DMARDs or disease-modifying antirheumatic drugs are a heterogeneous group of drugs used to treat rheumatoid arthritis. Methotrexate is a common first-choice DMARD with a more rapid onset than others. It works by inhibiting folic acid metabolism. Other DMARDs discussed include sulfasalazine, gold compounds, penicillamine, chloroquine, and leflunomide. While they have different mechanisms of action and chemical structures, DMARDs may halt or reverse the underlying disease process in rheumatoid arthritis.
Corticosteroids the often used but least understood drugAvijit Prusty
Corticosteroids are the most commonly used anti-inflammatory drugs. They are derived from hormones produced in the adrenal cortex and have both natural and synthetic forms. Corticosteroids work through multiple mechanisms to reduce inflammation by inhibiting immune cells and decreasing the production of inflammatory mediators. They are powerful immunosuppressants and have widespread effects throughout the body in maintaining homeostasis. Due to their potency and ability to treat inflammatory conditions, corticosteroids are invaluable drugs but also require an understanding of their mechanisms and appropriate clinical use.
The document discusses newer developments in treatments for diabetes. It describes several new classes of anti-diabetic drugs that target different pathways involved in blood glucose regulation, including DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, and amylin analogs. It also discusses newer insulin formulations like Glargine U-300 and technologies under development like oral insulin, smart insulin patches, and an artificial pancreas using a dual hormone approach.
Hydroxychloroquine (HCQ) is a derivative of chloroquine that is less toxic and more effective for malaria. HCQ is a weak base that is used to treat and prevent malaria as well as rheumatoid arthritis. Recent research has explored using HCQ as an experimental treatment for COVID-19. HCQ's mechanism involves increasing intracellular pH and interfering with lysosomal activity and autophagy. India is a major global producer and exporter of HCQ, manufacturing around 70% of the world's supply.
Methotrexate is an antifolate drug that inhibits dihydrofolate reductase (DHFR), blocking the production of nucleotides needed for DNA synthesis. It is used to treat cancers like acute lymphoblastic leukemia as well as autoimmune diseases like rheumatoid arthritis. Methotrexate is transported into cells and polyglutamated, increasing its intracellular activity and half-life. It causes cell death by inhibiting DNA synthesis and inducing strand breaks. Resistance can develop through reduced polyglutamation, increased DHFR levels, or drug efflux pumps. The cytotoxic effects of methotrexate are S-phase specific and depend on drug concentration and duration of exposure.
Highly Active Antiretroviral Therapy (HAART) involves using a combination of at least three antiretroviral drugs to suppress the HIV virus and stop the progression of HIV disease. HAART decreases the viral load, improves immune function, and prevents opportunistic infections. The goals of HAART are to prolong life, improve quality of life, achieve maximal viral suppression, restore immune function, reduce HIV transmission, and rationally sequence drugs to limit toxicity while maintaining treatment options. Current guidelines recommend starting ART for all individuals regardless of CD4 count. Second line regimens are recommended when clinical or immunological failure occurs on first line therapy. Managing adverse events and comorbidities like hepatitis co-infection is also
This document provides information on rheumatoid arthritis (RA) including its symptoms, causes, pathophysiology, diagnosis, and treatment. It discusses how RA is a chronic autoimmune disease that causes inflammation of the joints and can affect internal organs. Treatment involves NSAIDs, corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) like methotrexate, sulfasalazine, hydroxychloroquine, and biologic drugs that target cytokines like TNF-alpha. The goals of treatment are to reduce joint damage, pain, disability and maintain quality of life while minimizing adverse effects.
DMARDs or disease-modifying antirheumatic drugs are a heterogeneous group of drugs used to treat rheumatoid arthritis. Methotrexate is a common first-choice DMARD with a more rapid onset than others. It works by inhibiting folic acid metabolism. Other DMARDs discussed include sulfasalazine, gold compounds, penicillamine, chloroquine, and leflunomide. While they have different mechanisms of action and chemical structures, DMARDs may halt or reverse the underlying disease process in rheumatoid arthritis.
Corticosteroids the often used but least understood drugAvijit Prusty
Corticosteroids are the most commonly used anti-inflammatory drugs. They are derived from hormones produced in the adrenal cortex and have both natural and synthetic forms. Corticosteroids work through multiple mechanisms to reduce inflammation by inhibiting immune cells and decreasing the production of inflammatory mediators. They are powerful immunosuppressants and have widespread effects throughout the body in maintaining homeostasis. Due to their potency and ability to treat inflammatory conditions, corticosteroids are invaluable drugs but also require an understanding of their mechanisms and appropriate clinical use.
The document discusses newer developments in treatments for diabetes. It describes several new classes of anti-diabetic drugs that target different pathways involved in blood glucose regulation, including DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, and amylin analogs. It also discusses newer insulin formulations like Glargine U-300 and technologies under development like oral insulin, smart insulin patches, and an artificial pancreas using a dual hormone approach.
Hydroxychloroquine (HCQ) is a derivative of chloroquine that is less toxic and more effective for malaria. HCQ is a weak base that is used to treat and prevent malaria as well as rheumatoid arthritis. Recent research has explored using HCQ as an experimental treatment for COVID-19. HCQ's mechanism involves increasing intracellular pH and interfering with lysosomal activity and autophagy. India is a major global producer and exporter of HCQ, manufacturing around 70% of the world's supply.
