1) The study evaluated the effectiveness of different dopamine agonists and antagonists in treating hot flushes in post-menopausal women.
2) All treatments (bromocriptine, Liposom, veralipride, domperidone) were effective in alleviating hot flushes compared to placebo, but the pharmacological agents proved to be more effective.
3) The drugs may act through different mechanisms such as increasing endogenous opioid tone through hyperprolactinemia or direct/indirect effects on dopamine receptors in the hypothalamus.
This document provides information on paracetamol (acetaminophen) including its mechanism of action, metabolism, pharmacokinetics, efficacy, safety and clinical applications. The author declares no conflict of interest. Key points include:
- Paracetamol's mechanism of action is not fully understood but it likely involves inhibiting prostaglandin synthesis in the central nervous system.
- It is metabolized primarily by glucuronidation and sulfation and to a minor extent by cytochrome P450 enzymes, with a half-life of 2-4 hours in adults.
- The minimum effective plasma concentration for analgesia and antipyresis is 10 micrograms/mL, with the therapeutic
Rachmat Gunadi Wachjudi was born in Garut, Indonesia in 1955. He received his medical education in Indonesia, obtaining degrees in general medicine, internal medicine, and rheumatology. He has worked as a rheumatology staff member at Dr. Hasan Sadikin Hospital. He is a member of several Indonesian medical organizations. The document provides biographical information about Rachmat Gunadi Wachjudi's education, career, and professional affiliations.
The document discusses two major classes of analgesics - narcotic analgesics and non-narcotic analgesics (NSAIDs). It describes the classification of NSAIDs, their mechanism of action involving inhibition of cyclooxygenase enzymes, and their therapeutic uses for anti-inflammatory, analgesic, and antipyretic effects. Adverse effects including gastrointestinal issues and renal toxicity are also noted. The mechanisms and effects of opioid analgesics are then outlined, along with their clinical uses, side effects, toxicity, and treatment with naloxone or naltrexone.
This document summarizes information about histamine and antihistamines. It discusses how histamine is synthesized, catabolized, and functions through four histamine receptors. It then describes the molecular basis of action of histamine and how antihistamines work as inverse agonists. The rest of the document discusses the benefits and risks of H1-antihistamines and their use in treating allergic diseases like allergic rhinitis and chronic urticaria, as well as in special populations like the elderly.
1. A 35-year-old male presented with fever and body pain and was prescribed chloroquine by a private practitioner. After several days, the patient developed palpitations, weakness, muscle cramps and constipation.
2. Upon admission to the hospital, the patient was found to have hypokalemia which was determined to be caused by chloroquine overdose based on the Naranjo Scale assessment.
3. The patient recovered after being treated for hypokalemia and was discharged from the hospital.
Dr. Chit Soe's document discusses the long-term use of steroids in rheumatology. It provides an overview of how steroids were initially seen as a promising treatment for rheumatoid arthritis but were later found to have serious adverse effects with high doses. The document examines the controversy around low-dose steroid use and different regimens for corticosteroid pulse therapy. It also reviews potential benefits of steroids in improving symptoms and retarding erosion, as well as common short-term and long-term side effects associated with steroid treatment.
Introduction to autacoids and classificationDikshakaushal8
Local hormones, also known as autacoids, are physiologically active substances produced locally in the body that have short-lived, localized effects. Some key classes of local hormones include amine derivatives like histamine and serotonin, peptide derivatives like bradykinin and angiotensins, and lipid derivatives like prostaglandins, leukotrienes, and platelet activating factor. These endogenous compounds play important roles in physiological and pathological processes through their actions on local tissues.
This document summarizes a study examining the combination of interferon-beta (IFN-B) and temozolomide for treating neuroblastoma. The study found that IFN-B sensitizes neuroblastoma cells to temozolomide by downregulating the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT). In vitro, IFN-B pretreatment significantly decreased MGMT expression in two neuroblastoma cell lines and reduced cell counts when combined with temozolomide. In vivo mouse models also showed the combination of IFN-B and temozolomide reduced tumor burden more than either agent alone for both localized and disseminated neuroblastoma through decreased MGMT
This document provides information on paracetamol (acetaminophen) including its mechanism of action, metabolism, pharmacokinetics, efficacy, safety and clinical applications. The author declares no conflict of interest. Key points include:
- Paracetamol's mechanism of action is not fully understood but it likely involves inhibiting prostaglandin synthesis in the central nervous system.
- It is metabolized primarily by glucuronidation and sulfation and to a minor extent by cytochrome P450 enzymes, with a half-life of 2-4 hours in adults.
- The minimum effective plasma concentration for analgesia and antipyresis is 10 micrograms/mL, with the therapeutic
Rachmat Gunadi Wachjudi was born in Garut, Indonesia in 1955. He received his medical education in Indonesia, obtaining degrees in general medicine, internal medicine, and rheumatology. He has worked as a rheumatology staff member at Dr. Hasan Sadikin Hospital. He is a member of several Indonesian medical organizations. The document provides biographical information about Rachmat Gunadi Wachjudi's education, career, and professional affiliations.
The document discusses two major classes of analgesics - narcotic analgesics and non-narcotic analgesics (NSAIDs). It describes the classification of NSAIDs, their mechanism of action involving inhibition of cyclooxygenase enzymes, and their therapeutic uses for anti-inflammatory, analgesic, and antipyretic effects. Adverse effects including gastrointestinal issues and renal toxicity are also noted. The mechanisms and effects of opioid analgesics are then outlined, along with their clinical uses, side effects, toxicity, and treatment with naloxone or naltrexone.
This document summarizes information about histamine and antihistamines. It discusses how histamine is synthesized, catabolized, and functions through four histamine receptors. It then describes the molecular basis of action of histamine and how antihistamines work as inverse agonists. The rest of the document discusses the benefits and risks of H1-antihistamines and their use in treating allergic diseases like allergic rhinitis and chronic urticaria, as well as in special populations like the elderly.
1. A 35-year-old male presented with fever and body pain and was prescribed chloroquine by a private practitioner. After several days, the patient developed palpitations, weakness, muscle cramps and constipation.
2. Upon admission to the hospital, the patient was found to have hypokalemia which was determined to be caused by chloroquine overdose based on the Naranjo Scale assessment.
