The biggest issue in PK/PD and drug therapy is variability in
response. Variability factors that affect pharmacokinetics and pharmacodynamics influence clinical trials and dose regimen designs.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
PHARMACOKINETIC MODELS
Drug movement within the body is a complex process. The major objective is therefore to develop a generalized and simple approach to describe, analyse and interpret the data obtained during in vivo drug disposition studies.
The two major approaches in the quantitative study of various kinetic processes of drug disposition in the body are
Model approach, and
Model-independent approach (also called as non-compartmental analysis).
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
It is defined as “the predictive mathematical model that describes the relationship between in vitro property (such as rate & extent of dissolution) of a dosage form and in vivo response (such as plasma drug concentration or amount of drug absorbed)”.
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
Rate limiting steps in drug absorption [autosaved]Nagaraju Ravouru
Rate limiting steps in drug absorption 1.Disintegration time
2.Dissolution and solubility
3.Physical and chemical nature of active drug substance
4.Nature of excipients
5.Method of granulation
6.Dissolution test conditions
7.Gastric emptying
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
1. Measurement of Bioavailability:
Direct and indirect methods may be used to assess drug bioavailability. The in-vivo bioavailability of a drug product is demonstrated by the rate and extent of drug absorption, as determined by comparison of measured parameters, e.g., concentration of the active drug ingredient in the blood, cumulative urinary excretion rates, or pharmacological effects.
For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
The design of the bioavailability study depends on the objectives of the study, the ability to analyze the drug (and metabolites) in biological fluids, the pharmacodynamics of the drug substance, the route of drug administration, and the nature of the drug product.
Pharmacokinetic and/or pharmacodynamic parameters as well as clinical observations and in-vitro studies may be used to determine drug bioavailability from a drug product.
1.1. Pharmacokinetic methods:
These are very widely used and based upon the assumption that the pharmacokinetic profile reflects the therapeutic effectiveness of a drug. Thus these are indirect methods. The two major pharmacokinetic methods are:
The major pharmacokinetic methods are:
Plasma / blood level time profile.
o Time for peak plasma (blood) concentration (t max)
o Peak plasma drug concentration (Cmax)
o Area under the plasma drug concentration–time curve (AUC)
Urinary excretion studies.
o Cumulative amount of drug excreted in the urine (Du)
o Rate of drug excretion in the urine (dDu/dt)
o Time for maximum urinary excretion (t)
C. Other biological fluids
1.2. Pharmacodynamic methods:
IT involves direct measurement of drug effect on a (patho) physiological process as a function of time. Disadvantages of it may be high variability, difficult to measure, limited choices, less reliable, more subjective, drug response influenced by several physiological & environmental factors.
They involve determination of bioavailability from:
Acute pharmacological response.
Therapeutic response.
1.3. In-vitro dissolution studies
Closed compartment apparatus
Open compartment apparatus
Dialysis systems.
1.4. Clinical observations
Well-controlled clinical trials
Rate limiting steps in drug absorption [autosaved]Nagaraju Ravouru
Rate limiting steps in drug absorption 1.Disintegration time
2.Dissolution and solubility
3.Physical and chemical nature of active drug substance
4.Nature of excipients
5.Method of granulation
6.Dissolution test conditions
7.Gastric emptying
An in-vitro in-vivo correlation (IVIVC) has been defined by the U.S. Food and Drug Administration (FDA) as "a predictive mathematical model describing the relationship between an in-vitro property of a dosage form and an in-vivo response".
Methods For Assesment Of Bioavailability Anindya Jana
Bioavailability means the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. For drug products that are not intended to be absorbed into the bloodstream, bioavailability may be assessed by measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.
Bioavailability studies are important in the Primary stages of development of a suitable dosage form for a new drug entity, determination of influence of excipients, patient related factors & possible interaction with other drugs on the efficiency of absorption, development of new formulations of the existing drugs, control of quality of a drug product during the early stages of marketing in order to determine the influence of processing factors, storage & stability on drug absorption
Variations in Pk's in disease states.pdfSARADPAWAR1
Also the degree of plasma-protein binding, in turn, influences the distribution, action, metabolism and renal excretion of drugs. Thus changes in plasma protein binding of drugs, e.g. in diseased states, may give rise to altered pharmacokinetic and possibly altered drug response.