Methotrexate is an antifolate drug that inhibits dihydrofolate reductase (DHFR), blocking the production of nucleotides needed for DNA synthesis. It is used to treat cancers like acute lymphoblastic leukemia as well as autoimmune diseases like rheumatoid arthritis. Methotrexate is transported into cells and polyglutamated, increasing its intracellular activity and half-life. It causes cell death by inhibiting DNA synthesis and inducing strand breaks. Resistance can develop through reduced polyglutamation, increased DHFR levels, or drug efflux pumps. The cytotoxic effects of methotrexate are S-phase specific and depend on drug concentration and duration of exposure.
Highly Active Antiretroviral Therapy (HAART) involves using a combination of at least three antiretroviral drugs to suppress the HIV virus and stop the progression of HIV disease. HAART decreases the viral load, improves immune function, and prevents opportunistic infections. The goals of HAART are to prolong life, improve quality of life, achieve maximal viral suppression, restore immune function, reduce HIV transmission, and rationally sequence drugs to limit toxicity while maintaining treatment options. Current guidelines recommend starting ART for all individuals regardless of CD4 count. Second line regimens are recommended when clinical or immunological failure occurs on first line therapy. Managing adverse events and comorbidities like hepatitis co-infection is also
This document provides information on rheumatoid arthritis (RA) including its symptoms, causes, pathophysiology, diagnosis, and treatment. It discusses how RA is a chronic autoimmune disease that causes inflammation of the joints and can affect internal organs. Treatment involves NSAIDs, corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) like methotrexate, sulfasalazine, hydroxychloroquine, and biologic drugs that target cytokines like TNF-alpha. The goals of treatment are to reduce joint damage, pain, disability and maintain quality of life while minimizing adverse effects.
Sulfonylureas are oral hypoglycemic drugs that enhance insulin secretion from the pancreas. They work by blocking ATP-sensitive potassium channels in pancreatic beta cells, which leads to insulin release. Common side effects include hypoglycemia and weight gain. Examples include glibenclamide, glipizide, and glimepiride. Choice of sulfonylurea depends on factors like duration of action, renal function, and patient age. They are generally effective treatments for type 2 diabetes but require caution in elderly patients or those with kidney/liver problems.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of drugs for treating diabetes that work by blocking the DPP-4 enzyme, allowing glucagon-like peptide-1 (GLP-1) to remain active. GLP-1 stimulates the pancreas to release more insulin and less glucagon in response to food intake, lowering blood sugar levels. There are currently three DPP-4 inhibitors approved for use: sitagliptin, saxagliptin, and vildagliptin. DPP-4 inhibitors are effective at lowering blood sugar while having a low risk of hypoglycemia and not causing weight gain.
This document discusses oral hypoglycemic agents (OHAs) used to treat type 2 diabetes. It covers:
1) The classification and mechanisms of common OHAs including sulfonylureas, biguanides, thiazolidinediones, and meglitinides. Sulfonylureas work by stimulating insulin secretion while biguanides increase insulin sensitivity.
2) The structure, properties, uses and mechanisms of action of sulfonylureas, the largest class of OHAs. They lower blood glucose by blocking potassium channels in beta cells.
3) Other classes of OHAs like repaglinide, a meglitinide that stimulates insulin secretion, and acar
DPP-4 inhibitors work by inhibiting the breakdown of the incretin hormones GLP-1 and GIP, prolonging their effects and enhancing insulin secretion. They reduce blood glucose levels with a low risk of hypoglycemia and are weight neutral. Several DPP-4 inhibitors are available or in development for treating type 2 diabetes, including sitagliptin, saxagliptin, and linagliptin. DPP-4 inhibitors offer an effective treatment either alone or in combination with other drugs, with advantages like fewer side effects, safety in hepatic or renal impairment, and possible cardiovascular benefits. More research is still needed to fully evaluate their long-term safety profile.
Clinical, pharmacokinetic and technological aspects of the hydroxychloroquine...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
This document discusses various dissociative anesthetics including prescription drugs like ketamine, tiletamine, and amantadine as well as street drugs and over-the-counter drugs that can be abused for their dissociative effects. It provides information on drug names, forms, effects, uses, and risks. The document focuses on dissociative anesthetics that distort perceptions, produce feelings of detachment from self and environment, and alter glutamate distribution in the brain to impact pain, environmental responses, and memory.
This document discusses the treatment of diabetes with a focus on the drug Sitagliptin. It provides details on Sitagliptin's mechanism of action as an inhibitor of DPP-4, pharmacokinetics, clinical efficacy in reducing HbA1c and glucose levels, safety profile, recommended dosage, drug interactions, and regulatory approval history. Sitagliptin represents an effective newer treatment option for type 2 diabetes with a good tolerability profile.
Statins are a class of drugs that lower cholesterol by inhibiting its production in the liver. They have been shown to significantly reduce risks of cardiovascular events. While generally safe and effective for primary prevention when LDL is over 190 mg/dL, statins can cause side effects like muscle pain and cognitive issues. They work best when started before or after CABG to improve graft patency. Rosuvastatin and atorvastatin may provide the greatest benefits for postoperative CABG patients by allowing LDL to be lowered below 100 mg/dL. Maintaining LDL at this level can nearly double venous graft patency rates.
Drugs for treatment of Diabetes MellitusNaser Tadvi
These slides contain the brief description of Insulin and the other oral drugs indicated in the treatment of Diabetes Mellitus. Their mechanism of action, effects, uses, Adverse effects etc.
Vildagliptin is a DPP-4 inhibitor used to treat type 2 diabetes. It works by inhibiting the DPP-4 enzyme, increasing levels of GLP-1 and GIP to boost insulin secretion, decrease glucagon levels, and regulate blood sugar levels. Studies show vildagliptin is effective in reducing HbA1c and fasting plasma glucose when used alone or in combination with other oral hypoglycemic agents. While all DPP-4 inhibitors have similar glycemic effects, vildagliptin distinguishes itself by forming a reversible complex with the DPP-4 enzyme, leading to persistent inhibition even after drug clearance from circulation. Compared to other classes of oral agents
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.