3. The patient recovered after being treated for hypokalemia and was discharged from the hospital.
Dr. Chit Soe's document discusses the long-term use of steroids in rheumatology. It provides an overview of how steroids were initially seen as a promising treatment for rheumatoid arthritis but were later found to have serious adverse effects with high doses. The document examines the controversy around low-dose steroid use and different regimens for corticosteroid pulse therapy. It also reviews potential benefits of steroids in improving symptoms and retarding erosion, as well as common short-term and long-term side effects associated with steroid treatment.
Introduction to autacoids and classificationDikshakaushal8
Local hormones, also known as autacoids, are physiologically active substances produced locally in the body that have short-lived, localized effects. Some key classes of local hormones include amine derivatives like histamine and serotonin, peptide derivatives like bradykinin and angiotensins, and lipid derivatives like prostaglandins, leukotrienes, and platelet activating factor. These endogenous compounds play important roles in physiological and pathological processes through their actions on local tissues.
This document summarizes a study examining the combination of interferon-beta (IFN-B) and temozolomide for treating neuroblastoma. The study found that IFN-B sensitizes neuroblastoma cells to temozolomide by downregulating the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT). In vitro, IFN-B pretreatment significantly decreased MGMT expression in two neuroblastoma cell lines and reduced cell counts when combined with temozolomide. In vivo mouse models also showed the combination of IFN-B and temozolomide reduced tumor burden more than either agent alone for both localized and disseminated neuroblastoma through decreased MGMT
The document reports on a project to investigate the analgesic activity of the aqueous fruit extract of Tribulus terristris in rats. Key findings include:
- Phytochemical screening of the extract found alkaloids, flavonoids, triterpenoids and other compounds.
- Analgesic activity was evaluated using the Eddy's hot plate and acetic acid-induced writhing models. The extract showed analgesic effects in a dose-dependent manner.
- The study aims to provide evidence of the analgesic potential of T. terristris extract and its various phytochemical constituents.
Recent advances of antihistamines (H-3 and H-4 antagonist)Akhil Nagar
The presentation brief about the recent advances and recent modification over anti histamines. The drugs under clinical trials or under phase of clinical trials are explained. The drugs are with especial emphasis with H-3 and H-4 receptors antagonists. These drugs are somewhat similar action as H-1 and H-2 receptors antagonists.
This document summarizes neuropathic pain and the agents used to treat it. It discusses how neuropathic pain is initiated by damage or dysfunction in the nervous system and often presents as burning pain. It then describes various neuropathic pain conditions and classes of agents used to treat neuropathic pain, including antidepressants, anticonvulsants, and local anesthetics. It provides details on the mechanisms and indications for tricyclic antidepressants, SSRIs, SNRIs, and various anticonvulsants in treating different types of neuropathic pain.
Outline:
What is the antihistamines.
What is histamine.
What is the receptors.
What is the clinical uses of antihistamines.
Side effects of antihistamines.
What is the contraindications.
This document summarizes key points about iatrogenesis and drug-related risks in the elderly. It discusses age-related changes that increase risks, such as changes in body composition and drug distribution. Examples of high-risk drug classes are provided, like anticoagulants, psychotropic drugs, and antineoplastic agents. Specific situations that increase risks, such as polypharmacy and malnutrition, are also described.
This document summarizes information about serotonin and histamine, including their biosynthesis, pharmacological effects, mechanisms of action, and examples of agonists and antagonists. Serotonin is produced in the gastrointestinal tract and central nervous system. It has diverse effects, including acting as a neurotransmitter, regulating cardiovascular and gastrointestinal functions, and mediating platelet aggregation. Histamine acts through H1, H2, and H3 receptors and is involved in allergic responses. Examples are given of several drugs that act as serotonin or histamine receptor agonists or antagonists for conditions like migraine, depression, anxiety, motion sickness, and allergy treatment.
This document discusses histamine and antihistamines. It begins by introducing histamine, describing its discovery and roles in allergic reactions and as a neurotransmitter. It then covers histamine's chemistry, distribution in the body, synthesis, storage, and metabolism. The document discusses the four types of histamine receptors (H1-H4) and histamine's pharmacological effects. It also provides details on antihistamines, including their pharmacokinetics, mechanisms of action, side effects, and classifications of first versus second generation antihistamines. The document concludes by mentioning clinical uses of histamine and antihistamines for conditions like allergies and gastric hypersecretions.
3. Frank Buttgereit. Fin40 min ohne gc c&d dmar ds in the treatment of racrea-autoinmunidad
1. Disease-modifying antirheumatic drugs (DMARDs) are used to treat rheumatoid arthritis and include conventional synthetic DMARDs (csDMARDs) like methotrexate as well as biological DMARDs (bDMARDs) that target molecules like TNF-α.
2. Treatment should aim to achieve remission or low disease activity and include methotrexate, adjusting therapy if targets are not met. If csDMARDs are insufficient, bDMARDs should be added.
3. Biological originator drugs and biosimilars are available that target molecules like TNF-α, the IL-6 receptor, T cells, and B cells to treat rheumat
Drugs used in treatment of rheumatoid arthiritisPravin Prasad
This document summarizes drugs used to treat rheumatoid arthritis. It discusses disease-modifying antirheumatic drugs (DMARDs) which are used to modify disease progression, including conventional synthetic DMARDs like methotrexate and sulfasalazine, as well as biological DMARDs like TNF-alpha inhibitors. It provides details on the mechanisms of action, pharmacokinetics, uses, and adverse effects of various DMARDs. Nonsteroidal anti-inflammatory drugs are used for symptom relief while corticosteroids can provide prompt anti-inflammatory effects but do not alter disease progression. The document concludes that methotrexate is preferred as initial treatment and certain drugs should not be combined.
The document discusses the use of steroids in rheumatology. It notes that while steroids were initially hoped to dramatically alter the long-term course of rheumatoid arthritis, long-term high dose treatment can have serious adverse effects. Low dose steroids remain controversial for treating arthritis symptoms and progression. Corticosteroid pulse therapy, involving high intermittent IV doses, can provide clinical benefits but also risks like osteonecrosis. Overall, steroids may have an early role in controlling synovitis or bridging between disease-modifying drugs, but long-term use is not justified due to safety concerns.
