It is a very important topic in healthcare. Pharmacists must be aware of few important counselling points for every medicine. Community Pharmacist must be aware of counselling.
The document discusses research methods for studying alternative medical treatments. There are three main types of research projects: 1) studying physiological effects on healthy volunteers, 2) monitoring clinical progress by comparing treated and untreated patient groups, and 3) understanding how a treatment works by testing on healthy volunteers. Careful study design, standardized treatments, and use of control groups are important to draw valid conclusions.
Patients have high expectations for doctors including active listening, transparency, and building trust. Doctors should respect patients, provide clear explanations, and be available and empathetic to address patients' physical and emotional needs. Effective communication is important to help patients understand their conditions and feel comfortable asking questions.
This document discusses the importance of evaluating clinical literature and provides guidance on how to systematically approach literature evaluation. It describes how to identify the level and type of reference (tertiary, secondary, primary), and provides tips for evaluating different aspects of clinical studies, such as the objective, subjects, treatment administration, setting, methods, controls, and data analysis. The document also discusses how the FDA communicates important drug safety information to healthcare professionals and the public.
This slide contains in-dept knowledge about prescribing in geriatric patients. Steps how to overcome polypharmacy and how to increase medication adherence in geriatrics. It also tells about geriatrics care. Examples of case studies are also included.
This document discusses medication errors, including their definition, causes, types, and strategies to prevent them. Some key points:
- Medication errors are preventable events that may cause harm and can occur at any stage from prescribing to administration. They are common but underreported.
- Errors are often due to look-alike or sound-alike drug names, miscommunication, lack of knowledge, and environmental factors like interruptions.
- Common types of errors include prescribing errors, dispensing errors, and administration errors. Analgesics, antibiotics, anticoagulants are high-risk drug classes.
- Prevention strategies include education, standardized processes, double checks, limiting distractions, clear
Patient counseling involves providing patients with information about their medications, including how to take them properly, potential side effects, and lifestyle changes. The goal is to improve patient understanding and adherence to treatment regimens. Effective counseling establishes a relationship of trust, assesses the patient's needs and concerns, and ensures they comprehend key points about managing their condition and medications. The counseling process involves private discussions that cover topics like dosage, benefits, interactions, and storage in a way patients can understand.
It is a very important topic in healthcare. Pharmacists must be aware of few important counselling points for every medicine. Community Pharmacist must be aware of counselling.
The document discusses research methods for studying alternative medical treatments. There are three main types of research projects: 1) studying physiological effects on healthy volunteers, 2) monitoring clinical progress by comparing treated and untreated patient groups, and 3) understanding how a treatment works by testing on healthy volunteers. Careful study design, standardized treatments, and use of control groups are important to draw valid conclusions.
Patients have high expectations for doctors including active listening, transparency, and building trust. Doctors should respect patients, provide clear explanations, and be available and empathetic to address patients' physical and emotional needs. Effective communication is important to help patients understand their conditions and feel comfortable asking questions.
This document discusses the importance of evaluating clinical literature and provides guidance on how to systematically approach literature evaluation. It describes how to identify the level and type of reference (tertiary, secondary, primary), and provides tips for evaluating different aspects of clinical studies, such as the objective, subjects, treatment administration, setting, methods, controls, and data analysis. The document also discusses how the FDA communicates important drug safety information to healthcare professionals and the public.
This slide contains in-dept knowledge about prescribing in geriatric patients. Steps how to overcome polypharmacy and how to increase medication adherence in geriatrics. It also tells about geriatrics care. Examples of case studies are also included.
This document discusses medication errors, including their definition, causes, types, and strategies to prevent them. Some key points:
- Medication errors are preventable events that may cause harm and can occur at any stage from prescribing to administration. They are common but underreported.
- Errors are often due to look-alike or sound-alike drug names, miscommunication, lack of knowledge, and environmental factors like interruptions.
- Common types of errors include prescribing errors, dispensing errors, and administration errors. Analgesics, antibiotics, anticoagulants are high-risk drug classes.
- Prevention strategies include education, standardized processes, double checks, limiting distractions, clear
Patient counseling involves providing patients with information about their medications, including how to take them properly, potential side effects, and lifestyle changes. The goal is to improve patient understanding and adherence to treatment regimens. Effective counseling establishes a relationship of trust, assesses the patient's needs and concerns, and ensures they comprehend key points about managing their condition and medications. The counseling process involves private discussions that cover topics like dosage, benefits, interactions, and storage in a way patients can understand.
Slide 1 : Title: ROLE OF PHARMACIST IN INTENSIVE CARE UNIT
By: Falakaara Saiyed
Slide 2: Introduction
Medication management plays a crucial part in managing a critically ill patient.
When it comes to drug therapy, intensivist have plenty of decision making every day including drug selection, dosing, administration, and monitoring strategies to optimize effective pharmacotherapy.
Even though the patient receives appropriate drug, a suboptimal dose or overdosing may result in either therapeutic failure or drug toxicity.
The concept of having a clinical pharmacist in an intensivist-led multidisciplinary team evolved in the early 1980s in USA.
In Today’s World Intensive Care Unit (ICU), the skills of a Critical care pharmacist addresses adverse drug events caused due to drug-related problems and medication errors. It improves the appropriateness, quality of prescribing and increases patient safety.
Slide 5: Aims & Objective
This aims to evaluate the clinical pharmacist interventions with a focus on optimizing the quality of pharmacotherapy and patient safety.
Even though the contribution of critical care pharmacist to improve the quality of patient care is accepted worldwide, many ICUs have not recognized this important reserve.
This presentation is used to educate other healthcare professionals and administrators on impact of clinical pharmacist in the care of critically ill patients.
Slide 14: Pharmaceutical Care Process
Assess the patient
Identify the problems and opportunities
Develop care plan
Implement Plan
Evaluate for Efficacy and Safety
Slide 24: Desirable activities of ICU pharmacist
Includes formulating guidelines for the critically ill patients, active participation in research, and educating the ICU team.
Guidelines which have been developed and implemented by the clinical pharmacist in our ICU includes protocols for pain, sedation, delirium, stress, drug compatibility chart , drug administration, dilution guidelines, and toxicological management protocols.
Once the protocols are formulated, all the members of the ICU team are educated on how to use the protocol.
Most of these clinical pharmacist enforced protocols are nurse oriented, and hence, it becomes easy for optimizing patient care.
The effectiveness of these guidelines is under the supervision of a critical care pharmacist, and it is well studied in Western countries.
Slide 25: conclusion
Clinical pharmacist as a part of multidisciplinary team in an ICU is associated with a substantially lower rate of adverse drug event caused by medication errors, drug interactions, and drug incompatibilities.
Clinical pharmacists are essential to improve patient safety and outcome, reduce costs, and provide quality of care in critically ill patients.
