This document discusses pharmacokinetics and biotransformation. It covers the four main stages of pharmacokinetics: absorption, distribution, metabolism, and excretion. Metabolism, or biotransformation, involves enzymatic conversion of drugs by the liver and involves two phases - phase I and phase II reactions. Phase I introduces or exposes functional groups through oxidation, reduction or hydrolysis. Phase II involves conjugation through acetylation, methylation, glucuronidation or sulphation. Cytochrome P450 enzymes and microsomal enzymes are involved in phase I reactions. Factors like enzyme induction and inhibition can impact drug metabolism and clearance. Drugs and metabolites are primarily excreted through the kidneys
This document discusses drug metabolism and elimination. It begins by defining metabolism as the chemical alteration of drugs in the body, which is needed to make nonpolar compounds polar so they can be excreted. The major sites of drug metabolism are the liver, kidneys, intestines, lungs, and plasma. Drugs may be inactivated, converted to an active metabolite, or activated from an inactive prodrug through biotransformation. Biotransformation involves phase I (functionalization) and phase II (conjugation) reactions. The kinetics of drug elimination, including clearance, half-life, and order of elimination, are also covered. The document provides detailed information on the various enzyme systems, organ systems, and pathways involved in
Pharmacokinetics metabolism and excretionsumitmahato20
This document discusses the metabolism and excretion of drugs. It covers the following key points:
1. Drugs undergo biotransformation primarily in the liver through phase I (oxidation, reduction, hydrolysis) and phase II (conjugation) reactions to make them more polar and excretable.
2. The metabolites can be inactive, active, or activate prodrugs. Enzyme inhibition and induction can impact drug metabolism.
3. Excretion occurs mainly through the kidneys and liver into urine and bile. Lungs, saliva, sweat and milk are minor excretion routes.
4. The plasma half-life determines the dosing frequency needed to maintain therapeutic drug levels. D
This document summarizes key aspects of drug metabolism and renal excretion. It discusses two phases of drug metabolism - phase I involves reactions like oxidation and phase II involves conjugation reactions. The liver is the main site of drug metabolism via cytochrome P450 enzymes in the smooth endoplasmic reticulum. Renal excretion depends on factors like a drug's polarity, glomerular filtration, and tubular secretion/reabsorption. First-pass metabolism may substantially reduce the amount of drug reaching systemic circulation following oral administration.
This document discusses drug metabolism and excretion. It notes that drugs are chemically altered, or metabolized, in the body primarily by the liver. Metabolism can inactivate drugs, produce active metabolites, or activate prodrugs. Phase I reactions like oxidation and reduction modify drugs. Phase II conjugation reactions make drugs more polar and excretable by adding groups like glucuronide. Some drugs are extensively metabolized in the liver during first pass, reducing their oral bioavailability. Drugs and metabolites leave the body primarily through urine via glomerular filtration, tubular reabsorption and secretion. Drug elimination kinetics can be first-order or zero-order.
The document discusses various routes of drug excretion from the body. It describes renal excretion through glomerular filtration and tubular secretion/reabsorption in the kidneys. It also discusses non-renal routes of excretion including biliary excretion through the liver, pulmonary excretion through the lungs, and other minor routes like salivary, mammary, dermal, and gastrointestinal excretion. Key factors that influence the different excretion pathways include a drug's physicochemical properties, binding characteristics, urine and bile pH, and physiological conditions.
UNIT I: DRUG METABOLISM: S.Y. B. PHARMACY IV SEMESTERSONALI PAWAR
This document provides an overview of drug metabolism. It discusses the phases of metabolism including phase I reactions like oxidation mediated by cytochrome P450 enzymes and phase II conjugation reactions. It describes the key cytochrome P450 enzyme families and their role in drug metabolism. First pass metabolism and factors that influence it are also summarized.
This document discusses drug metabolism and elimination. It begins by defining metabolism as the chemical alteration of drugs in the body, which is needed to make nonpolar compounds polar so they can be excreted. The major sites of drug metabolism are the liver, kidneys, intestines, lungs, and plasma. Drugs may be inactivated, converted to an active metabolite, or activated from an inactive prodrug through biotransformation. Biotransformation involves phase I (functionalization) and phase II (conjugation) reactions. The kinetics of drug elimination, including clearance, half-life, and order of elimination, are also covered. The document provides detailed information on the various enzyme systems, organ systems, and pathways involved in
Pharmacokinetics metabolism and excretionsumitmahato20
This document discusses the metabolism and excretion of drugs. It covers the following key points:
1. Drugs undergo biotransformation primarily in the liver through phase I (oxidation, reduction, hydrolysis) and phase II (conjugation) reactions to make them more polar and excretable.
2. The metabolites can be inactive, active, or activate prodrugs. Enzyme inhibition and induction can impact drug metabolism.
3. Excretion occurs mainly through the kidneys and liver into urine and bile. Lungs, saliva, sweat and milk are minor excretion routes.
4. The plasma half-life determines the dosing frequency needed to maintain therapeutic drug levels. D
This document summarizes key aspects of drug metabolism and renal excretion. It discusses two phases of drug metabolism - phase I involves reactions like oxidation and phase II involves conjugation reactions. The liver is the main site of drug metabolism via cytochrome P450 enzymes in the smooth endoplasmic reticulum. Renal excretion depends on factors like a drug's polarity, glomerular filtration, and tubular secretion/reabsorption. First-pass metabolism may substantially reduce the amount of drug reaching systemic circulation following oral administration.
This document discusses drug metabolism and excretion. It notes that drugs are chemically altered, or metabolized, in the body primarily by the liver. Metabolism can inactivate drugs, produce active metabolites, or activate prodrugs. Phase I reactions like oxidation and reduction modify drugs. Phase II conjugation reactions make drugs more polar and excretable by adding groups like glucuronide. Some drugs are extensively metabolized in the liver during first pass, reducing their oral bioavailability. Drugs and metabolites leave the body primarily through urine via glomerular filtration, tubular reabsorption and secretion. Drug elimination kinetics can be first-order or zero-order.