This document provides an overview of antidiabetic drugs, classifying them based on their mechanisms of action and summarizing their uses, side effects, and contraindications. The main classes described include biguanides (e.g. metformin), sulfonylureas, meglitinides, incretin mimetics, DPP-4 inhibitors, SGLT-2 inhibitors, alpha-glucosidase inhibitors, and thiazolidinediones. Metformin is noted as the first-line oral medication for type 2 diabetes due to its efficacy, safety profile, and cost-effectiveness. All antidiabetic drugs require careful consideration of risks like hypoglycemia and drug interactions when prescribing based on a
The document discusses hyperlipidemia, which refers to high levels of lipids in the blood. Elevated LDL and low HDL are linked to increased risk of heart disease and stroke. Treatment involves lifestyle changes like a heart-healthy diet and exercise to lower lipids. If lipids remain high, medications like statins may be used. The goal of treatment is to lower total cholesterol, LDL, and triglycerides and raise HDL to reduce cardiovascular risks.
Insulin is a hormone produced in the pancreas that regulates blood sugar levels. It was discovered in 1921 and is used to treat diabetes by facilitating glucose entry into cells and inhibiting glucose production in the liver. There are various types of insulin preparations including regular, long-acting, and analogues produced through recombinant DNA technology to provide different durations of action.
This document discusses SGLT2 inhibitors and DPP-4 inhibitors for the treatment of type 2 diabetes. SGLT2 inhibitors work by increasing glucose excretion in the urine, independently of insulin. They modestly lower blood pressure and weight. DPP-4 inhibitors work by inhibiting the DPP-4 enzyme and increasing GLP-1 and GIP levels. Both classes have few hypoglycemia risks but SGLT2 inhibitors should be used with caution in those with kidney impairment. Empagliflozin and canagliflozin are recommended for patients with cardiovascular disease.
Clindamycin is an antibiotic of the lincosamide class used to treat infections caused by certain bacteria. It works by inhibiting bacterial protein synthesis. It is absorbed well orally or parenterally and distributes widely throughout the body. Common uses include treating respiratory, skin, bone, and intra-abdominal infections caused by anaerobic bacteria and some protozoa. Adverse effects include diarrhea and pseudomembranous colitis. It is commonly prescribed for dental infections when penicillin cannot be used due to allergy.
This document provides information on antirheumatic drugs used to treat rheumatoid arthritis (RA). It describes the pathophysiology of RA involving inflammatory cytokines like TNF, IL-6, IL-1. NSAIDs provide initial symptomatic relief but DMARDs like methotrexate, hydroxychloroquine, leflunomide, and sulfasalazine suppress disease progression. Biological DMARDs targeting TNF or non-TNF pathways like abatacept are used when traditional DMARDs are ineffective. The goals of treatment are to reduce symptoms, prevent joint damage, and maintain function. Adverse effects of various drugs are also outlined.
This document summarizes different drugs used for treating diabetes. It discusses the types of diabetes, mechanisms and types of insulin preparations including rapid-acting, intermediate-acting, and long-acting insulins. It also covers oral antidiabetic drugs like sulfonylureas, meglitinides, DPP-4 inhibitors, metformin, thiazolidinediones, alpha-glucosidase inhibitors, and SGLT-2 inhibitors; describing their mechanisms of action, pharmacokinetics and adverse effects. It concludes by listing common oral hypoglycemic agents and their usual daily doses and frequencies.
Anti Tubercular Drugs - Mechanism of Action and Adverse effects Thomas Kurian
A brief outline of the mechanism of action and adverse effects of anti tubercular drugs
Only First line and second line drugs are dealt with.First line drugs may be useful for MBBS students and the rest is directed for postgraduate students.
Hope you find it useful.
This study examined the effects of hydroxychloroquine treatment on outcomes in 1376 patients hospitalized with COVID-19 at Columbia University Irving Medical Center in New York City. The primary outcome was a composite of intubation or death. 811 patients (58.9%) received hydroxychloroquine treatment. There was no significant association between hydroxychloroquine use and the primary outcome after adjusting for baseline differences, with a hazard ratio of 1.04 (95% CI, 0.82 to 1.32). Randomized controlled trials are still needed to determine if hydroxychloroquine provides any benefit for COVID-19.
Vai trò của thuốc kháng virus trong đại dịch Covid 19EfenPhamNgoc
Tocilizumab provided benefit in reducing mortality and improving other outcomes in hospitalized COVID-19 patients in early studies. However, subsequent larger studies found no clear benefit, especially when given later in disease course. The drug may be most effective very early in severe cases, when hyperinflammation is predominant over viral replication. Overall, the efficacy of tocilizumab in COVID-19 remains unclear based on current evidence.
Sulfonylureas are oral hypoglycemic drugs that enhance insulin secretion from the pancreas. They work by blocking ATP-sensitive potassium channels in pancreatic beta cells, which leads to insulin release. Common side effects include hypoglycemia and weight gain. Examples include glibenclamide, glipizide, and glimepiride. Choice of sulfonylurea depends on factors like duration of action, renal function, and patient age. They are generally effective treatments for type 2 diabetes but require caution in elderly patients or those with kidney/liver problems.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of drugs for treating diabetes that work by blocking the DPP-4 enzyme, allowing glucagon-like peptide-1 (GLP-1) to remain active. GLP-1 stimulates the pancreas to release more insulin and less glucagon in response to food intake, lowering blood sugar levels. There are currently three DPP-4 inhibitors approved for use: sitagliptin, saxagliptin, and vildagliptin. DPP-4 inhibitors are effective at lowering blood sugar while having a low risk of hypoglycemia and not causing weight gain.