The document provides information on clinical analgesia including objectives, quiz questions, and details on pain mechanisms and treatment. It discusses non-opioid analgesics like acetaminophen and NSAIDs as well as adjuvant analgesics including antidepressants, anticonvulsants, corticosteroids, and muscle relaxants. The document also provides dosing information for various analgesics.
Chemistry of histamine and antihistamine drugs (H-1 and H-2 antagonist)Akhil Nagar
This document discusses the chemistry and pharmacology of histamine and antihistamine drugs. It provides details on:
- The discovery and properties of histamine.
- Histamine synthesis from histidine, release from mast cells and other tissues, and metabolism by histamine-N-methyltransferase and diamine oxidase.
- The four types of histamine receptors (H1-H4), their distribution, and role in various physiological effects.
- The pharmacological effects of histamine release including allergic reactions and anaphylaxis.
- Classes of antihistamine drugs including H1 and H2 receptor antagonists, as well as mast cell stabilizers that inhibit histamine release
Pharmacology of alfentanil and remifentanildocshri4
This document discusses the opioid analgesics alfentanil and remifentanil. It describes them as synthetic phenylpiperidine derivatives that are shorter acting than fentanyl, with alfentanil being less potent than fentanyl and remifentanil having similar potency to fentanyl. Their pharmacokinetics are summarized, with alfentanil having an elimination half-life of 84-90 minutes and remifentanil having an extremely short context-sensitive half-life of 3-10 minutes. Their clinical uses, dosages, and pharmacodynamic effects such as respiratory depression are also outlined.
Serotonin 5-HT3-receptor antagonists are used to prevent chemotherapy-induced, post-operative, and post-radiation nausea and vomiting by blocking serotonin receptors centrally and peripherally. They have half-lives ranging from 3.9 to 40 hours and are metabolized in the liver. According to clinical guidelines, they are highly effective for preventing acute nausea and vomiting from chemotherapy, especially when administered intravenously 30 minutes before treatment. Common side effects include constipation, diarrhea, headache, and dizziness.
Evaluating the ability of anti-cancer drugs Etoposide and Staurosporine to in...Davient Bala
Cervical cancer is considered one of the most prevalent cancers affecting Singaporean women.
Although many novel chemotherapeutics have been developed recently, little has been done to
determine the efficiency of current anti-cancer agents working in combination. Here, we aimed to
evaluate the apoptosis induction efficiency of Etoposide and Staurosporine in HeLa cells. Cell cultures
were subjected to either 50 μM Etoposide, 10 nM Staurosporine or both for 24 hours prior visualization
under a fluorescence microscope. We found that Etoposide alone had an efficiency of 16.1% while
Staurosporine alone had 18.3%. However, the polytherapy achieved an efficiency of up to 33.6%,
which indicates an additive effect of both drugs to induce apoptosis. Our results demonstrate that
Etoposide and Staurosporine are both capable of inducing apoptosis in HeLa cells. Furthermore, it
reveals the potential of Etoposide-Staurosporine polytherapy to be a potent combinative treatment
option for cervical cancer patients resistant or sensitive to conventional anti-cancer agents.
This document provides an overview of the treatment of rheumatoid arthritis (RA). It discusses the epidemiology and etiology of RA and outlines past, present, and future treatment paradigms. The importance of early diagnosis and treatment is emphasized. Diagnostic criteria and methods for assessing disease severity are presented. Guidelines are provided for using nonsteroidal anti-inflammatory drugs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biological response modifiers (BRMs) to treat RA. Specific DMARDs and BRMs discussed include methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, infliximab, and
This document discusses the pharmacokinetics and pharmacodynamics of paracetamol (acetaminophen). It provides an overview of its mechanism of action, metabolism, elimination, toxicity risks, and therapeutic drug monitoring. It notes that the mechanisms are not fully understood but likely involve inhibition of prostaglandin H2 synthases and interactions with the endocannabinoid system. Optimal plasma concentrations for analgesia are between 10-20 micrograms/mL while toxicity risk increases above 150 micrograms/mL. The document also reviews factors influencing absorption and pharmacokinetics after different routes of administration.
This document reviews the use of intravenous lipid emulsions (ILE) in the treatment of acute poisoning based on human and animal studies. It summarizes that ILE has been shown to increase survival rates in animal models of local anesthetic toxicity as well as other substances like clomipramine. The document also reviews evidence from case reports that ILE administration in humans experiencing cardiac toxicity from local anesthetics or other substances has resulted in normalization of heart function. However, the effectiveness of ILE appears to be substance-dependent, as it did not impact mortality in animal studies of nifedipine or propranolol toxicity. Overall, the review finds that ILE can positively impact hemodynamics and electrocardiograph
Este documento descreve uma implementação híbrida e paralela da Transformada Rápida de Fourier (FFT) no supercomputador Cray XD1, que combina processamento em CPU e FPGA. A abordagem é dividida entre software em C e hardware em VHDL, com diferentes tamanhos de entrada sendo processados em cada componente. Os resultados mostram um ganho de desempenho para certos tamanhos de entrada. Trabalhos futuros incluem melhorias no pipeline e uso de radix-4.
Morbo di Alzheimer, disturbi cognitivi amnesici leggeri, e disturbi della mem...MerqurioEditore_redazione
1) The document summarizes current understanding of Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment. It discusses pathogenesis, risk factors, progression, and potential for integrative prevention strategies.
2) Key points include that Alzheimer's initially impacts memory and progressively destroys cognitive abilities. Current drug therapies provide only temporary and limited benefits. Nutraceuticals show potential in randomized trials with better safety profiles than drugs.
3) Early intervention may be most effective, as pathology can be detected years before diagnosis. Amnestic mild cognitive impairment and age-associated memory impairment are early indicators offering opportunity for prevention. A multimodal lifestyle and nutritional approach holds promise.
The document reports on a project to investigate the analgesic activity of the aqueous fruit extract of Tribulus terristris in rats. Key findings include:
- Phytochemical screening of the extract found alkaloids, flavonoids, triterpenoids and other compounds.
- Analgesic activity was evaluated using the Eddy's hot plate and acetic acid-induced writhing models. The extract showed analgesic effects in a dose-dependent manner.
- The study aims to provide evidence of the analgesic potential of T. terristris extract and its various phytochemical constituents.