Slide 26: References
Kane-Gill SL, Jacobi J, Rothschild JM. Adverse drug events in intensive care units: Risk factors, impact, and the role of team care. Crit Care Med. 2010
The document discusses opportunities for pharmacy practice research in community settings. It begins by outlining the changing role of pharmacists from product-focused to patient-centered care. There is a need for pharmacy practice research in community settings to optimize medication use, support self-care, and improve health outcomes. The presentation then describes development of a clinical tool called STARZ-DRP, which is a step-by-step approach for minor illness consultation and triaging decisions in community pharmacies. A study was conducted to evaluate STARZ-DRP which found it improved identification of drug-related problems and referral decisions compared to usual care.
Patient counseling by pharmacists involves providing patients with information about their medications and conditions to ensure safe and effective use. During counseling, the pharmacist assesses the patient's understanding, provides individualized advice, and aims to improve adherence, health outcomes, and quality of life. The counseling process involves preparing, opening the session, discussing the medication and treatment plan, and closing by checking the patient's understanding. The goal is to educate patients and empower them to better manage their health.
Medication adherence refers to the extent to which a patient follows medical advice regarding prescribed medications. It is important for therapeutic outcomes, especially for chronic illnesses. While many factors can influence adherence, it is difficult to predict. Pharmacists are well-positioned to improve adherence through patient education about their medications, potential side effects, and the importance of adherence. Strategies like simplifying dosing regimens, using medication organizers, and addressing specific barriers can also help. Further research is still needed to better understand and promote adherence.
Communication is important for effective treatment and involves both verbal and non-verbal elements. Verbal communication uses speech while non-verbal communication conveys messages through gestures, facial expressions, eye contact, and body language. There are also different styles of communication such as assertive, aggressive, and passive. Effective communication requires strong listening skills to understand patients and asking questions to gather necessary information. Barriers like noise, time constraints, or psychological factors can interfere with communication. Confidentiality protects private patient information.
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
Here are the key steps I would take:
1. Return to Mrs. Veena immediately to inform her of the error and assess for any allergic reaction symptoms. Her safety is the top priority.
2. Notify the physician right away about the error so they can determine the appropriate treatment and monitoring plan for Mrs. Veena.
3. Fill out an incident report per hospital policy documenting exactly what occurred, the medications involved, actions taken, patient assessment and outcome.
4. Review the situation to understand what factors may have contributed to the error so I can learn and help prevent similar mistakes going forward. Proper documentation and reporting of all errors is important for quality improvement.
5. Apologize to
This document discusses medical research. It defines medical research as basic, applied, or translational research conducted to advance knowledge in medicine. It describes the main categories of medical research as clinical trials to evaluate new treatments, preclinical research to develop new therapeutic strategies, and translational research that feeds between basic and clinical research in iterative loops. It also lists some of the major fields that medical research covers, including public health, epidemiology, cancer, neuroscience, genetics, and more. It discusses the ethical principles of medical research involving humans from the Declaration of Helsinki and the role of qualitative research in evidence-based medicine.
This document outlines the research process from start to finish. It begins by defining research as a careful investigation aimed at discovering new information or revising current understanding. It then distinguishes between quantitative and qualitative research approaches. The document describes each step of the research process in detail, including refining an idea based on background research, conducting experiments or investigations, documenting work, evaluating results, and presenting findings. The overall process involves starting with an idea, investigating previous work, refining the idea, doing the core investigative work, evaluating outcomes, identifying future work, and disseminating the research.
This document outlines the process of patient counseling conducted by pharmacists. It defines patient counseling as providing information to help patients use medications appropriately. The objectives of counseling are to develop a working relationship with patients, improve understanding of disease and medication, and avoid medication-related problems. The counseling process involves establishing rapport, assessing patient knowledge, providing information using visual aids, and verifying understanding. Pharmacists must have knowledge and communication skills while patients must be willing to adhere to treatment and report experiences. Counseling covers disease, medication, administration, side effects, and other topics. Pharmacists should document counseling in medical records according to policies.
Patient Counselling is needed for
Better patient understanding to their illness and role of medication.
Improve medication adherence.
Improve dosage regimen adherence.
More effective Drug treatment.
Reduce incidence of adverse drug effect and unnecessary healthcare cost.
ADR reporting.
Improve quality of life for patient.
Raising image of Pharmacist & its profession.
This document summarizes a seminar presentation on the role of pharmacogenetics and pharmacogenomics in drug development and regulatory review. It discusses how genetic differences can impact how individuals metabolize and respond to drugs in terms of pharmacokinetics and pharmacodynamics. Specific polymorphisms in enzymes, receptors, and transporters were highlighted as factors that can influence a drug's effects. The importance of considering pharmacogenomic data during drug trials and regulatory reviews was emphasized in order to optimize dosing and labeling recommendations to improve drug efficacy and safety.
The document provides an outline of key information about hospital pharmacy including:
1) It defines hospital pharmacy as the department that procures, stores, dispenses, and distributes drugs in a hospital under the supervision of a qualified pharmacist.
2) It lists the main functions of hospital pharmacy such as purchasing drugs, proper storage, manufacturing medications, dispensing prescriptions, and providing drug information.
3) The objectives of hospital pharmacy are to ensure the availability of correct medications at low cost, professionalize pharmaceutical services, provide counseling, and participate in research and teaching.
ADRs
Classifications of ADRs
Thompson and DoTS system classification
Factors: age, gender, Co-morbidities, ethnicity, Pharmacogenetics,G6PD deficiency, porphyrias
Immunological reactions
Classifications
Epidemiology and pharmacovigilance of ADRs
Yellow card scheme,
Thalidomide tragedy
Factors that may raise or suppress suspicion of a drug
The document discusses reasons why therapeutic drug monitoring of diuretics is not commonly practiced, including that there are no sensitive methods for measuring blood diuretic levels and response can be assessed without levels. It notes that all diuretics are prodrugs and there is no established exposure-response relationship. It also describes how pindolol behaves as an agonist in the presence of a selective beta-1 agonist and as an antagonist in both the presence and absence of a selective beta-1 agonist.
This document provides counseling information for patients taking medications to treat hypertension. It discusses several classes of blood pressure medications including ACE inhibitors, ARBs, beta-blockers, calcium channel blockers, thiazide diuretics, and clonidine. Key points covered include the importance of continuing treatment even if feeling well, potential side effects to watch out for, drug interactions to be aware of, and guidelines for proper use of specific medications.
Drug discovery and development is a long and expensive process and over time has notoriously bucked Moore’s law that it now has its own law called Eroom’s Law named after it (the opposite of Moore’s). It is estimated that the attrition rate of drug candidates is up to 96% and the average cost to develop a new drug has reached almost $2.5 billion in recent years. One of the major causes for the high attrition rate is drug safety, which accounts for 30% of the failures.