This document discusses oral hypoglycemic agents (OHAs) used to treat type 2 diabetes. It covers:
1) The classification and mechanisms of common OHAs including sulfonylureas, biguanides, thiazolidinediones, and meglitinides. Sulfonylureas work by stimulating insulin secretion while biguanides increase insulin sensitivity.
2) The structure, properties, uses and mechanisms of action of sulfonylureas, the largest class of OHAs. They lower blood glucose by blocking potassium channels in beta cells.
3) Other classes of OHAs like repaglinide, a meglitinide that stimulates insulin secretion, and acar
DPP-4 inhibitors work by inhibiting the breakdown of the incretin hormones GLP-1 and GIP, prolonging their effects and enhancing insulin secretion. They reduce blood glucose levels with a low risk of hypoglycemia and are weight neutral. Several DPP-4 inhibitors are available or in development for treating type 2 diabetes, including sitagliptin, saxagliptin, and linagliptin. DPP-4 inhibitors offer an effective treatment either alone or in combination with other drugs, with advantages like fewer side effects, safety in hepatic or renal impairment, and possible cardiovascular benefits. More research is still needed to fully evaluate their long-term safety profile.
Clinical, pharmacokinetic and technological aspects of the hydroxychloroquine...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
This document discusses various dissociative anesthetics including prescription drugs like ketamine, tiletamine, and amantadine as well as street drugs and over-the-counter drugs that can be abused for their dissociative effects. It provides information on drug names, forms, effects, uses, and risks. The document focuses on dissociative anesthetics that distort perceptions, produce feelings of detachment from self and environment, and alter glutamate distribution in the brain to impact pain, environmental responses, and memory.
This document discusses the treatment of diabetes with a focus on the drug Sitagliptin. It provides details on Sitagliptin's mechanism of action as an inhibitor of DPP-4, pharmacokinetics, clinical efficacy in reducing HbA1c and glucose levels, safety profile, recommended dosage, drug interactions, and regulatory approval history. Sitagliptin represents an effective newer treatment option for type 2 diabetes with a good tolerability profile.
Statins are a class of drugs that lower cholesterol by inhibiting its production in the liver. They have been shown to significantly reduce risks of cardiovascular events. While generally safe and effective for primary prevention when LDL is over 190 mg/dL, statins can cause side effects like muscle pain and cognitive issues. They work best when started before or after CABG to improve graft patency. Rosuvastatin and atorvastatin may provide the greatest benefits for postoperative CABG patients by allowing LDL to be lowered below 100 mg/dL. Maintaining LDL at this level can nearly double venous graft patency rates.
Drugs for treatment of Diabetes MellitusNaser Tadvi
These slides contain the brief description of Insulin and the other oral drugs indicated in the treatment of Diabetes Mellitus. Their mechanism of action, effects, uses, Adverse effects etc.
Vildagliptin is a DPP-4 inhibitor used to treat type 2 diabetes. It works by inhibiting the DPP-4 enzyme, increasing levels of GLP-1 and GIP to boost insulin secretion, decrease glucagon levels, and regulate blood sugar levels. Studies show vildagliptin is effective in reducing HbA1c and fasting plasma glucose when used alone or in combination with other oral hypoglycemic agents. While all DPP-4 inhibitors have similar glycemic effects, vildagliptin distinguishes itself by forming a reversible complex with the DPP-4 enzyme, leading to persistent inhibition even after drug clearance from circulation. Compared to other classes of oral agents
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.
This document provides an overview of antidiabetic drugs, classifying them based on their mechanisms of action and summarizing their uses, side effects, and contraindications. The main classes described include biguanides (e.g. metformin), sulfonylureas, meglitinides, incretin mimetics, DPP-4 inhibitors, SGLT-2 inhibitors, alpha-glucosidase inhibitors, and thiazolidinediones. Metformin is noted as the first-line oral medication for type 2 diabetes due to its efficacy, safety profile, and cost-effectiveness. All antidiabetic drugs require careful consideration of risks like hypoglycemia and drug interactions when prescribing based on a
The document discusses hyperlipidemia, which refers to high levels of lipids in the blood. Elevated LDL and low HDL are linked to increased risk of heart disease and stroke. Treatment involves lifestyle changes like a heart-healthy diet and exercise to lower lipids. If lipids remain high, medications like statins may be used. The goal of treatment is to lower total cholesterol, LDL, and triglycerides and raise HDL to reduce cardiovascular risks.
Insulin is a hormone produced in the pancreas that regulates blood sugar levels. It was discovered in 1921 and is used to treat diabetes by facilitating glucose entry into cells and inhibiting glucose production in the liver. There are various types of insulin preparations including regular, long-acting, and analogues produced through recombinant DNA technology to provide different durations of action.
This document discusses SGLT2 inhibitors and DPP-4 inhibitors for the treatment of type 2 diabetes. SGLT2 inhibitors work by increasing glucose excretion in the urine, independently of insulin. They modestly lower blood pressure and weight. DPP-4 inhibitors work by inhibiting the DPP-4 enzyme and increasing GLP-1 and GIP levels. Both classes have few hypoglycemia risks but SGLT2 inhibitors should be used with caution in those with kidney impairment. Empagliflozin and canagliflozin are recommended for patients with cardiovascular disease.