The document discusses various routes of drug excretion from the body. It describes renal excretion through glomerular filtration and tubular secretion/reabsorption in the kidneys. It also discusses non-renal routes of excretion including biliary excretion through the liver, pulmonary excretion through the lungs, and other minor routes like salivary, mammary, dermal, and gastrointestinal excretion. Key factors that influence the different excretion pathways include a drug's physicochemical properties, binding characteristics, urine and bile pH, and physiological conditions.
UNIT I: DRUG METABOLISM: S.Y. B. PHARMACY IV SEMESTERSONALI PAWAR
This document provides an overview of drug metabolism. It discusses the phases of metabolism including phase I reactions like oxidation mediated by cytochrome P450 enzymes and phase II conjugation reactions. It describes the key cytochrome P450 enzyme families and their role in drug metabolism. First pass metabolism and factors that influence it are also summarized.
Drug metabolism- General pharmacology - various typesRaviMundugaru1
This document discusses drug biotransformation and metabolism. It notes that drugs are chemically altered within the body through processes like oxidation, reduction, hydrolysis, and conjugation. The liver is a major site of drug metabolism, which occurs in two phases - phase I involves processes like oxidation, and phase II involves conjugation reactions to make the drug more water soluble and able to be excreted. Factors like age, diet, disease states, and genetics can impact an individual's drug metabolism. Prodrugs are discussed as inactive forms of drugs that are converted to the active form after metabolism.
Biotransformation, or metabolism, refers to the chemical alteration of drugs in the body. The primary site is the liver, where drugs undergo two main phases of metabolism - phase I and phase II reactions. Phase I reactions like oxidation and hydrolysis functionally alter drugs, while phase II or conjugation reactions make drugs more polar and excretable by conjugating them to other molecules. Many drugs are activated or inactivated in these metabolic pathways. Metabolism can occur in other tissues as well and is mediated by various enzyme systems like the cytochrome P450 enzymes. Drug metabolism can be inhibited or induced, affecting the activity of other drugs a patient may be taking.
Drug metabolism involves two phases of biochemical reactions that transform lipophilic drugs into more water-soluble compounds that can be readily excreted. Phase I reactions like oxidation, reduction, and hydrolysis introduce or expose functional groups on drugs. Phase II reactions, through conjugation, form bonds between functional groups on drugs and endogenous compounds like glucuronic acid, sulfate, glutathione, or amino acids, further increasing water solubility. The liver is the primary site of drug metabolism, with cytochrome P450 enzymes playing a key role in many phase I oxidative reactions.
Biotransformation involves the chemical alteration of drugs in the body through phase 1 and phase 2 reactions. Phase 1 reactions like oxidation, reduction and hydrolysis activate or expose functional groups on drugs. Phase 2 reactions like conjugation make drugs more polar and excretable. The liver is the primary site of biotransformation through cytochrome P450 enzymes and UDP-glucuronyltransferases. First pass metabolism can decrease oral bioavailability. Drug interactions can occur through enzyme induction, increasing metabolism of other drugs, or enzyme inhibition, decreasing metabolism of other drugs.
The document discusses drug excretion and elimination from the body. It describes the various routes of excretion including renal, biliary, pulmonary, salivary, dermal and gastrointestinal. The key organs involved in excretion are the kidneys and liver. Drugs can be excreted unchanged or as metabolites, through glomerular filtration, tubular secretion or reabsorption in the kidneys. Non-renal routes depend on the drug's physicochemical properties and include biliary excretion of conjugated metabolites. Factors like urine pH, blood flow and drug interactions can influence renal excretion. Clearance is the volume from which the drug is completely removed per unit time and includes renal, hepatic and total body clearance
biotransformation of drug
Biotransformation/Xenobiotic metabolism/ drug metabolism/detoxification.
-Xenobiotics: a wide variety of foreign compounds to which humans get exposed in day to day life.
-It includes unknown compounds, drugs, environmental pollutants, toxins.
-Many xenobiotics can evoke biological responses.
DEFINITION
The biochemical alteration of drug or xenobiotic in the presence of various enzymes that acts as a catalyst which themselves not consumed in the reaction and there by may activate or deactivate the drug is called biotransformation.
Why Biotransformation is necessary?:
To easily eliminate the drug
To terminate drug action by inactivating it
Consequences of Biotransformation
Active to Inactive:
Phenobarbitone---- Hydroxyphenobarbitone
Inactive (prodrug) to Active :
L-Dopa ---- Dopamine
Parathion -- Paraoxon
Talampicillin -- Ampicillin
Active to equally active:
Diazepam -- Oxazepam
Amitriptyline -- Nortriptyline
Imipramine -- Des-imipramine
Codeine -- Morphine
Sites of biotransformation
In the body: Liver, small and large intestines, lungs, skin, kidney, nasal mucosa & brain.
Liver is considered “metabolite clearing house” for both endogenous substances and xenobiotics.
Intestines are considered “initial site of drug metabolism”.
FIRST PASS METABOLISM:
First pass metabolism or presystemic
metabolism or ‘first pass effect’
After oral administeration many drugs are absorbed from the small intestine - transported first via portal system to the liver, where they undergo extensive metabolism before reaching systemic circulation.
fundamental concepts in drug biotransformation
Lipid soluble drugs are poorly excreted in the urine. They tend to store in fat and/or circulate until they are converted (phase I biotransformation) to more water soluble metabolites or metabolites that conjugate (phase II biotransformation) with water soluble substances.
Water soluble drugs are more readily excreted in the urine. They may be metabolized, but generally not by the CYP enzyme systems.
