Clozapine Toxicity: Role Of Pharmacogenetic Variation In CYP Enzymes And Bioactivation Mechanisms In Patient Neutrophils
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
The treatment of mental disorders such as schizophrenia involves the administration of potent drug combinations to patients. Some individuals, however, do not respond to commonly-used antipsychotic drugs and their condition only improves with a unique drug called clozapine. The major problem with clozapine is its toxicity toward blood cells, heart and other organs. All people who receive clozapine must be monitored closely, especially in the first 3-4 months after starting therapy. Several new d ....The treatment of mental disorders such as schizophrenia involves the administration of potent drug combinations to patients. Some individuals, however, do not respond to commonly-used antipsychotic drugs and their condition only improves with a unique drug called clozapine. The major problem with clozapine is its toxicity toward blood cells, heart and other organs. All people who receive clozapine must be monitored closely, especially in the first 3-4 months after starting therapy. Several new drugs have been suggested to be safer versions of clozapine but these are all ineffective. Clozapine is the only agent that is effective in people who do not respond to the other drugs used to treat schizophrenia. Thus, clozapine toxicity, which necessitates discontinuation of the drug, is a devastating outcome because there is no alternative treatment that is available. Another significant problem with clozapine is that its rate of removal from the body is slowed down by many other drugs that are used concurrently. The problems with clozapine occur in some but not all individuals. This suggests that the patient's genetic makeup and their exposure to drugs and environmental agents determine the incidence of toxicity. The present project looks at how clozapine is removed from the body and how it is converted into a toxic product that damages cells. These processes will be examined, with emphasis on differences between individual patients, and strategies to protect cells from damage from the toxic derivative will be tested. Corresponding studies will be done in patients who are receiving clozapine as treatment for psychoses. We will be able to compare experimental and clinical findings in order to identify those patients who appear to be at risk. This will be possible before the toxic effects occur and will help us to identify subjects in whom the drug should only be used with great care. We may also devise strategies that will minimise the incidence of toxicity.Read moreRead less
Regulation Of Human Arylamine N-acetyltransferase Transcription, Translation And Protein Stability
Funder
National Health and Medical Research Council
Funding Amount
$470,958.00
Summary
Individuals respond very differently to many drugs and other chemicals in the diet and workplace. This variation can be a significant complication in treating patients and in attempting to determine risk with exposure to toxins. Genetic differences between individuals are a common reason for this variation. However, many enzymes and other proteins in humans are controlled by environmental factors that can either increase their activity or inhibit it. In this study, we will investigate how the ac ....Individuals respond very differently to many drugs and other chemicals in the diet and workplace. This variation can be a significant complication in treating patients and in attempting to determine risk with exposure to toxins. Genetic differences between individuals are a common reason for this variation. However, many enzymes and other proteins in humans are controlled by environmental factors that can either increase their activity or inhibit it. In this study, we will investigate how the activity of an important family of enzymes (the acetyltransferases) varies between individuals as a result of environmental factors. We will look at the genes for each of the enzymes and learn about this control mechanism. We will also look careful at the structure of the proteins and determine how this may change when challenged with external stimuli. The expected outcome will be a better understanding of these important enzymes that are involved in the metabolism of many drugs, and also provide a means of determining how different individuals may respond to foreign chemicals and drugs that use these enzymes in the body for metabolism.Read moreRead less
Centre Of Research Excellence In Post-market Surveillance Of Medicines And Medical Devices’
Funder
National Health and Medical Research Council
Funding Amount
$2,500,001.00
Summary
Medicines & medical devices constitute a significant cost to Australia’s health care system. Adverse events resulting from their use are similarly a significant expense that could be reduced by the development of Australia's capacity to use linked health data-sets to detect & monitor adverse events. This Centre aims to develop capacity, methods, knowledge & tools to enhance post-marketing surveillance systems to improve information on medicine & device safety, effectiveness & utilisation.
There are 140 million contact lens wearers worldwide. Use of contact lenses is associated with ocular inflammation (approximately 2-7% per year). We have developed novel antimicrobial coatings for contact lenses which we have shown in laboratory and animal models can reduce the ability of microbes to adhere to lenses and reduce associated inflammation. This Development project will enable us to generate proof-of-principle in a clinical cohort using existing contact lenses that have been coated u ....There are 140 million contact lens wearers worldwide. Use of contact lenses is associated with ocular inflammation (approximately 2-7% per year). We have developed novel antimicrobial coatings for contact lenses which we have shown in laboratory and animal models can reduce the ability of microbes to adhere to lenses and reduce associated inflammation. This Development project will enable us to generate proof-of-principle in a clinical cohort using existing contact lenses that have been coated using our patented processes.Read moreRead less
Improving The Safety And Quality Of Emergency Nursing Care
Funder
National Health and Medical Research Council
Funding Amount
$1,498,877.00
Summary
Failure to assess, treat comprehensively and escalate emergency patient care can be catastrophic. However, there is no emergency nursing framework in use for the 29,000+ emergency nurses working in Australia. We aim to improve access, consistency, safety and quality of emergency care for the best possible patient outcomes through system wide implementation of HIRAID - the only validated framework designed to teach emergency nurses how to systematically assess and manage emergency patients.
Immunisation Safety And Adverse Events: Improving Our Understanding Of Causes And Management
Funder
National Health and Medical Research Council
Funding Amount
$295,223.00
Summary
As the incidence of vaccine preventable diseases declines, adverse events following vaccination become increasingly important for both public and providers. This fellowship aims to improve our understanding of the risks of vaccination, potential causes, including genetic predisposition and long term clinical outcomes. A range of epidemiological, clinical and genetics studies will be performed. All these studies are targeted to understand who, what, how and why vaccine reactions occur and what ca ....As the incidence of vaccine preventable diseases declines, adverse events following vaccination become increasingly important for both public and providers. This fellowship aims to improve our understanding of the risks of vaccination, potential causes, including genetic predisposition and long term clinical outcomes. A range of epidemiological, clinical and genetics studies will be performed. All these studies are targeted to understand who, what, how and why vaccine reactions occur and what can be done to prevent or manage them better.Read moreRead less
Why Is There An Increased Risk Of Severe Adverse Perinatal Outcomes After The Use Of Clomiphene Citrate For Infertility Treatment?
Funder
National Health and Medical Research Council
Funding Amount
$570,065.00
Summary
Clomiphene citrate (CC) has been a first line treatment for female infertility internationally since the 1960’s. However, safety studies using routine prescribing practices were never performed, and numerous data sources now indicate that CC is associated with major adverse outcomes if the fetus is inadvertently exposed. We are linking prescription data to perinatal outcomes to confirm how CC is associated with adverse events so as to inform prescriber and practice change.
VACCINE SAFETY RESEARCH In Understudied And At Risk Groups: Critical Knowledge To Inform Practice And Policy.
Funder
National Health and Medical Research Council
Funding Amount
$290,041.00
Summary
Vaccines are typically given to healthy individuals and therefore safety issues loom high on the list of public concerns. Vaccine hesitancy due to safety concerns is an issue of increasing global interest and threatens to lower vaccine uptake. My research aims to understand why some people experience adverse reactions to vaccines, do genetic markers exist?, what are the long term outcomes of a vaccine reaction and how best to communicate vaccine risk/safety to the Australian community.