Clindamycin is an antibiotic of the lincosamide class used to treat infections caused by certain bacteria. It works by inhibiting bacterial protein synthesis. It is absorbed well orally or parenterally and distributes widely throughout the body. Common uses include treating respiratory, skin, bone, and intra-abdominal infections caused by anaerobic bacteria and some protozoa. Adverse effects include diarrhea and pseudomembranous colitis. It is commonly prescribed for dental infections when penicillin cannot be used due to allergy.
This document provides information on antirheumatic drugs used to treat rheumatoid arthritis (RA). It describes the pathophysiology of RA involving inflammatory cytokines like TNF, IL-6, IL-1. NSAIDs provide initial symptomatic relief but DMARDs like methotrexate, hydroxychloroquine, leflunomide, and sulfasalazine suppress disease progression. Biological DMARDs targeting TNF or non-TNF pathways like abatacept are used when traditional DMARDs are ineffective. The goals of treatment are to reduce symptoms, prevent joint damage, and maintain function. Adverse effects of various drugs are also outlined.
This document summarizes different drugs used for treating diabetes. It discusses the types of diabetes, mechanisms and types of insulin preparations including rapid-acting, intermediate-acting, and long-acting insulins. It also covers oral antidiabetic drugs like sulfonylureas, meglitinides, DPP-4 inhibitors, metformin, thiazolidinediones, alpha-glucosidase inhibitors, and SGLT-2 inhibitors; describing their mechanisms of action, pharmacokinetics and adverse effects. It concludes by listing common oral hypoglycemic agents and their usual daily doses and frequencies.
Anti Tubercular Drugs - Mechanism of Action and Adverse effects Thomas Kurian
A brief outline of the mechanism of action and adverse effects of anti tubercular drugs
Only First line and second line drugs are dealt with.First line drugs may be useful for MBBS students and the rest is directed for postgraduate students.
Hope you find it useful.
This study examined the effects of hydroxychloroquine treatment on outcomes in 1376 patients hospitalized with COVID-19 at Columbia University Irving Medical Center in New York City. The primary outcome was a composite of intubation or death. 811 patients (58.9%) received hydroxychloroquine treatment. There was no significant association between hydroxychloroquine use and the primary outcome after adjusting for baseline differences, with a hazard ratio of 1.04 (95% CI, 0.82 to 1.32). Randomized controlled trials are still needed to determine if hydroxychloroquine provides any benefit for COVID-19.
Vai trò của thuốc kháng virus trong đại dịch Covid 19EfenPhamNgoc
Tocilizumab provided benefit in reducing mortality and improving other outcomes in hospitalized COVID-19 patients in early studies. However, subsequent larger studies found no clear benefit, especially when given later in disease course. The drug may be most effective very early in severe cases, when hyperinflammation is predominant over viral replication. Overall, the efficacy of tocilizumab in COVID-19 remains unclear based on current evidence.
This study examined the association between hydroxychloroquine use and intubation or death in 1376 patients hospitalized with COVID-19 at Columbia University Irving Medical Center in New York City. The primary outcome was a composite of intubation or death. 811 patients (58.9%) received hydroxychloroquine. There was no significant association between hydroxychloroquine use and intubation or death in the primary analysis or sensitivity analyses. Randomized controlled trials are still needed to determine if hydroxychloroquine is effective for treating COVID-19.
Nejm clinical outcomes of hydroxychlorquine in patients with covid19.pdf.pdfgisa_legal
This study evaluated the effects of hydroxychloroquine treatment in 63 hospitalized patients with COVID-19. Patients were divided into a hydroxychloroquine treatment group (32 patients) and a supportive care only group (31 patients). The primary outcomes measured were need for escalation of respiratory support, change in lymphocyte count, and change in neutrophil-to-lymphocyte ratio. The results showed that hydroxychloroquine treatment was associated with a higher need for escalation of respiratory support compared to the supportive care only group. There were no significant benefits of hydroxychloroquine treatment on lymphocyte counts or neutrophil-to-lymphocyte ratios. The study concludes that hydroxychloroquine did not provide benefits and
This patient is a 77-year-old woman admitted to the ICU with a stroke who has now developed hospital-acquired pneumonia. She has risk factors including COPD, recent intubation, and NG tube feeding. Laboratory results show increased white blood cell count and creatinine. Initial empiric antimicrobial therapy should cover typical and atypical pathogens, including Pseudomonas if risk factors are present. Therapy should be de-escalated once culture results are available. Generally, 7-8 days of antimicrobial therapy is sufficient for hospital-acquired pneumonia.
1) A randomized controlled trial of 72 COVID-19 patients in Bangladesh investigated the effects of a 5-day course of ivermectin alone or ivermectin combined with doxycycline on viral clearance time and safety.
2) The study found that viral clearance time was significantly reduced in the ivermectin-only group compared to the placebo group, taking 9.7 days versus 12.7 days on average.
3) No severe adverse drug events occurred, and a 5-day course of ivermectin appeared to be safe and effective for treating mild COVID-19 based on this preliminary study. However, larger trials are still needed to confirm these results.
PCR Assay Turned Positive in 25 Discharged COVID-19 PatientsValentina Corona
1) The study found that 14.5% (25/172) of discharged COVID-19 patients in China later tested positive again for the virus based on RT-PCR testing after being discharged from the hospital.
2) These patients met criteria for discharge but tested positive again within 2-13 days without worsening symptoms.
3) The study suggests that more than two negative RT-PCR tests separated by 48 hours or combining RT-PCR tests with antibody and other immunological markers may be needed to confirm viral clearance before discharge.