Enzymes catalyzing phase I biotransformation reactions
Enzymes catalyzing phase I biotransformation reactions include:
cytochrome P-450
aldehyde and alcohol dehydrogenase
deaminases
esterases
amidases
epoxide hydratases
Addition of water
Cleavage of R-O or R-N bond accompanied by addition of H2O
CYTOCHROME P450
The cytochrome P-450 families are referred to using an arabic numeral, e.g., CYP1, CYP2, etc.
Each family has a number of subfamilies denoted by an upper case letter, e.g., CYP2A, CYP2B, etc.
The individual enzymes within each subfamily are denoted by another arabic numeral, e.g., CYP3A1, CYP3A2, etc.
1) Biotransformation, or metabolism, involves the chemical alteration of drugs in the body by enzymes to make them more water soluble and easier to eliminate. This occurs mainly in the liver.
2) Phase I metabolism involves oxidation, reduction, and hydrolysis reactions using cytochrome P450 enzymes to introduce functional groups. Phase II metabolism involves conjugation reactions like glucuronidation and sulfation to further increase water solubility.
3) Factors like age, sex, disease states, genetic variations, and drug-drug interactions can impact drug metabolism by inducing or inhibiting metabolizing enzymes. Understanding a drug's metabolism is important for efficacy, safety, and interactions.
This document discusses biotransformation, or the metabolism of drugs in the body. It covers the key topics of:
- Phases of metabolism, including phase 1 reactions like oxidation and reduction mediated by cytochrome P450 enzymes, and phase 2 conjugation reactions.
- Important cytochrome P450 enzyme families, specifically CYP3A4 which metabolizes over 50% of drugs.
- Factors that can influence biotransformation like concurrent drug use, genetic polymorphisms, and pathological states.
- The role of biotransformation in drug discovery and development through in vitro and in silico studies.
1. Drug metabolism involves enzymatic modification of drugs by the body with the goal of making them more water soluble and easier to excrete.
2. Metabolism can occur in many tissues like the liver, kidneys, lungs, and intestines and is primarily carried out by the cytochrome P450 enzyme system.
3. Metabolism can result in inactive, active, or more active drug metabolites and influences the drug's pharmacokinetic and pharmacodynamic properties. Certain drugs are able to induce or inhibit the cytochrome P450 enzyme system, altering metabolism of other drugs metabolized by the same enzymes.
This document discusses drug metabolism. It defines drug metabolism as the chemical reactions that occur in the body to convert drugs into water-soluble compounds that can be easily excreted from the body. The main organs involved in drug metabolism are the liver, kidneys, lungs, intestine, skin, and brain. There are two phases of drug metabolism - phase I involves reactions like oxidation, reduction, and hydrolysis that make the drug more polar. Phase II involves conjugation reactions like glucuronidation and acetylation that make the drug even more hydrophilic to facilitate excretion. Factors like genetic variations, diseases, age, and gender can affect an individual's drug metabolism.
This document discusses drug metabolism and biotransformation. It describes how drugs are structurally modified inside the body through Phase I and Phase II metabolic pathways. Phase I metabolism involves oxidation, reduction and hydrolysis reactions by cytochrome P450 enzymes and flavin monooxygenases. This makes the drugs more hydrophilic but can also activate some drugs. Phase II conjugation reactions like glucuronidation and sulfation catalyzed by transferase enzymes further increases hydrophilicity and promotes excretion of drug metabolites. The liver is the major site of drug metabolism though other tissues also play a role. Enzyme induction and inhibition can impact drug metabolism.
The document discusses biotransformation, which is the biochemical alteration of drugs inside the body. The main site of biotransformation is the liver, with other sites including the kidneys, lungs, intestine, and skin. Biotransformation makes drugs more polar, water soluble, and less lipid soluble to promote excretion. It can convert active drugs into inactive metabolites or active metabolites. The two main phases are phase I reactions, which use oxidation, reduction, and hydrolysis to introduce or remove functional groups, and phase II reactions, which produce non-toxic conjugates through glucoronidation, acetylation, methylation, and other conjugation reactions. Factors that can influence biotransformation include patient factors like age and genetics
Basic Princioles of Pharmacokinetics 05 02 2023 BAA.pptxmaamedokuah233
The document discusses the basic principles of pharmacokinetics, which is the study of what the body does to drugs. It covers the key processes of absorption, distribution, metabolism, and excretion (ADME) that drugs undergo in the body. Absorption refers to how drugs enter the bloodstream, distribution is the movement of drugs between tissues, metabolism chemically alters drugs to aid excretion, and excretion is how drugs are removed from the body. Understanding a drug's pharmacokinetics is important for ensuring safe and effective use.
This document discusses metabolism and excretion of drugs in the body. It covers the following key points in 3 sentences:
Metabolism, primarily in the liver, transforms drugs through phase I and phase II reactions to make them more polar and easily excreted. The major phase I reactions are oxidation, reduction, and hydrolysis catalyzed by cytochrome P450 enzymes, while phase II conjugation reactions make drugs more hydrophilic through conjugation to compounds like glucuronic acid. The kidneys are the primary route of drug excretion, where drugs are filtered from the blood and either reabsorbed or actively secreted from the body, though other routes include bile, feces, lungs, sweat and breast milk.
Metabolism, or biotransformation, is the process by which drugs are chemically altered in the body. Drugs undergo two main phases of metabolism: Phase I involves processes like oxidation, reduction, and hydrolysis that make the drug more polar. Phase II involves conjugating reactions like glucuronidation that allow for excretion of the metabolite. Many drugs are metabolized in the liver by cytochrome P450 enzymes, and first-pass metabolism can reduce oral bioavailability. Factors like age, sex, diet, and concurrent medications can impact an individual's drug metabolism.
