A new synthetic approach for preparation of Efavirenz
- Authors: Chada, Sravanthi
- Date: 2017
- Subjects: Antiretroviral agents , Asymmetric synthesis , Enzyme inhibitors , HIV (Viruses) -- Enzymes
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/15512 , vital:28265
- Description: Efavirenz, a drug that is still inaccessible to millions of people worldwide, is potent non nucleoside reverse transcriptase inhibitor (NNRTI), is one of the preferred agents used in combination therapy for first-line treatment of the human immunodeficiency virus (HIV). NNRTIs attach to and block an HIV enzyme called reverse transcriptase, by blocking reverse transcriptase; NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body. Efavirenz can't cure HIV/AIDS, but taken in combination with other HIV medicines (called an HIV regimen) every day helps people with HIV live longer healthier lives. Efavirenz also reduces the risk of HIV transmission and can be used by children who are suffering from HIV/AIDS. All the above therapeutic uses of efavirenz prompted us to identify the novel and hopefully cost efficient synthetic methodology for the preparation of efavirenz. In this thesis a new synthetic method for asymmetric synthesis of efavirenz is described. This route started from commercially available starting materials and it is first established in traditional batch chemistry and further the parameters transferred to a semi continuous flow protocol for optimization.
- Full Text:
- Date Issued: 2017
- Authors: Chada, Sravanthi
- Date: 2017
- Subjects: Antiretroviral agents , Asymmetric synthesis , Enzyme inhibitors , HIV (Viruses) -- Enzymes
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10948/15512 , vital:28265
- Description: Efavirenz, a drug that is still inaccessible to millions of people worldwide, is potent non nucleoside reverse transcriptase inhibitor (NNRTI), is one of the preferred agents used in combination therapy for first-line treatment of the human immunodeficiency virus (HIV). NNRTIs attach to and block an HIV enzyme called reverse transcriptase, by blocking reverse transcriptase; NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body. Efavirenz can't cure HIV/AIDS, but taken in combination with other HIV medicines (called an HIV regimen) every day helps people with HIV live longer healthier lives. Efavirenz also reduces the risk of HIV transmission and can be used by children who are suffering from HIV/AIDS. All the above therapeutic uses of efavirenz prompted us to identify the novel and hopefully cost efficient synthetic methodology for the preparation of efavirenz. In this thesis a new synthetic method for asymmetric synthesis of efavirenz is described. This route started from commercially available starting materials and it is first established in traditional batch chemistry and further the parameters transferred to a semi continuous flow protocol for optimization.
- Full Text:
- Date Issued: 2017
Evaluating neuropsychiatric symptomology in HIV-positive patients on efavirenz in public-sector clinics and psychiatric hospitals
- Gaida, Razia, Grobler, Christoffel
- Authors: Gaida, Razia , Grobler, Christoffel
- Date: 2017
- Subjects: Drugs -- Side effects -- South Africa , HIV (Viruses) -- Enzymes , Antiretroviral agents -- South Africa , Anti-infective agents -- Side effects -- South Africa
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/29772 , vital:30776
- Description: Background: South Africa has the highest number of people living with human immunodeficiency virus (HIV) infection in the world. In 2014, an estimated 10.2% of the population was HIV-positive which amounted to 5.51 million people. Efavirenz forms part of the triple therapy backbone used in South Africa and is part of the firstline treatment for HIV. Efavirenz has been strongly associated with causing neuropsychiatric side effects in at least 50.0% of patients to whom it is prescribed. These side effects cause hesitation amongst healthcare professionals to prescribe this agent to patients with active mental illnesses. Aim: The aim of the study was to evaluate the neuropsychiatric side effects of efavirenz in HIV-positive psychiatric and non-psychiatric patients and to determine whether this drug may be recommended for use in an HIV-positive psychiatric patient population. Method: The study was divided into two parts, namely a quantitative portion and a qualitative portion. The quantitative study was a prospective drug utilisation study, while the qualitative portion consisted of semi-structured interviews carried out with healthcare professionals working with people living with HIV/AIDS (PLWHA). The study included five municipal clinics in the Nelson Mandela Metropole as well as two public-sector psychiatric facilities in the Eastern Cape where medical records were reviewed to obtain the information required. Patients were followed in both instances for a period of 24 weeks with follow-up assessments carried out at two, four, 12 and 24 week intervals. In terms of the qualitative study, nurses at the clinics and doctors at the hospitals were contacted and appointments for interviews were made. The interviews were recorded using a voice recorder and were transcribed and analysed using theoretical framework analysis. Results: The review of 126 medical records at the clinics revealed that no patient had suffered from or complained of a neuropsychiatric side effect. This may indicate that patients were not suffering from clinically significant side effects, side effects were not being adequately recorded by healthcare staff, or the healthcare staff were not questioning patients regarding side effects. A total of 26 hospitalised patients were followed for 24 weeks in the psychiatric facilities. Almost half of the patients using efavirenz experienced an improvement in symptoms to the extent that they were iii discharged from the facility. The majority of patients (66.7%) not on an efavirenzcontaining regimen did not improve to the point of discharge. Healthcare staff were vague when providing a definition of neuropsychiatric side effects. There were conflicting ideas on whether or not efavirenz should be used in patients with an active psychiatric illness. Conclusions: Further studies need to be performed in public-sector institutions to obtain a clearer picture of the side effects experienced by patients using efavirenz. Healthcare staff need to be encouraged to keep complete records to allow for meaningful analysis. The further integration of mental health services into existing HIV programmes is essential for holistic treatment. Patients in psychiatric hospitals demonstrated that even patients with psychiatric disorders on efavirenz can experience positive outcomes and stabilisation of psychiatric symptoms, which may indicate that these may not have due to efavirenz use. Further elucidation concerning the use of efavirenz in patients with psychiatric disorders, a description of the neuropsychiatric side effects, as well as management strategies must be provided in subsequent HIV guidelines.