Recent advances of antihistamines (H-3 and H-4 antagonist)Akhil Nagar
The presentation brief about the recent advances and recent modification over anti histamines. The drugs under clinical trials or under phase of clinical trials are explained. The drugs are with especial emphasis with H-3 and H-4 receptors antagonists. These drugs are somewhat similar action as H-1 and H-2 receptors antagonists.
This document summarizes neuropathic pain and the agents used to treat it. It discusses how neuropathic pain is initiated by damage or dysfunction in the nervous system and often presents as burning pain. It then describes various neuropathic pain conditions and classes of agents used to treat neuropathic pain, including antidepressants, anticonvulsants, and local anesthetics. It provides details on the mechanisms and indications for tricyclic antidepressants, SSRIs, SNRIs, and various anticonvulsants in treating different types of neuropathic pain.
Outline:
What is the antihistamines.
What is histamine.
What is the receptors.
What is the clinical uses of antihistamines.
Side effects of antihistamines.
What is the contraindications.
This document summarizes key points about iatrogenesis and drug-related risks in the elderly. It discusses age-related changes that increase risks, such as changes in body composition and drug distribution. Examples of high-risk drug classes are provided, like anticoagulants, psychotropic drugs, and antineoplastic agents. Specific situations that increase risks, such as polypharmacy and malnutrition, are also described.
This document summarizes information about serotonin and histamine, including their biosynthesis, pharmacological effects, mechanisms of action, and examples of agonists and antagonists. Serotonin is produced in the gastrointestinal tract and central nervous system. It has diverse effects, including acting as a neurotransmitter, regulating cardiovascular and gastrointestinal functions, and mediating platelet aggregation. Histamine acts through H1, H2, and H3 receptors and is involved in allergic responses. Examples are given of several drugs that act as serotonin or histamine receptor agonists or antagonists for conditions like migraine, depression, anxiety, motion sickness, and allergy treatment.
This document discusses histamine and antihistamines. It begins by introducing histamine, describing its discovery and roles in allergic reactions and as a neurotransmitter. It then covers histamine's chemistry, distribution in the body, synthesis, storage, and metabolism. The document discusses the four types of histamine receptors (H1-H4) and histamine's pharmacological effects. It also provides details on antihistamines, including their pharmacokinetics, mechanisms of action, side effects, and classifications of first versus second generation antihistamines. The document concludes by mentioning clinical uses of histamine and antihistamines for conditions like allergies and gastric hypersecretions.
3. Frank Buttgereit. Fin40 min ohne gc c&d dmar ds in the treatment of racrea-autoinmunidad
1. Disease-modifying antirheumatic drugs (DMARDs) are used to treat rheumatoid arthritis and include conventional synthetic DMARDs (csDMARDs) like methotrexate as well as biological DMARDs (bDMARDs) that target molecules like TNF-α.
2. Treatment should aim to achieve remission or low disease activity and include methotrexate, adjusting therapy if targets are not met. If csDMARDs are insufficient, bDMARDs should be added.
3. Biological originator drugs and biosimilars are available that target molecules like TNF-α, the IL-6 receptor, T cells, and B cells to treat rheumat
Drugs used in treatment of rheumatoid arthiritisPravin Prasad
This document summarizes drugs used to treat rheumatoid arthritis. It discusses disease-modifying antirheumatic drugs (DMARDs) which are used to modify disease progression, including conventional synthetic DMARDs like methotrexate and sulfasalazine, as well as biological DMARDs like TNF-alpha inhibitors. It provides details on the mechanisms of action, pharmacokinetics, uses, and adverse effects of various DMARDs. Nonsteroidal anti-inflammatory drugs are used for symptom relief while corticosteroids can provide prompt anti-inflammatory effects but do not alter disease progression. The document concludes that methotrexate is preferred as initial treatment and certain drugs should not be combined.
The document discusses the use of steroids in rheumatology. It notes that while steroids were initially hoped to dramatically alter the long-term course of rheumatoid arthritis, long-term high dose treatment can have serious adverse effects. Low dose steroids remain controversial for treating arthritis symptoms and progression. Corticosteroid pulse therapy, involving high intermittent IV doses, can provide clinical benefits but also risks like osteonecrosis. Overall, steroids may have an early role in controlling synovitis or bridging between disease-modifying drugs, but long-term use is not justified due to safety concerns.
The document provides information on clinical analgesia including objectives, quiz questions, and details on pain mechanisms and treatment. It discusses non-opioid analgesics like acetaminophen and NSAIDs as well as adjuvant analgesics including antidepressants, anticonvulsants, corticosteroids, and muscle relaxants. The document also provides dosing information for various analgesics.
Chemistry of histamine and antihistamine drugs (H-1 and H-2 antagonist)Akhil Nagar
This document discusses the chemistry and pharmacology of histamine and antihistamine drugs. It provides details on:
- The discovery and properties of histamine.
- Histamine synthesis from histidine, release from mast cells and other tissues, and metabolism by histamine-N-methyltransferase and diamine oxidase.
- The four types of histamine receptors (H1-H4), their distribution, and role in various physiological effects.
- The pharmacological effects of histamine release including allergic reactions and anaphylaxis.
- Classes of antihistamine drugs including H1 and H2 receptor antagonists, as well as mast cell stabilizers that inhibit histamine release
Pharmacology of alfentanil and remifentanildocshri4
This document discusses the opioid analgesics alfentanil and remifentanil. It describes them as synthetic phenylpiperidine derivatives that are shorter acting than fentanyl, with alfentanil being less potent than fentanyl and remifentanil having similar potency to fentanyl. Their pharmacokinetics are summarized, with alfentanil having an elimination half-life of 84-90 minutes and remifentanil having an extremely short context-sensitive half-life of 3-10 minutes. Their clinical uses, dosages, and pharmacodynamic effects such as respiratory depression are also outlined.
Serotonin 5-HT3-receptor antagonists are used to prevent chemotherapy-induced, post-operative, and post-radiation nausea and vomiting by blocking serotonin receptors centrally and peripherally. They have half-lives ranging from 3.9 to 40 hours and are metabolized in the liver. According to clinical guidelines, they are highly effective for preventing acute nausea and vomiting from chemotherapy, especially when administered intravenously 30 minutes before treatment. Common side effects include constipation, diarrhea, headache, and dizziness.
