Has information about - Drug tolerance - definition, types, sub-types, it's examples; cross tolerance; tachyphylaxis; Drug intolerance - examples; analgesics tolerance
Has information about - Drug tolerance - definition, types, sub-types, it's examples; cross tolerance; tachyphylaxis; Drug intolerance - examples; analgesics tolerance
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
Metabolic Changes of Drugs and Related Organic Compounds describes the human metabolic processes of various functional groups found in therapeutic agents.
The importance of a chapter on metabolism lies in the fact that drug interactions are based on these processes.
For pharmacists, it is necessary for them to understand why certain drugs are contraindicated with other drugs.
This chapter attempts to describe the various phases of drug metabolism, the sites where these biotransformation will occur, the role of specific enzymes, metabolism of specific functional groups, and several examples of the metabolism of currently used therapeutic agents.
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
A brief presentation about the transport of drugs across the cell membrane including the many mechanisms and various transporters and a brief overview of the ABC and SLC superfamily of transporters.
“ 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."
Presentation covers the basics of pharmacokinetic. Mechanism for the transport of drug molecule. Absorption, factors affecting on absorption of drugs. Concept of bioavailability. Distribution, plasma protein binding, tissue binding, barriers.
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
Metabolic Changes of Drugs and Related Organic Compounds describes the human metabolic processes of various functional groups found in therapeutic agents.
The importance of a chapter on metabolism lies in the fact that drug interactions are based on these processes.
For pharmacists, it is necessary for them to understand why certain drugs are contraindicated with other drugs.
This chapter attempts to describe the various phases of drug metabolism, the sites where these biotransformation will occur, the role of specific enzymes, metabolism of specific functional groups, and several examples of the metabolism of currently used therapeutic agents.
The slides describe concept of distribution, Volume of distribution, factors affecting volume of distribution and the barriers to distribution. Blood brain barrier and placental barrier.
A brief presentation about the transport of drugs across the cell membrane including the many mechanisms and various transporters and a brief overview of the ABC and SLC superfamily of transporters.
“ 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."
Presentation covers the basics of pharmacokinetic. Mechanism for the transport of drug molecule. Absorption, factors affecting on absorption of drugs. Concept of bioavailability. Distribution, plasma protein binding, tissue binding, barriers.
Pharmacokinetics of Drug_Pharmacology Course_Muhammad Kamal Hossain.pptxMuhammad Kamal Hossain
Pharmacokinetics is defined as the kinetics of drug absorption, distribution, metabolism and excretion (ADME) and their relationship with the pharmacological, therapeutic or toxicological response in man and animals.
Pharmacokinetics, sometimes described as what the body does to a drug, refers to the movement of drug into, through, and out of the body—the time course of its absorption, bioavailability, distribution, metabolism, and excretion.
Similar to Absorption and distribution of drugs (20)
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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!
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
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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.
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
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
2. Pharmacokinetics :
It determines how much of an administered
dose will reach its sites of action.
There are four phases of P.K
Absorption
Distribution
Metabolism
Excretion
3. Absorption
Absorption is the transfer of a drug from its site of administration to blood
stream
Factors affecting drug absorption:
1. Rate of Dissolution:
2. Particle size
3. Physical states
4. Lipid solubility
5. Formulation
6. pH & Ionization
7. Gastrointestinal transit time
8. Area of the absorbing surface
9. Blood flow
10.Metabolism of drugs
11. Disease states
4. 1. Rate of Dissolution:
1. Drugs in formulation that allow rapid dissolution have faster onset
than drugs formulated for slow dissolution
2. Particle size:
1. Smaller the particles size greater is the rate of absorption
1. Physical states:
1. Liquids are better absorbed than solid
2. Crystalline “ “ than colloids
3. Amorphorous “ “ than crystalloid
2. Lipid solubility:
1. Highly lipid soluble unionized drugs are absorbed more rapidly
than those drugs which lipid solubility is low
2. Examples : fat soluble Vit A, D, E, K are better absorbed
3. Formulation:
1. Substance like sucrose, lactose, starch & calcium phosphate are
used as inert diluents in formulating tablets. These agents may
interfere with active drugs & affect its absorption
2. Sustained release dosage- delay absorption
5. 6. pH & Ionization
pH of the gastrointestinal fluid & blood may interfere
with the absorption of drugs
Acidic drugs are better absorbed in stomach
e.g aspirin ( weak acid) remain unionized form in acidic
medium of stomach, it favour their absorption
Basic drugs ( morphine ) better absorbed in intestine
7. Gastrointestinal emptying time (GET)
The presence of food, volume & tonicity of the stomach
or gastric contents can influence drug absorption by
altering the GET
Rapid absorption occurs if the drug is given before meals
E.g : atropine -- increase GET--- impair absorption
8. Area of the absorbing surface
Larger the surface area, faster absorption will be. So
orally administered drugs are usually absorbed from
small intestine rather than stomach becoz of large
surface area.
