The document discusses pharmacokinetics, which is the quantitative study of how drugs move through the body via processes like absorption, distribution, metabolism and excretion. It describes how drugs are transported across membranes via passive diffusion or specialized transporters. Key factors that influence a drug's absorption, bioavailability and distribution are explained, such as solubility, route of administration, plasma protein binding and metabolism. Phase I and Phase II biotransformation reactions that metabolize drugs are also summarized.
I. This document discusses the processes involved in determining the concentration of a drug at its site of action, including absorption, distribution, tissue localization, biotransformation, and excretion. It also covers the movement of drugs across biological membranes via passive diffusion, facilitated transport, and active transport.
II. Drugs pass through biological membranes based on their size, shape, lipid solubility, and degree of ionization, which is affected by pH. Transport mechanisms include passive diffusion down a concentration gradient, as well as specialized carrier-mediated transport systems like facilitated diffusion and active transport.
III. Understanding these pharmacokinetic processes is important for determining a drug's pharmacodynamic effects and producing the desired therapeutic response without unwanted side effects
This document discusses various routes of drug administration including sublingual/buccal, rectal, parenteral (intravenous, intraarterial, intramuscular, subcutaneous), topical, ocular, inhalational, intranasal, and vaginal. For each route, it describes the absorption mechanism, onset of action, examples of drugs used, advantages, and factors influencing drug delivery and absorption. The document provides detailed information on considerations for different administration routes and factors affecting drug absorption through various tissues like skin, nasal mucosa, lungs etc.
Physico-chemical factors affecting drug absorption from the gastrointestinal tract include particle size, crystal form, solubility, and pH partitioning. Smaller particle sizes increase surface area and dissolution rate, improving absorption for poorly soluble drugs. Different crystal forms of the same drug can have differing dissolution rates and absorption. Drugs must be in solution prior to absorption, so factors influencing solubility such as pH, salts, and complexation also impact absorption. The pH partitioning theory explains how a drug's ionization state influences its absorption, based on both its pKa and the pH of absorption sites. Dosage form characteristics such as solution versus tablet can also significantly affect drug absorption rates.
This document discusses pharmacokinetics and specifically the absorption process. It defines absorption as the movement of a drug from its site of administration into the bloodstream. The four main processes involved in pharmacokinetics - absorption, distribution, metabolism, and elimination (ADME) - are initially outlined. Several mechanisms of drug absorption in the gastrointestinal tract are then described in detail, including passive diffusion, carrier-mediated transport, phagocytosis, and others. Factors that can influence drug absorption and bioavailability are also summarized, such as pharmaceutical factors like drug solubility and formulation, as well as pharmacological factors like gastric emptying time.
The document summarizes several patient-related factors that can affect drug absorption from the gastrointestinal tract. It discusses how age can impact gastric pH and intestinal surface area in infants and the elderly. It also outlines how gastric emptying rate, intestinal transit time, gastrointestinal pH, blood flow to the GI tract, and presystemic metabolism can all influence the degree and rate of drug absorption. Disease states like gastrointestinal disorders and cardiovascular conditions are also noted as potential factors.
Drug distribution refers to the reversible transfer of drugs from the bloodstream to tissues throughout the body. Once absorbed, drugs diffuse from areas of high concentration (blood) to areas of lower concentration (tissues). This process continues until equilibrium is reached.
The rate and extent of distribution is influenced by several factors. These include a drug's physicochemical properties like size and solubility, tissue permeability, blood flow to organs, and binding of drugs to plasma proteins and tissues. Physiological barriers like the blood-brain barrier also control distribution to certain tissues. The non-uniform distribution of drugs throughout the body is due to tissues absorbing drugs at different rates and to varying extents based on these distribution factors.
1. Distribution involves the reversible transfer of a drug between compartments like plasma, tissues, and organs. It plays a role in the onset, intensity, and duration of a drug's effects.
2. The volume of distribution is used to quantify how a drug is distributed between plasma and the rest of the body. It is defined as the volume needed to contain the total amount of drug at the observed plasma concentration.
3. Many factors influence how a drug is distributed among tissues, including tissue permeability, blood flow, size of the tissue, and binding to proteins or other components. Highly perfused tissues are rapidly equilibrated while distribution to less vascular tissues is slower.
This document discusses factors that affect the absorption of drugs in the body. It explains that absorption is the movement of drugs from the site of administration into blood circulation. The rate and extent of absorption determine the duration and intensity of drug action. Absorption is influenced by physico-chemical properties of drugs, dosage form, concentration, blood flow, area of absorbing surface, and route of administration. Drugs are mainly absorbed from the gastrointestinal tract and parenterally via intramuscular or subcutaneous injection sites or through inhalation into the lungs.
I. This document discusses the processes involved in determining the concentration of a drug at its site of action, including absorption, distribution, tissue localization, biotransformation, and excretion. It also covers the movement of drugs across biological membranes via passive diffusion, facilitated transport, and active transport.
II. Drugs pass through biological membranes based on their size, shape, lipid solubility, and degree of ionization, which is affected by pH. Transport mechanisms include passive diffusion down a concentration gradient, as well as specialized carrier-mediated transport systems like facilitated diffusion and active transport.
III. Understanding these pharmacokinetic processes is important for determining a drug's pharmacodynamic effects and producing the desired therapeutic response without unwanted side effects
This document discusses various routes of drug administration including sublingual/buccal, rectal, parenteral (intravenous, intraarterial, intramuscular, subcutaneous), topical, ocular, inhalational, intranasal, and vaginal. For each route, it describes the absorption mechanism, onset of action, examples of drugs used, advantages, and factors influencing drug delivery and absorption. The document provides detailed information on considerations for different administration routes and factors affecting drug absorption through various tissues like skin, nasal mucosa, lungs etc.
Physico-chemical factors affecting drug absorption from the gastrointestinal tract include particle size, crystal form, solubility, and pH partitioning. Smaller particle sizes increase surface area and dissolution rate, improving absorption for poorly soluble drugs. Different crystal forms of the same drug can have differing dissolution rates and absorption. Drugs must be in solution prior to absorption, so factors influencing solubility such as pH, salts, and complexation also impact absorption. The pH partitioning theory explains how a drug's ionization state influences its absorption, based on both its pKa and the pH of absorption sites. Dosage form characteristics such as solution versus tablet can also significantly affect drug absorption rates.
This document discusses pharmacokinetics and specifically the absorption process. It defines absorption as the movement of a drug from its site of administration into the bloodstream. The four main processes involved in pharmacokinetics - absorption, distribution, metabolism, and elimination (ADME) - are initially outlined. Several mechanisms of drug absorption in the gastrointestinal tract are then described in detail, including passive diffusion, carrier-mediated transport, phagocytosis, and others. Factors that can influence drug absorption and bioavailability are also summarized, such as pharmaceutical factors like drug solubility and formulation, as well as pharmacological factors like gastric emptying time.
The document summarizes several patient-related factors that can affect drug absorption from the gastrointestinal tract. It discusses how age can impact gastric pH and intestinal surface area in infants and the elderly. It also outlines how gastric emptying rate, intestinal transit time, gastrointestinal pH, blood flow to the GI tract, and presystemic metabolism can all influence the degree and rate of drug absorption. Disease states like gastrointestinal disorders and cardiovascular conditions are also noted as potential factors.
Drug distribution refers to the reversible transfer of drugs from the bloodstream to tissues throughout the body. Once absorbed, drugs diffuse from areas of high concentration (blood) to areas of lower concentration (tissues). This process continues until equilibrium is reached.
The rate and extent of distribution is influenced by several factors. These include a drug's physicochemical properties like size and solubility, tissue permeability, blood flow to organs, and binding of drugs to plasma proteins and tissues. Physiological barriers like the blood-brain barrier also control distribution to certain tissues. The non-uniform distribution of drugs throughout the body is due to tissues absorbing drugs at different rates and to varying extents based on these distribution factors.
1. Distribution involves the reversible transfer of a drug between compartments like plasma, tissues, and organs. It plays a role in the onset, intensity, and duration of a drug's effects.
2. The volume of distribution is used to quantify how a drug is distributed between plasma and the rest of the body. It is defined as the volume needed to contain the total amount of drug at the observed plasma concentration.
3. Many factors influence how a drug is distributed among tissues, including tissue permeability, blood flow, size of the tissue, and binding to proteins or other components. Highly perfused tissues are rapidly equilibrated while distribution to less vascular tissues is slower.
This document discusses factors that affect the absorption of drugs in the body. It explains that absorption is the movement of drugs from the site of administration into blood circulation. The rate and extent of absorption determine the duration and intensity of drug action. Absorption is influenced by physico-chemical properties of drugs, dosage form, concentration, blood flow, area of absorbing surface, and route of administration. Drugs are mainly absorbed from the gastrointestinal tract and parenterally via intramuscular or subcutaneous injection sites or through inhalation into the lungs.
The small intestine, specifically the duodenum and jejunum, is the primary site of drug absorption from the gastrointestinal tract due to its large surface area and favorable permeability. Factors like gastrointestinal pH, transit time, enzyme activity and presence of bile/digestive juices influence the absorption of drugs administered orally. The absorption window for most drugs is in the small intestine, before the contents empty into the large intestine where conditions are less favorable for absorption.
Module 2 pharmacokinetics and drug metabolismjulialoiko
This document provides an overview of pharmacokinetics concepts related to drug absorption, distribution, metabolism and elimination in the body. It discusses how drugs move through membranes via passive diffusion or active transport processes. Key determinants of absorption include a drug's lipid solubility and ionization state, which affect its ability to pass cell membranes. The liver plays a major role in drug metabolism and elimination through first-pass clearance of orally administered drugs. Pharmacokinetic parameters like volume of distribution, clearance and half-life help characterize a drug's disposition in the body.