Effect of a single high dose of vitamin d3 on hospital lengthmodi11
This randomized clinical trial involved 240 hospitalized patients with moderate to severe COVID-19 in Brazil. Patients were assigned to receive either a single oral dose of 200,000 IU of vitamin D3 or a placebo. The primary outcome was length of hospital stay. The study found that a single high dose of vitamin D3, compared to placebo, did not significantly reduce length of hospital stay, which was a median of 7 days in both groups. No significant differences were found between the groups for other secondary outcomes like mortality, intensive care unit admission, or need for mechanical ventilation. The findings do not support using a high dose of vitamin D3 to treat moderate to severe COVID-19 in hospitalized patients.
Effect of a Single High Dose ofVitamin D3 on Hospital LengthEvonCanales257
This randomized clinical trial studied the effects of a single high dose of vitamin D3 (200,000 IU) vs placebo on hospital length of stay in 240 patients with moderate to severe COVID-19 in Brazil. The median length of stay was not significantly different between groups (7.0 days for both). Secondary outcomes including mortality, ICU admission, and need for mechanical ventilation also did not significantly differ. A single high dose of vitamin D3 did not demonstrate benefits for treatment of moderate to severe COVID-19 in hospitalized patients.
The document discusses repurposed drugs and safety monitoring during the COVID-19 pandemic. It describes how known drugs are being used in a different context than originally approved to treat COVID-19. Two such drugs are chloroquine/hydroxychloroquine and remdesivir. While initial studies of hydroxychloroquine showed promise in vitro, subsequent large trials found no significant benefits. Remdesivir was found to decrease recovery time based on NIH trials but the WHO recommends against its use due to low certainty of benefit. Both drugs present drug interaction risks that require careful safety monitoring.
This document summarizes clinical data from 53 patients with severe Covid-19 who were treated with the investigational antiviral remdesivir through a compassionate use program. Key findings include:
- 68% (36 patients) showed improvement in oxygen support needs, including 57% of those on mechanical ventilation being extubated.
- 47% (25 patients) were discharged from the hospital, and 13% (7 patients) died, with a higher mortality among those receiving invasive ventilation.
- Remdesivir appeared to have a favorable safety profile based on previous experience in Ebola patients, though efficacy will need to be determined through ongoing randomized controlled trials.
Journal Club
Adaptive Covid-19 Treatment Trial 1 - A critical appraisal
Review of the ACTT - 1 trial from a critical and statistical analysis perspective
Delamanid for multidrug resistant pulmonary tuberculosisHaroon Rashid
Delamanid is a new drug that inhibits mycolic acid synthesis in Mycobacterium tuberculosis. This randomized controlled trial evaluated the safety and efficacy of Delamanid (100 mg or 200 mg twice daily) plus background regimen compared to placebo plus background regimen in 481 patients with multidrug-resistant pulmonary tuberculosis over 2 months. Patients receiving Delamanid had higher rates of sputum culture conversion at 2 months compared to placebo, indicating Delamanid enhances treatment options for multidrug-resistant tuberculosis. However, the short 2-month treatment period was a limitation.
Journal club on Hydrcortisone for Severe Community acquired pneumoniaWondwosenMulatu
This study aimed to evaluate whether early treatment with hydrocortisone reduces mortality among patients admitted to the ICU for severe community-acquired pneumonia. The randomized controlled trial assigned 800 patients to receive either hydrocortisone or placebo within 24 hours of meeting severity criteria. The primary outcome was death from any cause by day 28. Treatment with hydrocortisone resulted in lower 28-day mortality compared to placebo (11.9% vs 18.0%), fewer patients requiring invasive mechanical ventilation or vasopressors, and no increase in safety outcomes. The results provide evidence that early hydrocortisone treatment reduces mortality for patients with severe community-acquired pneumonia admitted to the ICU.
Integration of pharmacokinetics (PK)-pharmacodynamics (PD) data to predict th...Ahmed Ali
1. The document discusses using a PK/PD approach to predict the efficacy of repurposed antiviral drugs for COVID-19. It analyzes drugs like lopinavir/ritonavir, remdesivir, favipiravir, and hydroxychloroquine.
2. For lopinavir/ritonavir, the high protein binding restricts achievement of therapeutic drug levels in the lungs. Clinical trials showed a lack of efficacy.
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1. H Y D R O X Y C H L O R O Q U I N E
Rami Bechara, PhD
1
Potential Drugs for Covid-19
treatment
2. Hydroxychloroquine
Rami Bechara, PhD
2
Prescription medicine
Variant of chloroquine with proven greater worth
Approved decades ago to treat malaria.
Also used to treat autoimmune diseases like
rheumatoid arthritis and lupus.
It is sometimes referred to by its brand name,
Plaquenil, and is closely related to chloroquine,
which is also used to treat malaria.
It is seen as one of the main hopes in fighting
CoronaVirus
3. Advantage of Chloroquine
Rami Bechara, PhD
3
Most important, the maximum tolerable dose for
HCQ is 1200 mg, which has an antiviral effect
equivalent to 750 mg CQ (for which the maximum
tolerable dose is 500 mg).
Thus HCQ can be administered at a higher dosage
and may therefore achieve a more powerful antiviral
effect.
4. Mechanism
Rami Bechara, PhD
4
Weak base with characteristic ‘deep’ volume of
distribution and a half-life of around 50 days.
Increases the intracellular pH
Interferes with lysosomal activity and autophagy,
Interacts with membrane stability
Alters signaling pathways and transcriptional activity
Results in inhibition of cytokine production and
modulation of certain co-stimulatory molecules.
6. Reasons for hope
Rami Bechara, PhD
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Drug can rein in an overactive immune system
Reason it is used to treat lupus and rheumatoid
arthritis.
In some severe cases of Covid-19, the immune
system becomes overactive and causes inflammation
that can damage the lungs and other organs.