Even if a drug is approved in market, it could be withdrawn due to safety problems. Therefore, evaluating drug safety extensively as early as possible is paramount in accelerating drug discovery and development. This talk provides a high-level overview of the current process of rational drug design that has been in place for many decades and covers some of the major areas where the application of AI, Deep learning and ML based techniques have had the most gains.
Specifically, this talk covers a variety of drug safety related AI and ML based techniques currently in use which can generally divided into 3 main categories:
1. Discovery,
2. Toxicity and Safety, and
3. Post-Market Monitoring.
We will address the recent progress in predictive models and techniques built for various toxicities. It will also cover some publicly available databases, tools and platforms available to easily leverage them.
We will also compare and contrast various modeling techniques including deep learning techniques and their accuracy using recent research. Finally, the talk will address some of the remaining challenges and limitations yet to be addressed in the area of drug discovery and safety assessment.
This document discusses research projects for PharmD students. It emphasizes that research and problem solving are important for pharmacists and the pharmacy profession. Pharmacists can conduct research to help guide drug therapy and should understand the research process to interpret knowledge generated by others. The document provides guidance to students on formulating a research problem, including reviewing literature, developing a logical research problem statement, and considering factors like interest, magnitude, measurement and expertise when selecting a problem. It aims to help students develop skills for their PharmD research projects.
This document provides an overview of how to read clinical papers and summarizes their typical structure and components. It explains that clinical papers are used by medical representatives to present evidence for product claims and understand what is being discussed. The key parts of clinical papers are typically the title, authors, abstract, introduction, methods, results, discussion, and references. The document provides details on each of these sections and advises the reader to critically analyze the research questions, study design, results and conclusions. It emphasizes comparing the reported data to the authors' analysis and relating the findings to prior research.
in this presentation i have tried to briefly discuss about diuretics (water pills), their classification, mechanism of action, pharmacokinetics and pharmacodynamics of these drugs
Slide 1 : Title: ROLE OF PHARMACIST IN INTENSIVE CARE UNIT
By: Falakaara Saiyed
Slide 2: Introduction
Medication management plays a crucial part in managing a critically ill patient.
When it comes to drug therapy, intensivist have plenty of decision making every day including drug selection, dosing, administration, and monitoring strategies to optimize effective pharmacotherapy.
Even though the patient receives appropriate drug, a suboptimal dose or overdosing may result in either therapeutic failure or drug toxicity.
The concept of having a clinical pharmacist in an intensivist-led multidisciplinary team evolved in the early 1980s in USA.
In Today’s World Intensive Care Unit (ICU), the skills of a Critical care pharmacist addresses adverse drug events caused due to drug-related problems and medication errors. It improves the appropriateness, quality of prescribing and increases patient safety.
Slide 5: Aims & Objective
This aims to evaluate the clinical pharmacist interventions with a focus on optimizing the quality of pharmacotherapy and patient safety.
Even though the contribution of critical care pharmacist to improve the quality of patient care is accepted worldwide, many ICUs have not recognized this important reserve.
This presentation is used to educate other healthcare professionals and administrators on impact of clinical pharmacist in the care of critically ill patients.
Slide 14: Pharmaceutical Care Process
Assess the patient
Identify the problems and opportunities
Develop care plan
Implement Plan
Evaluate for Efficacy and Safety
Slide 24: Desirable activities of ICU pharmacist
Includes formulating guidelines for the critically ill patients, active participation in research, and educating the ICU team.
Guidelines which have been developed and implemented by the clinical pharmacist in our ICU includes protocols for pain, sedation, delirium, stress, drug compatibility chart , drug administration, dilution guidelines, and toxicological management protocols.
Once the protocols are formulated, all the members of the ICU team are educated on how to use the protocol.
Most of these clinical pharmacist enforced protocols are nurse oriented, and hence, it becomes easy for optimizing patient care.
The effectiveness of these guidelines is under the supervision of a critical care pharmacist, and it is well studied in Western countries.
Slide 25: conclusion
Clinical pharmacist as a part of multidisciplinary team in an ICU is associated with a substantially lower rate of adverse drug event caused by medication errors, drug interactions, and drug incompatibilities.
Clinical pharmacists are essential to improve patient safety and outcome, reduce costs, and provide quality of care in critically ill patients.
Slide 26: References
Kane-Gill SL, Jacobi J, Rothschild JM. Adverse drug events in intensive care units: Risk factors, impact, and the role of team care. Crit Care Med. 2010
The document discusses opportunities for pharmacy practice research in community settings. It begins by outlining the changing role of pharmacists from product-focused to patient-centered care. There is a need for pharmacy practice research in community settings to optimize medication use, support self-care, and improve health outcomes. The presentation then describes development of a clinical tool called STARZ-DRP, which is a step-by-step approach for minor illness consultation and triaging decisions in community pharmacies. A study was conducted to evaluate STARZ-DRP which found it improved identification of drug-related problems and referral decisions compared to usual care.
Patient counseling by pharmacists involves providing patients with information about their medications and conditions to ensure safe and effective use. During counseling, the pharmacist assesses the patient's understanding, provides individualized advice, and aims to improve adherence, health outcomes, and quality of life. The counseling process involves preparing, opening the session, discussing the medication and treatment plan, and closing by checking the patient's understanding. The goal is to educate patients and empower them to better manage their health.
Medication adherence refers to the extent to which a patient follows medical advice regarding prescribed medications. It is important for therapeutic outcomes, especially for chronic illnesses. While many factors can influence adherence, it is difficult to predict. Pharmacists are well-positioned to improve adherence through patient education about their medications, potential side effects, and the importance of adherence. Strategies like simplifying dosing regimens, using medication organizers, and addressing specific barriers can also help. Further research is still needed to better understand and promote adherence.
Communication is important for effective treatment and involves both verbal and non-verbal elements. Verbal communication uses speech while non-verbal communication conveys messages through gestures, facial expressions, eye contact, and body language. There are also different styles of communication such as assertive, aggressive, and passive. Effective communication requires strong listening skills to understand patients and asking questions to gather necessary information. Barriers like noise, time constraints, or psychological factors can interfere with communication. Confidentiality protects private patient information.
Nomograms and tabulations in design of dosage regimens pavithra vinayak
Nomograms and tabulations in the design of dosage regimens --- NOMOGRAM IN UREMIC PATIENTS: NOMOGRAM FOR RELATIONSHIP BETWEEN CREATININE CLEARANCE AND ELIMINATION RATE CONSTANT FOR FOUR DRUGS clinical pharmacokinetics and therapeutic drug monitoring ---fifth PharmD notes
Here are the key steps I would take:
1. Return to Mrs. Veena immediately to inform her of the error and assess for any allergic reaction symptoms. Her safety is the top priority.
2. Notify the physician right away about the error so they can determine the appropriate treatment and monitoring plan for Mrs. Veena.