The document discusses absorption and distribution of drugs. It defines absorption as the movement of drugs from the site of administration into circulation. It is affected by drug properties like solubility, molecular weight, and route of administration. Distribution refers to the reversible transfer of drugs between blood and tissues, determined by factors like lipid solubility, protein binding, and regional blood flow. The apparent volume of distribution describes the theoretical volume required to contain the entire drug dose at the same concentration as plasma.
This document provides an overview of pharmacokinetics, which is the quantitative study of how the body acts on drugs. It describes the four main components of pharmacokinetics - absorption, distribution, metabolism, and excretion. Absorption refers to how drugs enter the bloodstream, distribution is how drugs spread to tissues, metabolism is how drugs are chemically altered, and excretion is how drugs and their metabolites leave the body. Key factors that determine a drug's pharmacokinetic properties and how it behaves in the body are also discussed.
The document discusses the process of excretion in the human body. Medications are eliminated from the body through excretion, which primarily occurs through the kidneys. The kidneys filter waste from the blood through glomerular filtration and either reabsorb or actively secrete drugs and other molecules into the urine through tubular transport processes for excretion from the body.
The document discusses the absorption of drugs from the gastrointestinal tract. It defines absorption as the movement of an unchanged drug from the site of administration into systemic circulation. There are several mechanisms of drug absorption including passive diffusion down a concentration gradient, carrier-mediated transport like facilitated diffusion and active transport, and endocytosis. The key sites of drug absorption in the GI tract are the stomach, small intestine, and to a lesser extent the large intestine. Factors like pH, transit time, surface area, and mechanisms of absorption determine how well and how quickly a drug is absorbed from the GI tract.
Factors affecting each of the proceses- Absorption, Distribution, Metabolism and Elimination of Drugs and associated Pharmacokinetic Parameters- Bioavailability, Volume of Distribution, Half life of drug, Rate of Clearance
Here is an outline of the advantages and disadvantages of the specified routes of drug administration:
Oral route:
- Advantages: Ease of administration, patient acceptance
- Disadvantages: Extensive first-pass metabolism in liver, variable absorption, gastrointestinal irritation
Sublingual route:
- Advantages: Rapid onset, avoids first-pass metabolism
- Disadvantages: Small surface area, drug must be soluble and pass buccal mucosa
Rectal route:
- Advantages: Avoidance of first-pass metabolism, noninvasive
- Disadvantages: Variable and slow absorption, not suitable for all drugs, socially unacceptable
Inhalational route:
- Advantages
Pharmacokinetics is the study of how drugs move through the body, including absorption, distribution, metabolism, and excretion. Absorption is the process by which drugs enter systemic circulation from the site of administration. Several factors influence a drug's absorption, including its physicochemical properties, dosage form characteristics, and patient factors. The document discusses various mechanisms of drug absorption like passive diffusion, facilitated diffusion, active transport, and endocytosis. It also covers concepts like pH partition theory, factors affecting dissolution, and the importance of a drug's ionization for absorption.
The dynamics of drug ABSORPTION and DISTRIBUTIONHimaniTailor
The document discusses the dynamics of drug absorption and distribution. It describes how physicochemical factors like molecular size, ionization, and lipid solubility determine how drugs pass through membranes. Drugs can cross cell membranes through passive diffusion, facilitated transport, or active transport. Absorption involves drugs crossing membranes and entering blood circulation, which depends on factors like solubility, molecular size, and dosage form. Distribution involves drugs spreading throughout tissues, influenced by blood flow, protein binding, and access to different compartments like the brain or placenta.
This document discusses factors that influence drug absorption in the gastrointestinal tract (GIT). It covers membrane physiology, GIT motility, the effect of age, clinical factors like diseases, and how food and drugs can impact drug absorption in the GIT. Key factors mentioned are gastric emptying rate, intestinal pH, surface area, transit time, blood flow, and how these can be altered by disease states or drugs, influencing a drug's absorption and bioavailability.
PHYSIOLOGIC FACTORS RELATED TO DRUG ABSORPTIONN Anusha
ROUTES OF DRUG ADMINISTRATION
The route of administration (ROA) that is chosen has a large impact on how fast the drug is taken up and how much of it arrives at its destination in an active form.
MEMBRANE PHYSIOLOGY
The cell membrane also known as the plasma membrane or cytoplasmic membrane is a biological membrane that separates the interior of all cells from the outside environment.
GSTERO-INTESTINAL PHYSIOLOGY
AGE
Drugs are eliminated from the body through metabolism and excretion. The major routes of excretion include renal (kidney), biliary (bile), fecal, alveolar (lungs), and minor routes like skin, saliva, sweat, hair, and milk. The kidney is the most common route and filters drugs through glomerular filtration while tubular secretion and reabsorption also influence renal excretion. Certain drugs can interact by competing for tubular secretion. Biliary excretion and enterohepatic circulation recirculate some drugs through the liver and intestines. Adjusting urine pH can enhance the excretion of acidic or alkaline drugs. Accumulation may occur if drugs rely on renal excretion and
This document discusses pharmacokinetics, specifically absorption, distribution, metabolism, and excretion of drugs. It covers the following key points:
- Drug absorption occurs through various routes like the gastrointestinal tract, lungs, skin and is influenced by factors like pH, blood flow and lipid solubility.
- Distribution of drugs depends on capillary permeability, blood flow, protein binding and is described using the volume of distribution.
- Metabolism occurs mainly in the liver through cytochrome P450 enzymes and conjugation reactions, and can inactivate drugs, produce active metabolites, or activate prodrugs.
- Absorption, distribution and metabolism determine the bioavailability of drugs and their delivery to sites of action.
This document discusses several patient-related factors that can affect oral drug absorption, including physiological factors like gastric emptying time, gastrointestinal motility, disease states, food, and drug interactions. It provides details on how each of these factors can impact drug dissolution, permeability through membranes, and transit time in the gastrointestinal tract, ultimately influencing drug bioavailability. Certain diseases are noted to alter gastric pH, intestinal permeability and blood flow, motility, or surface area, thereby impacting absorption of some drugs. The effects of food, age, and other drugs that may change gastric emptying or motility are also summarized.
The document discusses drug absorption, which is the movement of unchanged drug molecules from the site of administration into systemic circulation. There are several mechanisms of drug absorption, including passive diffusion down a concentration gradient, carrier-mediated transport using protein transporters, and active transport against a concentration gradient using cellular energy. The rate and amount of drug absorption depends on its physicochemical properties as well as the absorption site. Facilitated diffusion and active transport allow for faster absorption than passive diffusion alone.
This document provides an overview of drug distribution and clearance. It discusses several key points:
1) Drug distribution refers to the reversible transfer of drugs between compartments in the body, reaching equilibrium between blood and tissues. The rate and extent of distribution provides information about a drug's pharmacokinetics.
2) The volume of distribution is used to quantify how a drug is distributed between plasma and tissues after dosing. It represents the apparent volume required for the total amount of drug administered.
3) Many factors influence a drug's distribution, including physicochemical properties, protein and tissue binding, blood flow rates, and physiological barriers. Highly perfused tissues equilibrate quickly with lipid-soluble drugs.
Patient-related factors can affect drug absorption in several ways. Age affects absorption, as infants have high gastric pH and low intestinal surface area while the elderly have altered gastric emptying, decreased intestinal surface, higher achlorhydria, and bacterial overgrowth. Gastric emptying is the rate at which the stomach empties into the intestine, and is a rate-limiting step for absorption. Rapid emptying is advisable for some drugs, while delayed emptying is advisable for others. Intestinal transit also influences absorption, as prolonged transit in the small intestine allows for more complete absorption. Gastrointestinal pH, blood flow, diseases, and presynaptic metabolism can also impact drug bioavailability.
1) Many physiological factors affect drug absorption from the gastrointestinal tract, including age, gastric emptying time, intestinal transit time, gastrointestinal pH, disease states, blood flow through the GI tract, contact time with the GI mucosa, and gastrointestinal contents.
2) Specifically, drug absorption is impacted by changes in a person's age, as well as factors that can speed up or slow down gastric emptying and intestinal transit, such as the type and volume of food consumed, body position, exercise, and certain diseases.
3) The pH levels throughout the GI tract also influence drug absorption by impacting drug stability, dissolution, and disintegration in the stomach versus intestines. Disease states like gastric disorders can further impact
This document provides an overview of pharmacokinetic principles including definitions of pharmacology and pharmacokinetics. It describes how drugs are absorbed, distributed, and eliminated in the body. Key points include how drugs pass through membranes via passive diffusion, active transport, or vesicles. Distribution depends on plasma protein binding, tissue binding, and physicochemical properties. The liver and kidneys aid in drug metabolism and excretion from the body. Factors like pH, blood flow, dosage form, and route of administration influence drug absorption and disposition.
The document discusses pharmacokinetics, which is the quantitative study of how drugs move through the body. It describes the pharmacokinetic processes of absorption, distribution, metabolism, and excretion that determine how drugs act in the body. These processes are influenced by factors like a drug's chemical properties, formulation, route of administration, and interactions with other substances. Understanding a drug's pharmacokinetics is important for determining dosing to achieve optimal therapeutic effects without toxicity.
This document discusses pharmacokinetics and provides details about absorption, distribution, and bioavailability of drugs. It defines key pharmacokinetic terms and describes factors that influence absorption such as solubility, concentration, route of administration, and mechanisms of absorption including passive diffusion, active transport, and pinocytosis. Membrane permeability and drug properties like pH and lipid solubility are discussed. The document also covers volume of distribution, plasma protein binding, tissue storage, and barriers to drug distribution like the blood-brain barrier.