Doctors hope hydroxychloroquine might calm the
condition, sometimes called a cytokine storm
7. Motivation for clinical trial
Rami Bechara, PhD
7
Early demonstration of anti-SARS-CoV activity in
vitro
Hydroxychloroquine clinical safety profile
Better than that of chloroquine (during long-term use)
Allows higher daily dose
Has fewer concerns about drug-drug interactions
Clinical Trial undertaken by D. Raoult
8. Inclusion / Exclusion criteria
Rami Bechara, PhD
8
2 primary criteria for patient inclusion
: i) age >12 years;
ii) PCR documented SARS-CoV-2 carriage in nasopharyngeal
sample at admission
Excluded patients
Allergy to hydroxychloroquine or chloroquine
A known contraindication to treatment with the study drug,
including retinopathy, G6PD deficiency and QT prolongation.
Breastfeeding and pregnant patients were excluded based on
their declaration and pregnancy test results when required
9. Procedure
Rami Bechara, PhD
9
Day 0: Patients seen for enrolment, initial data collection and
treatment
Each day for 14 days: patients received a standardized clinical
examination and when possible, a nasopharyngeal sample was
collected. Data collection done using standardized questionnaires.
Patients proposed oral hydroxychloroquine sulfate 200 mg, three
times per day during ten days
Patients who refused the treatment or had an exclusion criteria,
served as controls
Patients who did not receive hydroxychloroquine served as controls.
Symptomatic treatment and antibiotics as a measure to prevent
bacterial super-infection was provided by investigators based on
clinical judgment.
Hydroxychloroquine was provided by the National Pharmacy of
France on nominative demand.
10. Patient Categories
Rami Bechara, PhD
10
Asymptomatic
With upper respiratory tract infection (URTI) when
presenting with rhinitis, pharyngitis, or isolated low-
grade fever and myalgia
With lower respiratory tract infections (LRTI) when
presenting with symptoms of pneumonia or
bronchitis.
11. Outcomes
Rami Bechara, PhD
11
The primary endpoint was virological clearance at
day-6 post-inclusion.
Secondary outcomes were
virological clearance overtime during the study period,
clinical follow-up (body temperature, respiratory rate, long of
stay at hospital and mortality)
occurrence of side-effects.
12. Patient treatment
Rami Bechara, PhD
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36 out of 42 patients met inclusion criteria
26 patients received hydroxychloroquine and 16 were control patients.
Six hydroxychloroquine-treated patients were lost in follow-up during
the survey because of early cessation of treatment.
Reasons are as follows:
three patients were transferred to intensive care units
one transferred on day2 post-inclusion who was PCR-positive on day1,
one transferred on day3 post-inclusion who was PCR-positive on days1-2
one transferred on day4 post-inclusion who was PCR-positive on day1 and day3
one patient died on day3 post inclusion and was PCR-negative on day2;
one patient decided to leave the hospital on day3 post-inclusion and was
PCR-negative on days1-2.
finally, one patient stopped the treatment on day3 post-inclusion because of
nausea and was PCR-positive on days1-2-3.
Results are for 36: 20 treated 16 control
13. Effect of hydroxychloroquine
Rami Bechara, PhD
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Proportion of patients with negative PCR at day6
post-inclusion,
70% of hydroxychloroquine-treated patients were virologicaly
cured
Vs. 12.5% in the control group (p= 0.001).
14. Addition of azithromyc
Rami Bechara, PhD
14
Patients with negative PCR results at day6 post-
inclusion
100% of patients treated with hydroxychloroquine and
azithromycin combination were virologicaly cured
Vs. 57.1% in patients treated with hydroxychloroquine only
and 12.5% in the control group (p<0.001).
Drug effect was significantly higher in patients with
symptoms of URTI and LRTI, as compared to
asymptomatic patients with p<0.05 (data not show).
16. Chinese Clinical Trial
Rami Bechara, PhD
16
February 4 28, 2020, 142 patients with confirmed COVID-19
admitted.
Selection criteria:
1. Age ≥ 18 years;
2. Laboratory (RT-PCR) positive of SARS-CoV-2;
3. Chest CT with pneumonia;
4. SaO2/SPO2 ratio > 93% or PaO2/FIO2 ratio > 300 mmHg under the condition
in the hospital room (mild illness);
5. Willing to receive a random assignment to any designated treatment group and
not participating in another study at the same time.
Exclusion criteria among others:
1. Severe and critical illness patients 2. Retinopathy and other retinal diseases;
3. Conduction block and other arrhythmias;
4. Severe liver disease (e.g., Child-Pugh score ≥ C or AST> twice the upper limit);
5. Pregnant or breastfeeding;
17. Patient selection
Rami Bechara, PhD
17
62 admitted patients randomly assigned in two groups
All received the standard treatment (oxygen therapy, antiviral
agents, antibacterial agents, and immunoglobulin, with or without
corticosteroids)
Patients in the HCQ treatment group received additional oral HCQ
(hydroxychloroquine sulfate tablets, Shanghai Pharma) 400 mg/d
(200 mg/bid) between days 1 and 5 (Figure 1),
Patients in the control group with the standard treatment only.
Randomization was performed through a computer-generated list
stratified by site.
Treatments were assigned after confirming the correctness of the
admission criteria.
Neither the research performers nor the patients were aware of the
treatment assignments.
18. EndPoint
Rami Bechara, PhD
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Observation Endpoint : 5 days after enrollment or severe adverse
reactions appeared
Changes in time to clinical recovery (TTCR) and clinical
characteristics of patients were evaluated after administration.
TTCR is defined as the return of body temperature and cough relief,
maintained for more than 72 h.
