This document discusses clinical pharmacokinetics and factors affecting drug absorption and bioavailability. It defines pharmacokinetics as what the body does to a drug, including absorption, distribution, metabolism and excretion. Absorption depends on patient factors like age, gastric emptying time, and presence of food, as well as physicochemical drug properties and pharmaceutical formulation characteristics. Understanding factors influencing absorption can help optimize drug therapy.
DRUG INTERACTIONS (MECHANISMS OF DRUG-DRUG INTERACTIONS)N Anusha
A Drug interaction is an interaction between a drug and some other substance, such as another drug or a certain type of food, which leads to interaction that could manifest as an increase or decrease in the effectiveness or an adverse reaction or a totally new side effect that is not seen with either drug alone that can be severe enough to alter the clinical outcome.
Every time a drug is administered with any other prescription medicine, OTC products, herbs or even food we expose ourselves to the risk of a potentially dangerous interaction.
Pharmacokinetic concepts and principles in humans in order to design individualized dosage regimens which optimize the therapeutic response of a medication while minimizing the chance of an adverse drug reaction.
General pharmacology and pharmocokineticsSwapnil Singh
Basic pharmacology and Pharmacokinetics principles and concepts covering routes of drug administration, absorption phenomena, metabolism and excretion from the body.
DRUG INTERACTIONS (MECHANISMS OF DRUG-DRUG INTERACTIONS)N Anusha
A Drug interaction is an interaction between a drug and some other substance, such as another drug or a certain type of food, which leads to interaction that could manifest as an increase or decrease in the effectiveness or an adverse reaction or a totally new side effect that is not seen with either drug alone that can be severe enough to alter the clinical outcome.
Every time a drug is administered with any other prescription medicine, OTC products, herbs or even food we expose ourselves to the risk of a potentially dangerous interaction.
Pharmacokinetic concepts and principles in humans in order to design individualized dosage regimens which optimize the therapeutic response of a medication while minimizing the chance of an adverse drug reaction.
General pharmacology and pharmocokineticsSwapnil Singh
Basic pharmacology and Pharmacokinetics principles and concepts covering routes of drug administration, absorption phenomena, metabolism and excretion from the body.
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
Clinical pharmacokinetic studies are performed to examine the absorption, distribution, metabolism, and excretion of a drug under investigation in healthy volunteers and/or patients
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
Pharmacodynamics and kinetics during pregnancyReem Alyahya
This presentation discuss the following objectives:
-Drug therapy during pregnancy, childbirth, and lactation.
-Physiological changes of drugs in pregnant women.
-Drug toxicity
-Cross-placental transfer of drugs
-Exertion of drugs in breast milk
-Drug safety + ABCDX
Clinical pharmacokinetics and its application--
1)definition
2) APPLICATIONS OF CLINICAL PHARMACOKINETICS
Design of dosage regimens:
a) Nomograms and Tabulations in designing dosage regimen,
b) Conversion from intravenous to oral dosing,
c) Determination of dose and dosing intervals,
d) Drug dosing in the elderly and pediatrics and obese patients.
Pharmacokinetics of Drug Interaction:
a) Pharmacokinetic drug interactions
b) Inhibition and Induction of Drug metabolism
c) Inhibition of Biliary Excretion.
Therapeutic Drug monitoring:
a) Introduction
b) Individualization of drug dosage regimen (Variability – Genetic, Age and Weight, disease, Interacting drugs).
c) Indications for TDM. Protocol for TDM.
d) Pharmacokinetic/Pharmacodynamic Correlation in drug therapy.
e) TDM of drugs used in the following disease conditions: cardiovascular disease, Seizure disorders, Psychiatric conditions, and Organ transplantations
Dosage adjustment in Renal and Hepatic Disease.
a. Renal impairment
b. Pharmacokinetic considerations
c. General approach for dosage adjustment in renal disease.
d. Measurement of Glomerular Filtration rate and creatinine clearance.
e. Dosage adjustment for uremic patients.
f. Extracorporeal removal of drugs.
g. Effect of Hepatic disease on pharmacokinetics.
