This document discusses various pharmacokinetic parameters including absorption, distribution, metabolism, excretion, and dosing regimens. It defines key terms like bioavailability, volume of distribution, clearance, half-life, and therapeutic drug monitoring. Factors that influence these parameters like protein binding, blood flow, and drug interactions are also covered. The relationships between concepts like clearance, volume of distribution, half-life, and how they impact dosing are explained through mathematical equations.
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).
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).
KINETICS OF MULTIPLE DOSING under the Unit Multicompartment Models According to New PCI syllabus 2017 by Ms. Preeti Patil-Vibhute, Assistant Professor, Sarojini College of Pharmacy, Kolhapur.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
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.
KINETICS OF MULTIPLE DOSING under the Unit Multicompartment Models According to New PCI syllabus 2017 by Ms. Preeti Patil-Vibhute, Assistant Professor, Sarojini College of Pharmacy, Kolhapur.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
DISSOLUTION
Dissolution is defined as a process in which a solid substance solubilises in a given solvent.
(i.e. mass transfer from the solid surface to the liquid phase.)
Three Theories:
Diffusion layer model / Film theory
Danckwert’s model / Penetration or Surface renewal theory
Interfacial barrier model / Double barrier or Limited solvation theory
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.
This presentation is about the process by which prolonged therapeutic activity of drug is achieved and it's importance. By this presentation you will learn about dosage regimen, steady state concentration, principle of superposition, drug accumulation, repetitive intravenous injections etc. By this you will also learn how to adjust the dose to the patient.
Health informathics part passive reabsorption2.pptxMelakeselamGedamu
passive reabsorption Occurs by simple diffusion.
Drugs should be in their non-ionized form to undergo passive reabsorption.
Hence, polar drugs are more readily excreted through the kidneys.
When the urine is acidic, the degree of
ionization of basic drug increase and their reabsorption decreases.
When the urine is more alkaline, the degree of ionization of acidic drug increases and the
reabsorption decreases.
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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.
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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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
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Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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.
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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NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
- 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
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2. Outline
• Enumeration and brief overview of different pharmacokinetic
parameters-
• Absorption-
• Bioavailability
• Distribution-
• Volume of distribution
• Metabolism and Excretion-
• Clearance
• Half life and order of elimination
• Elimination constant
• Dosing regimens
• Therapeutic drug monitoring
3. Concentration time graph
• Peak plasma concentration
• Time of peak plasma
concentration
• Area under the curve
• Minimum effective
concentration
• Maximum safe
concentration
• Onset of action
• Time of onset
• Duration of action
• Intensity of action
• Therapeutic range
• Therapeutic index
Maximum
4. Bioavailability (F)
• Fraction of administered drug which
reaches systemic circulation in unchanged
form
• It is expressed as fraction or percentage and
can range between 0 and 1
• In a concentration time graph, the area
under curve (AUC) represents the total dose
of drug in plasma
• Thus, bioavailability can be calculated as-
5. Bioavailability
• Factors affecting bioavailability of a drug include-
• Particle size
• Degree of ionization and pH at the site of absorption
• Gastric emptying & GI motility (TCA and anti histamines)
• Food and other substances (Grapefruit juice and felodipine)
• First pass metabolism (Sublingual vs Oral)
• Drug interactions (Tetracyclines forming complexes with iron and antacids
in gut lumen, bisphosphonates with calcium)
• Route of administration
• Area and perfusion of site of drug administration (Muscle vs Fat)
6. Distribution of drug
• One compartment model-
• Few drugs (Aminoglycosides) are
rapidly distributed in tissues and
aren’t significantly accumulated in
tissues such that the entire body
works like a single compartment.
• Their plasma concentration will
decrease mostly due to clearance or
metabolism and thus they will show
continuous logarithmic decline in
concentration time graph.
7. Distribution of drug
• Two compartment model-
• Few drugs are slowly absorbed into
peripheral tissues like Vancomycin
and Digoxin.
• Their plasma concentration graph will
show two slopes of decline which are
of redistribution and elimination.
8. Distribution of drug
• Factors determining rate of distribution and amount of drug
distributed to different body tissues-
• Regional blood flow to the tissue
• Capillary permeability
• Volume of tissue and tissue selectivity of drug (Incorporation of
Bisphosphonates into bone)
• Extent of plasma protein binding of drug as only the unbound fraction is
available for transport into tissues
• Presence of barriers (Blood brain barrier)
9. Volume of distribution (Vd)
• It is an apparent volume available for
administered amount of drug to
disperse considering the whole human
body as a homogenous solution
• Volume of distribution = Quantity of
drug administered/ Plasma
concentration (C)
• It shows the extent of redistribution or
accumulation of drug in tissues
• Eg- Warfarin has low (Vd) owing to its
high plasma protein binding while
Chloroquine has high (Vd) because of
its accumulation into peripheral fat.
10. Volume of distribution
• It is used to determine the loading dose of a drug
• Loading dose = Target concentration X Volume of distribution
Suppose the target concentration of a drug is 15mg/ml and Volume of
distribution of the same drug is 30 L.