3. Fill out an incident report per hospital policy documenting exactly what occurred, the medications involved, actions taken, patient assessment and outcome.
4. Review the situation to understand what factors may have contributed to the error so I can learn and help prevent similar mistakes going forward. Proper documentation and reporting of all errors is important for quality improvement.
5. Apologize to
This document discusses medical research. It defines medical research as basic, applied, or translational research conducted to advance knowledge in medicine. It describes the main categories of medical research as clinical trials to evaluate new treatments, preclinical research to develop new therapeutic strategies, and translational research that feeds between basic and clinical research in iterative loops. It also lists some of the major fields that medical research covers, including public health, epidemiology, cancer, neuroscience, genetics, and more. It discusses the ethical principles of medical research involving humans from the Declaration of Helsinki and the role of qualitative research in evidence-based medicine.
This document outlines the research process from start to finish. It begins by defining research as a careful investigation aimed at discovering new information or revising current understanding. It then distinguishes between quantitative and qualitative research approaches. The document describes each step of the research process in detail, including refining an idea based on background research, conducting experiments or investigations, documenting work, evaluating results, and presenting findings. The overall process involves starting with an idea, investigating previous work, refining the idea, doing the core investigative work, evaluating outcomes, identifying future work, and disseminating the research.
This document outlines the process of patient counseling conducted by pharmacists. It defines patient counseling as providing information to help patients use medications appropriately. The objectives of counseling are to develop a working relationship with patients, improve understanding of disease and medication, and avoid medication-related problems. The counseling process involves establishing rapport, assessing patient knowledge, providing information using visual aids, and verifying understanding. Pharmacists must have knowledge and communication skills while patients must be willing to adhere to treatment and report experiences. Counseling covers disease, medication, administration, side effects, and other topics. Pharmacists should document counseling in medical records according to policies.
Patient Counselling is needed for
Better patient understanding to their illness and role of medication.
Improve medication adherence.
Improve dosage regimen adherence.
More effective Drug treatment.
Reduce incidence of adverse drug effect and unnecessary healthcare cost.
ADR reporting.
Improve quality of life for patient.
Raising image of Pharmacist & its profession.
This document summarizes a seminar presentation on the role of pharmacogenetics and pharmacogenomics in drug development and regulatory review. It discusses how genetic differences can impact how individuals metabolize and respond to drugs in terms of pharmacokinetics and pharmacodynamics. Specific polymorphisms in enzymes, receptors, and transporters were highlighted as factors that can influence a drug's effects. The importance of considering pharmacogenomic data during drug trials and regulatory reviews was emphasized in order to optimize dosing and labeling recommendations to improve drug efficacy and safety.
The document provides an outline of key information about hospital pharmacy including:
1) It defines hospital pharmacy as the department that procures, stores, dispenses, and distributes drugs in a hospital under the supervision of a qualified pharmacist.
2) It lists the main functions of hospital pharmacy such as purchasing drugs, proper storage, manufacturing medications, dispensing prescriptions, and providing drug information.
3) The objectives of hospital pharmacy are to ensure the availability of correct medications at low cost, professionalize pharmaceutical services, provide counseling, and participate in research and teaching.
ADRs
Classifications of ADRs
Thompson and DoTS system classification
Factors: age, gender, Co-morbidities, ethnicity, Pharmacogenetics,G6PD deficiency, porphyrias
Immunological reactions
Classifications
Epidemiology and pharmacovigilance of ADRs
Yellow card scheme,
Thalidomide tragedy
Factors that may raise or suppress suspicion of a drug
The document discusses reasons why therapeutic drug monitoring of diuretics is not commonly practiced, including that there are no sensitive methods for measuring blood diuretic levels and response can be assessed without levels. It notes that all diuretics are prodrugs and there is no established exposure-response relationship. It also describes how pindolol behaves as an agonist in the presence of a selective beta-1 agonist and as an antagonist in both the presence and absence of a selective beta-1 agonist.
This document provides counseling information for patients taking medications to treat hypertension. It discusses several classes of blood pressure medications including ACE inhibitors, ARBs, beta-blockers, calcium channel blockers, thiazide diuretics, and clonidine. Key points covered include the importance of continuing treatment even if feeling well, potential side effects to watch out for, drug interactions to be aware of, and guidelines for proper use of specific medications.
Drug discovery and development is a long and expensive process and over time has notoriously bucked Moore’s law that it now has its own law called Eroom’s Law named after it (the opposite of Moore’s). It is estimated that the attrition rate of drug candidates is up to 96% and the average cost to develop a new drug has reached almost $2.5 billion in recent years. One of the major causes for the high attrition rate is drug safety, which accounts for 30% of the failures.
Even if a drug is approved in market, it could be withdrawn due to safety problems. Therefore, evaluating drug safety extensively as early as possible is paramount in accelerating drug discovery and development. This talk provides a high-level overview of the current process of rational drug design that has been in place for many decades and covers some of the major areas where the application of AI, Deep learning and ML based techniques have had the most gains.
Specifically, this talk covers a variety of drug safety related AI and ML based techniques currently in use which can generally divided into 3 main categories:
1. Discovery,
2. Toxicity and Safety, and
3. Post-Market Monitoring.
We will address the recent progress in predictive models and techniques built for various toxicities. It will also cover some publicly available databases, tools and platforms available to easily leverage them.
We will also compare and contrast various modeling techniques including deep learning techniques and their accuracy using recent research. Finally, the talk will address some of the remaining challenges and limitations yet to be addressed in the area of drug discovery and safety assessment.
This document discusses research projects for PharmD students. It emphasizes that research and problem solving are important for pharmacists and the pharmacy profession. Pharmacists can conduct research to help guide drug therapy and should understand the research process to interpret knowledge generated by others. The document provides guidance to students on formulating a research problem, including reviewing literature, developing a logical research problem statement, and considering factors like interest, magnitude, measurement and expertise when selecting a problem. It aims to help students develop skills for their PharmD research projects.
This document provides an overview of how to read clinical papers and summarizes their typical structure and components. It explains that clinical papers are used by medical representatives to present evidence for product claims and understand what is being discussed. The key parts of clinical papers are typically the title, authors, abstract, introduction, methods, results, discussion, and references. The document provides details on each of these sections and advises the reader to critically analyze the research questions, study design, results and conclusions. It emphasizes comparing the reported data to the authors' analysis and relating the findings to prior research.
in this presentation i have tried to briefly discuss about diuretics (water pills), their classification, mechanism of action, pharmacokinetics and pharmacodynamics of these drugs
Diuretics are drugs that promote the excretion of sodium and water from the body by acting on the kidney. They work by interfering with sodium transport mechanisms in different segments of the nephron. The main types are loop diuretics which act on the thick ascending limb of the loop of Henle, thiazide diuretics which act on the early distal tubule, and potassium-sparing diuretics which act on the late distal tubule and collecting duct. Diuretics are important drugs used to treat hypertension, heart failure, and edema.