Population Pharmacokinetics.
a) Introduction to Bayesian Theory.
b) Adaptive method or Dosing with feedback.
c) Analysis of Population pharmacokinetic Data
Clinical pharmacokinetic studies are performed to examine the absorption, distribution, metabolism, and excretion of a drug under investigation in healthy volunteers and/or patients
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
Pharmacodynamics and kinetics during pregnancyReem Alyahya
This presentation discuss the following objectives:
-Drug therapy during pregnancy, childbirth, and lactation.
-Physiological changes of drugs in pregnant women.
-Drug toxicity
-Cross-placental transfer of drugs
-Exertion of drugs in breast milk
-Drug safety + ABCDX
Distribución de Fármacos. Farmacología General 2012 ISergio Cáceres
Presentación del tema de Distribución de Fármacos en la Asignatura de Farmacología General para el 2012 - I en la Universidad Nacional de Colombia.
Presentada: 23 de marzo de 2012.
Bioavailability and bioequivalence
Bioavailability-
Whenever a drug is given by oral route it has to go through certain pathway to reach the systemic circulation. Eg. If 100 mg drug is given orally, and if 80 mg is absorbed and 20 mg gets excreted then 80 mg absorbed drug reaches liver through portal system. In liver it gets metabolized, here if 30 mg gets metabolized by the liver 50 mg reaches the systemic circulation in the unchanged from. But Bioavailability is expressed in mg it has to be expressed in fraction. So Bioavailability is basically the fraction of unchanged from of the drug that reaches the systemic circulation following administration by any route.
As the drug given by intravenous route reaches directly into the systemic circulation. So the Bioavailability of drug given i.v is 100 %. % Bioavailability can be calculated as- Area under the curve (AUC oral)/ (AUC i.v) *100.
Bioavailability depends on both the rate and extent of absorption.
Rate of absorption depends on- site of adminstration and the drug formulation.
Extent (amount) of absorption depends on- route of drug administration
Factors affecting absorption and Bioavailability-
Pharmaceutical and pharmacological factors:
Pharmaceutical factors include- particle size, crystal from, salt form, water of hydration, Nature of excipients and adjuvants, degree of ionisation.
Pharmacological factors- gastric emptying & g.i mobility, g.i diseases, food and other substances, first-pass effect, Drug-drug interaction, pharmacogenetics, miscellaneous factors like route of administration, area of absorbing surface, state of circulation at site of absorption.
Whenever a drug is given orally it has to go through certain pathway to reach systemic circulation.
E.g out of 100 mg drug given orally if 80 mg gets absorbed & 20 gets excreted. 80 mg of absorbed drug then reaches the liver through portal vein. Liver is highly saturated with enzymes so it doesn't allow the drug to pass freely through it without metabolizing certain amount of drug. . So if 30 mg of absorbed drug gets metabolized in the liver remaining 50 mg of drug reaches the systemic circulation in the unchanged form. But Bioavailability is never expressed in mg it is always expressed in fraction. So Bioavailability is basically the fraction of unchanged from of the drug that reaches the systemic circulation following administration by any route.
Whenever drug is given intravenously 100% drug reaches the systemic circulation in an unchanged form. So the Bioavailability of the drug given intravenously is 100%, while that of the drug given orally is < 100%
Bioavailability of a drug depends on the rate and extent of absorption.
Rate of drug administration is determined by: site of drug administration and drug formulation.
Extent (amount) of drug absorption is determined by: route of drug administration.
Factors affecting drug absorption and Bioavailability- There are various pharmaceutical and pharmacological factors that affect the drug absorption.