Normalization and mitigation criteria included the following:
a. Body temperature ≤ 36.6 °C on the surface, ≤ 37.2 °C under the armpit and
mouth or ≤ 37.8 °C in the rectum and tympanic membrane. Body temperature,
cough check three times daily to calculate the average level.
b. Cough from patients’ reports, slight or no cough was in the asymptomatic
range. B For radiological changes, the chest CT results in one day before (Day 0)
and one day after (Day 6) the study for evaluation. Pulmonary recovery is defined
as three levels: exacerbated, unchanged, and improved, moderately improved
when less than 50 % of pneumonia were absorbed, and more than 50 % means
significantly improved
19. Results
Rami Bechara, PhD
19
Body temperature recovery time significantly shortened
in the HCQ treatment group [2.2 (0.4) days] vs. control
group [3.2 (1.3) days].
The cough remission time was significantly reduced in
the HCQ treatment group. Notably, a total of 4 of the 62
patients progressed to severe illness, all of which
occurred in the control group not receiving HCQ
treatment.
For adverse effects, 2 patients with mild adverse
reactions in the HCQ treatment group, one patient
developed a rash, and one patient experienced a
headache, none severe side effects appeared among
them.
20. Effect on Pneumonia
Rami Bechara, PhD
20
Compared and analyzed the chest CT of patients on
day 0 and day 6.
Pneumonia was improved in 67.7% (42/62) of
patients, with 29.0% moderately absorbed and
38.7% significantly improved.
A larger proportion of patients with improved
pneumonia in the HCQ treatment group (80.6%, 25
of 31) compared with the control group (54.8%, 17 of
31).
Besides, 61.3% of patients in the HCQ treatment
group had a significant pneumonia absorption.
21. Model based results
Rami Bechara, PhD
21
Pharmacological activity tested using SARS-CoV-2
infected Vero cells.
Physiologically-based pharmacokinetic models
implemented for both drugs separately by
integrating their in vitro data.
Using the PBPK models, hydroxychloroquine
concentrations in lung fluid were simulated under 5
different dosing regimens to explore the most
effective regimen whilst considering the drug’s safety
profile.
22. Result of model based testing
Rami Bechara, PhD
22
Hydroxychloroquine (EC50=0.72 μM) was found to
be more potent than chloroquine (EC50=5.47 μM) in
vitro.
Based on PBPK models results, a loading dose of 400
mg twice daily of hydroxychloroquine sulfate given
orally, followed by a maintenance dose of 200 mg
given twice daily for 4 days is recommended for
SARS-CoV-2 infection, as it reached three times the
potency of chloroquine phosphate when given 500
mg twice daily 5 days in advance
24. Actions of HCQ
Rami Bechara, PhD
24
Regulation in pro-inflammatory cytokines [e.g.
Tumor necrosis factor-α (TNF-α), interleukin-1 (IL-
1), interleukin-1 (IL-6)], antioxidant activities.
Antiviral and autoimmune regulation effects, HCQ
should be a protector in SARS-CoV-2 infection.
In the present study, the reduced risk of progression
to severe illness in patients with HCQ treatment also
explained the intervention effect of HCQ on the
pathological process of the COVID-19.
25. Side effects
Rami Bechara, PhD
25
Retinopathy is one of the major adverse reactions of
long-term therapy with HCQ.
Besides, patients with rheumatoid diseases treated with
HCQ occasionally experience arrhythmias.
Other rare adverse reactions caused by HCQ include
gastrointestinal reactions, cramps, liver dysfunction,
itching, headache, dizziness, insomnia, peripheral
neuropathy.
Fortunately, deciding on individual treatment plans
scientifically, monitoring adverse reactions timely, to
avoid overdose, short-term application of HCQ is
relatively safe
26. Critique
Rami Bechara, PhD
26
Despite the results, it is too early to say if
hydroxychloroquine has the potential or not to treat
COVID-19.
Today, there is insufficient clinical evidence
to draw any conclusion.
Large clinical studies are being conducted to assess
the safety and efficacy of hydroxychloroquine in
COVID-19 patients.
27. Challenges
Rami Bechara, PhD
27
Unknown dose–response relationships
Lack of definitions of the minimum dose needed for
clinical efficacy
Lack of definition of what doses are toxic
Patient non-adherence and possible context-
dependent variations in blood drug levels.
Available mechanistic data give insights into the
immunomodulatory potency of hydroxychloroquine
and provide the rationale to search for more potent
and/or selective inhibitors.
28. Trump announcement
Rami Bechara, PhD
28
Early on, before extensive clinical trials, US
President Donald Trump indicated that
hydroxychloroquine was a potential drug to fight
CoronaVirus
This has prompted global drainage of this drug as
well as its misuse
Moreover, it may have given non-scientific hope in
this drug
But it has nonetheless prompted a global search for
drug validation
29. Production of HCQ
Rami Bechara, PhD
29
70% of the world's supply of hydroxychloroquine
manufactured in India
Main producers ramped up production to meet the
sudden surge in demand from 3 metric tons per
month to 20 and even 30 metric tons per month and
even 40-50 t/month
Producing companies: backward integrated for
production, which means that they have the
necessary raw materials and key starting ingredients.
Problem: production tightly controlled by small
group of manufacturers
30. Lebanese in action for HCQ
Rami Bechara, PhD
30
It is interesting to note that the HCQ team in
Marseille contains a great number of Lebanese
people highlighting the country’s fight against this
disease
31. Conclusion
Rami Bechara, PhD
31
HCQ is a potential drug to fight coronavirus
Successful first trials waiting for more detailed ones
Best to take with additional drugs
One not studied route is combining the medicine
with remdesivir, another potential drug