This document provides information on diuretic drugs, including their mechanisms and sites of action, indications for use, and adverse effects. It discusses loop diuretics like furosemide and bumetanide that act in the thick ascending loop of Henle, thiazide diuretics like hydrochlorothiazide that act in the distal tubule, and potassium-sparing diuretics like amiloride and spironolactone that act in the collecting ducts. It also covers carbonic anhydrase inhibitors and osmotic diuretics. Non-diuretic uses and combinations with other drugs are mentioned. Resistance, interactions, and specific adverse effects are summarized for each drug class.
The document discusses kidney function and urine formation processes. It then summarizes the key functions of the kidneys, which include regulating electrolyte and fluid balance and removing waste from the blood. It describes the three main processes involved in urine formation - filtration, reabsorption, and secretion. The document then focuses on hypertension, describing classifications of blood pressure and types of hypertension. It outlines mechanisms for blood pressure control and discusses non-pharmacological and pharmacological approaches to hypertension management.
Diuretics and antidiuretics detail STUDYNittalVekaria
diuretics and antidiuretics detail study
-diuretic are the drug which increase the urine formation and excretion.
- antidiuretic work by decrease the urine formation.
classification, mechanism of action, use ,pharmacokinetic, pharmacodynamic,adverse effect
-newer drug
-banned diuretic and antidiuretic drug
This document discusses different classes of diuretic medications, their mechanisms of action, indications, and side effects. It describes:
1) Loop diuretics which inhibit sodium reabsorption in the loop of Henle, causing increased excretion of sodium, chloride, and water. Their main indications include heart failure and edema.
2) Thiazide diuretics which inhibit sodium reabsorption in the distal convoluted tubule. They are used to treat hypertension and have fewer side effects than loop diuretics.
3) Carbonic anhydrase inhibitors which inhibit bicarbonate reabsorption in the proximal tubule, causing a metabolic acidosis. Their main use is for glaucoma.
This document discusses different classes of diuretic drugs, including their sites of action in the nephron, mechanisms of action, therapeutic uses, and side effects. It covers osmotic diuretics, carbonic anhydrase inhibitors, thiazide diuretics, loop diuretics, and potassium-sparing diuretics. The main points are that diuretics work by inhibiting transport in different parts of the nephron like the proximal tubule, loop of Henle, or distal convoluted tubule. They are used to treat conditions like edema, hypertension, and heart failure. Common side effects among the classes include electrolyte imbalances and metabolic alterations.
The document discusses the mechanisms and effects of different classes of diuretic drugs, including thiazide and loop diuretics. It explains that thiazides act in the distal tubule to inhibit sodium reabsorption, causing a modest diuresis. Loop diuretics act in the ascending loop of Henle and cause a greater natriuresis than thiazides. Both can cause hypokalemia and other electrolyte abnormalities as side effects. The document outlines the clinical uses of these diuretics to treat conditions like edema, hypertension, and hypocalciuria. It also discusses factors that can contribute to diuretic resistance.
The document summarizes renal physiology and kidney function. It discusses:
1) The structure of the kidney including nephrons, collecting ducts, and microvasculature. Nephron number is established prenatally and cannot be replaced if lost.
2) Urine formation through selective retention and elimination of solutes and water by different nephron segments including the glomerulus, proximal tubule, loop of Henle, and collecting ducts.
3) Causes, types (prerenal, intrarenal, postrenal), phases, prevention and management of acute renal failure and end-stage renal disease where dialysis or transplantation is needed for survival.
The document discusses drugs that act on the kidney to promote urine formation and regulate fluid and electrolyte balance. It describes the major processes involved in urine formation and the functions of the renal system. It then discusses different classes of diuretic drugs, including loop diuretics, thiazide diuretics, potassium-sparing diuretics, osmotic diuretics, vasopressin antagonists, and adenosine receptor antagonists. It explains their mechanisms of action, clinical uses, side effects, and drug interactions. Conditions like diuretic resistance are also mentioned.
1. Thiazide and loop diuretics act at different sites along the nephron to inhibit sodium reabsorption and cause increased sodium and water excretion.
2. They are used to treat edema, hypertension, and other conditions. Common side effects include hypokalemia, hypomagnesemia, and metabolic alterations.
3. The effects, pharmacokinetics, clinical uses and adverse effects of thiazide and loop diuretics are described and compared in detail. Combination diuretic therapy and managing diuretic resistance are also discussed.
This document discusses diuretics, with a special focus on hydrochlorothiazide. It provides details on renal physiology and pharmacology. It describes the main types of diuretics and their mechanisms of action. It discusses thiazide diuretics in depth, including common examples like hydrochlorothiazide, their effects, kinetics, side effects, and clinical uses, especially for hypertension.
This document provides an overview of diuretics, including their definition, classification, mechanisms of action, and side effects. It discusses the physiology of urine formation and the roles of the kidney in homeostasis. Specific sections cover thiazide diuretics, loop diuretics, their mechanisms in inhibiting sodium reabsorption in the distal tubule and thick ascending limb, respectively. Adverse effects include hypokalemia, hyperuricemia, and effects on calcium and magnesium levels. The document compares the potencies and durations of action of different diuretic classes and individual drugs.
This ppt tells us about the topics diuretics and antidiuretics.
It also indicates us about their classification, mechanism of action, side effects and many more.
The document provides information on diuretics and their mechanisms of action. It begins with an overview of kidney anatomy and function. It then discusses the four major anatomical sites of sodium reabsorption along the nephron. The types of diuretics are classified based on their sites of action, including carbonic anhydrase inhibitors, loop diuretics, thiazide diuretics, potassium-sparing diuretics, and others. The mechanisms of action and structure-activity relationships are described for each class. Carbonic anhydrase inhibitors act in the proximal tubule by inhibiting the enzyme carbonic anhydrase. Loop diuretics such as furosemide act in the ascending loop of Henle by
This a is a slide set (42 slides) covering clinically used drugs for lipid lowering. This is an updated version of the lecture series for the 2021-2022 academic year. Suitable for intermediate level learners
The document announces a virtual conference on June 30th, 2021 hosted by the IUPHAR Education Section to discuss future-proofing pharmacology education. The conference consists of two sessions:
Session 1 from 9:00-10:30 am UTC will feature a keynote by Professor Ray Land on transformational approaches to pharmacology education, followed by Q&A on prerecorded presentations on student-led pharmacology research and transforming pharmacology practicals for blended learning.
Session 2 from 21:00-22:30 pm UTC will include a workshop on core concepts and concept inventories led by Professor Paul White, followed by Q&A on prerecorded presentations about coming together as a society to future
The document announces an IUPHAR virtual conference on June 30th, 2021 about future-proofing pharmacology education. The conference consists of two sessions.