FIRST PASS METABOLISM:-
The drug given orally first pass through GI wall and then reaches the liver through portal system. The drug can also be metabolized in the gut wall CYP3A4 enzyme which is a substrate for P-gp {P-glycoprotein (P-gp) is an active transporter which pumps drug out of the gut wall cells back into the gut lumen against the concentration gradient.) Normally, drug enters the intestinal lumen by passive diffusion (i.e along the concentration gradient). But P-gp causes drug efflux or drug wastage (i.e against the concentration gradient); The amount of drug that disappears contribute first pass metabolism. But first pass metabolism occur in LIVER > INTESTINE.
Some amount of drug while passing through the liver gets metabolized in the liver for the first time before reaching the systemic circulation this known as first pass metabolism.
Bioequivalence- it as comparison of 2 different brand products of a same drug.
E.g. if Drug company X designs a new drug - (BRANDED DRUG) it gets patency for suppose 20 yrs. So that no other company can legally copy this drug. But once the patency expires any other company can legally copy this drug (GENERIC DRUG) but requires approval by FDA. and FDA asks for BIOEQUIVALENCE certificate (i.e it checks if the compound produced by other company is equivalent to that of BRANDED DRUG.) It has to prove that amount as well as rate of absorption is similar. No company can copy the drug 100% as it is. therefore the acceptable range is +/- 20-25%. The drug can be chemically, pharmaceutically, Therapeutically & clinically equivalent.
Thank you
Absorption, Bioavailability and Bioequivalance.pdfShaikh Abusufyan
At the end of this e-learning session you are able to…
A. Explain factor affecting drug absorption, bioavailability and bioequivalence.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
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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
General pharmacology Diploma in pharmacy second year YogeshShelake
The General pharmacology ,Toxicology & Pharmacotherapeutics
To Undastanding the general pharmacology & Definitions of PHARMACODYNAMECIS ,PHARMACOKINITICS (Absorbation,Distribution,Metabolism,Excreation )Pharmacology ,Toxicology ,Pharmacotherapeutic ,
Advantages of Routs of Administration & Their Disadvantages
Factors affecting of absorpation ,excreation of drug,factor modifing deug action
Similar to Clinical pharmacokinetics part 1 dr jayesh vaghela (20)
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
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
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!
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
3. Introduction
• Application of pharmacokinetic concepts and
principles in humans to design individualized
dosage regimens,
- To optimize the therapeutic response of a
medication
- To minimize the chance of an adverse drug
reaction
30-Dec-13 3
4. PHARMACOKINETICS
• Simply means, the science which deals with
“ What the Body does to the drug ”
• Includes 4 stages –
30-Dec-13 4
PHARMACOKINETICS
ABSORPTION DISTRIBUTION METABOLISM EXCRETION
8. BIOAVAILABILITY
• DEFINITION :-
“ The Rate at which & the Extent to which the
Active Concentration of drug is available at the desired
site of action. ”
• Concept came into existence when an unusual incidence
occurred in Australia in 1968.
• Phenytoin toxicity in Epileptic patients.
30-Dec-13 9
9. BIOEQUIVALENCE
Definition :
• If two or more dosage forms of the same drug reach the
blood circulation at the same relative rate & same
relative extent, they are called Bioequivalent
preparations of the generic drug.
• Clinically important for the drugs having steep dose-
response relationship,
• e.g.
Zero order kinetics ( phenytoin, warfarin )
Narrow margin of safety ( Theophylline, Tetracycline )
30-Dec-13 10
10. Measurement of Bioavailability
• Oral administration of 2 brand products of same drug
⇓
Plasma concentration – Time curve is obtained
⇓
3 characteristics noted & compared :
1) Cmax
2) Tmax
3) AUC
30-Dec-13 11
Rate of Absorption
Extent of Absorption
12. Calculation of AUC
Planimeter :
- An instrument to mechanically measure the area of
plain figures
Cut & Weigh method :
- Cut the area on rectilinear graph paper & weighing it by
analytical method
Mathematical :
- Trapezoidal rule
30-Dec-13 13
13. Quantitative Evaluation of Bioavailability
Drug Bioavailability ( % ) = AUC ( Oral ) x 100
AUC ( I.V. )
AUC (oral) = AUC obtained after oral administration of
single dose
AUC (IV) = AUC obtained after IV administration of same
drug in the same dose.