6. 9. Blood flow:
Drugs are absorbed most rapidly from sites where
blood flow is high
10. Metabolism of drugs
Rapid degradation of a drugs by liver during first pass
metabolism affect absorption & bioavailability
11. Disease states
Absorption can be affected in condition like
thyrotoxicosis, achlorhydria & liver cirrhosis
7. Drug has to cross membranes inorder to reach
the target sites
Three ways to cross membrane:
1. Passage through channels or pores
2.Passage with the help of transport system
3. Direct penetration of the membrane
8. 1. Channels or pores:
1. Very few drugs cross membrane by channels or
pores. The channels in membranes are
extremely small ( 4 angstroms), Only small
compound ( mol wt < 200) can use these routes
2. Example : sodium, potassium
2. Transport systems:
1. Passive transport
2. Active transport
3. Vesicular transport
9. 1. Passive transport:
1. Drug molecule pass cross the membrane in direction
of its conc gradient i.e from region of higher conc to
lower conc.
2. Most of the lipid soluble drugs are transferred by
passive diffusion
2. Active transport:
1. Needs specific carries protein
2. Moves against conc gradient
Example : steroids, cephalosporin, large molecular size
10. 3.. Vesicular transport:
1. It is process by which the substance is engulfed
by the cell membrane & carried into cell.
2. Example : iron , vit B12
4. Direct penetration of the membrane
Large molecules with lack of transport system
follow this pathways
So for direct penetration drug must be lipid
soluble.
12. HOW CHANGE IN ABSORPTION PATTERNABSORPTION PATTERN MODIFY THE
THERAPEUTIC EFFECT…….
12
Think of all the
EXTREME
possibilities in
relation to
absorption and
try to imagine
the
consequences..
13. Pharmacokinetic parameter governed by
absorption is …..BIOAVAILABILITY….
BIOAVAILABILITY ---It measures the fraction
(F) of administered dose of a drug that reaches
the systemic circulation in unchanged form.
If BA is 100 % I.V parenteral dose
BA is calculated by AUC (Area Under Curve)
13
14. PLASMA CONCENTRATION TIME
CURVE
14
Concentration
Time1 2 3 4 5 6
Drug A
Drug B
7 8 9
NOW WE WILL STUDY
FRIGHTENING TERMINOLOGIES!!!
1.Cmax Peak(maximum) plasma
concentration
2.Tmax time at which maximum
concentration is obtained
3.AUC (Area Under
Curve)
Minimum
Effective
Concentration
Maximum safe
concentration
15. 15
Bioavailability =
AUC after oral dose
AUC after IV dose
X 100
Cmax & Tmax measures the rate of absorption,
AUC measures the extent of absorption.
16. Drug Distribution
It is defined as the movement of drugs throughout
the body
Drug distribution is the process by which a drug
reversibly leaves the blood stream and enter the
interstitial and cell of the tissues.
Rate and extent being dependent on
Capillary permeability
Lipid solubility
Ionization at physiological pH
Extent of binding to plasma and tissue protein
Blood flow 16
18. Drug is administered
HOW CHANGE IN DISTRIBUTION PATTERNDISTRIBUTION PATTERN MODIFY THE
THERAPEUTIC EFFECT…….
18
19. 1.Blood flow:
Blood flow to the brain, liver and kidney is greater than
that to the skeletal muscles, whereas adipose tissue has
a lower rate of blood flow.
2.Capillary permeability
Capillary permeability is determined by capillary
structure and by the chemical nature of the drug.
19
20. a. Capillary structure:
Capillary structure varies widely in terms of the fraction
of the basement membrane that is exposed by slit
junctions between endothelial cells.
In the brain, the capillary structure is continuous, and
there are no slit junctions. This contrasts
with the liver and spleen, where a large part of the
basement membrane is exposed due to large,
discontinuous capillaries through which large plasma
proteins can pass.