Evaluating the ability of anti-cancer drugs Etoposide and Staurosporine to in...Davient Bala
Cervical cancer is considered one of the most prevalent cancers affecting Singaporean women.
Although many novel chemotherapeutics have been developed recently, little has been done to
determine the efficiency of current anti-cancer agents working in combination. Here, we aimed to
evaluate the apoptosis induction efficiency of Etoposide and Staurosporine in HeLa cells. Cell cultures
were subjected to either 50 μM Etoposide, 10 nM Staurosporine or both for 24 hours prior visualization
under a fluorescence microscope. We found that Etoposide alone had an efficiency of 16.1% while
Staurosporine alone had 18.3%. However, the polytherapy achieved an efficiency of up to 33.6%,
which indicates an additive effect of both drugs to induce apoptosis. Our results demonstrate that
Etoposide and Staurosporine are both capable of inducing apoptosis in HeLa cells. Furthermore, it
reveals the potential of Etoposide-Staurosporine polytherapy to be a potent combinative treatment
option for cervical cancer patients resistant or sensitive to conventional anti-cancer agents.
This document provides an overview of the treatment of rheumatoid arthritis (RA). It discusses the epidemiology and etiology of RA and outlines past, present, and future treatment paradigms. The importance of early diagnosis and treatment is emphasized. Diagnostic criteria and methods for assessing disease severity are presented. Guidelines are provided for using nonsteroidal anti-inflammatory drugs, corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biological response modifiers (BRMs) to treat RA. Specific DMARDs and BRMs discussed include methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, infliximab, and
This document discusses the pharmacokinetics and pharmacodynamics of paracetamol (acetaminophen). It provides an overview of its mechanism of action, metabolism, elimination, toxicity risks, and therapeutic drug monitoring. It notes that the mechanisms are not fully understood but likely involve inhibition of prostaglandin H2 synthases and interactions with the endocannabinoid system. Optimal plasma concentrations for analgesia are between 10-20 micrograms/mL while toxicity risk increases above 150 micrograms/mL. The document also reviews factors influencing absorption and pharmacokinetics after different routes of administration.
This document reviews the use of intravenous lipid emulsions (ILE) in the treatment of acute poisoning based on human and animal studies. It summarizes that ILE has been shown to increase survival rates in animal models of local anesthetic toxicity as well as other substances like clomipramine. The document also reviews evidence from case reports that ILE administration in humans experiencing cardiac toxicity from local anesthetics or other substances has resulted in normalization of heart function. However, the effectiveness of ILE appears to be substance-dependent, as it did not impact mortality in animal studies of nifedipine or propranolol toxicity. Overall, the review finds that ILE can positively impact hemodynamics and electrocardiograph
Este documento descreve uma implementação híbrida e paralela da Transformada Rápida de Fourier (FFT) no supercomputador Cray XD1, que combina processamento em CPU e FPGA. A abordagem é dividida entre software em C e hardware em VHDL, com diferentes tamanhos de entrada sendo processados em cada componente. Os resultados mostram um ganho de desempenho para certos tamanhos de entrada. Trabalhos futuros incluem melhorias no pipeline e uso de radix-4.
Morbo di Alzheimer, disturbi cognitivi amnesici leggeri, e disturbi della mem...MerqurioEditore_redazione
1) The document summarizes current understanding of Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment. It discusses pathogenesis, risk factors, progression, and potential for integrative prevention strategies.
2) Key points include that Alzheimer's initially impacts memory and progressively destroys cognitive abilities. Current drug therapies provide only temporary and limited benefits. Nutraceuticals show potential in randomized trials with better safety profiles than drugs.
3) Early intervention may be most effective, as pathology can be detected years before diagnosis. Amnestic mild cognitive impairment and age-associated memory impairment are early indicators offering opportunity for prevention. A multimodal lifestyle and nutritional approach holds promise.
We set the pace at our company. We are always innovating and developing new technologies and solutions to solve our customers' problems. Our goal is to be the leader in our industry through continuous improvement and by empowering our employees to think creatively.
Effetto dei liposomi di fosfolipidi ipotalamici in pazienti trattati con sulp...MerqurioEditore_redazione
The study evaluated the efficacy of treating depressed patients with sulpiride and schizophrenic patients with haloperidol, with or without adjunctive hypothalamic phospholipid liposomes.
Results showed that treatment with hypothalamic phospholipid liposomes enhanced the therapeutic efficacy of sulpiride and haloperidol, as measured by greater improvements on diagnostic tests, compared to treatment with the drugs alone. Additionally, the increase in plasma prolactin levels caused by haloperidol was significantly reduced when treated adjunctively with hypothalamic phospholipid liposomes.
This document discusses drug-drug interactions from pharmacokinetic and pharmacodynamic perspectives. Pharmacokinetic interactions can occur through competition for plasma protein binding, displacement from tissue binding sites, or alterations in barriers like the blood-brain barrier. While competition for plasma protein binding can briefly increase unbound drug concentrations, displaced drugs are usually cleared quickly. Concurrent administration of two nephrotoxic drugs can cause kidney damage even at low individual doses due to enhanced toxicity. Whether an interaction produces adverse effects depends on individual susceptibility and clinical monitoring. The document then provides several examples of specific drug interactions.
1. The document describes an experiment investigating drug interactions and the effects of the liver on drug action in mice. Various groups of mice were administered different combinations of drugs including thiopentone, pentobarbitone, phenobarbitone, and carbon tetrachloride.
2. The duration of drug effects were measured and recorded for each mouse. Preliminary results show that starvation prior to drug administration increased the duration of drug effects for some groups. Pretreatment with other drugs also increased duration of effects for some groups.
3. Further analysis of the results is needed to fully understand the interactions between the different drugs and effects of liver function and pretreatments. The study aims to provide insights into how multiple drug use
The document summarizes a clinical trial that evaluated the efficacy and safety of the herbal supplement Tribulus terrestris for male sexual dysfunction. 180 men with mild-to-moderate erectile dysfunction were randomized to receive either Tribulus terrestris or a placebo for 12 weeks. The primary outcome was a change in the International Index of Erectile Function score from baseline to end of study. Secondary outcomes included changes in other domains of sexual function, safety assessments, and lipid and hormone levels. Results indicated that Tribulus terrestris significantly improved erectile function and overall sexual satisfaction compared to placebo, without significant safety issues.