30-Dec-13 14
24. Drug transport process
DRUGS ARE TRANSPORTED ACROSS
THE MENBRANE
PASSIVE DIFFUSION
AND FILTRATION
SPECIALIZED
TRANSPORT
CARRIER
MEDIATED
FACILITATED
DIFFUSION
ACTIVE
TRANSPORT
PRIMARY SECONDORY
PINOCYTOSIS
30-Dec-13 25
28. Active transport
PRIMARY
◦ Energy obtained directly
from ATP
◦ Eg. Na+ K+ ATPase
SECONDARY
◦ Energy obtained from
movment of other solute
(Na+)
◦ Eg- SERT, DAT
30-Dec-13 29
29. • Primary Active transport
AA
M
E
M
B
R
A
N
E
ATP ADP
30-Dec-13 30
30. • Secondary Active Transport
AA
M
E
M
B
R
A
N
E
Na+ K +
ATPase
ATP ADP
Na+ K +
ATPase
H+ H+
GLUCOSE
Na+
K+
30-Dec-13 31
31. Pinocytosis / Cell Drinking
30-Dec-13 34
• Uptake of fluid solutes
E.g.
- Sabine polio vaccine (orally
administered)
32. • Pore transport / Convective Transport :
◦ Absorption occurs through narrow, aqueous filled channels or
pores in the membrane structure
◦ Ex.
- Water, Sugars, Urea.
- LMW drugs
• Ion-pair formation :
Ionized drug + opposite charged ion
⇩
Ion pair ( Neutral )
⇩
Diffuses more easily through membrane
e.g. – Quaternary Ammonium Compounds
30-Dec-13 35
33. (2) Age :
Infants :
◦ High gastric pH
◦ Less intestinal surface & blood flow
Elderly :
◦ Achlorhydria
◦ Less intestinal blood flow
◦ Altered gastric emptying
30-Dec-13 36
34. (3) Gastric Emptying Time
• Volume of Ingested Material • Bulky material tends to empty
more slowly than liquids
• Type of Meal • carbohydrates > proteins > fats
• Body Position • Lying on the left side decreases
emptying rate,
• Right side promotes it
• Drugs
• Anticholinergics
• Narcotic analgesics
• Ethanol
• Reduction in rate of emptying
• Emotional state • Anxiety promotes,
• depression retards it
• Disease states • Hypothyroidism retards it,
• Hyperthyroidism promotes it.
30-Dec-13 37
35. (4) Intestinal Transit Time
• Delayed Time is desirable for –
A) Drugs that dissolve or release slowly from their
dosage form (sustained release products)
B) Drugs that dissolve only in intestine (enteric
coated formulations)
C) Drugs absorbed from specific sites in the intestine
(Vit B)
30-Dec-13 38
36. (5) Presence of food
FOOD INCREASES THE
ABSORPTION OF ..
Chloroquine
Carbamazapine
Griseofulvin
FOOD DECREASES THE
ABSORPTION OF ..
Ampicilline
Aspirin
Captopril
Levodopa
Rifamicin
Tetracycline
To be
taken
before
meals
To be
taken
after
meals
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40. 2) Particle size and effective surface area:
◦ Dissolution rate of solid particles ∝ surface area
◦ Smaller particle size → greater surface area → higher
dissolution rate
◦ e.g. Bishydroxycoumarin
Digoxin
Griseofulvin
Two types of surface area
◦ 1) Absolute surface area
◦ 2) Effective surface area (More important)
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41. 30-Dec-13 44
Oral Administration of Drug
To fine particles
Tab or Cap
Drug in solution
Powders &
Suspensions
Solutions
Available for absorption in GIT
42. 3) Polymorphism & Amorphism :
◦ Depending upon internal structure, forms of solid may
be – Crystalline or
Amorphous form
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1. Polymorphism:
- Differ from each other
in physical properties
e.g. Solubility, Density
- Ex.- Riboflavin
Polymorph 3 is more water
soluble than polymorph 1.