By the end of this lecture, students should:
Explain why drug metabolism is essential
Describe the phases of drug metabolism
Explain the role of cytochrome p 450 enzyme system in drug metabolism
Definition
Chemical reactions which occur in the body to change drugs from nonpolar lipid soluble forms to polar water soluble forms that are easily excreted by the kidney.
The major organs involved in drug excretion are the kidneys and liver. The kidneys excrete drugs through glomerular filtration, tubular secretion, and tubular reabsorption in the nephron. The liver excretes some drugs and their metabolites into bile. Pulmonary excretion eliminates gaseous and volatile substances through expiration.
Pharmakokinetic Variations in Kidney diseases.Maleha Sial
The kidney plays an important role in drug excretion and metabolism. Renal diseases and impairment can significantly impact the pharmacokinetics of drugs in multiple ways. Kidney function affects absorption, distribution, metabolism and elimination of drugs. Specifically, impaired renal function can decrease drug protein binding, increase volume of distribution, decrease metabolism of some drugs while increasing metabolism of others, and greatly reduce drug clearance by eliminating the kidney's excretory pathway. These alterations in pharmacokinetics require careful dosage adjustments for many drugs used in patients with renal diseases.
Metabolism,Excretion,prodrug,Therapeutic Drug monitoringSrinivasSree11
1. Metabolism and excretion are important processes that determine the duration and intensity of a drug's effects in the body. Metabolism involves chemical alteration of drugs through phase I and phase II reactions, while excretion removes drugs and metabolites from the body through renal, hepatic, pulmonary and other routes.
2. Factors like age, diet, diseases, genetic factors and simultaneous administration of other drugs can influence drug metabolism by inducing or inhibiting drug-metabolizing enzymes. Metabolism can convert drugs to active, inactive or less active forms.
3. Prodrugs are inactive forms administered to deliver the active drug selectively or improve pharmacokinetics. They are converted to active drugs through metabolic processes
This document discusses considerations for dosage form design, including reasons drugs are incorporated into dosage forms, types of dosage forms, and information needed for preformulation studies. It covers drug degradation mechanisms, drug instability, stability studies, and approaches to stabilize drugs. Factors in dosage form design include therapeutic use, administration route, patient age and condition. Common oral dosage forms are tablets and capsules, while injections can be used for emergency or inability to take oral medications. Design must also consider issues like difficulty swallowing, multiple medication therapy in elderly patients, and performulation studies to characterize the drug substance.
Capsules are solid dosage forms where the drug is enclosed within a shell, typically made of gelatin. There are two main types - hard gelatin capsules which contain powders, granules, or pellets and release their contents rapidly; and soft gelatin capsules which contain liquids or pastes and provide rapid release. Capsules offer advantages like masking unpleasant tastes and smells, easy swallowing, and sustained or delayed release depending on the formulation. They are manufactured through processes like dipping, spinning, drying, stripping, trimming, and joining. Finished capsules are evaluated for content uniformity, disintegration time, moisture content, and dissolution.
Drug metabolism- General pharmacology - various typesRaviMundugaru1
This document discusses drug biotransformation and metabolism. It notes that drugs are chemically altered within the body through processes like oxidation, reduction, hydrolysis, and conjugation. The liver is a major site of drug metabolism, which occurs in two phases - phase I involves processes like oxidation, and phase II involves conjugation reactions to make the drug more water soluble and able to be excreted. Factors like age, diet, disease states, and genetics can impact an individual's drug metabolism. Prodrugs are discussed as inactive forms of drugs that are converted to the active form after metabolism.
Biotransformation, or metabolism, refers to the chemical alteration of drugs in the body. The primary site is the liver, where drugs undergo two main phases of metabolism - phase I and phase II reactions. Phase I reactions like oxidation and hydrolysis functionally alter drugs, while phase II or conjugation reactions make drugs more polar and excretable by conjugating them to other molecules. Many drugs are activated or inactivated in these metabolic pathways. Metabolism can occur in other tissues as well and is mediated by various enzyme systems like the cytochrome P450 enzymes. Drug metabolism can be inhibited or induced, affecting the activity of other drugs a patient may be taking.
Drug metabolism involves two phases of biochemical reactions that transform lipophilic drugs into more water-soluble compounds that can be readily excreted. Phase I reactions like oxidation, reduction, and hydrolysis introduce or expose functional groups on drugs. Phase II reactions, through conjugation, form bonds between functional groups on drugs and endogenous compounds like glucuronic acid, sulfate, glutathione, or amino acids, further increasing water solubility. The liver is the primary site of drug metabolism, with cytochrome P450 enzymes playing a key role in many phase I oxidative reactions.
Biotransformation involves the chemical alteration of drugs in the body through phase 1 and phase 2 reactions. Phase 1 reactions like oxidation, reduction and hydrolysis activate or expose functional groups on drugs. Phase 2 reactions like conjugation make drugs more polar and excretable. The liver is the primary site of biotransformation through cytochrome P450 enzymes and UDP-glucuronyltransferases. First pass metabolism can decrease oral bioavailability. Drug interactions can occur through enzyme induction, increasing metabolism of other drugs, or enzyme inhibition, decreasing metabolism of other drugs.
The document discusses drug excretion and elimination from the body. It describes the various routes of excretion including renal, biliary, pulmonary, salivary, dermal and gastrointestinal. The key organs involved in excretion are the kidneys and liver. Drugs can be excreted unchanged or as metabolites, through glomerular filtration, tubular secretion or reabsorption in the kidneys. Non-renal routes depend on the drug's physicochemical properties and include biliary excretion of conjugated metabolites. Factors like urine pH, blood flow and drug interactions can influence renal excretion. Clearance is the volume from which the drug is completely removed per unit time and includes renal, hepatic and total body clearance
biotransformation of drug
Biotransformation/Xenobiotic metabolism/ drug metabolism/detoxification.
-Xenobiotics: a wide variety of foreign compounds to which humans get exposed in day to day life.