20
21. b.
Blood-brain barrier:
To enter the brain, drugs must pass through the
endothelial cells of the capillaries of the CNS or be
actively transported.
Lipid-soluble drugs readily penetrate into the CNS
because they can dissolve in the membrane of the
endothelial cells.
Ionized or polar drugs generally fail to enter the
CNS because they are unable to pass through the
endothelial cells of the CNS, which have no slit
junctions.
21
22. Blood brain barrier
The capillary boundary that is present between the
blood and brain is called BBB
In the brain capillaries, the endothelial cells are
joined by tight junctions.
Only the lipid soluble and unionized form of drugs
can pass through BBB and reach the brain, e.g.
barbiturates, diazepam, volatile anaestthetics etc.
Lipid insoluble and ionized particles do not cross the
BBB e.g. dopamine, aminoglycosides
23. Pathological states like meningitis,
encephalitis increase the permeability of the
BBB and allow the normally impermeable
substance to enter the brain
For example penicillin in normal condition has
poor penetration through BBB but its
penetration increase during meningitis.
24. c. Drug structure:
The chemical nature of a drug strongly influences its
ability to cross cell membranes.
Hydrophobic drugs, which have a uniform distribution
of electrons and no net charge, readily move across
most biologic membranes.
These drugs can dissolve in the lipid membranes and,
therefore, permeate the entire cell's surface.
Hydrophilic drugs, which have either a nonuniform
distribution of electrons or a positive or negative
charge, do not readily penetrate cell membranes, and
therefore, must go through the slit junctions.
24
25. 3.Binding of drugs to plasma proteins
Reversible binding to plasma proteins sequesters
drugs in a nondiffusible form and slows their transfer
out of the vascular compartment.
Plasma albumin is the major drug-binding protein
and may act as a drug reservoir;
--- As the concentration of the free drug decreases
due to elimination by metabolism or excretion, the
bound drug dissociates from the protein.
This maintains the free-drug concentration as a
constant fraction of the total drug in the plasma.
25
26. Plasma protein binding
Many drugs bind to plasma proteins like albumin,
α1 acid glycoprotein etc
Clinical importance of PPB:
1. Plasma protein binding favour drug absorption
2.Drugs that are highly bound to plasma protein
have a low volume of distribution
3. Plasma protein binding delay the metabolism of
drugs
27. 4. Highly protein bound drugs have longer duration of
action e.g. sulphadoxine is highly plasma protein
bound and has duration of 1 week
5. In case of poisoning, highly PPB drugs are difficult
to be removed
6. Disease states like anemia, renal failure, chronic
liver disease have low plasma albumin level so there
will be increase in the free form of the drug which
can lead to drug toxiciy
7. Plasma protein binding can cause displacement
interactions.
28. Placenta barrier
The lipid membrane between the mother and foetus
is called placenta barrier.
Unionized and lipid soluble drugs can freely pass the
placenta barrier e.g anaesthetic, alcohol, morphine
etc
Certain drugs when given during pregnancy may
cross the placenta and cause various dangerous effects
in the foetus. This is called teratogenesis
E.g ---thalidomide -- phocomelia
Tetracycline-- yellowish teeth
29. Administration during first trimester cause abortion
and affect organogenesis and produce structural
abnormalities
Second and third trimester can affect growth and
development of foetus
Hence administration during pregnancy shoud be
retricted
30.
31. Apparent Volume of
Distribution
The Apparent volume of distribution ( Vd )is a hypothetical volume
of fluid into which a drug is distributed.
V = dose administered i.v
plasma concentration
A. Water compartments in the body
1.Plasma compartment:
If a drug has a very large molecular weight or binds extensively to
plasma proteins, it is too large to move out through the endothelial
slit junctions of the capillaries and, thus, is effectively trapped
within the plasma (vascular) compartment.
Plasma --- 5%
In a 70-kg individual, about 4 L of body fluid.
Heparin shows this type of distribution.
31
32. 2.Extracellular fluid:
If a drug has a low molecular weight but is hydrophilic,
move through the endothelial slit junctions
------------------- interstitial fluid.
Hydrophilic drugs cannot move across the lipid
membranes of cells to enter the water phase inside the
cell.
Extracellular fluids ( 20%)---- plasma (5%) and the
interstitial fluid 15%
About 14 L in a 70-kg individual.
