"The atypical antipsychotic drug olanzapine (OLZ, Fig. 1a) is amongst the most commonly prescribed antipsychotic drugs, not only for adults      but also for youths  . Treatment with OLZ is associated with several health risks, including cardiovascular complications, an increased risk of sudden cardiac death (SCD) , diabetic complications ranging from ''mild glucose intolerance to diabetic ketoacidosis'' , a lowered seizure threshold level in epilepsy   and fatal status epilepticus . "
[Show abstract][Hide abstract] ABSTRACT: Olanzapine (OLZ) is amongst the most commonly prescribed antipsychotic drugs and is associated with substantial instability. The aim of this study was to investigate the instability of OLZ and to identify the degradants formed from its breakdown. Three experiments were conducted to monitor the degradation of OLZ and the formation of degradants in blood (1), water (2), and post-extraction at 4 °C (3). All three sample sets were analysed in duplicate and repeated in the absence (A) and presence (B) of 0.25% ascorbic acid. One degradant was identified in sample sets 2A and 3A with m/z 329 and confirmed as 2-hydroxymethyl-OLZ (2-OH-OLZ) using LC-MS techniques. The addition of 0.25% ascorbic acid slowed the degradation of OLZ down in all three experiments and inhibited the formation of 2-OH-OLZ in sample sets 2A and 3A. To investigate the influence of oxygen on the degradation of OLZ and the formation of 2-OH-OLZ in water, an additional experiment (4) was conducted. Sample sets were prepared containing different vortexing or sonication steps in order to alter the oxygen content in the samples. Statistical analysis confirmed that degradation increased significantly following vortexing for 1 min while sonication did not affect the rate of degradation of OLZ further suggesting the involvement of oxygen in the degradative processes. 2-OH-OLZ was only identified as a degradant of OLZ in aqueous solutions. It also degrades over time but its product is currently unknown and is under investigation.
Forensic science international 02/2012; 220(1-3):74-9. DOI:10.1016/j.forsciint.2012.01.029 · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Second generation antipsychotic medications have become synonymous with "atypicality." To support the clinical lore of equivalent efficacy with reduced risk of extrapyramidal symptoms, clinical trials have overwhelmingly chosen a high-potency first-generation antipsychotic (e.g., haloperidol) as a comparator. Very few clinical trials have compared a second-generation antipsychotic with a low- or mid-potency first-generation antipsychotic medication.
We identified eight completed, published, double-blind, randomized clinical trials that compared a second-generation antipsychotic with a low- or mid-potency first-generation antipsychotic and reviewed outcome measures for efficacy and extrapyramidal symptoms; 1,241 patients were represented in these eight trials.
Although data are very limited, mid- and low-potency first-generation antipsychotics show efficacy and extrapyramidal side effects that are comparable to those of second-generation antipsychotics.
Aside from clozapine, first-generation and second-generation antipsychotics represent a diverse group of medications that have heterogenous receptor profiles and side effects but comparable clinical efficacy and potential to cause extrapyramidal symptoms. Clinicians may provide better treatment for patients by considering the unique pharmacological and side-effect profile of each particular antipsychotic independent of its classification as a first- or second-generation agent.
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