This document presents a case report of levofloxacin-induced seizures in a 68-year-old male patient admitted with fever and abdominal pain. After 5 days of treatment including ceftriaxone and pantoprazole without improvement, levofloxacin was added. Within 10 minutes, the patient had a tonic-clonic seizure. Levofloxacin was stopped and the patient recovered without further seizures. Laboratory results and the patient's history ruled out other potential causes. The reaction was deemed probable to be caused by levofloxacin based on the WHO causality assessment scale criteria. Fluoroquinolones can lower the seizure threshold through GABA inhibition. This case illustrates the need to
This document presents a case report of levofloxacin-induced seizures in a 68-year-old male patient admitted with fever and abdominal pain. After 5 days of treatment with antibiotics, the patient was given levofloxacin and experienced a seizure within 10 minutes. Levofloxacin was stopped and the patient recovered without further seizures. Based on the temporal relationship and positive de-challenge, levofloxacin was assessed as the probable cause of seizures. Fluoroquinolones like levofloxacin are known to lower the seizure threshold possibly through GABA inhibition. This case highlights the need to monitor for neurological adverse effects when using fluoroquinolone antibiotics.
臨床研究文獻 Human clinical studies with mora devices Dr. Michael GalleWei Chung Chang
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Effetto dell’applicazione di diversi agonisti ed antagonisti della dopamina nelle vampate post-menopausali
1. Maturitus, 8 (1986) 229-237 229
Elsevier
MAT 00399
Effects of different dopamine agonists
and antagonists on post-menopausal hot flushes
L. Zichella ‘ P. Falaschi *, P. Fioretti 3, G.B. Melis 3, A. Cagnacci 3,
,
M. Gambacciani 3 and S. Mancini 3
’I Clinicu Ostetrica e Ginecologica ‘L.u Sapienra ‘ Policlinico
, Umberto J,
Department of Obstetrics and Gynaecologv I, and
’ Department of Internal Medicine V, Unioersitv of Rome; and
-’Department of Obstetrics and Qnaecologv, Unioersiti degli Studi, Pisu. Jta!v
(Received 14 May 1985; revision received 30 December 1985; accepted 13 June 1986)
The dopaminergic system seems to be involved in both pulsatile luteinizing hormone (LH) secretion
and hot flushes in post-menopausal women. With the aim of further clarifying its role, the effectiveness
of dopaminergic and antidopaminergic drugs in the treatment of hot flushes was studied. Self-assessed
scores for vasomotor symptoms were evaluated in 5 groups of 15 patients treated for 20 days with one of
the following agents: placebo; the dopamine receptor agonist, bromocriptine; the indirect dopaminergic
agent, Liposom: the antidopaminergic drug, veralipride or the peripheral antidopaminergic agent,
domperidone. All of these treatment regimens were effective in alleviating hot flushes, but the pharmaco-
logical agents proved to be more effective than the placebo. A direct dopaminergic action is hypothesized
in the case of bromocriptine and Liposom, while the antidopaminergic drugs might act through different
indirect mechanisms such as the short-loop feedback exerted by hyperprolactinaemia on tuberoinfundib-
ular dopamine (TIDA) neurons with a secondary dopamine-like activity, or stimulation of the opioid
system.
(Key words: Dopamine, Agonists, Antagonists, Hot flushes)
Introduction
Hot flushes are perhaps the most common of all the vasomotor symptoms
experienced by post-menopausal women, occurring in about 80% of cases. They are
described as an intense feeling of heat centred on the upper body, often associated
with a visible reddening of the face and neck. This feeling of heat rapidly becomes
generalised, and is accompanied by palpitations and profuse sweating.
It has been established objectively that there is a clear correlation between hot
flushes and an elevation of finger temperature, as well as a reduction in skin
resistance [ 1,2].
Correspondence to: Dr. G.B. Melis. Clinica Ostetrica e Ginecologica, Universita degii Studi, via Roma 37.
56100 Pisa, Italy.
0378-5122/86/$03.50 0 1986 Elsevier Science Publishers B.V. (Biomedical Division)
2. 230
Various neuroendocrine changes have also been observed during hot flushes [3],
but the main accompanying neuroendocrine event manifests itself as luteinizing
hormone (LH) pulses [4,5]. Pulsatile LH secretion is enhanced in post-menopausal
women and almost 85% of pulses correlate temporally with hot flushes [5,6].
However, it has been clearly established that LH pulses alone cannot induce hot
flushes, but are more probably the hormonal expression of the altered neurotrans-
mitter functions within the hypothalamus which are mainly responsible for vasomo-
tor symptoms in post-menopausal subjects [7,8].
Modifications in the hypothalamic neurotransmitter system are present in hypo-
gonadal animals [9,10] and, in particular, an increased norepinephrine/dopamine
(NE/DA) ratio has been reported in the hypothalamus of ovariectomised rats [ll].
Despite the conflicting data [12,13], dopamine and dopaminergic drugs would
appear to reduce LH pulsatility and secretion in both animals and humans [14,15].
Although a pituitary site of action cannot be completely excluded in humans, this
effect is probably exerted on hypothalamic LH releasing factor (LHRF) secreting
cells, as has been demonstrated in animals [14,15].
These data suggest that a reduction in endogenous dopaminergic tone may be
one .of the possible mechanisms involved in both the enhanced pulsatile LH
secretion and the pathogenesis of hot flushes in post-menopausal women.
Some investigators, however, maintain that the intrahypothalamic dopaminergic
tone is enhanced in post-menopausal women, suggesting that the administration of
antidopaminergic drugs could be useful in the treatment of hot flushes [16].
In view of these conflicting data, we evaluated the clinical changes in vasomotor
symptoms which follow pharmacological manipulation of the dopaminergic system
with both agonist and antagonist drugs.
Subjects and methods
Twenty-five women aged 45-55 yr volunteered to participate in the study. The
patients had all undergone physiological menopause l-2 yr before the start of the
study and were experiencing severe vasomotor symptoms. They had not received
endocrinologically active drugs for at least the preceding 6 mth.