2. Amorphism:
- Not having internal
Crystalline structure
More water soluble than
crystalline form
- Ex.- Novobiocin
Amorphous form is more
water soluble
43. 4) pH-Partition Theory :
• Absorption is governed by –
Dissociation constant pKa of the drug.
Lipid solubility of the un-ionized drug.
pH at the absorption site.
Amount of drug that exists in un-ionized form and in ionized
form is a function of –
pKa of drug, &
pH of the fluid at the absorption site,
• It can be determined by Handerson-Hasselbach equation:
30-Dec-13 46
45. Effect of pH on drug absorption:
• Acidic drugs (HA) release a proton (H+), causing a
charged anion (A–) to form:
HA ⇔ H+ + A-
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46. • Weak bases (BH+) can also release an H+.
◦ the protonated form of basic drugs is usually charged,
◦ loss of a proton produces the uncharged base (B)
BH+ ⇔ B + H+
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47. 5) Drug stability :
◦ A drug for oral use may be destabilized either during its
shelf life or in the GIT.
◦ Problems resulting in poor bioavailability of an orally
administered drug are –
Degradation of the drug into inactive form
Interactions with different components of drug itself or
that present in GIT.
30-Dec-13 50
48. B) Pharmaceutical factors :
Disintegration time :
Rapid disintegration
⇓
Less disintegration time
⇓
Rapid absorption
◦ Ex.-
• Coated tablets – more disintegration time
slow absorption
• Fine dispersible tablets – less disintegration time
fast absorption
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50. Nature & type of dosage form :
◦ As a general rule, Bioavailability of different dosage forms
in decreasing order is as following
◦ Solutions > Emulsions > Suspensions > Capsules > Tablets >
Enteric Coated Tablets > Sustained Release Products.
Product age & storage condition :
◦ Ex. –
• Precipitation of the drug in solution
• Hardening of tablet
• Change in particle size of suspension
30-Dec-13 53
51. Methods to Delay Absorption
1. Using Appropriate Dosage Form :
• Slow & Sustained absorption of drugs –
- Retard tablets ( pot. Chloride retard tablets )
- Depot injections ( Fluphenazine depot injectons )
- Subcutaneous implants ( testosterone pellets )
2. Changing Physical characteristics of drug :
• e.g. Procaine PnG
- Slightly water soluble
- When given i.v. ⇨ slowly absorbed & action is
prolonged
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52. Contd…
3. Adding a Vasoconstrictor Drug :
- Noradrenaline + Local Anaesthetic ( Xylocaine )
⇓
- Prolongs effect of local anaesthetic effect
- Reduces absorption into Systemic circulation &
systemic toxicity
4. Applying a Tourniquet :
- Tourniquet application ⇨ injection of L.A. below it
⇓
Delays systemic absorption
Prolongs action of L.A.