Session 1 runs from 9-10:30 am UTC and features a keynote by Professor Ray Land on threshold concepts and troublesome knowledge in pharmacology education. It also includes prerecorded presentations on student-led pharmacology research, transforming pharmacology practicals for blended learning, incorporating gamification to engage learners, and the IUPHAR Pharmacology Education Project.
Session 2 runs from 9-10:30 pm UTC and includes a workshop on core concepts and concept inventories led by Professor Paul White. It also features prerecorded presentations on
40 slides that focus on the drugs used to treat epilepsy (anti-epileptic drugs) and their their primary molecular mechanisms of action. Produced by Stephen Kelley (University of Dundee, UK).
This document provides an overview of epilepsy pharmacotherapy, including classification of seizures and epilepsy. It discusses the pathophysiology and causes of epilepsy, classification of seizure types, management strategies, first aid for seizures, and considerations for pregnancy. Key points covered include the definition of seizures and epilepsy, that up to 1/3 of cases are idiopathic while others are symptomatic, classification of focal and generalized seizures, and first-line treatment involving antiepileptic drugs.
A teaching slide set describing the mechanisms of action and clinical use of local anaesthetics. This session is a basic introduction to the pharmacodynamics and pharmacokinetics of local anaesthetics. It is aimed at preclinical medical or dental students, or students in the early years of a pharmacology degree.
This 11-slide slide set created with PowerPoint describes the organic nitrates and their use in the treatment of angina pectoris. Contributed by Christopher Fowler, Umeå University, Sweden.
This set of 17 slides introduces students to the some of the basic physiological processes that are the targets of many analgesic drug classes. It is suitable for beginner/intermediate level learners.
This slide set provides an introduction at new learner to intermediate level to some of the most common drugs that are used clinically to modulate the rate and force of contraction of the heart. Created by Prof. JA Peters, University of Dundee School of Medicine.
This 20-slide slide set created with PowerPoint describes prostanoid synthesis and their effects on the body; mechanisms of action, beneficial and adverse effects of NSAIDS; the difference between the effects of low and high dose aspirin; and the effects and toxicity of paracetamol (acetaminophen). This is an introduction to the topic of NSAIDS which would be appropriate for beginners. Contributed by Christopher Fowler, Umeå University, Sweden.
This 9-slide slide set created with PowerPoint is a short introduction to corticosteroids, in particular, the glucocorticoids, describing their receptor-mediated effects as well as why they exert both wanted and unwanted effects when used as anti-inflammatory and immunosuppressant drugs. This introduction to the topic of corticosteroids would be appropriate for beginners. Contributed by Christopher Fowler, Umeå University, Sweden.
This 12-slide slide set created with PowerPoint presents an introduction into the pharmacology of opioid analgesics in order to provide a basic background to facilitate later understanding of more detailed pharmacology of opioid analgesics. Topics covered include: opioid receptors, their signaling mechanisms and responses; and pharmacological effects of opioid receptor ligands. This introduction to the topic of opioid analgesics would be appropriate for intermediate level learners. Contributed by Christopher Fowler, Umeå University, Sweden.
This 13-slide slide set created with PowerPoint provides an introduction to antidepressants describing their discovery and development; their modes of action and relationship to the monoamine hypothesis of depression; and their efficacy, latency and unwanted actions. The beginner level introduction is tailored to aid the understanding of individual antidepressants. Contributed by Christopher Fowler, Umeå University, Sweden.
This document provides information about drugs used in hematology, including anticoagulants, antiplatelet agents, and thrombolytic agents. It begins with learning outcomes and an outline of topics to be covered, including disorders of inappropriate blood clotting that these drugs treat. The document then discusses the normal coagulation process and thrombosis. It describes the two main types of thrombus and how anticoagulants, antiplatelet agents, and thrombolytic agents work to prevent and treat them. Specific drug classes are covered in more depth, including heparin and low molecular weight heparins, warfarin, and fibrinolytic agents. Clinical uses and guidelines for these drugs are also summarized.
This document provides an overview of receptor pharmacology and key concepts. It defines drugs and how they act through receptors and other targets. It explains the terms agonist, antagonist, affinity, efficacy and potency. It describes competitive and non-competitive antagonism and their effects on concentration-response curves. The learning objectives are to understand these pharmacological concepts and be able to interpret graphs of drug-receptor interactions.
This is a 16 slide presentation covering the the classes of drugs used in T2DM and their molecular mechanisms of action. Provided by Professor John A Peters, University of Dundee.
Slide set for medical students discussing the physiology and pharmacology of nausea and vomiting. Provided by Professor John A Peters, University of Dundee.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
This slide is special for master students (MIBS & MIFB) in UUM. Also useful for readers who are interested in the topic of contemporary Islamic banking.
Executive Directors Chat Leveraging AI for Diversity, Equity, and InclusionTechSoup
Let’s explore the intersection of technology and equity in the final session of our DEI series. Discover how AI tools, like ChatGPT, can be used to support and enhance your nonprofit's DEI initiatives. Participants will gain insights into practical AI applications and get tips for leveraging technology to advance their DEI goals.
Main Java[All of the Base Concepts}.docxadhitya5119
This is part 1 of my Java Learning Journey. This Contains Custom methods, classes, constructors, packages, multithreading , try- catch block, finally block and more.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
How to Add Chatter in the odoo 17 ERP ModuleCeline George
In Odoo, the chatter is like a chat tool that helps you work together on records. You can leave notes and track things, making it easier to talk with your team and partners. Inside chatter, all communication history, activity, and changes will be displayed.
Thinking of getting a dog? Be aware that breeds like Pit Bulls, Rottweilers, and German Shepherds can be loyal and dangerous. Proper training and socialization are crucial to preventing aggressive behaviors. Ensure safety by understanding their needs and always supervising interactions. Stay safe, and enjoy your furry friends!
Strategies for Effective Upskilling is a presentation by Chinwendu Peace in a Your Skill Boost Masterclass organisation by the Excellence Foundation for South Sudan on 08th and 09th June 2024 from 1 PM to 3 PM on each day.
1. Drugs Acting on the Kidney (1 and 2)
Professor John Peters
E-mail j.a.peters@dundee.ac.uk
2. Learning Objectives
Following this lecture, students should be able to:
Recall the range of drugs that act upon the kidney
Identify the major sites of diuretic action in the nephron
Describe in detail the mechanism of action of the loop diuretics
List the clinical uses and main adverse effects of the loop diuretics
Describe in detail the mechanism of action of the thiazide diuretics
List the clinical uses and main adverse effects of the thiazide
diuretics
Explain why loop and thiazide diuretics cause hypokalaemia
Describe the mechanisms of action of the potassium sparing
diuretics noting the distinct modes of action of aldosterone
antagonists and blockers of the epithelial sodium channel, ENaC
Describe the clinical uses of the potassium sparing diuretics and
their adverse effects
Recommended reading
• Neal (2016). ‘Medical Pharmacology at a Glance (8th.ed.) Chapter 14
• Rang, Ritter, Flower and Henderson (2016). 'Rang and Dale's
Pharmacology’ (8th. ed.). Chapter 29.