Variations in Pk's in disease states.pdfSARADPAWAR1
Pharmacokinetic variation is when there is variability in the drug concentration at the effector site after administration of a standard dose. This can result in one dose of a drug being ineffective in one patient, but potentially toxic with unwanted side effects in another.
Variations in Pk's in disease states.pptxSARADPAWAR1
Also the degree of plasma-protein binding, in turn, influences the distribution, action, metabolism and renal excretion of drugs. Thus changes in plasma protein binding of drugs, e.g. in diseased states, may give rise to altered pharmacokinetic and possibly altered drug response.
In 1945 Robert Burns Woodward gave certain rules for correlating λmax with molecular structure. In 1959 Louis Frederick Fieser modified these rules with more experimental data, and the modified rule is known as Woodward-Fieser Rules
sex-hormones belong to the steroid class of compounds and are produced in the gonads, i.e., testes in the male and ovaries in the female. In fact, their activity seems to be controlled and monitored by the hormones that are produced in the interior.
"Application of pharmacokinetics and bioavailability in clinical situations"Faizan Akram
The success of drug therapy is highly dependent on the choice of the drug, the drug product, and the design of the dosage regimen. The choice of the drug is generally made by the physician after careful patient diagnosis and physical assessment. The choice of the drug product (eg, immediate release vs modified release) and dosage regimen is based on the patient’s individual characteristics and known pharmacokinetics.
ATOMIC ABSORPTION SPECTROSCOPY by Faizan AkramFaizan Akram
Atomic absorption spectroscopy is a technique for determining the concentration of a particular metal element in a sample. Atomic absorption spectroscopy can be used to analyze the concentration of over 62 different metals in a solution.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
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New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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Faizan Akram 4th Prof
BIOPHARMACEUTICS
&
PHARAMCOKINETICS
PHARMACOKINETICS VARIATIONS IN
DISEASE STATES
2. P a g e | 2
Faizan Akram 4th Prof
Contents
Definitions
General Introduction
Effect of Liver Disease on PK
Effect of Kidney Disease on PK
Effect of Cardiac Disease on PK
Effect of Burns on PK
Biopharmaceutics
Definition:
Biopharmaceutics that consider the inter-relationship of physiochemical properties of the
drug form in which the drug is given and the route of administration on the rate and extent
of systemic drug absorption.
Pharmacokinetics vs. Pharmacodynamics
Pharmacokinetics
Definition:
Study of kinetics of absorption, distribution, metabolism and excretion.
Pharmacodynamics
Definition:
The study of biochemical & physiological effects of drugs & the mechanism of their actions
including the correlation of their action & effect with their chemical structure.
Bioavailability vs. Bioequivalence
Bioavailability
Definition:
Bioavailability means that rate and extent to which the active ingredients or active moiety
reaches the systemic circulation and becomes available at the site of action.
Bioequivalence
Definition:
Rate and extent of the absorption of test drug that do not show significant difference from
the rate and extent of absorption of the reference drug when administered at same molar
doses of therapeutic ingredient under similar experimental conditions in either single or
multiple dose.
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Structure of Pharmacokinetics
Pharmacokinetic consist of 4 major parts of its basic structure:
Absorption
Distribution
Metabolism
Excretion
Effect of Disease State on Pharmacokinetics
Disease is the abnormal state of the body it may affect the physiological
immunological & movement of the body, also can lead to death.
As the functions of the body is altered so it can also effect the physic-chemical
properties of the drugs, pharmacokinetics & pharmacodynamics of the drugs.
The many diseases can affect the pharmacokinetics of the drugs as well as its
pharmacodynamics these are given below.
o Liver Diseases.
o Kidney Diseases.
o Cardiac Diseases.
Liver
Acute liver impairment interferes with drug metabolism and elimination.
Chronic liver impairment affects all parameters of pharmacokinetic.
Because most drugs are metabolized by the liver, it is susceptible to drug toxicity.
Impaired liver function greatly increases the risks of adverse drug effects.
Many drugs change liver function tests without clinical signs of liver dysfunction.
Hepatotoxicity is potentially life threatening.
Liver is able to function with as little as 10% of undamaged hepatic cells.