The small intestine, specifically the duodenum and jejunum, is the primary site of drug absorption from the gastrointestinal tract due to its large surface area and favorable permeability. Factors like gastrointestinal pH, transit time, enzyme activity and presence of bile/digestive juices influence the absorption of drugs administered orally. The absorption window for most drugs is in the small intestine, before the contents empty into the large intestine where conditions are less favorable for absorption.
Module 2 pharmacokinetics and drug metabolismjulialoiko
This document provides an overview of pharmacokinetics concepts related to drug absorption, distribution, metabolism and elimination in the body. It discusses how drugs move through membranes via passive diffusion or active transport processes. Key determinants of absorption include a drug's lipid solubility and ionization state, which affect its ability to pass cell membranes. The liver plays a major role in drug metabolism and elimination through first-pass clearance of orally administered drugs. Pharmacokinetic parameters like volume of distribution, clearance and half-life help characterize a drug's disposition in the body.
The document discusses absorption and distribution of drugs. It defines absorption as the movement of drugs from the site of administration into circulation. It is affected by drug properties like solubility, molecular weight, and route of administration. Distribution refers to the reversible transfer of drugs between blood and tissues, determined by factors like lipid solubility, protein binding, and regional blood flow. The apparent volume of distribution describes the theoretical volume required to contain the entire drug dose at the same concentration as plasma.
This document provides an overview of pharmacokinetics, which is the quantitative study of how the body acts on drugs. It describes the four main components of pharmacokinetics - absorption, distribution, metabolism, and excretion. Absorption refers to how drugs enter the bloodstream, distribution is how drugs spread to tissues, metabolism is how drugs are chemically altered, and excretion is how drugs and their metabolites leave the body. Key factors that determine a drug's pharmacokinetic properties and how it behaves in the body are also discussed.
The document discusses the process of excretion in the human body. Medications are eliminated from the body through excretion, which primarily occurs through the kidneys. The kidneys filter waste from the blood through glomerular filtration and either reabsorb or actively secrete drugs and other molecules into the urine through tubular transport processes for excretion from the body.
The document discusses the absorption of drugs from the gastrointestinal tract. It defines absorption as the movement of an unchanged drug from the site of administration into systemic circulation. There are several mechanisms of drug absorption including passive diffusion down a concentration gradient, carrier-mediated transport like facilitated diffusion and active transport, and endocytosis. The key sites of drug absorption in the GI tract are the stomach, small intestine, and to a lesser extent the large intestine. Factors like pH, transit time, surface area, and mechanisms of absorption determine how well and how quickly a drug is absorbed from the GI tract.
Factors affecting each of the proceses- Absorption, Distribution, Metabolism and Elimination of Drugs and associated Pharmacokinetic Parameters- Bioavailability, Volume of Distribution, Half life of drug, Rate of Clearance
Here is an outline of the advantages and disadvantages of the specified routes of drug administration:
Oral route:
- Advantages: Ease of administration, patient acceptance
- Disadvantages: Extensive first-pass metabolism in liver, variable absorption, gastrointestinal irritation
Sublingual route:
- Advantages: Rapid onset, avoids first-pass metabolism
- Disadvantages: Small surface area, drug must be soluble and pass buccal mucosa
Rectal route:
- Advantages: Avoidance of first-pass metabolism, noninvasive
- Disadvantages: Variable and slow absorption, not suitable for all drugs, socially unacceptable
Inhalational route:
- Advantages
Pharmacokinetics is the study of how drugs move through the body, including absorption, distribution, metabolism, and excretion. Absorption is the process by which drugs enter systemic circulation from the site of administration. Several factors influence a drug's absorption, including its physicochemical properties, dosage form characteristics, and patient factors. The document discusses various mechanisms of drug absorption like passive diffusion, facilitated diffusion, active transport, and endocytosis. It also covers concepts like pH partition theory, factors affecting dissolution, and the importance of a drug's ionization for absorption.
The dynamics of drug ABSORPTION and DISTRIBUTIONHimaniTailor
The document discusses the dynamics of drug absorption and distribution. It describes how physicochemical factors like molecular size, ionization, and lipid solubility determine how drugs pass through membranes. Drugs can cross cell membranes through passive diffusion, facilitated transport, or active transport. Absorption involves drugs crossing membranes and entering blood circulation, which depends on factors like solubility, molecular size, and dosage form. Distribution involves drugs spreading throughout tissues, influenced by blood flow, protein binding, and access to different compartments like the brain or placenta.
This document discusses factors that influence drug absorption in the gastrointestinal tract (GIT). It covers membrane physiology, GIT motility, the effect of age, clinical factors like diseases, and how food and drugs can impact drug absorption in the GIT. Key factors mentioned are gastric emptying rate, intestinal pH, surface area, transit time, blood flow, and how these can be altered by disease states or drugs, influencing a drug's absorption and bioavailability.
PHYSIOLOGIC FACTORS RELATED TO DRUG ABSORPTIONN Anusha
ROUTES OF DRUG ADMINISTRATION
The route of administration (ROA) that is chosen has a large impact on how fast the drug is taken up and how much of it arrives at its destination in an active form.
MEMBRANE PHYSIOLOGY
The cell membrane also known as the plasma membrane or cytoplasmic membrane is a biological membrane that separates the interior of all cells from the outside environment.
GSTERO-INTESTINAL PHYSIOLOGY
AGE
Drugs are eliminated from the body through metabolism and excretion. The major routes of excretion include renal (kidney), biliary (bile), fecal, alveolar (lungs), and minor routes like skin, saliva, sweat, hair, and milk. The kidney is the most common route and filters drugs through glomerular filtration while tubular secretion and reabsorption also influence renal excretion. Certain drugs can interact by competing for tubular secretion. Biliary excretion and enterohepatic circulation recirculate some drugs through the liver and intestines. Adjusting urine pH can enhance the excretion of acidic or alkaline drugs. Accumulation may occur if drugs rely on renal excretion and
This document discusses pharmacokinetics, specifically absorption, distribution, metabolism, and excretion of drugs. It covers the following key points:
- Drug absorption occurs through various routes like the gastrointestinal tract, lungs, skin and is influenced by factors like pH, blood flow and lipid solubility.
- Distribution of drugs depends on capillary permeability, blood flow, protein binding and is described using the volume of distribution.
- Metabolism occurs mainly in the liver through cytochrome P450 enzymes and conjugation reactions, and can inactivate drugs, produce active metabolites, or activate prodrugs.
- Absorption, distribution and metabolism determine the bioavailability of drugs and their delivery to sites of action.
This document discusses several patient-related factors that can affect oral drug absorption, including physiological factors like gastric emptying time, gastrointestinal motility, disease states, food, and drug interactions. It provides details on how each of these factors can impact drug dissolution, permeability through membranes, and transit time in the gastrointestinal tract, ultimately influencing drug bioavailability. Certain diseases are noted to alter gastric pH, intestinal permeability and blood flow, motility, or surface area, thereby impacting absorption of some drugs. The effects of food, age, and other drugs that may change gastric emptying or motility are also summarized.
The document discusses drug absorption, which is the movement of unchanged drug molecules from the site of administration into systemic circulation. There are several mechanisms of drug absorption, including passive diffusion down a concentration gradient, carrier-mediated transport using protein transporters, and active transport against a concentration gradient using cellular energy. The rate and amount of drug absorption depends on its physicochemical properties as well as the absorption site. Facilitated diffusion and active transport allow for faster absorption than passive diffusion alone.
This document provides an overview of drug distribution and clearance. It discusses several key points:
1) Drug distribution refers to the reversible transfer of drugs between compartments in the body, reaching equilibrium between blood and tissues. The rate and extent of distribution provides information about a drug's pharmacokinetics.
2) The volume of distribution is used to quantify how a drug is distributed between plasma and tissues after dosing. It represents the apparent volume required for the total amount of drug administered.
3) Many factors influence a drug's distribution, including physicochemical properties, protein and tissue binding, blood flow rates, and physiological barriers. Highly perfused tissues equilibrate quickly with lipid-soluble drugs.
Patient-related factors can affect drug absorption in several ways. Age affects absorption, as infants have high gastric pH and low intestinal surface area while the elderly have altered gastric emptying, decreased intestinal surface, higher achlorhydria, and bacterial overgrowth. Gastric emptying is the rate at which the stomach empties into the intestine, and is a rate-limiting step for absorption. Rapid emptying is advisable for some drugs, while delayed emptying is advisable for others. Intestinal transit also influences absorption, as prolonged transit in the small intestine allows for more complete absorption. Gastrointestinal pH, blood flow, diseases, and presynaptic metabolism can also impact drug bioavailability.
1) Many physiological factors affect drug absorption from the gastrointestinal tract, including age, gastric emptying time, intestinal transit time, gastrointestinal pH, disease states, blood flow through the GI tract, contact time with the GI mucosa, and gastrointestinal contents.
2) Specifically, drug absorption is impacted by changes in a person's age, as well as factors that can speed up or slow down gastric emptying and intestinal transit, such as the type and volume of food consumed, body position, exercise, and certain diseases.
3) The pH levels throughout the GI tract also influence drug absorption by impacting drug stability, dissolution, and disintegration in the stomach versus intestines. Disease states like gastric disorders can further impact
This document provides an overview of pharmacokinetic principles including definitions of pharmacology and pharmacokinetics. It describes how drugs are absorbed, distributed, and eliminated in the body. Key points include how drugs pass through membranes via passive diffusion, active transport, or vesicles. Distribution depends on plasma protein binding, tissue binding, and physicochemical properties. The liver and kidneys aid in drug metabolism and excretion from the body. Factors like pH, blood flow, dosage form, and route of administration influence drug absorption and disposition.