3. Drugs Acting on the Kidney
Drugs acting on the kidney include
Diuretics are the most commonly used agents that:
increase urine flow, normally by inhibiting the reabsorption of
electrolytes (mainly sodium salts) at various sites in the nephron
Diuretics
Vasopressin (antidiuretic hormone; ADH) receptor agonists and
antagonists
Uricosuric drugs (agents promoting excretion of uric acid into the
urine)
are used to enhance excretion of salt and water in conditions where
an increase in the volume of interstitial fluid (i.e. oedema) causes
tissue swelling
Inhibitors of sodium-glucose co-transporter 2 (SGLT2)
Those used in renal failure
Those that alter the pH of the urine
4. Formation of interstitial fluid is proportional to: (Pc – Pi) – (p - i)
Disease states that increase Pc or decrease p and produce
oedema include:
• the nephrotic syndrome
Oedema
results from an imbalance between the rate of formation and
absorption of interstitial fluid
Pc p
Pi i
Capillary
Interstitial fluid
• hepatic cirrhosis with ascites
• congestive heart failure
5. Diseases Associated With Oedema Responding to
Diuretic Drug Therapy
The Nephrotic Syndrome
Involves a disorder of glomerular filtration, allowing protein
(largely albumin) to appear in the filtrate (proteinuria)
Decreased p
formation of
interstitial fluid
blood volume
cardiac output
Oedema
Activation of the
RAAS
Na+ and H20
retention
Pc, p
6. Congestive Heart Failure
Arises from reduced cardiac
output. Subsequent renal
hypoperfusion activates the renin-
angiotensin system
Expansion of blood volume
contributes to increased venous
and capillary pressures which,
combined with reduced p, causes
pulmonary and peripheral oedema
Hepatic Cirrhosis With Ascites
Increased pressure in the hepatic
portal vein, combined with decreased
production of albumin, causes loss of
fluid into the peritoneal cavity and
oedema (ascites)
Activation of the renin-angiotensin
system occurs in response to
decreased circulating volume
Oedema fluid mobilization by
diuretics. Note that collapse and
danger of thrombosis only occur
if massive use of diuretics is
employed). From Lüllmann et al.
(2000) Color Atlas of
Pharmacology
7. Sodium Reabsorption and the Major Sites of
Diuretic Action in the Nephron
Proximal convoluted tubule
1. Na+ (passive Cl- absorption)
2. Na+/H+ exchange (blocked by
carbonic anhydrase inhibitors)
Thick ascending limb of the loop of Henle
3. Na+/K+/2Cl- co-transport (blocked
by loop diuretics)
Distal convoluted tubule
4. Na+/H+ exchange (blocked by
carbonic anhydrase inhibitors)
5. Na+/Cl- co-transport (blocked by
thiazide diuretics)
Collecting tubule
6. Na+/K+ exchange (blocked by
potassium-sparing diuretics)
1
2
3
4
5
6
8. Diuretics – General Aspects
A very large proportion of NaCl and H2O that passes into the filtrate
via the glomerulus is reabsorbed – hence even a small inhibition of
reuptake can cause a marked increase in Na+ excretion
The site of action of many diuretics (thiazides, loop agents, potassium
sparing) is the apical membrane of tubular cells hence, if hydrophilic,
they must enter the filtrate to access that site
Entry to the filtrate is by either:
o glomerular filtration (for drug not bound to plasma protein)
o secretion via transport process in the proximal tubule
o two transport systems are important
• the organic anion transporters (OATs) – transport acidic drugs (e.g.
thiazides and loop agents)
• the organic cation transporters (OCTs) – transport basic drugs (e.g.
triamterene and amiloride)
o secretion results in the concentration of diuretic in the filtrate being higher
than that in blood, contributing to pharmacological selectivity
9. Secretion of Diuretics in the Proximal Tubule
Organic anion transporters (OATs)
o At the basolateral membrane organic
anions (OA-) enter cell by either diffusion,
or in exchange for α-ketoglutarate (α-KG)
via OATs
o α-KG is transported into cell (against a
concentration gradient) via a Na+-
dicarboxylate transporter
o At the apical membrane, OA- enters the
lumen via either multidrug resistance
protein 2 (MRP2), or OAT4 (in exchange for
α-KG)
Organic cation transporters (OCTs)
o At the basolateral membrane organic cations
(OC+) enter the cell either by diffusion, or
OCT, (both driven by negative potential of
cell interior and against a concentration
gradient)
o At the apical membrane, OC+ enters the
lumen via either multidrug resistance protein
1 (MRP1), or OC+/H+ antiporters (OCTN)
10. Mechanism of Action of Loop Diuretics
Na+
Na+
Na+
K+K+
K+ K+
Cl-2Cl- Cl-
Zona occludens
+ve -ve4-10 mV
Lumen Interstitium
Mg2+
Ca2+
Mg2+
Ca2+
Loop
diuretics
block
Maintainhightonicity
ofthemedulla
Tubular epithelium
of the TAL
Triple transporter
(Na+/K+/2Cl- co-
transporter; NKCC2)
K+/Cl- co-transporter
Na+/K+ ATPase
Key
K channel (ROMK)
Cl channel
TAL = thick
ascending limb of
the loop of Henlé
11. Pharmacodynamics
Inhibit the Na+/K+/2Cl- carrier by binding to the Cl- site and thus:
Loop Diuretics (1)
Principal drugs: Furosemide and Bumetanide
Possess an additional, indirect, venodilator action (before diuresis)
that is beneficial in pulmonary oedema cause by heart failure–
possibly results from: 1) increased formation of vasodilating
prostaglandins; 2) decreased responsiveness to angiotensin II and
noradrenaline; 3) opening of K+ channels in resistance vessels
o increase the load of Na+ delivered to distal regions of the nephron
(causing K+ loss)
o decrease the tonicity of the interstitium of the medulla
o prevent dilution of the filtrate in the thick ascending limb
o increase excretion of Ca2+ and Mg2+
Are ‘high ceiling’ agents causing 15-25% of filtered load of Na+ to
be excreted – rapid onset following IV administration
12. Loop Diuretics (2)
To treat hypertension (in patients resistant to other diuretics or anti-
hypertensive drugs - usually in the presence of renal insufficiency)
To reduce acutely elevated calcium levels in the serum
(hypercalcaemia) - note paracellular pathway in the thick
ascending limb of the loop of Henle
To increase urine volume in acute kidney failure
Clinical indications
To reduce salt and water overload associated with:
Acute pulmonary oedema (IV) Chronic heart failure
Chronic kidney failure Nephrotic syndrome