-It includes unknown compounds, drugs, environmental pollutants, toxins.
-Many xenobiotics can evoke biological responses.
DEFINITION
The biochemical alteration of drug or xenobiotic in the presence of various enzymes that acts as a catalyst which themselves not consumed in the reaction and there by may activate or deactivate the drug is called biotransformation.
Why Biotransformation is necessary?:
To easily eliminate the drug
To terminate drug action by inactivating it
Consequences of Biotransformation
Active to Inactive:
Phenobarbitone---- Hydroxyphenobarbitone
Inactive (prodrug) to Active :
L-Dopa ---- Dopamine
Parathion -- Paraoxon
Talampicillin -- Ampicillin
Active to equally active:
Diazepam -- Oxazepam
Amitriptyline -- Nortriptyline
Imipramine -- Des-imipramine
Codeine -- Morphine
Sites of biotransformation
In the body: Liver, small and large intestines, lungs, skin, kidney, nasal mucosa & brain.
Liver is considered “metabolite clearing house” for both endogenous substances and xenobiotics.
Intestines are considered “initial site of drug metabolism”.
FIRST PASS METABOLISM:
First pass metabolism or presystemic
metabolism or ‘first pass effect’
After oral administeration many drugs are absorbed from the small intestine - transported first via portal system to the liver, where they undergo extensive metabolism before reaching systemic circulation.
fundamental concepts in drug biotransformation
Lipid soluble drugs are poorly excreted in the urine. They tend to store in fat and/or circulate until they are converted (phase I biotransformation) to more water soluble metabolites or metabolites that conjugate (phase II biotransformation) with water soluble substances.
Water soluble drugs are more readily excreted in the urine. They may be metabolized, but generally not by the CYP enzyme systems.
Enzymes catalyzing phase I biotransformation reactions
Enzymes catalyzing phase I biotransformation reactions include:
cytochrome P-450
aldehyde and alcohol dehydrogenase
deaminases
esterases
amidases
epoxide hydratases
Addition of water
Cleavage of R-O or R-N bond accompanied by addition of H2O
CYTOCHROME P450
The cytochrome P-450 families are referred to using an arabic numeral, e.g., CYP1, CYP2, etc.
Each family has a number of subfamilies denoted by an upper case letter, e.g., CYP2A, CYP2B, etc.
The individual enzymes within each subfamily are denoted by another arabic numeral, e.g., CYP3A1, CYP3A2, etc.
1) Biotransformation, or metabolism, involves the chemical alteration of drugs in the body by enzymes to make them more water soluble and easier to eliminate. This occurs mainly in the liver.
2) Phase I metabolism involves oxidation, reduction, and hydrolysis reactions using cytochrome P450 enzymes to introduce functional groups. Phase II metabolism involves conjugation reactions like glucuronidation and sulfation to further increase water solubility.
3) Factors like age, sex, disease states, genetic variations, and drug-drug interactions can impact drug metabolism by inducing or inhibiting metabolizing enzymes. Understanding a drug's metabolism is important for efficacy, safety, and interactions.
This document discusses biotransformation, or the metabolism of drugs in the body. It covers the key topics of:
- Phases of metabolism, including phase 1 reactions like oxidation and reduction mediated by cytochrome P450 enzymes, and phase 2 conjugation reactions.
- Important cytochrome P450 enzyme families, specifically CYP3A4 which metabolizes over 50% of drugs.
- Factors that can influence biotransformation like concurrent drug use, genetic polymorphisms, and pathological states.
- The role of biotransformation in drug discovery and development through in vitro and in silico studies.
1. Drug metabolism involves enzymatic modification of drugs by the body with the goal of making them more water soluble and easier to excrete.
2. Metabolism can occur in many tissues like the liver, kidneys, lungs, and intestines and is primarily carried out by the cytochrome P450 enzyme system.
3. Metabolism can result in inactive, active, or more active drug metabolites and influences the drug's pharmacokinetic and pharmacodynamic properties. Certain drugs are able to induce or inhibit the cytochrome P450 enzyme system, altering metabolism of other drugs metabolized by the same enzymes.
This document discusses drug metabolism. It defines drug metabolism as the chemical reactions that occur in the body to convert drugs into water-soluble compounds that can be easily excreted from the body. The main organs involved in drug metabolism are the liver, kidneys, lungs, intestine, skin, and brain. There are two phases of drug metabolism - phase I involves reactions like oxidation, reduction, and hydrolysis that make the drug more polar. Phase II involves conjugation reactions like glucuronidation and acetylation that make the drug even more hydrophilic to facilitate excretion. Factors like genetic variations, diseases, age, and gender can affect an individual's drug metabolism.
This document discusses drug metabolism and biotransformation. It describes how drugs are structurally modified inside the body through Phase I and Phase II metabolic pathways. Phase I metabolism involves oxidation, reduction and hydrolysis reactions by cytochrome P450 enzymes and flavin monooxygenases. This makes the drugs more hydrophilic but can also activate some drugs. Phase II conjugation reactions like glucuronidation and sulfation catalyzed by transferase enzymes further increases hydrophilicity and promotes excretion of drug metabolites. The liver is the major site of drug metabolism though other tissues also play a role. Enzyme induction and inhibition can impact drug metabolism.
The document discusses biotransformation, which is the biochemical alteration of drugs inside the body. The main site of biotransformation is the liver, with other sites including the kidneys, lungs, intestine, and skin. Biotransformation makes drugs more polar, water soluble, and less lipid soluble to promote excretion. It can convert active drugs into inactive metabolites or active metabolites. The two main phases are phase I reactions, which use oxidation, reduction, and hydrolysis to introduce or remove functional groups, and phase II reactions, which produce non-toxic conjugates through glucoronidation, acetylation, methylation, and other conjugation reactions. Factors that can influence biotransformation include patient factors like age and genetics
Basic Princioles of Pharmacokinetics 05 02 2023 BAA.pptxmaamedokuah233
The document discusses the basic principles of pharmacokinetics, which is the study of what the body does to drugs. It covers the key processes of absorption, distribution, metabolism, and excretion (ADME) that drugs undergo in the body. Absorption refers to how drugs enter the bloodstream, distribution is the movement of drugs between tissues, metabolism chemically alters drugs to aid excretion, and excretion is how drugs are removed from the body. Understanding a drug's pharmacokinetics is important for ensuring safe and effective use.