The document discusses pharmacokinetics, which is the quantitative study of how drugs move through the body. It describes the pharmacokinetic processes of absorption, distribution, metabolism, and excretion that determine how drugs act in the body. These processes are influenced by factors like a drug's chemical properties, formulation, route of administration, and interactions with other substances. Understanding a drug's pharmacokinetics is important for determining dosing to achieve optimal therapeutic effects without toxicity.
This document discusses pharmacokinetics and provides details about absorption, distribution, and bioavailability of drugs. It defines key pharmacokinetic terms and describes factors that influence absorption such as solubility, concentration, route of administration, and mechanisms of absorption including passive diffusion, active transport, and pinocytosis. Membrane permeability and drug properties like pH and lipid solubility are discussed. The document also covers volume of distribution, plasma protein binding, tissue storage, and barriers to drug distribution like the blood-brain barrier.
Presentation covers the basics of pharmacokinetic. Mechanism for the transport of drug molecule. Absorption, factors affecting on absorption of drugs. Concept of bioavailability. Distribution, plasma protein binding, tissue binding, barriers.
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This document discusses the key concepts of pharmacokinetics including absorption, distribution, and bioavailability of drugs in the human body. It explains that pharmacokinetics is the quantitative study of how drugs move through the body and the factors that determine absorption rates like solubility, vascularity, and route of administration. It also describes the different mechanisms of transport including passive diffusion, carrier transport, and active transport. Distribution of drugs depends on factors like plasma protein binding and volume of distribution, which is the theoretical volume in which the drug is evenly distributed based on plasma concentration.
This document provides an overview of pharmacology and drug absorption. It defines pharmacology as the science of drugs and describes pharmacokinetics as what the body does to drugs and pharmacodynamics as what drugs do to the body. The key parameters of pharmacokinetics - absorption, distribution, metabolism and excretion - are explained. Drug absorption mechanisms like passive diffusion, carrier-mediated transport and active transport are summarized. Factors affecting drug absorption like solubility, concentration and route of administration are also highlighted. The document concludes by defining bioavailability and bioequivalence.
The document discusses various aspects of pharmacokinetics including drug absorption, distribution, metabolism, and excretion. It explains that pharmacokinetics involves four main processes: absorption of drugs from their site of administration into circulation, distribution of drugs from blood to tissues, metabolism of drugs by the liver and other organs, and excretion of drugs and their metabolites from the body. It also discusses factors that influence these pharmacokinetic processes such as drug and biological properties.
This document discusses pharmacokinetics related to drug absorption and distribution. It defines key terms like absorption, bioavailability, bioequivalence, apparent volume of distribution, and plasma protein binding. Several factors that influence drug absorption via different routes of administration are described, including solubility, concentration gradient, vascularity, and drug interactions. Drug distribution is affected by lipid/water solubility, protein binding, tissue affinity, and disease states. The volume of distribution represents the hypothetical volume needed to contain the administered dose at the observed plasma concentration.
This document discusses pharmacokinetics and factors that influence drug absorption. It defines pharmacokinetics as the study of the movement of drugs in the body, including absorption, distribution, metabolism and excretion. It describes the various routes of drug administration and factors that influence the rate and extent of drug absorption such as physicochemical properties, dosage form, presence of food or other drugs, and pH of the gastrointestinal tract. It also explains the different mechanisms of drug absorption, including passive diffusion, facilitated diffusion, active transport, filtration and endocytosis.
1. Drug absorption involves the movement of a drug from its site of administration into the bloodstream or lymphatic system without being chemically altered.
2. There are several mechanisms of drug absorption including passive diffusion, carrier-mediated transport, endocytosis, exocytosis, and pore transport.
3. Factors that influence the rate and extent of drug absorption include the drug's physical and chemical properties, the dosage form characteristics, physiological factors in the body, and the route of administration. Understanding these factors is important for determining drug bioavailability and dosing.
This document discusses pharmacokinetics, which is the quantitative study of how drugs move through the body. It describes how drugs are transported across biological membranes via passive diffusion, facilitated diffusion, or active transport. It then discusses absorption, distribution, metabolism, and excretion of drugs. Absorption is affected by factors like solubility, concentration, and route of administration. Distribution depends on lipid solubility, protein binding, and regional blood flow. Drugs undergo biotransformation primarily in the liver and are metabolized to inactive or active forms. Excretion occurs primarily through urine or feces, with some drugs excreted in sweat, saliva, exhaled air, or milk.
The document discusses pharmacokinetics, which is the quantitative study of how drugs move through the body. It covers the key processes of absorption, distribution, metabolism, and excretion (ADME) that drugs undergo. Absorption governs how drugs enter circulation after administration. Distribution determines where drugs go in tissues. Metabolism, or biotransformation, alters drugs' chemical structures, often making them more water-soluble for excretion. These processes determine a drug's effects over time.
This document discusses the basic principles of pharmacokinetics, which describes how the body handles drugs over time. It covers the key processes of drug absorption, distribution, metabolism and excretion that determine a drug's levels in tissues. Drug absorption involves passing through cell membranes, which is influenced by a drug's size, lipid solubility, ionization state and other physicochemical properties. The document then discusses the various routes of drug administration and factors affecting absorption through each route. It also introduces concepts like bioavailability and bioequivalence. In distribution, drugs enter the bloodstream and distribute to tissues, with highly perfused organs receiving more drug initially.
1. Absorption is the movement of a drug into the blood circulation. Drugs can cross cell membranes through passive transport like diffusion or facilitated diffusion, or through active transport using carrier proteins and ATP.
2. Passive transport includes diffusion down a concentration gradient, facilitated diffusion using carrier proteins, filtration through membrane pores, and osmosis. Active transport moves drugs against a concentration gradient using ATP, including primary transport directly using ATP or secondary co-transport coupling to another gradient.
3. Many factors influence drug absorption, including lipid solubility, molecular size, particle size, degree of ionization, physical and chemical form, dosage form, concentration, area of absorptive surface, vascularity, pH,
This document discusses factors that affect oral drug absorption. It describes three main categories of factors: physiological, physical-chemical, and formulation factors. Under physiological factors, it discusses membrane physiology, how drugs pass membranes through different transport mechanisms like passive diffusion and active transport, and gastrointestinal physiology. It provides details on the anatomy and environments of different parts of the GI tract and how they impact drug absorption. It also discusses gastric emptying time and how it affects drug absorption.
Membranes play an important role in drug transport. Drugs can pass through membranes via passive diffusion down a concentration gradient, facilitated diffusion using transporters, or active transport against a gradient using energy. Passive diffusion depends on a drug's lipid solubility, molecular size, ionization state, and concentration differences. Facilitated diffusion utilizes transporters to aid movement of substrates like glucose. Active transport selectively accumulates drugs on one side of the membrane using energy.
This document discusses the pharmacokinetics of drug absorption and distribution. It begins by defining pharmacokinetics as the quantitative study of how the body acts on drugs. It then discusses the different mechanisms of drug transportation across cell membranes, including passive diffusion, filtration, and carrier-mediated transport like facilitated diffusion and active transport. It describes factors that affect drug absorption like solubility, concentration, and route of administration. It also discusses concepts like bioavailability, bioequivalence, distribution, redistribution, barriers to drug movement, and plasma protein binding. In summary, it provides an overview of how drugs move into, through, and out of the body after administration.
This document discusses the pharmacokinetics of drug absorption and distribution. It covers several key topics in 3 paragraphs:
Membrane transporters, including passive diffusion, carrier-mediated transport processes like facilitated diffusion and active transport, allow drugs to be absorbed into the bloodstream. Factors like a drug's solubility, size and lipid solubility determine which transport mechanisms are used.
Absorption refers to the movement of drugs from the site of administration into circulation. The rate and extent of absorption depends on factors like solubility, concentration, administering area, vascularity and route. Oral drugs are affected by things like acidity, particle size and food. Injection routes see faster absorption.
Distribution
This document discusses pharmacokinetics, specifically absorption and distribution of drugs. It covers several key topics:
1. Modes of permeation and transport across cell membranes including passive diffusion, carrier-mediated transport, pinocytosis, and filtration.
2. Factors that influence absorption including drug properties like size, ionization, and lipid solubility as well as routes of administration.
3. Distribution of drugs in the body and factors that affect it like lipid solubility, ionization, and drug-drug interactions.
Introduction to Biopharmaceutics and PharmacokineticsFulchand Kajale
This document provides an introduction to biopharmaceutics and pharmacokinetics. It discusses how biopharmaceutics examines the relationship between a drug's physical/chemical properties, dosage form, and route of administration on systemic absorption. The four key aspects of pharmacokinetics are also introduced: absorption, distribution, metabolism, and excretion. Various mechanisms of drug absorption across cell membranes are then described in detail, including passive diffusion, active transport, and carrier-mediated transport systems.
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Dispensing of drugs to inpatients, types of drug distribution systems, charging policy and labelling, Dispensing of drugs to ambulatory patients, and Dispensing of controlled drugs.
Community Pharmacy
Organization and structure of retail and wholesale drug store, types and design, Legal requirements for establishment and maintenance of a drug store, Dispensing of proprietary products, maintenance of records of retail
and wholesale drug store
The document discusses various aspects of managing a community pharmacy, including:
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Definition, functions of hospital pharmacy, Organization structure, Location, Layout and staff requirements, and Responsibilities and
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Definition, Classification of hospital- Primary, Secondary and Tertiary hospitals, Classification based on clinical and non- clinical basis, Organization Structure of a Hospital, and Medical staffs involved in the
hospital and their functions.