- Full Text:
- Date Issued: 2017
- Authors: Gaida, Razia , Grobler, Christoffel
- Date: 2017
- Subjects: Drugs -- Side effects -- South Africa , HIV (Viruses) -- Enzymes , Antiretroviral agents -- South Africa , Anti-infective agents -- Side effects -- South Africa
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/29772 , vital:30776
- Description: Background: South Africa has the highest number of people living with human immunodeficiency virus (HIV) infection in the world. In 2014, an estimated 10.2% of the population was HIV-positive which amounted to 5.51 million people. Efavirenz forms part of the triple therapy backbone used in South Africa and is part of the firstline treatment for HIV. Efavirenz has been strongly associated with causing neuropsychiatric side effects in at least 50.0% of patients to whom it is prescribed. These side effects cause hesitation amongst healthcare professionals to prescribe this agent to patients with active mental illnesses. Aim: The aim of the study was to evaluate the neuropsychiatric side effects of efavirenz in HIV-positive psychiatric and non-psychiatric patients and to determine whether this drug may be recommended for use in an HIV-positive psychiatric patient population. Method: The study was divided into two parts, namely a quantitative portion and a qualitative portion. The quantitative study was a prospective drug utilisation study, while the qualitative portion consisted of semi-structured interviews carried out with healthcare professionals working with people living with HIV/AIDS (PLWHA). The study included five municipal clinics in the Nelson Mandela Metropole as well as two public-sector psychiatric facilities in the Eastern Cape where medical records were reviewed to obtain the information required. Patients were followed in both instances for a period of 24 weeks with follow-up assessments carried out at two, four, 12 and 24 week intervals. In terms of the qualitative study, nurses at the clinics and doctors at the hospitals were contacted and appointments for interviews were made. The interviews were recorded using a voice recorder and were transcribed and analysed using theoretical framework analysis. Results: The review of 126 medical records at the clinics revealed that no patient had suffered from or complained of a neuropsychiatric side effect. This may indicate that patients were not suffering from clinically significant side effects, side effects were not being adequately recorded by healthcare staff, or the healthcare staff were not questioning patients regarding side effects. A total of 26 hospitalised patients were followed for 24 weeks in the psychiatric facilities. Almost half of the patients using efavirenz experienced an improvement in symptoms to the extent that they were iii discharged from the facility. The majority of patients (66.7%) not on an efavirenzcontaining regimen did not improve to the point of discharge. Healthcare staff were vague when providing a definition of neuropsychiatric side effects. There were conflicting ideas on whether or not efavirenz should be used in patients with an active psychiatric illness. Conclusions: Further studies need to be performed in public-sector institutions to obtain a clearer picture of the side effects experienced by patients using efavirenz. Healthcare staff need to be encouraged to keep complete records to allow for meaningful analysis. The further integration of mental health services into existing HIV programmes is essential for holistic treatment. Patients in psychiatric hospitals demonstrated that even patients with psychiatric disorders on efavirenz can experience positive outcomes and stabilisation of psychiatric symptoms, which may indicate that these may not have due to efavirenz use. Further elucidation concerning the use of efavirenz in patients with psychiatric disorders, a description of the neuropsychiatric side effects, as well as management strategies must be provided in subsequent HIV guidelines.
- Full Text:
- Date Issued: 2017
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