This document discusses metabolism and excretion of drugs in the body. It covers the following key points in 3 sentences:
Metabolism, primarily in the liver, transforms drugs through phase I and phase II reactions to make them more polar and easily excreted. The major phase I reactions are oxidation, reduction, and hydrolysis catalyzed by cytochrome P450 enzymes, while phase II conjugation reactions make drugs more hydrophilic through conjugation to compounds like glucuronic acid. The kidneys are the primary route of drug excretion, where drugs are filtered from the blood and either reabsorbed or actively secreted from the body, though other routes include bile, feces, lungs, sweat and breast milk.
Metabolism, or biotransformation, is the process by which drugs are chemically altered in the body. Drugs undergo two main phases of metabolism: Phase I involves processes like oxidation, reduction, and hydrolysis that make the drug more polar. Phase II involves conjugating reactions like glucuronidation that allow for excretion of the metabolite. Many drugs are metabolized in the liver by cytochrome P450 enzymes, and first-pass metabolism can reduce oral bioavailability. Factors like age, sex, diet, and concurrent medications can impact an individual's drug metabolism.
By the end of this lecture, students should:
Explain why drug metabolism is essential
Describe the phases of drug metabolism
Explain the role of cytochrome p 450 enzyme system in drug metabolism
Definition
Chemical reactions which occur in the body to change drugs from nonpolar lipid soluble forms to polar water soluble forms that are easily excreted by the kidney.
The major organs involved in drug excretion are the kidneys and liver. The kidneys excrete drugs through glomerular filtration, tubular secretion, and tubular reabsorption in the nephron. The liver excretes some drugs and their metabolites into bile. Pulmonary excretion eliminates gaseous and volatile substances through expiration.
Pharmakokinetic Variations in Kidney diseases.Maleha Sial
The kidney plays an important role in drug excretion and metabolism. Renal diseases and impairment can significantly impact the pharmacokinetics of drugs in multiple ways. Kidney function affects absorption, distribution, metabolism and elimination of drugs. Specifically, impaired renal function can decrease drug protein binding, increase volume of distribution, decrease metabolism of some drugs while increasing metabolism of others, and greatly reduce drug clearance by eliminating the kidney's excretory pathway. These alterations in pharmacokinetics require careful dosage adjustments for many drugs used in patients with renal diseases.
Metabolism,Excretion,prodrug,Therapeutic Drug monitoringSrinivasSree11
1. Metabolism and excretion are important processes that determine the duration and intensity of a drug's effects in the body. Metabolism involves chemical alteration of drugs through phase I and phase II reactions, while excretion removes drugs and metabolites from the body through renal, hepatic, pulmonary and other routes.
2. Factors like age, diet, diseases, genetic factors and simultaneous administration of other drugs can influence drug metabolism by inducing or inhibiting drug-metabolizing enzymes. Metabolism can convert drugs to active, inactive or less active forms.
3. Prodrugs are inactive forms administered to deliver the active drug selectively or improve pharmacokinetics. They are converted to active drugs through metabolic processes
Similar to pharmacokinetics-ii-170215132744.pdf (20)
This document discusses considerations for dosage form design, including reasons drugs are incorporated into dosage forms, types of dosage forms, and information needed for preformulation studies. It covers drug degradation mechanisms, drug instability, stability studies, and approaches to stabilize drugs. Factors in dosage form design include therapeutic use, administration route, patient age and condition. Common oral dosage forms are tablets and capsules, while injections can be used for emergency or inability to take oral medications. Design must also consider issues like difficulty swallowing, multiple medication therapy in elderly patients, and performulation studies to characterize the drug substance.
Capsules are solid dosage forms where the drug is enclosed within a shell, typically made of gelatin. There are two main types - hard gelatin capsules which contain powders, granules, or pellets and release their contents rapidly; and soft gelatin capsules which contain liquids or pastes and provide rapid release. Capsules offer advantages like masking unpleasant tastes and smells, easy swallowing, and sustained or delayed release depending on the formulation. They are manufactured through processes like dipping, spinning, drying, stripping, trimming, and joining. Finished capsules are evaluated for content uniformity, disintegration time, moisture content, and dissolution.
The document discusses powders as a pharmaceutical dosage form. It defines powders as finely divided solid drugs or chemicals meant for internal or external use. It describes various methods of preparing powders, including spatulation, trituration, geometric dilution, sifting, and tumbling. Powders are classified based on their intended use, such as bulk powders, simple/compound powders, powders in capsules/cachets, and compressed powders. Weighing techniques and packaging of powders are also outlined.
The document discusses various topics related to pharmacokinetics and drug administration and absorption. It defines key terms like pharmacokinetics, bioavailability, and first-pass effect. It describes different routes of drug administration like oral, sublingual, rectal, inhalation, and parental with their advantages and disadvantages. It explains different mechanisms of drug absorption including passive diffusion, active transport, and facilitated diffusion. It also lists factors that can affect drug absorption like molecular weight, lipid solubility, ionization, dosage form, and gastrointestinal conditions.
The document discusses various pharmaceutical dosage forms and drug delivery systems categorized by route of administration including oral, parenteral, topical, rectal, and others. It describes solid dosage forms like tablets and capsules as well as liquid forms including solutions, suspensions, and emulsions. Modified and controlled release delivery systems are also outlined. The document provides examples of different dosage forms and delivery technologies.