This document provides information on aminoglycoside and macrolide antibiotics. It discusses the mechanism of action, toxicity, and examples of various aminoglycoside antibiotics like streptomycin, gentamicin, tobramycin, and erythromycin. The key points are that aminoglycosides inhibit bacterial protein synthesis by binding to bacterial ribosomes, but can cause ototoxicity and nephrotoxicity as side effects. Erythromycin was the first macrolide antibiotic discovered and works by binding to bacterial ribosomes to inhibit protein synthesis.
The document discusses tetracyclines and chloramphenicol antibiotics. It describes that tetracyclines are broad-spectrum antibiotics derived from soil actinomycetes that are bacteriostatic and inhibit protein synthesis. Chloramphenicol also inhibits bacterial protein synthesis. Both have broad antimicrobial spectra but resistance has developed. Adverse effects include bone marrow suppression for chloramphenicol and irritation.
Sulfonamides were the first effective antimicrobial agents against bacterial infections. They work by inhibiting the bacterial enzyme involved in folic acid synthesis. While sulfonamides were widely used, resistance emerged rapidly and newer antibiotics proved safer and more effective. Cotrimoxazole is a combination of sulfamethoxazole and trimethoprim that causes sequential blockade of folate metabolism and has activity against a wide range of bacteria. It is commonly used for urinary tract infections, respiratory infections, and Pneumocystis pneumonia in AIDS patients. Adverse effects are similar to those of sulfonamides and include nausea, rash, and bone marrow suppression in high risk groups.
This document provides information on beta-lactam antibiotics, with a focus on penicillins. It discusses the classes of penicillins including penicillin G, semisynthetic penicillins, extended spectrum penicillins, and penicillinase inhibitors. It also covers cephalosporins, dividing them into first, second, third, and fourth generation compounds. Key points about the mechanisms of action, spectra of activity, and uses of various beta-lactam antibiotics are summarized.
The document discusses adverse drug reactions (ADRs). It defines an ADR as an undesirable effect from drug administration. ADRs can range from trivial to fatal and exclude overdoses or poisonings. An adverse drug event is any untoward medical occurrence during treatment that may not have a causal relationship. The epidemiology section notes ADRs are a leading cause of death in hospitals, with estimates of 6.7% incidence of serious ADRs and 0.3-7% of hospital admissions due to ADRs. Risk is higher in the elderly, children, and those with multiple diseases or medications. ADRs can be classified as type A, predictable effects, or type B, unpredictable immunological reactions
This document summarizes the different types of clinical studies, including clinical trials, cohort studies, and case control studies. It then provides detailed descriptions of clinical trials, including phases of clinical trials from pre-clinical animal studies to post-marketing surveillance. Clinical trials aim to evaluate safety and efficacy of new drugs and are conducted in a phased manner from small healthy volunteer studies to large multicenter studies in patients. Rigorous ethical and scientific standards are followed to ensure safety and quality of clinical research.
The autonomic nervous system functions below consciousness to control visceral functions. It has two divisions - the sympathetic and parasympathetic nervous systems. The sympathetic nervous system uses norepinephrine as its primary neurotransmitter, while the parasympathetic nervous system uses acetylcholine. Neurotransmission in the autonomic nervous system involves impulse conduction, transmitter release from synaptic vesicles, transmitter action on postjunctional membranes, generation of a postjunctional potential, and termination of transmitter action through reuptake or degradation. Many neurons also release cotransmitters that can modify or substitute the action of the primary transmitter.
This document discusses the cholinergic system and drugs that act on it. It covers cholinergic transmission including the synthesis, storage, and destruction of acetylcholine. It also discusses cholinoceptors and cholinergic drugs such as cholinomimetics and anticholinesterases. Specific drugs are discussed including pilocarpine, physostigmine, neostigmine, tacrine, rivastigmine, and donepezil. The uses of cholinergic drugs are summarized, including their use in glaucoma, myasthenia gravis, cobra bites, drug overdoses, and Alzheimer's disease.
This document discusses anticholinergic drugs, with a focus on atropine as the prototype drug. It describes how anticholinergic drugs act by blocking muscarinic acetylcholine receptors in the autonomic nervous system and central nervous system. Specifically, it summarizes atropine's pharmacological actions, including stimulating the CNS and heart rate, causing dilation of the pupils, relaxing smooth muscles, decreasing secretions from glands, and slightly raising body temperature. It also lists some common anticholinergic drugs and their uses, such as treating peptic ulcers, intestinal spasms, asthma, and as a pre-anesthetic medication.
1. The document discusses the adrenergic system, including synthesis, storage, release, and metabolism of catecholamines like norepinephrine and epinephrine. It also describes alpha and beta adrenergic receptors.
2. Various adrenergic drugs are discussed, including their uses as nasal decongestants, anorectics, and for conditions like hypotension, cardiac issues, asthma, allergies, and more.
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The document discusses the principles of pharmacodynamics, which is the study of how drugs act on the body. It describes how drugs interact with receptors like G-protein coupled receptors, ion channels, and transmembrane receptors to exert their effects. The mechanisms of drug action include receptor binding and activation of downstream signaling pathways like the cAMP pathway or phospholipase C pathway. The document provides examples of how different receptors and signaling pathways influence various physiological processes in the body.
Mechanisms and Applications of Antiviral Neutralizing Antibodies - Creative B...Creative-Biolabs
Neutralizing antibodies, pivotal in immune defense, specifically bind and inhibit viral pathogens, thereby playing a crucial role in protecting against and mitigating infectious diseases. In this slide, we will introduce what antibodies and neutralizing antibodies are, the production and regulation of neutralizing antibodies, their mechanisms of action, classification and applications, as well as the challenges they face.
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Recent theoretical progress indicates that spacetime and gravity emerge together from the entanglement structure of an underlying microscopic theory. These ideas are best understood in Anti-de Sitter space, where they rely on the area law for entanglement entropy. The extension to de Sitter space requires taking into account the entropy and temperature associated with the cosmological horizon. Using insights from string theory, black hole physics and quantum information theory we argue that the positive dark energy leads to a thermal volume law contribution to the entropy that overtakes the area law precisely at the cosmological horizon. Due to the competition between area and volume law entanglement the microscopic de Sitter states do not thermalise at sub-Hubble scales: they exhibit memory effects in the form of an entropy displacement caused by matter. The emergent laws of gravity contain an additional ‘dark’ gravitational force describing the ‘elastic’ response due to the entropy displacement. We derive an estimate of the strength of this extra force in terms of the baryonic mass, Newton’s constant and the Hubble acceleration scale a0 = cH0, and provide evidence for the fact that this additional ‘dark gravity force’ explains the observed phenomena in galaxies and clusters currently attributed to dark matter.
SDSS1335+0728: The awakening of a ∼ 106M⊙ black hole⋆Sérgio Sacani
Context. The early-type galaxy SDSS J133519.91+072807.4 (hereafter SDSS1335+0728), which had exhibited no prior optical variations during the preceding two decades, began showing significant nuclear variability in the Zwicky Transient Facility (ZTF) alert stream from December 2019 (as ZTF19acnskyy). This variability behaviour, coupled with the host-galaxy properties, suggests that SDSS1335+0728 hosts a ∼ 106M⊙ black hole (BH) that is currently in the process of ‘turning on’. Aims. We present a multi-wavelength photometric analysis and spectroscopic follow-up performed with the aim of better understanding the origin of the nuclear variations detected in SDSS1335+0728. Methods. We used archival photometry (from WISE, 2MASS, SDSS, GALEX, eROSITA) and spectroscopic data (from SDSS and LAMOST) to study the state of SDSS1335+0728 prior to December 2019, and new observations from Swift, SOAR/Goodman, VLT/X-shooter, and Keck/LRIS taken after its turn-on to characterise its current state. We analysed the variability of SDSS1335+0728 in the X-ray/UV/optical/mid-infrared range, modelled its spectral energy distribution prior to and after December 2019, and studied the evolution of its UV/optical spectra. Results. From our multi-wavelength photometric analysis, we find that: (a) since 2021, the UV flux (from Swift/UVOT observations) is four times brighter than the flux reported by GALEX in 2004; (b) since June 2022, the mid-infrared flux has risen more than two times, and the W1−W2 WISE colour has become redder; and (c) since February 2024, the source has begun showing X-ray emission. From our spectroscopic follow-up, we see that (i) the narrow emission line ratios are now consistent with a more energetic ionising continuum; (ii) broad emission lines are not detected; and (iii) the [OIII] line increased its flux ∼ 3.6 years after the first ZTF alert, which implies a relatively compact narrow-line-emitting region. Conclusions. We conclude that the variations observed in SDSS1335+0728 could be either explained by a ∼ 106M⊙ AGN that is just turning on or by an exotic tidal disruption event (TDE). If the former is true, SDSS1335+0728 is one of the strongest cases of an AGNobserved in the process of activating. If the latter were found to be the case, it would correspond to the longest and faintest TDE ever observed (or another class of still unknown nuclear transient). Future observations of SDSS1335+0728 are crucial to further understand its behaviour. Key words. galaxies: active– accretion, accretion discs– galaxies: individual: SDSS J133519.91+072807.4
Sexuality - Issues, Attitude and Behaviour - Applied Social Psychology - Psyc...PsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Candidate young stellar objects in the S-cluster: Kinematic analysis of a sub...Sérgio Sacani
Context. The observation of several L-band emission sources in the S cluster has led to a rich discussion of their nature. However, a definitive answer to the classification of the dusty objects requires an explanation for the detection of compact Doppler-shifted Brγ emission. The ionized hydrogen in combination with the observation of mid-infrared L-band continuum emission suggests that most of these sources are embedded in a dusty envelope. These embedded sources are part of the S-cluster, and their relationship to the S-stars is still under debate. To date, the question of the origin of these two populations has been vague, although all explanations favor migration processes for the individual cluster members. Aims. This work revisits the S-cluster and its dusty members orbiting the supermassive black hole SgrA* on bound Keplerian orbits from a kinematic perspective. The aim is to explore the Keplerian parameters for patterns that might imply a nonrandom distribution of the sample. Additionally, various analytical aspects are considered to address the nature of the dusty sources. Methods. Based on the photometric analysis, we estimated the individual H−K and K−L colors for the source sample and compared the results to known cluster members. The classification revealed a noticeable contrast between the S-stars and the dusty sources. To fit the flux-density distribution, we utilized the radiative transfer code HYPERION and implemented a young stellar object Class I model. We obtained the position angle from the Keplerian fit results; additionally, we analyzed the distribution of the inclinations and the longitudes of the ascending node. Results. The colors of the dusty sources suggest a stellar nature consistent with the spectral energy distribution in the near and midinfrared domains. Furthermore, the evaporation timescales of dusty and gaseous clumps in the vicinity of SgrA* are much shorter ( 2yr) than the epochs covered by the observations (≈15yr). In addition to the strong evidence for the stellar classification of the D-sources, we also find a clear disk-like pattern following the arrangements of S-stars proposed in the literature. Furthermore, we find a global intrinsic inclination for all dusty sources of 60 ± 20◦, implying a common formation process. Conclusions. The pattern of the dusty sources manifested in the distribution of the position angles, inclinations, and longitudes of the ascending node strongly suggests two different scenarios: the main-sequence stars and the dusty stellar S-cluster sources share a common formation history or migrated with a similar formation channel in the vicinity of SgrA*. Alternatively, the gravitational influence of SgrA* in combination with a massive perturber, such as a putative intermediate mass black hole in the IRS 13 cluster, forces the dusty objects and S-stars to follow a particular orbital arrangement. Key words. stars: black holes– stars: formation– Galaxy: center– galaxies: star formation
PPT on Alternate Wetting and Drying presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
PPT on Sustainable Land Management presented at the three-day 'Training and Validation Workshop on Modules of Climate Smart Agriculture (CSA) Technologies in South Asia' workshop on April 22, 2024.