Hepatic cirrhosis with ascites
Pharmacokinetics
Well absorbed from the G.I. tract
Strongly bound to plasma protein
Enter nephron by the organic anion transport mechanism
13. Loop Diuretics (3)
Potassium loss producing low serum potassium levels
(hypokalaemia) – corrected by the concomitant use of potassium
sparing diuretics or potassium supplements
(note increases toxicity of digoxin and Class III antidysrhythmic drugs)
Increased plasma uric acid (hyperuricaemia) – partially
explained by competition between uric acid and loop agents
for the organic acid secretory mechanism in the proximal
tubule
Depletion of calcium and magnesium (paracellular pathway)
Decreased volume of circulating fluid (hypovolaemia) and
hypotension (particularly in the elderly)
Shift in acid-base towards alkaline side (metabolic alkalosis) –
caused by increased H+ secretion from intercalated cells in
collecting tubule
Adverse effects
14. Mechanism of Action of Thiazide Diuretics
Na+
Na+
Na+
+
K+
K+
Cl-
Cl- Cl-
Zona occludens
Lumen Interstitium
Thiazide
diuretics
block
Tubular epithelium
of the early distal
tubule
Na+/Cl- co-transporter
K+/Cl- co-transporter
Na+/K+ ATPase
Key
Cl- channel
K+ channel
K+
K+
15. Pharmacodynamics
Inhibit the Na+/Cl- carrier by binding to the Cl- site and thus:
Cause up to 5% of Na+ to be excreted, producing a modest
diuresis
Possess an additional, indirect, vasodilator action (mechanism
uncertain) that contributes to their effectiveness in the treatment
of hypertension (where they are used in combination with other
antihypertensive agents)
Thiazide Diuretics and Thiazide-Like (1)
Principal drugs: Bendroflumethiazide (thiazide): indapamide
and chlortalidone (thiazide-like)
o prevent the dilution of filtrate in the early distal tubule
o increase the load of Na+ delivered to the collecting tubule (causing
K+ loss)
o increase reabsorption of Ca2+ (cf. loop agents) (mechanism debatable)
16. Thiazide Diuretics (2)
Nephrogenic diabetes insipidus [caused by diminished
vasopressin responsiveness of the collecting ducts (paradoxically,
thiazides decrease the volume of urine – mechanism poorly
understood]
Renal stone disease (nephrolithiasis). Reduced urinary excretion
of Ca2+ discourages Ca2+ stone formation (mainly aggregates of
particles of calcium oxalate)
Severe resistant oedema (with a loop agent)
…and additionally in:
Clinical indications
Widely used in:
Mild heart failure Hypertension
Pharmacokinetics
Well absorbed from the G.I. tract
Enter nephron by the organic anion transport mechanism
(proximal tubule)
17. Thiazide Diuretics (3)
Adverse effects
Male sexual dysfunction
Hyperuricaemia – mechanism as for loop agents – may
precipitate gout
Metabolic alkalosis
Depletion of magnesium (not calcium)
Hypovolaemia and hypotension (particularly in the elderly)
Hypokalaemia, particularly likely and corrected as for loop
diuretics
Impaired glucose tolerance
18. Mechanism by which Loop and Thiazide Diuretics
Cause Potassium Loss – Relevant Physiology
Aldosterone, a steroid hormone,
acts via cytoplasmic receptors to:
1. increase synthesis of the
Na+/K+ATPase
2. increase synthesis of a protein
that activates the epithelial Na+
channel (ENaC)
increase the number of H2O channels
(aquaporins) in the cell membrane
ADH (vasopressin), a peptide
hormone, acts via G-protein
coupled receptors to:
Na+
Na+
K+
K+
Zona occludens
Lumen Interstitium
Late distal and collecting tubule
H2O
Cl-
Cl-
H2O
Na+
K+
K+ Channels (ROMK), secrete K+
into the urine in the collecting
tubule
Note that K+ effectively exchanges
for reabsorbed Na+
19. Mechanism by which Loop and Thiazide Diuretics
Cause Potassium Loss
Na+
Na+
K+
K+
Zona occludens
Lumen Interstitium
Late distal and collecting tubule
H2O
Cl-
Cl-
H2O
Na+
K+
1. Increased Na+ load caused by loop
or thiazide diuretic produces
enhanced reabsorption of Na+
2. Resulting charge separation
makes lumen more negative
and depolarizes the lumenal
vs. basolateral membrane
-ve
3. Increased driving force on K+
across the lumenal membrane
leads to enhanced secretion of
K+. (Secretion of H+ is similarly
affected)
4. Secreted K+ (and H+) ‘washed
away’ by increased urinary
flow rate – development of
hypokalaemia (and metabolic
alkalosis)
20. Mechanism of Action of the Potassium Sparing
Diuretics
Spironolactone and
Eplerenone
Compete with aldosterone for binding
to intracellular receptors causing:
1. decreased gene expression and
reduced synthesis of a protein
mediator that activates Na+
channels in the apical membrane
(site 1)
2. decreased numbers of
Na+/K+ATPase pumps in the
basolateral membrane (site 2)
Amiloride and Triamterene
Block the apical sodium channel
decrease Na reabsorption
Na+
Na+
K+
K+
Zona occludens
Lumen Interstitium
Late distal and collecting tubule
H2O
Cl-
Cl-
H2O
Na+
K+
X site 1
site 2
21. Potassium Sparing Diuretics
Spironolactone and eplerenone
Have limited diuretic action (modulated by aldosterone levels)
Competitively antagonise the action of aldosterone at cytoplasmic
aldosterone receptors, gain access to cytoplasm via the basolateral
membrane
Increase and decrease the excretion of Na+ and K+ respectively
Are well absorbed from the G.I. tract and in the case of spironolactone
rapidly metabolised to canrenone (which accounts for most of the
action of the drug)
Amiloride and Triamterene
Block lumenal sodium channels in the collecting tubules. Effect on ion
fluxes are similar to those of spironolactone
Enter the nephron via the organic cation transport system in the
proximal tubule
Triamterene is well absorbed from the G.I tract, absorption of amiloride
is poor
22. Clinical indications
The major use of potassium sparing diuretics is in conjunction
with other agents that cause potassium loss. Given alone, they
cause hyperkalaemia
Aldosterone antagonists are used in the treatment of:
o heart failure
o primary hyperaldosteronism (Conn’s syndrome)
o resistant essential hypertension
o secondary hyperaldosteronism (due to hepatic cirrhosis with
ascites)
Thiazide and loop diuretics activate the renin-angiotensin-
aldosterone system (in response to reduced blood pressure)
Aldosterone antagonists potentiate the actions of thiazide and
loop agents by blocking the effect of aldosterone