30-Dec-13 55
53. Methods to Facilitate Absorption
• Addition of enzyme Hyaluronidase (breaks down
intercellular matrix)
⇓
Speeds absorption
• Increasing the local blood flow to the tissue
⇓
Increased absorption
30-Dec-13 56
55. Drug may get Distributed into -
30-Dec-13 58
Body water Various TissuesEthanol
I2 in Thyroid,
Fluoride in bones,
Vit A & CHQ in liver,
Griseofulvin in keratin
Extracellular
Intracellular K+ ions, Sucrose
I- ions,
d-TC,
Gentamicin
Intravascular Interstitial
Mannitol,
Dextran,
Heparin
Digoxin,
emetine
56. Special Compartments for Drug Distribution
Plasma Protein Binding :
Free Drug + Protein ⇔ Drug-Protein Complex
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Free Drug Protein bound Drug
Pharmacologically Active Inert
Can diffuse through
capillary wall
Not accessible to capillary
diffusion, metabolism or
excretion
57. Proteins contributing to Drug Binding
Plasma Albumin :
• Most important contributor
• Binds to Acidic drugs - Warfarin
- Penicillin
α1 Acid Glycoproteins :
• Binds to Basic drugs - Quinidine
- Imipramine
Tissue Proteins & Nucleoproteins :
• Digoxin
Miscellaneous binding proteins :
• Transcortin – corticosteroid binding protein
30-Dec-13 60
58. Clinical significance of PPB
Highly protein bound drugs
⇓
Largely restricted to vascular compartment
Lower Vd
Difficult to be removed by dialysis
Hypoalbuminaemia ( e.g. Liver diseases )
• higher concentration of free drug
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59. Hyperalbuminaemia (e.g. M.I., Inflammation )
• higher concentration of Bound drug
Displacement reactions :
• drug having Higher affinity
⇓
displaces the drug having lower affinity
• e.g. – Sulfonamides & Vit K
⇓
Displaces bilirubin
⇓
Kernicterus in neonates
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60. Physiological Barriers to Drug Distribution
Blood Brain Barrier
Blood – CSF Barrier
CSF – Brain Barrier
Placental Barrier
Significance :
Prevent entry of the drug into organ & possible toxicity
Contain P-glycoprotein which effluxes the drug from
organ to back into blood circulation. e.g.- GIT,
Brain, Kidney
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62. Clinical example
• Digoxin :
• In 70 kg patient,
• 500 μg dose →
plasma concentration of 0.78 μg/L
So, if 0.78 μg of digoxin is in 1 litre of
plasma
⇓
500 μg would require 641 L of plasma
⇓
Not possible
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63. Apparent Volume of Distribution (aVd)
• Simply means,
“ the total space which should apparently be
available in the body to contain the known amount of the
drug ”
aVd = Total amount of drug in body ( mg/kg )
plasma concentration of drug ( mg/L )
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64. Clinical significance
30-Dec-13 67
If drug does not cross capillary membrane
- given by intravenous route
⇓
Vd = Plasma water i.e. 3 L
e.g. – Heparin, Insulin
High plasma protein bound
Less Tissue protein bound
e.g. – Tolbutamide
Reverse is true for drugs like Metoprolol
Low Vd value
65. If Vd is much more than the actual body volume
⇓
Widely distributed in body (adipose tissue, etc.)
⇓
Difficult to remove by dialysis if toxicity occurs
e.g. – Digoxin, Imipramine.
Vd < 5 L ⇨ drug within vascular compartment
e.g. – Heparin, Insulin, Warfarin
Vd ~ 15 L ⇨ drug restricted to Extracellular fluid
e.g. – Aspirin, Tolbutamide
Vd > 20 L ⇨ distributed in Total body water (Ethanol)
or penetration in tissues (Digoxin)
30-Dec-13 68
66. Redistribution of drugs
IV injection of Thiopentone
⇓
Enters brain very rapidly (1 minute after injection)
(highly lipid soluble)
⇓
General anaesthesia
⇓
Being highly lipid soluble,
Diffuses back to circulation from Brain
⇓
Redistributed to muscles & fat
Action is terminated
So, i.v. Thiopentone is ultra short acting
30-Dec-13 69
67. References
• Principles of Pharmacology, HL Sharma KK Sharma,
2nd Edition
• Applied Biopharmaceutics & Pharmacokinetics,
Leon Shargel, 5th Edition
• Lippincott’s Illustrated Reviews, Pharmacology 5th ed. -
M. Clark, et. al., (Lippincott, 2012, )
• Goodman & Giman’s The Pharmacological Basis of
Therapeutics, 12th edition
• Essentials of MedicalPharmacology, KD Tripathi, 6th
Edition
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