Evidence of Jet Activity from the Secondary Black Hole in the OJ 287 Binary S...Sérgio Sacani
Wereport the study of a huge optical intraday flare on 2021 November 12 at 2 a.m. UT in the blazar OJ287. In the binary black hole model, it is associated with an impact of the secondary black hole on the accretion disk of the primary. Our multifrequency observing campaign was set up to search for such a signature of the impact based on a prediction made 8 yr earlier. The first I-band results of the flare have already been reported by Kishore et al. (2024). Here we combine these data with our monitoring in the R-band. There is a big change in the R–I spectral index by 1.0 ±0.1 between the normal background and the flare, suggesting a new component of radiation. The polarization variation during the rise of the flare suggests the same. The limits on the source size place it most reasonably in the jet of the secondary BH. We then ask why we have not seen this phenomenon before. We show that OJ287 was never before observed with sufficient sensitivity on the night when the flare should have happened according to the binary model. We also study the probability that this flare is just an oversized example of intraday variability using the Krakow data set of intense monitoring between 2015 and 2023. We find that the occurrence of a flare of this size and rapidity is unlikely. In machine-readable Tables 1 and 2, we give the full orbit-linked historical light curve of OJ287 as well as the dense monitoring sample of Krakow.
2. 1.2 Pharmacokinetics
Membrane transport,
absorption,
distribution,
metabolism and
excretion of drugs
Enzyme induction,
enzyme inhibition,
kinetics of elimination
3. Pharmacokinetics is the quantitative study of drug
movement in, through and out of the body.
Schematic depiction of pharmacokinetic processes
4. Biological membrane
This is a bilayer (about 100 Å thick) of
phospholipid and cholesterol molecules, the
polar groups (glyceryl phosphate attached to
ethanolamine/choline or hydroxyl group of
cholesterol) of these are oriented at the
two surfaces and the nonpolar hydrocarbon
chains are embedded in the matrix to form a
continuous sheet.
Extrinsic and intrinsic protein molecules are
adsorbed on the lipid bilayer .
Glycoproteins or glycolipids are formed on
the surface by attachment to polymeric
sugars, aminosugars or sialic acids.
5. Drugs are transported across the membranes by:
(a) Passive diffusion and filtration
(b) Specialized transport
(a) Passive diffusion
The drug diffuses across the membrane in the
direction of its concentration gradient, the
membrane playing no active role in the process.
This is the most important mechanism for
majorityof drugs; drugs are foreign substances
(xenobiotics), and specialized mechanisms are
developed by the body primarily for normal
metabolites
Illustration of passive diffusion and filtration
across the lipoidal biological membrane with aqueous
pores
6. Passive diffusion
Lipid solubility
Influence of pH
Influence of pH difference on two sides of a biological membrane on the
steady-state distribution of a weakly acidic drug with pKa = 6
7. Passive diffusion
Implications of this consideration are:
(a) Acidic drugs, e.g. aspirin (pKa 3.5) are largely unionized at acid gastric pH and
are absorbed from stomach, while bases, e.g. atropine (pKa 10) are largely ionized
and are absorbed only
when they reach the intestines.
(b)The unionized form of acidic drugs which crosses the surface membrane of
gastric mucosal cell, reverts to the ionized form within the cell (pH 7.0) and then
only slowly passes to the extracellular fluid.This is called ion trapping
(c) Basic drugs attain higher concentration intracellularly (pH 7.0 vs 7.4 of plasma).
(d) Acidic drugs are ionized more in alkaline urine—do not back diffuse in the
kidney tubules and are excreted faster. Accordingly, basic drugs are excreted
faster if urine is acidified.
8. (b) Specialized transport
Carrier transport
a. Facilitated diffusion
b. Active transport - Primary active transport
Illustration of different types of carrier mediated transport across
biological membrane
ABC—ATP-binding cassettee transporter; SLC—Solute carrier
transporter; M—Membrane
A. Facilitated diffusion: the carrier (SLC) binds and
moves the poorly diffusible substrate along its
concentration gradient (high to low) and does not
require energy
B. Primary active transport: the carrier (ABC)
derives energy directly by hydrolysing ATP and
moves the substrate against its concentration
gradient (low to high)
9. Secondary active transport
C. Symport: the carrier moves the
substrate ‘A’ against its concentration
gradient by utilizing energy from
downhill movement of another
substrate ‘B’ in the same direction
D. Antiport: the carrier moves the
substrate ‘A’ against its concentration
gradient and is energized by the
downhill movement of another
substrate ‘B’ in the opposite direction
10. ABSORPTION
Absorption is movement of the drug from its site of administration into the
circulation.
Not only the fraction of the administered dose that gets
absorbed, but also the rate of absorption is important.
factors affecting absorption are:
Aqueous solubility - Drugs given in solid form must dissolve in the aqueous biophase
before they are absorbed.
Concentration- Passive diffusion depends on concentration gradient; drug given as
concentrated solution is absorbed faster than from dilute
solution.
Area of absorbing surface -Larger is the surface area, faster is the absorption.
Vascularity of the absorbing surface- Blood circulation removes the drug from the site
of absorption and maintains the concentration gradient across the absorbing surface
Route of administration This affects drug absorption, because each route has its own
peculiarities.
11. Oral
The effective barrier to orally administered drugs is the epithelial lining of
the gastrointestinal tract, which is lipoidal.
Nonionized lipid soluble drugs, e.g. ethanol are readily absorbed from
stomach as well as intestine at rates proportional to their lipid : water
partition coefficient.
Acidic drugs, e.g. salicylates, barbiturates, etc. are predominantly
unionized in the acid gastric juice and are absorbed from stomach, while
basic drugs, e.g. morphine,quinine, etc. are largely ionized and are
absorbed only on reaching the duodenum.
However, even for acidic drugs absorption from stomach is slower, because
the mucosa is thick, covered with mucus and the surface area is small.
Absorbing surface area is much larger in the small intestine due to villi.
Thus, faster gastric emptying accelerates drug absorption in general.
12. Oral
Presence of food dilutes the drug and retards absorption. Further, certain
drugs form poorly absorbed complexes with food constituents, e.g.
tetracyclines with calcium present in milk; moreover food delays gastric
emptying.
Certain drugs are degraded in the gastrointestinal tract, e.g. penicillin G by
acid, insulin by peptidases, and are ineffective orally. Enteric
coated tablets (having acid resistant coating) and sustained release
preparations
Absorption of a drug can be affected by other concurrently ingested drugs.
This may be a luminal effect: formation of insoluble complexes, e.g.
tetracyclines and iron preparations with calcium salts and antacids,
phenytoin with sucralfate.
13. Subcutaneous and Intramuscular
By these routes the drug is deposited directly in the vicinity of the capillaries.
Lipid soluble drugs pass readily across the whole surface of the capillary
endothelium.
Capillaries having large paracellular spaces do not obstruct absorption of
even large lipid insoluble molecules or ions.
Thus, many drugs not absorbed orally are absorbed parenterally.
Absorption from s.c. site is slower than that from i.m. site, but both are
generally faster and more consistent/ predictable than oral absorption.
Application of heat and muscular exercise accelerate drug absorption by
increasing blood flow, while vasoconstrictors, e.g. adrenaline injected with the
drug (local anaesthetic) retard absorption.