The patients were randomly divided into 5 groups of 15 subjects and received
either placebo or drug treatment for 20 days. The following drugs were adminis-
tered: bromocriptine (BCT, 3.75 mg/day per OS) as a direct dopamine receptor
agonist [15]; Liposom (40 mg/day intramuscularly), an extract of hypothalamic
phospholipids, as an indirect dopamine receptor stimulating agent [17,18]; veralipride
(VER, 100 mg/day per OS), as a specific dopamine receptor blocking agent with
central effects [16]; and domperidone (DOM, 10 mg/day per OS), as a specific
dopamine receptor blocking agent with no central effects, since it does not cross the
blood-brain barrier [19].
The severity of the vasomotor symptoms was self-assessed before and after
treatment. The patients were required to fill in a chart reporting both the frequency
and intensity of hot flushes, scored from O-3 according to the scheme shown in
3. 231
TABLE I
SCORING SCHEME FOR THE EVALUATION OF THE FREQUENCY AND INTENSITY OF
POST-MENOPAUSAL VASOMOTOR SYMPTOMS
Hot flushes
Frequency Intensity
0 0
< S/day Slight
> 5, < lo/day Moderate
> lo/day Severe
Table I. The values for both frequency and intensity were totalled and the
pretreatment mean was compared with that after each treatment using Student’s
t-test for paired data.
The differences between the pharmacological treatments and the placebo were
also evaluated by means of the r-test. In addition, the statistical significance of the
differences between the efficacy of the drug treatments and that of the placebo were
evaluated using the Fisher test.
The mean vasomotor symptom scores computed for each group of patients
before and after treatment are set out in Table II. No significant differences
between the groups were detected before treatment. A significant improvement in
the mean vasomotor score was observed in all groups at the end of treatment
(P < 0.05 with placebo, P -c 0.001 with BCT, Liposom, VER and DOM). However,
comparison of the scores at the end of the treatment revealed that all drugs used
had reduced the scores more than the placebo (P -c 0.05).
*
TABLE II
MEAN VASOMOTOR SYMPTOMS SCORES BEFORE AND AFTER TREATMENT WITH DIF-
FERENT COMPOUNDS
Compound a Before After Significance
(paired f-test)
Placebo 3.0+0.2 2.4 +O.l P < 0.05
BCT 3.4 f 0.4 * 0.85 +O.l ** P < 0.001
Liposom 3.0+0.3 * 1.0 kO.1 ** P i 0.001
VER 3.5*0.3 * 1.2 +0.1 ** P < 0.001
DOM 3.6kO.5 * 1.2 io.3 ** P i 0.001
* No significant difference in relation to placebo group.
** P i 0.05 in relation to placebo group.
a BCT, bromocriptine; VER, veralipride: DOM, domperidone.
4. 232
TABLE III
COMPARISON OF THE EFFICACY OF DIFFERENT DRUGS AND PLACEBO IN THE TREAT-
MENT OF POST-MENOPAUSAL HOT FLUSHES
Compound ’ Number of patients Significance
Improvement No improvement (Fisher test)
Placebo 6 9 _
BCT 14 1 P i 0.01
Liposom 13 2 P < 0.05
VER 14 1 P < 0.01
DOM 13 2 P < 0.05
a BCT, bromocriptine; VER, veralipride; DOM, domperidone.
Moreover, a significantly greater number of patients experienced an improvement
in vasomotor symptoms after pharmacological treatment than after placebo admin-
istration (P < 0.01 with BCT and VER, P < Cr.05 with Liposom and DOM) (Table
III). Indeed, the placebo was completely ineffective in 9 patients, even though it
markedly reduced hot flushes in 3 patients and completely abolished them in
another 3 (Table III). BCT and VER, on the other hand, were each ineffective in
only one patient, and Liposom and DOM in only two.
Complete disappearance of hot flushes was observed in 6 subjects treated with
Liposom or DOM, in 5 patients treated with BCT and in 3 patients treated with
VER. The remaining patients experienced a marked reduction in vasomotor symp-
toms (9 on BCT, 7 on Liposom, 11 on VER and 7 on DOM) (Table III).
No side-effects were reported with either the placebo or Liposom. BCT induced
nausea, constipation and hypotension in 13 patients, but these side-effects disap-
peared in all but two of the patients within the first week of treatment. DOM and
VER caused mastodynia in 6 and 10 patients, respectively, while galactorrhoea was
observed in 2 patients after VER treatment.
Discussion
Hot flushes are a common symptom caused by reduced oestrogen secretion in
women mainly after the menopause [20]. Although oestrogen replacement therapy is
the most effective treatment for this complaint [20], other drugs are also able to
alleviate or to abolish hot flushes [l&21-23]. Indeed, some investigators maintain
that placebos are more effective in the treatment of vasomotor symptoms than in
other conditions [21,22].
Current data confirms these results and it has been shown in a group of 15
post-menopausal subjects that placebo treatment induced a slight but significant
decrease in the intensity and frequency of hot flushes. It is difficult to explain the
so-called placebo effect completely, but some data clearly demonstrate that a
placebo exerts its effects, or at least its analgesic effect, through an increase in
endogenous opioid activity [24].
5. 233
It has also been shown that clonidine treatment improves neurovegetative symp-
toms in post-menopausal women [21]. Although clonidine’ main pharmacological
s
action seems to be its alpha-receptor blocking activity, its therapeutic effect might
also be explained through the enhancement of endogenous opioid activity that it
produces [20,21,25,26].
These observations led some workers to formulate the opioid-adrenergic explana-
tion of the origin of hot flushes [20].
The involvement of opioids in the control of the thermoregulatory system has
been demonstrated in animals [27-291. Opioid or opiate administration reduces
thermic sensitivity in animals [27,29]. The acute morphine withdrawal syndrome
induced by naloxone administration is followed by changes in skin temperature and
conductance similar to those observed during hot flushes [28]. On the other hand,
there are many similarities between the clinical manifestations of heroin withdrawal
syndrome in humans and the neurovegetative post-menopausal syndrome [20,30].
A direct correlation exists between peripheral and central opioid levels and
circulating oestrogen levels in both animals and humans [31-331. In post-menopausal
women peripheral opioid levels are low, as is central opioid activity [33-351. In
hypogonadal subjects, exogenous steroid administration can increase peripheral
opioid levels, restore central opioid activity and alleviate subjective hot flushes
120,361.