• Since, the Volume of distribution of a drug in a patient doesn’t depend on the
amount of drug administered or the route of administration, it will remain
same
Then, the loading dose will be 15mg/ml X 30L = 1.5g/L X 30L i.e, 45 g
11. Volume of distribution
• Factors affecting volume of distribution
• Lipid solubility of the drug
• Ionization of the drug at physiological pH
• Plasma protein binding of the drug
• Limitation- It is assumed that the concentration of drug in different
tissues corresponds to the plasma concentration and that the
response of drug varies in accordance with the plasma concentration
which may not be true in each case.
12. Kinetics of drug elimination
• First order kinetics (A) - The rate
of drug elimination varies
proportionately to the plasma
concentration of drug. Most of
the drugs follow this pattern of
elimination.
• Here, as plasma concentration of
drug decrease, the rate of drug
elimination decreases and vice
versa. (Rate of drug elimination is
the amount of drug removed
from blood per unit time)
13. Kinetics of drug elimination
• Saturation kinetics (B) - The rate of drug
elimination becomes constant after a
certain level of plasma concentration is
reached i.e., A fixed amount of drug will
be removed from blood in unit time. The
drugs include Phenytoin, Ethanol,
Salicylates
• For few drugs(C), (Valproate and
Disopyramide), as the plasma
concentration increases, the plasma
protein gets saturated and the
concentration of unbound drug increases
leading to disproportionately increased
elimination of drug
14. Clearance
• Volume of plasma that contains the amount of drug that is removed
from body per unit time
• Suppose, the rate of elimination of drug is 10mg/min and plasma
concentration of drug is 5mg/ml. Then,
Clearance = 10 mg/min/5mg/ml = 2ml/min i.e, 2ml of plasma is cleared of drug
every minute
• It remains constant for drugs showing first order metabolism
• The clearance of a drug include-
• Hepatic clearance
• Renal clearance
• Others
15. Clearance
• Factors affecting clearance of a drug include-
• Extraction ratio of organ (liver, kidney)- The
fraction of drug removed from plasma flowing
through the organ per unit of time. i.e., If a drug
X has a concentration of 15mg/ml in portal vein
(CA) and concentration of 10mg/ml in hepatic
vein (CV). Then, hepatic extraction ratio will be-
CA - CV/ CA = 5/15 = 1/3
• Plasma protein binding of drug
• Blood flow to the organ (liver, kidney)
• Functional state of kidney, liver
• Interactions with other drugs (enzyme
inducers/inhibitors)
16. Steady-state concentration
• When the drug is administered at a
constant rate or at regular intervals, the
cumulative accumulation of drug and
simultaneous elimination are balanced
and a steady concentration is reached
• For maintenance of steady state
concentration, the vol of drug that is
cleared of drug must be replenished
continuously. Thus, clearance is used for
calculating maintenance dose as under-
where, Cp is the plasma concentration of
drug, CL is clearance and F is bioavailability
of drug
17. Elimination rate constant (Ke)
• Fraction of drug that is excreted from the body per unit time
• Rate of elimination = Ke X Concentration of drug in plasma
• Thus, Ke = Clearance/Volume of distribution
• The relationship between concentration at a time t (C) after
administering the drug and the steady state concentration (Css) of the
drug is derived as-
• Thus, we can calculate plasma concentration at a time t by knowing
the elimination rate constant and steady state concentration of the
drug
18. Half life (t1/2)
• Half life of a drug is the time taken for its plasma concentration to
drop to half of the peak plasma concentration
• Half life of a drug determines
• Duration of action of drug after a single dose
• Time required to reach steady state concentration
• Dosing frequency
• For a drug following first order kinetics, the half life can be derived as-
i.e, the half life depends on both volume of distribution and clearance of the
drug
19. Dosage regimens
• Ideal dosage regimen- Dosing intervals and amount of drug given in each dose is such that the
plasma concentration of drug stays above the minimum effective concentration within the
therapeutic window
• The dosage regimen for different drugs is arrived through different ways-
• For drugs where physical parameters can be assessed (BP, Blood glucose), a trial and error
method is used where the dose and intervals are titrated accordingly
• Few drugs have wide range of therapeutic window (Penicillins) where maximum efficacy is
desired
• The change in plasma concentration (ΔC) after a single oral dose-
• Thus, the loading dose becomes-
• For maintenance dose-
(where T is the dosing interval)
20. Therapeutic drug monitoring
• Purpose- To adjust plasma concentration and maintain it within a specified
range.
• Measurement of both values of minimum and maximum concentrations
are to be recorded.
• The necessary dose adjustment is done considering the clearance of drug
to remain constant.
• Applied when-
• The drug has a low therapeutic index
• There is a good plasma concentration- biological response relationship
• There are no other easily measurable physiological parameters
• Or, to monitor adherence or adverse drug reactions
21. Therapeutic drug monitoring
• Sampling of blood is to be done
only after steady state of plasma
concentration is reached, ie, after
five half lives except in case of
toxicity
• After the steady state is reached,
sampling to be done after proper
time for distribution of drug to
finish.
• A therapeutic range of plasma
concentration is used to guide the
desired concentration of drug