14. Topical sites (skin, cornea, mucous membranes)
Systemic absorption after topical application depends primarily on lipid solubility of
drugs.
However, only few drugs significantly penetrate intact skin. Hyoscine, fentanyl, GTN,
nicotine, testosterone, and estradiol have been used in this manner.
Organophosphate insecticides coming in contact with skin
can produce systemic toxicity.
Cornea is permeable to lipid soluble, unionized physostigmine but not to highly
ionized
neostigmine.
Drugs applied as eye drops may get absorbed through the nasolacrimal duct, e.g.
timolol eye drops may produce bradycardia and precipitate asthma.
Mucous membranes of mouth, rectum, vagina absorb lipophilic drugs: estrogen
cream applied vaginally has produced gynaecomastia in the male partner
15. BIOAVAILABILITY
Bioavailability refers to the rate and extent of
absorption of a drug from a dosage form as
determined by its concentration-time curve in
blood or by its excretion in urine .
It is a measure of the fraction (F ) of administered
dose of a drug that reaches the systemic
circulation in the unchanged form.
Plasma concentration-time curves depicting
bioavailability differences between three preparations of
a drug containing the same amount
Note that formulation B is more slowly absorbed than A,
and though ultimately both are absorbed to the same
extent (area under the curve same), B may not produce
therapeutic effect; C is absorbed to a lesser extent—
lower bioavailability
16. BIOAVAILABILITY
Bioavailability of drug injected i.v. is 100%, but is frequently lower
after oral ingestion because –
(a) the drug may be incompletely absorbed.
(b) the absorbed drug may undergo first pass metabolism in the
intestinal wall/liver or be excreted in bile.
17. Bioequivalence
Oral formulations of a drug from different manufacturers or different
batches from the same manufacturer may have the same
amount of the drug (chemically equivalent) but may not yield the
same blood levels—biologically inequivalent.
Two preparations of a drug are considered bioequivalent when the
rate and extent of bioavailability of the active drug from them
is not significantly different under suitable test conditions.
18. DISTRIBUTION
Once a drug has gained access to the blood stream, it gets distributed to other tissues
that initially had no drug, concentration gradient being in the direction of plasma to
tissues.
The extent and pattern of distribution of a drug depends on its:
• lipid solubility
• ionization at physiological pH (a function of its pKa)
• extent of binding to plasma and tissue proteins
• presence of tissue-specific transporters
• differences in regional blood flow.
Movement of drug proceeds until an equilibrium is established between unbound drug in
the plasma and the tissue fluids.
19. Apparent volume of distribution (V)
Presuming that the body behaves as a single homogeneous
compartment with volume V into which the drug gets immediately
and uniformly distributed
concept of apparent volume of distribution (V)
Pathological states, e.g. congestive heart
failure, uraemia, cirrhosis of liver, etc. can alter
the V of many drugs by altering distribution of
body water, permeability of membranes, binding
proteins or by accumulation of metabolites that
displace the drug from binding sites.
20. Redistribution
Highly lipid-soluble drugs get initially distributed to organs with high blood
flow, i.e. brain, heart, kidney, etc.
Later, less vascular but more bulky tissues (muscle, fat) take up the drug—
plasma concentration falls and the drug is withdrawn from the highly
perfused sites.
21. Penetration into brain and CSF
The capillary endothelial cells in brain have
tight junctions and lack large paracellular
spaces.
Further, an investment of neural tissue covers
the capillaries.Together they constitute the so
called blood-brain barrier (BBB).
Both these barriers are lipoidal and limit the
entry of nonlipidsoluble drugs, e.g.
streptomycin, neostigmine, etc.
Only lipid-soluble drugs, therefore, are able to
penetrate and have action on the central
nervous
system.
A. Usual capillary with large paracellular spaces through which
even large lipid-insoluble molecules diffuse
B. Capillary constituting blood brain or blood-CSF barrier.Tight
junctions between capillary endothelial cells and investment of
glial processes or choroidal epithelium
do not allow passage of non lipid-soluble molecules/ions
Passage of drugs across capillaries
22. Passage across placenta
Placental membranes are lipoidal and allow free passage of lipophilic
drugs, while restricting hydrophilic drugs.
Placenta is a site for drug metabolism as well, which may
lower/modify exposure of the foetus to the administered drug.
23. Plasma protein binding
Most drugs possess physicochemical affinity for plasma proteins and get reversibly
bound to these.
Acidic drugs generally bind to plasma albumin and basic drugs to α1 acid glycoprotein.
Binding to albumin is quantitatively more important.
The clinically significant implications of plasma protein binding are:
(i) Highly plasma protein bound drugs are largely restricted to the vascular compartment because
protein bound drug does not cross membranes
(ii)The bound fraction is not available for action. However, it is in equilibrium with the free drug
in plasma and dissociates when the concentration of the latter is reduced due to elimination.
(iii) High degree of protein binding generally makes the drug long acting, because bound fraction is
not available for metabolism or excretion, unless it is actively extracted by liver or by kidney
tubules
(iv)The generally expressed plasma concentrations of the drug refer to bound as well as free
drug.
(v) One drug can bind to many sites on the albumin molecule. Conversely, more than one drug can
bind to the same site.This can give rise to
displacement interactions among drugs bound to the same site(s).The drug bound with higher
affinity will displace that bound with lower affinity.
24. BIOTRANSFORMATION (Metabolism)
Biotransformation means chemical alteration of the drug in the body.
It is needed to render nonpolar (lipid-soluble) compounds polar
(lipidinsoluble) so that they are not reabsorbed in the renal tubules and are
excreted.
The primary site for drug metabolism is liver; others are—kidney, intestine,
lungs and plasma
Biotransformation of drugs may lead to -
(i) Inactivation
(ii) Active metabolite from an active drug
(iii) Activation of inactive drug - Few drugs are inactive as such and need
conversion in the body to one or more active metabolites. Such a drug is
called a prodrug
25. Biotransformation reactions can be classified into:
(a) Nonsynthetic/Phase I/Functionalization reactions: a functional
group is generated or exposed— metabolite may be active or
inactive.
(b) Synthetic/Conjugation/ Phase II reactions: an endogenous radical
is conjugated to the drug— metabolite is mostly inactive; except
few drugs, e.g. glucuronide conjugate of morphine and sulfate
conjugate of minoxidil are active.
26. Nonsynthetic/Phase I/Functionalization reactions:
(i) Oxidation This reaction involves addition of oxygen/negatively charged
radical or removal of hydrogen/positively charged radical. Oxidations are
the most important drug metabolizing reactions.
Various oxidation reactions are: hydroxylation; oxygenation at C, N or S atoms; N or
O-dealkylation, oxidative deamination, etc.
Barbiturates, phenothiazines, imipramine, propranolol, ibuprofen, paracetamol,
steroids, phenytoin, benzodiazepines, theophylline and
many other drugs are oxidized in this way.
(ii) Reduction- This reaction is the converse of oxidation and involves
cytochrome P-450 enzymes working in the opposite direction. Alcohols,
aldehydes, quinones are reduced.
27. (iii) Hydrolysis - This is cleavage of drug molecule by taking up a
molecule of water.
Examples of hydrolysed drugs are choline esters, procaine, lidocaine,
procainamide, aspirin, carbamazepine-epoxide,
pethidine, oxytocin.
(iv) Cyclization - This is formation of ring structure from a straight
chain compound, e.g. proguanil.
(v) Decyclization - This is opening up of ring structure of the cyclic
drug molecule, e.g. barbiturates, phenytoin.This is generally a
minor pathway.
Nonsynthetic/Phase I/Functionalization reactions:
28. Synthetic/Conjugation/ Phase II reactions:
These involve conjugation of the drug or its phase I metabolite with an
endogenous substrate, usually derived from carbohydrate or amino acid, to
form a polar highly ionized organic acid, which
is easily excreted in urine or bile.
(i) Glucuronide conjugation - This is the most important synthetic reaction
carried out by a group of UDP-glucuronosyl transferases (UGTs).
Compounds with a hydroxyl or carboxylic acid group are easily conjugated
with glucuronic acid which is derived from glucose.
Examples are— chloramphenicol, aspirin, paracetamol, diazepam,
lorazepam, morphine, metronidazole
29. (ii) Acetylation - Compounds having amino or hydrazine residues are
conjugated with the help of acetyl coenzyme-A, e.g. sulfonamides,
isoniazid, PAS, dapsone, hydralazine, clonazepam, procainamide.
(iii) Methylation- The amines and phenols can be methylated by
methyl transferases (MT); methionine and cysteine acting as methyl
donors, e.g. adrenaline, histamine, nicotinic acid, methyldopa,
captopril, mercaptopurine.
(iv) Sulfate conjugation The phenolic compounds and steroids are
sulfated by sulfotransferases (SULTs), e.g. chloramphenicol,
methyldopa, adrenal and sex steroids.
Synthetic/Conjugation/ Phase II reactions:
30. (v) Glycine conjugation - Salicylates, nicotinic acid and other drugs
having carboxylic acid group are conjugated with glycine, but this
is not a major pathway of metabolism.
(vi) Glutathione conjugation - This is carried out by glutathione-S-
transferase (GST) forming a mercapturate. It is normally a minor
pathway. e.g. paracetamol.
(vii) Ribonucleoside/nucleotide synthesis - This pathway is
important for the activation of many purine and pyrimidine
antimetabolites used
in cancer chemotherapy
Synthetic/Conjugation/ Phase II reactions:
32. Microsomal enzymes
These are located on smooth endoplasmic reticulum (a system of
microtubules inside the cell), primarily in liver, also in kidney,
intestinal mucosa and lungs.
The monooxygenases, cytochrome P450, UGTs, epoxide
hydrolases, etc. are microsomal enzymes.
