenced by cardiovascular comorbidities and shared genetic markers. Considering the use of olanzapine in patients with severe liver or kidney diseases requires careful evaluation. Although these organs play crucial roles in olanzapine excretion and metabolism, current pharmacological research suggests that dosage adjustment may not be necessary even in the presence of severe organ disease. Olanzapine acts on D2 and 5HT2A receptors, alleviating both positive and negative symptoms of schizophrenia. However, the metabolism and clearance of olanzapine exhibit substantial inter-individual variability influenced by factors such as gender, age, ethnicity, smoking habits, and co-medication. Additionally, olanzapine may induce unwanted side effects, including prolactin release, metabolic dysregulation, and liver-related complications. The present study aims to investigate whether dosage adjustment of olanzapine is necessary for individuals with comorbid moderate liver and severe kidney disease. While the study remains ongoing, preliminary findings using a pharmacokinetic model predict that dosage adjustment may not be required in these patients. The expected olanzapine plasma concentration in individuals with both conditions is estimated to be 18.14ng/ml, which is considerably below the identified toxic dosage threshold of 100ng/ml. However, further investigations are warranted to validate the findings and establish definitive guidelines and personalize treatment strategies for individuals with both liver and kidney disease.展开更多
Double-stranded RNA-mediated interference (RNAi), antisense oligonucleotides (ASO), and ribozymes have excellent specificity to their target oncogenic mRNA. They also seem to show great promise when it comes to treati...Double-stranded RNA-mediated interference (RNAi), antisense oligonucleotides (ASO), and ribozymes have excellent specificity to their target oncogenic mRNA. They also seem to show great promise when it comes to treating cancer. The problem is that RNAi, ASO, and ribozymes have poor stability and are constantly being degraded by nucleases. Researchers have made some efforts to increase antisense oligonucleotides’ stability by creating phospharimidate and Phosphorothioate. Currently, ribozymes, antisense oligonucleotides, and (RNAi) are the three main methods used to target RNA. These methods are currently undergoing clinical trials for the purpose of focusing on specific RNAs involved in disorders like cancer and neurodegeneration. In fact, ASOs that target amyotrophic lateral sclerosis and spinal muscular atrophy have produced promising results in clinical trials. The formation of chemical alterations that boost affinity and selectivity while reducing noxiousness owing to off-target impacts are two benefits of ASOs. Another benefit is increased affinity. With a focus on RNAi and ASOs, this review illustrated the main therapeutic strategies of RNA therapy now in use.展开更多
文摘Schizophrenia is a prevalent and disabling disorder, commonly treated with medications such as clozapine and olanzapine. However, long-term side effects and limitations of these drugs, coupled with treatment resistance in a significant proportion of patients, necessitate alternative strategies. Furthermore, individuals with schizophrenia are at an increased risk of developing kidney and liver diseases, which may be influenced by cardiovascular comorbidities and shared genetic markers. Considering the use of olanzapine in patients with severe liver or kidney diseases requires careful evaluation. Although these organs play crucial roles in olanzapine excretion and metabolism, current pharmacological research suggests that dosage adjustment may not be necessary even in the presence of severe organ disease. Olanzapine acts on D2 and 5HT2A receptors, alleviating both positive and negative symptoms of schizophrenia. However, the metabolism and clearance of olanzapine exhibit substantial inter-individual variability influenced by factors such as gender, age, ethnicity, smoking habits, and co-medication. Additionally, olanzapine may induce unwanted side effects, including prolactin release, metabolic dysregulation, and liver-related complications. The present study aims to investigate whether dosage adjustment of olanzapine is necessary for individuals with comorbid moderate liver and severe kidney disease. While the study remains ongoing, preliminary findings using a pharmacokinetic model predict that dosage adjustment may not be required in these patients. The expected olanzapine plasma concentration in individuals with both conditions is estimated to be 18.14ng/ml, which is considerably below the identified toxic dosage threshold of 100ng/ml. However, further investigations are warranted to validate the findings and establish definitive guidelines and personalize treatment strategies for individuals with both liver and kidney disease.
文摘Double-stranded RNA-mediated interference (RNAi), antisense oligonucleotides (ASO), and ribozymes have excellent specificity to their target oncogenic mRNA. They also seem to show great promise when it comes to treating cancer. The problem is that RNAi, ASO, and ribozymes have poor stability and are constantly being degraded by nucleases. Researchers have made some efforts to increase antisense oligonucleotides’ stability by creating phospharimidate and Phosphorothioate. Currently, ribozymes, antisense oligonucleotides, and (RNAi) are the three main methods used to target RNA. These methods are currently undergoing clinical trials for the purpose of focusing on specific RNAs involved in disorders like cancer and neurodegeneration. In fact, ASOs that target amyotrophic lateral sclerosis and spinal muscular atrophy have produced promising results in clinical trials. The formation of chemical alterations that boost affinity and selectivity while reducing noxiousness owing to off-target impacts are two benefits of ASOs. Another benefit is increased affinity. With a focus on RNAi and ASOs, this review illustrated the main therapeutic strategies of RNA therapy now in use.