- Pharmacokinetics is the study of how the body affects drugs through absorption, distribution, metabolism, and excretion. Pharmacodynamics is the study of how drugs affect the body through their mechanisms and effects.
- Common routes of drug administration include oral, sublingual, rectal, and inhalation. Oral administration is easy but can cause first pass metabolism. Sublingual administration avoids first pass metabolism but is not suitable for frequent use. Rectal administration is suitable for children and vomiting but can cause irritation.
- Drugs are absorbed through passive diffusion, active transport, and facilitated diffusion. Absorption is affected by factors like lipid solubility, ionization, dosage form, blood flow,
This document provides an overview of dosage form design and formulation considerations. It discusses the need for dosage forms to safely deliver accurate drug doses. Key points covered include preformulation studies to characterize drug substances, approaches to incorporating different physical forms of drugs into dosage forms, and general design considerations for factors like therapeutic use, patient age and condition, and stability. The document also outlines various dosage form types and reasons for their use.
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Tags: Information Security, ISO/IEC 27001, ISO/IEC 42001, Artificial Intelligence, GDPR
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5. •Involves enzymic conversion of one chemical entity to
another within the body.
• Occurs between absorption of the drug into the
circulation and its elimination.
• Renders non polar (lipid soluble) compounds polar
(lipid insoluble).
• Sites- liver, GIT, lungs, kidneys, brain, skin.
6. Consequences in a biotransformation reaction:
Formation of an inactive metabolite from a
pharmacologically active drug.
Eg: 6- Mercaptopurine 6- Mercapturic acid
(Active drug) (Inactive metabolite)
Formation of an active metabolite from an inactive or a
lesser active drug.
Eg: L- dopa Dopamine in basal ganglia
(Inactive) (Active)
7. Formation of an active metabolite from an equally
active drug.
Eg: Diazepam Oxazepam
(Active) (Active metabolite)
Formation of a toxic metabolite from an active drug.
Eg: Paracetamol N- acetyl- p- benzoquinoneimine
(Active) (Toxic metabolite)
8. MICROSOMAL ENZYMES
• Drug metabolizing enzymes associated with smooth
endoplasmic reticulum of the liver.
•Principal enzymes involved:
- Mixed Function Oxidase
- Cytochrome P450
•Non specific in action.
•Can be induced, activated. Can metabolize only lipid
soluble drugs.
•Primarily concerned with phase I oxidation and
reduction.
9. The activity of MFO’s require a reducing agent
(nicotinamide adenine dinucleotide phosphate [NADPH])
and molecular oxygen.
In a typical reaction, one molecule of oxygen is
consumed (reduced) per substrate molecule, with one
oxygen atom appearing in the product and the other in
the form of water.
Drug + O2 + NADPH + H+ Drug metabolite + H2O +
NADP+
10. Cytochrome P450 abbreviated as P450 or CYP- a
haemoprotein.
Classified into families designated as 1,2,3,4 and
subfamilies by letters A, B, C, D.
Another number is added to indicate specific
isoenzyme. Eg: CYP2A6.
11.
12. These enzymes differ from one another in:
Amino acid sequence.
Sensitivity to inhibitors and inducing agents.
Specificity of the reactions they catalyse.
15. PHASE I REACTIONS
Functions to convert lipophilic molecules into polar
molecules by introducing or unmasking a polar
functional group like –OH or –NH2 .
Involves Oxidation, Reduction and Hydrolysis.
16. OXIDATION:
Microsomal oxidation causes aromatic or aliphatic
hydroxylation, deamination, dealkylation or S-oxidation.
These reactions involve reduced nicotinamide adenine
dinucleotide phosphate(NADP), molecular O2 and one
or more group of CYP450.
Drug + O2 + NADPH + H+ Drug- OH + H2O + NADP+
Can also involve other MFO’s like flavin containing
monooxygenases or epoxide hydrolases.
17.
18.
19. REDUCTION:
Reduction requires reduced NADP-cytochrome-c
reductase or reduced NAD-cytochrome b5 reductase.
HYDROLYSIS:
These reactions do not involve hepatic microsomal
enzymes.
Occur in plasma and other tissues.
Both ester and amide bonds are susceptible to
hydrolysis.
20.
21. PHASE II REACTIONS
Consists of conjugation reactions.
Drugs already possessing an –OH, -NH2 , -COOH
group may enter phase II directly without prior phase I
metabolism.
Involves acetylation, methylation, glucuronidation,
sulphation, mercaptopuric acid formation, glutathione
conjugation.
22. AMINO ACID REACTIONS:
Glycine and glutamine are chiefly involved.
Glycine forms conjugates with nicotinic acid and
salicylates.
Glutamine forms conjugates with p-aminosalicylates.
23. ACETYLATION:
Acetate derived from acetyl coA conjugates with drugs
like isoniazid, sulfonamides.
This activity resides in the cytosol and occurs in the
leucocytes, gastrointestinal epithelium and the liver.
24. GLUCURONIDATION:
Catalysed by UDP- glucuronyl tranferase enzyme.
Conjugation reactions between glucuronic acid and
carboxyl groups are involved in the metabolism of
bilirubin, diazepam etc.
26. METHYLATION:
Proceeds by a pathway involving S-adenosyl
methionine as methyl donor to drugs with free amino,
hydroxyl or thiol groups.
Eg: Catechol-O-methyl transferase.
Present in the cytosol.
27. Methylates the terminal – NH2 residue of noradrenaline
to form adrenaline in the adrenal medulla
Catalyses the transfer of a methyl group to
catecholamines, inactivating noradrenaline, dopamine
and adrenaline.
28.
29. ENZYME INDUCTION
Some P450 substrate drugs, on repeated
administration induce P450 expression by enhancing the
rate of its synthesis.
Leads to accelerated drug metabolism leading to:
Decreased plasma drug concentrations.