They catalyse most of the oxidations, reductions, hydrolysis and
glucuronide conjugation.
Microsomal enzymes are inducible by drugs, diet and other
agencies.
33. Nonmicrosomal enzymes
These are present in the cytoplasm and mitochondria of
hepatic cells as well as in other tissues including plasma.
The esterases, amidases, some flavoprotein oxidases
and most conjugases are nonmicrosomal.
Hofmann elimination - This refers to inactivation of the drug in
the body fluids by spontaneous molecular rearrangement
without the agency of any enzyme, e.g. atracurium.
34. INHIBITION OF DRUG METABOLISM
One drug can competitively inhibit the metabolism of another if it
utilizes the same enzyme or cofactors.
A drug may inhibit one isoenzyme while being itself a substrate of
another isoenzyme, e.g. quinidine is metabolized mainly by
CYP3A4 but inhibits CYP2D6.
Clinically significant inhibition of drug metabolism occurs in case
of drugs having affinity for the same isoenzyme.
35. MICROSOMAL ENZYME INDUCTION
Many drugs, insecticides and carcinogens interact with DNA and
increase the synthesis of microsomal enzyme protein, especially
cytochrome P-450 and UGTs . As a result rate of metabolism of inducing
drug itself and/or other drugs is increased.
Different inducers are relatively selective for certain cytochrome P-450
isoenzyme families, e.g.:
• Anticonvulsants (phenobarbitone, phenytoin, carbamazepine),
rifampin, glucocorticoids induce CYP3A isoenzymes.
• Phenobarbitone also induces CYP2B1 and rifampin also induces
CYP2D6.
Isoniazid and chronic alcohol consumption induce CYP2E1.
36. MICROSOMAL ENZYME INDUCTION
uses of enzyme induction
1. Congenital nonhaemolytic jaundice: It is due to deficient
glucuronidation of bilirubin; phenobarbitone hastens clearance of
jaundice.
2. Cushing’s syndrome: phenytoin may reduce the manifestations
by enhancing degradation of adrenal steroids which are produced
in excess.
3. Chronic poisonings: by faster metabolism of the accumulated
poisonous substance.
4. Liver disease.
37. FIRST PASS (PRESYSTEMIC) METABOLISM
This refers to metabolism of a drug during its passage from the
site of absorption into the systemic circulation.
All orally administered drugs are exposed to drug metabolizing
enzymes in the intestinal wall and liver (where they first reach
through the portal vein).
Presystemic metabolism in the gut and liver can be avoided by
administering the drug through sublingual, transdermal
or parenteral routes.
38. EXCRETION
Excretion is the passage out of systemically absorbed drug.
Drugs and their metabolites are excreted in:
1. Urine - Through the kidney. It is the most important channel of excretion for majority
of drugs .
2. Faeces - Apart from the unabsorbed fraction, most of the drug present in faeces is
derived from bile.
3. Exhaled air- Gases and volatile liquids (general anaesthetics, alcohol) are eliminated
by lungs, irrespective of their lipid solubility. Alveolar transfer of the gas/vapour
depends on its partial pressure in the blood.
4. Saliva and sweat - These are of minor importance for drug excretion. Lithium, pot.
iodide, rifampin and heavy metals are present in these secretions in significant
amounts.
5. Milk - The excretion of drug in milk is not important for the mother, but the suckling
infant inadvertently receives the drug.
39. RENAL EXCRETION
The kidney is responsible for excreting all water
soluble substances.
The amount of drug or its metabolites ultimately present in urine is the
sum total of glomerular filtration, tubular reabsorption and tubular
secretion
Net renal= (Glomerular filtration + tubular excretion secretion) – tubular
reabsorption
40. Schematic depiction of glomerular filtration,
tubular reabsorption and tubular secretion of drugs
FD—free drug; BD—bound drug; UD—unionized drug;
ID—ionized drug; Dx—actively secreted organic acid (or
base) drug
41. Glomerular filtration
Glomerular capillaries have pores larger than usual; all nonprotein
bound drug (whether lipid-soluble or insoluble) presented
to the glomerulus is filtered.
Thus, glomerular filtration of a drug depends on its plasma protein
binding and renal blood flow.
Glomerular filtration rate (g.f.r.), normally ~ 120 ml/min, declines
progressively after the age of 50, and is low in renal failure.
42. Tubular reabsorption
This occurs by passive diffusion and depends on lipid solubility and
ionization of the drug at the existing urinary pH.
Lipid-soluble drugs filtered at the glomerulus back diffuse in the
tubules because 99% of glomerular filtrate is reabsorbed, but
nonlipid-soluble and highly ionized drugs are unable to do so.
Thus, rate of excretion of such drugs, e.g. aminoglycoside antibiotics,
quaternary ammonium compounds parallels g.f.r. (or creatinine
clearance).
Changes in urinary pH affect tubular reabsorption of drugs that are partially
ionized—
•Weak bases ionize more and are less reabsorbed in acidic urine.
•Weak acids ionize more and are less reabsorbed in alkaline urine.
43. Tubular secretion
This is the active transfer of organic acids and bases by two
separate classes of relatively nonspecific transporters (OAT and
OCT) which operate in the proximal tubules.
In addition, efflux transporters P-gp and MRP2 are located in the
luminal membrane of proximal tubular cells.
Active transport of the drug across tubules reduces concentration
of its free form in the tubular vessels and promotes dissociation of
protein bound drug, which then becomes available for secretion
44. Tubular secretion
(a) Organic acid transport (through OATP) operates for penicillin, probenecid,
uric acid, salicylates, indomethacin, sulfinpyrazone, nitrofurantoin,
methotrexate, drug glucuronides and
sulfates, etc.
(b) Organic base transport (through OCT) operates for thiazides, amiloride,
triamterene, furosemide, quinine, procainamide, choline, cimetidine, etc.
Tubular transport mechanisms are not well developed at birth. As a result,
duration of action of many drugs, e.g. penicillin, cephalosporins, aspirin is longer
in neonates.
These systems mature during infancy. Renal function again progressively
declines after the age of 50 years; renal clearance of most drugs is substantially
lower in the elderly (>75 yr).
45. KINETICS OF ELIMINATION
The knowledge of kinetics of elimination of a drug provides the basis
for, as well as serves to devise rational dosage regimens and to modify
them according to individual needs.
Drug elimination is the sumtotal of metabolic inactivation and
excretion.
Clearance (CL) - The clearance of a drug is the theoretical volume of
plasma from which the drug is completely removed in unit time.
CL = Rate of elimination/C
where C is the plasma concentration
46. Illustration of the concept of drug clearance.
A fraction of the drug molecules present in plasma are removed on
each passage through the organs of elimination. In the case shown, it
requires 50 mL of plasma to account for the amount of drug being
eliminated every minute: clearance is 50 mL/min
47. First order kinetics - The rate of elimination is directly proportional
to the drug concentration, CL remains constant; or a constant
fraction of the drug present in the body is eliminated in unit
time.
This applies to majority of drugs which do not saturate the
elimination processes (transporters, enzymes, blood flow, etc.)
Semilog plasma concentration-time plot of a
drug eliminated by first order kinetics after intravenous
injection
48. Zero order kinetics
The rate of elimination remains constant irrespective of drug
concentration, CL decreases with increase in concentration; or a
constant amount of the drug is eliminated in unit time, e.g. ethyl
alcohol.
This is also called capacity limited elimination or Michaelis-Menten
elimination.
Relationship between dose rate and
average steady-state plasma
concentration of drugs eliminated
by first order and Michaelis Menten
(zero order) kinetics
phenytoin, tolbutamide,
theophylline, warfarin
49. Plasma half-life
The Plasma half-life (t½) of a drug is the time taken for its
plasma concentration to be reduced to half of its original
value.
50. Plateau principle
When constant dose of a drug is repeated
before the expiry of 4 t½, it would achieve
higher peak concentration, because some
remnant of the previous dose will be present in
the body.
This continues with every dose until
progressively increasing rate of elimination
(which increases with increase in
concentration) balances the amount
administered over the dose interval.
Subsequently plasma concentration plateaus
and fluctuates about an average steady-state
level.This is known as the plateau principle of
drug accumulation.
Plateau principle of drug accumulation on
repeated oral dosing.
51. Target level strategy
For drugs whose effects are not easily quantifiable and safety margin
is not big, e.g. anticonvulsants, antidepressants, lithium,
antiarrhythmics, theophylline, some antimicrobials, etc. or those
given to prevent an event, it is best to aim at achieving a certain
plasma concentration which has been defined to be in the therapeutic
range; such data are now available for most drugs of this type.
Drugs with short t½ (upto 2–3 hr) administered at conventional
intervals (6–12 hr) achieve the target levels only intermittently and
fluctuations in plasma concentration are marked.
52. Target level strategy
For drugs with longer t½ a dose that is sufficient to attain the target
concentration after single administration, if repeated will accumulate
according to plateau principle and produce toxicity
later on.
Loading dose - This is a single or few quickly repeated doses given in the
beginning to attain target concentration rapidly.
Maintenance dose - This dose is one that is to be repeated at specified
intervals after the attainment of target Cpss so as to maintain the same
by balancing elimination.
steady state plasma concentration (Cpss)
Relationship between dose rate and averagesteady-state plasma concentration of drugs eliminatedby first order and Michaelis Menten (zero order) kinetics Relationship between dose rate and averagesteady-state plasma concentration of drugs eliminatedby first order and Michaelis Menten (zero order) kinetics Relationship between dose rate and averagesteady-state plasma concentration of drugs eliminatedby first order and Michaelis Menten (zero order) kinetics