Aminoglycoside antibiotics show this type of
distribution.
32
33. 3.Total body water:
If a drug has a low molecular weight & hydrophobic,
not -- move into the interstitium through the slit
junctions & the intracellular fluid.
About 42 L in a 70-kg individual.
Ethanol exhibits this apparent volume of
distribution
4. Other sites: In pregnancy, the fetus may take up
drugs and thus increase the volume of distribution.
Drugs that are extremely lipid-soluble, such as
thiopental may also have unusually high volumes of
distribution.
33
34. Apparent volume of distribution
Determination of Vd
a. Distribution of drug in the absence of elimination:
The apparent volume into which a drug distributes, Vd, is determined
by injection of a standard dose of drug, which is initially contained
entirely in the vascular system.
The agent may then move from the plasma into the interstitium and
into cells, causing the plasma concentration to decrease with time.
Assume for simplicity that the drug is not eliminated from the body;
the drug then achieves a uniform concentration that is sustained with
time . The concentration within the vascular compartment is the total
amount of drug administered, divided by the volume into which it
distributes, Vd:
34
35. Assume for simplicity that the drug is not eliminated from the body;
the drug then achieves a uniform concentration that is sustained with
time.
The concentration within the vascular compartment is the total
amount of drug administered, divided by the volume into which it
distributes, Vd:
C=D/Vd
Or Vd= D/C
C = plasma concentration of drugs
D = total amount of drug in the body
For example, if 25 mg of a drug (D = 25 mg) are administered and the plasma
concentration is 1 mg/L, then Vd = 25 mg/1 mg/L = 25 L.
35
36. b.Distribution of drug when elimination is present:
The initial decrease in plasma concentration is due to a rapid
distribution phase in which the drug is transferred from the plasma
into the interstitium and the intracellular water.
This is followed by a slower elimination phase during which the drug
leaves the plasma compartment and is lost from the body
The rate at which the drug is eliminated is usually proportional to the
concentration of drug, C; that is, the rate for most drugs is first-order
and shows a linear relationship with time
36
37. c. Calculation of drug concentration if distribution
is instantaneous:
Assume that the elimination process began at the time of
injection and continued throughout the distribution
phase. Then, the concentration of drug in the plasma, C,
can be extrapolated back to time zero (the time of
injection) to determine C0, which is the concentration of
drug that would have been achieved if the distribution
phase had occurred instantly.
For example, if 10 mg of drug are injected into a patient
and the plasma concentration is extrapolated to time zero,
the concentration is C0 = 1 mg/L , and then Vd = 10 mg/1
mg/L = 10 L.
37
38. 2. Effect of a large Vd on the half-life of a drug
Delivery of drug to the organs of elimination depends not
only on blood flow, but also on the fraction of the drug in
the plasma.
If the Vd for a drug is large, most of the drug is in the
extraplasmic space and is unavailable to the excretory
organs.
Therefore, any factor that increases the volume of
distribution can lead to an increase in the half-life and
extend the duration of action of the drug.
[Note: An exceptionally large Vd indicates considerable
sequestration of the drug in some organ or compartment.]
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39. Redistribution
Highly lipid soluble drugs given i.v or by inhalation, initially get
distributed to organs with high blood flow, e.g brain, heart ,
kidney etc.
Later, less vascular but more bulky tissues ( muscles, fat) take
up the drug- plasma concentration falls and the drug is
withdrawn from these sites.
If the site of action of drug was in one of the highly perfused
organs, redistribution results in termination of drug action.
Anaesthetic action of thiopentone is terminated in few minutes
due to redistribution. How ever, when the same drug is given
repeatedly or continously over long periods, the low perfusion
high capacity sites get progressively filled and the drug become
long acting.
40. Questions :
1. What is absorption and bioavailability? Explain
the factors affecting absorption with suitable e.g.
2.Describe different mechanism by which drug
cross various biological membrane
3. Write brifely on:
1. First pass effect
2. Volume of distribution and its clinical
significance
3. Redistribution
4. BBB
5. Placenta barrier
6. Clinical importance of plasma protein binding
4.Define drug distribution. Mention the factor that
affect drug distribution in detail.
Editor's Notes
Drugs can be ionised in an aqueous environment.
Non-ionised drug is more lipid soluble than ionised species.
Non-ionised species diffuse across cell membranes more easily than ionised species.