With severe hepatic impairment, extrahepatic metabolism becomes more important.
Patient at risk for impaired liver function include:
Primary liver disease (e.g. hepatitis, cirrhosis).
Diseases that impair blood flow to the liver (heart failure, shock, major surgery, or
trauma).
Hepatotoxic drugs.
Absorption & Liver
Some oral drugs are extensively metabolized in the liver.
This process is called the first-pass effect or presystemic metabolism.
With cirrhosis, oral drugs are distributed directly into the systemic circulation.
This means that oral drugs metabolized in the liver must be given in reduced doses.
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Faizan Akram 4th Prof
Metabolism in Liver
Most drugs are metabolized by enzymes in the liver.
They are called the cytochrome P450 [CYP] or the microsomal enzymes.
Drugs Effect on Liver
With chronic administration, some drugs increase metabolizing enzymes in the liver:
enzyme induction.
Enzyme induction accelerates drug metabolism and larger doses is required.
Rapid metabolism also increases the production of toxic metabolites.
Enzyme induction does not occur for 1-3 weeks because new enzymes must be
synthesized.
Enzyme inducers consist of: phenytoin, rifampin, phenobarbital, ethanol, and
cigarette smoking.
Tolerance and cross-tolerance are attributed to activation of liver metabolizing
enzymes.
They also are attributed to decreased sensitivity or numbers of receptor sites.
Metabolism can be decreased in a process called enzyme inhibition.
It occurs with co-administration of drugs that compete for the same metabolizing
enzymes.
In this case, smaller doses of the slowly metabolized drug is needed to avoid toxicity.
Enzyme inhibition occurs within hours or days of starting an inhibiting agent.
Enzyme inhibitors consist of: Cimetidine, fluoxetine, and ketoconazole.
Kidney
Kidney is the major organ of excretion.
Other organs also play important role in the excretion.
If the kidney is compromised its can affect the all parameter of pharmacokinetics.
In the presence of renal diseases some metabolic functions seem to be impaired.
What Kind Of Drugs Can Be Excreted Through Kidney!!!???
Renal route of drug elimination is the major route for drugs that are:
o Polar drugs
o Water soluble drugs
o Low molecular weight drugs
o Slowly bio transformed/metabolizing drugs
Renal Impairment
Use of drugs in renal impairment can give rise to problems for several reasons:
Failure to excrete a drug or its metabolites may produce toxicity.
Sensitivity to some drugs is increased even if elimination is impaired.
Many side effects are tolerated poorly in patients with renal impairment.
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Faizan Akram 4th Prof
Some cease to be effective when renal function is reduced.
Renal Impairment & Absorption
In renal failure:
o Gastric pH increases
Result:
o Reduced absorption of many drugs
Renal Impairment & Distribution
Impaired renal function is associated with important changes in the binding of some drugs
to plasma proteins
Renal Impairment & Metabolism
Uremia slows the rate of phase I metabolism due to this there is decreased hydrolysis
& oxidation & also in phase II metabolism.
Even if drug is metabolized in liver the excretion of metabolites depends upon the
renal excretion.
Renal Impairment & Excretion
Renal handling of drugs depends upon:
o Glomerular Filtration
o Tubular Secretion
o Tubular Reabsorption
o GFR decrease than renal clearance decrease due to which plasma half-life increases.
Cardiac System
Complex progressive disorder.
Heart unable to pump sufficient amount of blood.
Cardiovascular Disease & Absorption
Effect on Absorption:
In Depressed cardiovascular state decrease perfusion to
o GIT
o Muscle
Result:
Erratic absorption of drug
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Faizan Akram 4th Prof
Cardiovascular Disease & Distribution
Cardiac impairment leads to
o Diminished perfusion to organs
o Low volume of distribution
o Increase plasma drug concentration
o Decrease blood flow to tissue
o Presence of edema cause increase distribution of water soluble drugs
Cardiovascular Disease & Metabolism
o Cardiac impairment
o Decrease hepatic perfusion
o Hepatocellular enzyme activity diminished
o Leads to Impaired metabolism
Cardiovascular Disease & Excretion
Depressed circulatory state cause Reduction in
o Cardiac output
o Hepatic blood flow
o Renal blood flow
Result
o Decrease clearance of drugs