All these data suggest that hot flushes could be the main symptom of oestrogen
withdrawal and the consequent endogenous opioid withdrawal that this causes [20].
Different neuroactive drugs that are able to influence the central opioid system
might therefore be effective in the treatment of hot flushes.
We have shown that antidopaminergic drugs, such as VER or DOM, are able to
relieve vasomotor symptoms in post-menopausal subjects. Their efficacy was found
to be significantly greater than that of placebo, as indeed had previously been
shown by ourselves and other investigators [16,22]. Antidopaminergic drugs are able
to increase plasma levels and hypothalamic concentrations of opioid peptides when
injected into animals [37,38]. They also increase circulating opioid levels in humans
[40,41]. This action could be exerted through direct blocking of the dopamine
receptors present in hypothalamic-pituitary opiodergic cells [41], but an indirect
effect exerted through hyperprolactinaemia has been reported to enhance central
opioid tonus in animals [42-441. Increased opioid neuroendocrine activity has also
been demonstrated in women suffering from hyperprolactinaemia due to pituitary
adenoma [45].
All these findings may explain how the hyperprolactinaemia induced by VER
and DOM administration is in itself able to increase endogenous opioid tonus in
post-menopausal subjects and consequently to reduce neurovegetative symptoms,
these effects being similar to what is seen during treatment with oestrogens
[16,20,22,23].
On the basis of these data it may be postulated that pharmacological hyperpro-
lactinaemia may correct the endogenous opioid withdrawal syndrome that results
from oestrogen lack in post-menopausal women [20,42-441. Similarly, in other
hypo-oestrogenic conditions, such as those in patients with amenorrhoea or pitui-
6. 234
tary adenoma, the presence of hyperprolactinaemia could explain the absence of hot
flushes even though the levels of circulating oestrogens are very low [45]. Another
possible explanation of the efficacy of antidopaminergic drugs in the treatment of
hot flushes that merits consideration could be a pharmacological effect mediated
through the blocking of central dopaminergic receptors.
Buvat et al., who maintain that hot flushes are due to the increase in central
dopaminergic tone that follows the decrease in oestrogen concentrations, claimed
that VER might reduce dopaminergic tone at the anterior hypothalamic level, where
the main thermoregulatory centres are located [16]. This explanation is at variance
with the fact that castration has been shown to reduce rather than increase
hypothalamic dopaminergic activity in rats [46,47]. In addition, VER should exert a
central action at the brain level and it is known that benzamides easily cross the
blood-brain barrier [16]. Moreover, DOM is also able to exert therapeutic effects
similar to those obtained with VER even though its antidopaminergic activity is
only peripheral [19]. All these data suggest that the therapeutic effect of these drugs
is not mediated through their central antidopaminergic properties.
However, it cannot be completely excluded that antidopaminergic drugs might
paradoxically exert a dopaminergic action indirectly; hyperprolactinaemia induced
by peripherally-acting antidopaminergic drugs might increase TIDA neuron-activity
via a short-loop feedback mechanism [23,48]. Previous studies in ovariectomised
women have demonstrated that BCT, which exerts direct and potent dopaminergic
effects, is able to reduce pulsatile LH secretion-the main endocrine event corre-
lated with hot flushes [4-8,151. Since the major thermoregulatory nucleus and the
medial preoptic area involved in pulsatile LRF secretion are closely related anatomi-
cally within the hypothalamus and can be affected by the same neurotransmitter
alterations, it has been hypothesised that the reduction in hypothalamic dopaminergic
tone might also be involved in the pathogenesis of hot flushes [6,10]. The present
study shows that the administration of dopaminergic drugs such as BCT or Liposom
is able to reduce vasomotor symptoms.
These findings confirm previous results obtained in our laboratory with BCT
showing that this drug was more effective than placebo in improving vasomotor
symptoms in a group of post-menopausal women [22,23]. Moreover, in a previous
cross-over study in which we analyzed endocrine and clinical responsiveness to BCT
and VER administration in 10 post-menopausal women, we observed that the two
drugs have opposite endocrine effects [23]. BCT reduces prolactin plasma levels to
values lower than 5 ng/ml and decreases pulsatile LH secretion from about 1.8
pulses/h to about 1.1 pulses/h. In constrats, VER markedly increases prolactin
levels to values of about 120 ng/ml after 3 weeks of treatment, but has no effect on
LH secretion. Paradoxically, both drugs show similar therapeutic efficacy in the
treatment of hot flushes [23].
It is known that BCT has some alphalytic properties and it has been suggested
that it might influence LH secretion and hot flushes by directly decreasing the
activity of the noradrenergic system [49]. The present data indicate that this
hypothesis seems very unlikely. Indeed, the administration of Liposom, which
increases the activity of the endogenous dopaminergic system and has no alphalytic
7. 235
action, also alleviates vasomotor symptoms [17,18]. It is accordingly suggested that
the fall in steroid plasma levels in hypogonadal subjects induces a reduction in the
hypothalamic dopaminergic tone which is responsible for both increased pulsatile
LH secretion and hot flushes [10,14,15].
In conclusion, it is suggested that the fall in steroid plasma levels in post-
menopausal women may induce a reduction in both the hypothalamic dopaminergic
tone and the opioidergic tone. These neurotransmitter changes are probably in-
volved in the pathogenesis of hot flushes. We consider that any drug that is able to
substitute or restore dopamine and opioid activity is also capable of alleviating the
post-menopausal vasomotor syndrome.
Acknowledgements
This research was supported by the Cons&ho Nazionale delle Ricerche (CNR)
through the ‘ Endocrinology Group’ and the ‘Mechanisms of Ageing’ project.
We also wish to thank Emilio Madrigali, Gino Narducci and Silvano Orcesi for
their technical assistance.
References
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assessment of postmenopausal hot flushes, Obstet Gynecol 1981; 57: 340.
3 Meldrum DR, Tataryn IV, Frumar AM, Erlik YE, Lu JKH, Judd HL. Gonadotropins, estrogens and
adrenal steroids during the menopause hot flashes, J Clin Endocrinol Metab 1980; 50: 685.
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