Decreased drug activity if metabolite is inactive.
Increased drug activity if metabolite is active.
Decreased therapeutic drug effect.
30. CLINICAL RELEVANCE
Drug- drug interaction:
Eg: Phenytoin accelerates Vitamin D3 metabolism
Osteomalacia.
Failure of OCP if potent inducers like rifampicin or
phenytoin are used.
Drug toxicity:
Eg: Risk of hepatotoxicity is more in Ethanol drinkers
than in those having Paracetamol overdose.
31. ENZYME INHIBITION
One drug may inhibit the metabolism of another drug
resulting in an increase in the circulating levels of the
slowly metabolized drug.
A drug may inhibit one isoenzyme while itself being a
substrate of another isoenzyme.
Eg: Quinidine is metabolized mainly by CYP3A4 but it
inhibits CYP2D6.
32. Inhibition of CYP isoenzyme activity is an important
source of drug interactions that leads to serious adverse
events.
Eg: Omeprazole is a potent inhibitor of 3 CYP
isoenzymes responsible for warfarin metabolism.
33.
34. Inhibition of drug metabolism
Increased plasma levels over time and with long
term medications.
Prolonged pharmacological drug effect.
Increased drug induced toxicities.
35. FIRST PASS METABOLISM
All drugs taken orally pass through GIT and portal
system before reaching the systemic circulation.
In first pass metabolism, metabolism of drugs occur
before the drug enters systemic circulation.
Net result is decreased bioavailabilty of the drug
leading to diminished therapeutic response.
38. Most drugs and drug metabolites are eliminated from
the body through renal (most common) and biliary
excretion.
Relies on the lipophilic character of the drug or
metabolite.
39. RENAL EXCRETION OF DRUGS:
Renal blood comprises 25% total systemic blood flow.
Rate of drug elimination through kidneys depend on:
balance of drug filtration
secretion
reabsorption rate.
40. Afferent arteriole Free drug and plasma protein
bound drug glomerulus.
However only the free drug is filtered into the renal
tubule.
Renal blood flow, GFR and drug binding to plasma
protein affect the amount of drug entering the tubule at
the glomerulus.
41. Rapid excretion of the drug is caused by:
Enhancing the blood flow.
Increasing the GFR
Decreasing plasma protein binding.
42.
43. GLOMERULAR FILTRATION:
Drugs enter the kidney through renal arteries which
divide to form glomerular capillary plexus.
Free drug flows through the capillary slits into the
Bowman’s space as a part of glomerular filtrate.
Glomerular capillaries allow drug molecules of
molecular weight below 20,000.
Lipid solubility and pH do not influence passage of
drugs into the glomerular filtrate.
44. TUBULAR SECRETION:
Upto 20% of renal plasma flow is filtered through the
glomerulus.
80% pass on to the peritubular capillaries of the
proximal tubules.
Here, the drug molecules are transferred to the tubular
lumen by two independent and relatively non selective
carrier systems- OAT and OCT.
OAT transports acidic drugs while OCT handles organic
bases.
45.
46. Unlike glomerular filtration, carrier mediated transport
can achieve maximal drug clearance even when most of
the drug is bound to plasma protein.
Many drugs compete for the same transport system
leading to drug interactions.
Eg: Probenecid prolongs the action of penicillin by
retarding its tubular secretion.
47. TUBULAR REABSORPTION:
The concentration of the drug increases as it moves
towards the distal convoluted tubule.
If the drug is uncharged, it may diffuse out of the
nephric lumen back into the systemic circulation.
For an ionised drug, reabsorption in the tubule can be
enhanced or inhibited by chemical adjustment of urinary
pH.
48. Weak acids can be eliminated by alkanisation of urine
while weak bases can be eliminated by acidification of
urine- ion trapping.
Eg: Phenobarbitol overdose can be treated with sodium
bicarbonate.
It alkanises the urine, keeps the drug ionised and
decreases its reabsorption.
If overdose is with a weak base, such as cocaine,
acidification of the urine with NH4Cl leads to protonation
of the drug and an increase in its clearance.
49. BILIARY EXCRETION:
Various hydrophilic drug conjugates particularly
glucuronides are concentrated in the bile and delivered
to the intestine.
Here the glucuronide is hydrolysed, releasing the active
drug once more.
This free drug is reabsorbed and the cycle is repeated-
enterohepatic circulation.
50.
51. CLEARANCE
Defined as the rate of elimination of the drug in relation
to its concentration.
Clearance = Rate of elimination
Concentration
Elimination of the drug may involve processes occuring
in the kidney, liver, lungs etc..
Clearance(total) = Clearance(renal) + Clearance (hepatic) +
Clearance(others).
52. KINETICS OF ELIMINATION
Most of the elimination reactions (includes both
metabolism and excretion) follow Michaelis- Menten
kinetics:
Rate of elimination= E= Vmax [C]
Km+ C
Where,
Vmax Maximum rate of drug elimination.
Km drug concentration at which rate of elimination is
½ Vmax (Michaelis constant).
C Concentration of the drug in the plasma.
53. FIRST ORDER KINETICS:
Here the concentration of the drug is much less than
the Michaelis constant Km.
Hence the equation reduces to,
E = Vmax [C]
Km
That is, rate of drug elimination is directly proportional
to the concentration of the free drug.
54.
55. ZERO ORDER KINETICS:
In a few drugs like aspirin, ethanol and phenytoin,
[C] is much greater than Km.
Hence the equation reduces to,
E = Vmax [C] = Vmax
[C]
Rate of elimination remains constant over time.
56. REFERENCES:
Rang and Dales pharmacology.
Basic and clinical pharmacology – Katzung.
Lippincott’s illustrated reviews.
David E Golan’s Principles of pharmacology.
Text book of clinical pharmacolgy- James Ritter
HL Sharma
KD Tripathi