This document discusses pharmacokinetics and the processes involved in the absorption, distribution, metabolism, and excretion of drugs in the body. It describes the four main steps in ADME: absorption, which involves drug entry into systemic circulation; distribution throughout the body; metabolism, or biotransformation of drugs; and elimination of drugs and metabolites from the body. Key concepts covered include factors influencing drug absorption, distribution dependent on tissue properties, hepatic and renal clearance pathways, and the importance of drug solubility and other properties in determining ADME profile.
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
A power point presentation on general aspects of Pharmacokinetics suitable for undergraduate medical students beginning to study Pharmacology. Also suitable for Post Graduate students of Pharmacology and Pharmaceutical Sciences.
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
A power point presentation on general aspects of Pharmacokinetics suitable for undergraduate medical students beginning to study Pharmacology. Also suitable for Post Graduate students of Pharmacology and Pharmaceutical Sciences.
A power point presentation on Pharmacodynamics (what drug does to the body) suitable for undergraduate medical students beginning to study Pharmacology
For More Medicine Free PPT - http://playnever.blogspot.com/
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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 power point presentation on Pharmacodynamics (what drug does to the body) suitable for undergraduate medical students beginning to study Pharmacology
For More Medicine Free PPT - http://playnever.blogspot.com/
For Health benefits and medicine videos Subscribe youtube channel - https://www.youtube.com/playlist?list=PLKg-H-sMh9G01zEg4YpndngXODW2bq92w
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.
Dosage form design - Biopharmaceutical considerationAniruddha Roy
Dosage form design - Biopharmaceutical consideration: Understanding how physicochemical characteristics of a drug and formulation component affect bioactivity
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.
- Routes of administration
- First pass metabolism, bioavailablilty, drug distribution,
- Drug interactions with proteins, Drug metabolism, elimination, Half-life
Pharmacokinetics is the study of the movement of drug molecules in the body. It includes absorption, distribution, metabolism, and excretion of drugs. Pharmacokinetics is the study of what happens to drugs once they enter the body (the movement of the drugs into, within, and out of the body). For a drug to produce its specific response, it should be present in adequate concentrations at the site of action. This depends on various factors apart from the dose.
Four pharmacokinetic properties determine the onset, intensity, and the duration of drug action (Figure 1.6.1):
• Absorption: First, absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
• Distribution: Second, the drug may then reversibly leave the bloodstream and distribute it into the interstitial and intracellular fluids.
• Metabolism: Third, the drug may be biotransformed by metabolism by the liver or other tissues.
• Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces.
In short, pharmacokinetics means what the body does to the drug.
Announcement about my previous presentations - Thank youAreej Abu Hanieh
ANNOUNCEMENT Thank you for all of you, my followers who sent me messages with a lot of love and appreciations, I finally graduated after 6 years of studying in Birzeit University , In doctor of Pharmacy department I hope all of you benefited from all the presentations posted before Thank you a new PharmD GraduatedAreej ^^
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
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.
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.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
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
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.
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.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
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.
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
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.
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...
Basic principles in pharmacology pharmacokinetics - pharmacology
1.
2. Pharmacology: is the study of drugs, their uses and
how they affect organisms
◦ Pharmacokinetics: describes what the body does to a
drug.
◦ Pharmacodynamics: describes what the drug does to the
body.
3.
4. ADME
◦ Absorption
◦ Distribution
◦ Metabolism
◦ Elimination
ADME determine:
◦ The speed of onset of drug action
◦ The intensity of the drug effect
◦ The duration of drug action
Lippincott's Illustrated Reviews 6th edition
5. Absorption: The drug absorption from the site of
administration which permits the entry of the
therapeutic agent into the plasma
Distribution: Reversible process, the drug leaves the
bloodstream and distributes into the interstitial and
intracellular fluids
Metabolism: Biotransformation of the drug into
metabolites by the liver or other tissues
Elimination: The drug and its metabolites are
eliminated into urine, bile or feces
7. Determined by
◦ Properties of the drug
Water or lipid solubility
Ionization
◦ Therapeutic objective
Rapid onset
Prolonged effect
Local effect
8. Oral administration:
◦ Advantages
Easily self-administered
Low risk of systemic infections (compared to parenteral)
Easier to manage toxicity
◦ Disadvantages
Inactivation of drugs due to first pass effect or stomach acidity
◦ Enteric coated
To protect the stomach (e.g. Aspirin)
To protect the drug from stomach acidity
◦ Extended release
To control how fast the drug is released from the pill to the body
9. Sublingual: Drug diffuses into the capillary
network to the systemic circulation
◦ Advantages
Rapid absorption
Convenience
Low incidence of infection
Bypass GI
Bypass first pass effect
10. Direct administration of the drug across body
barriers into the systemic circulation
◦ Used for: 1. Drugs with poor GI absorption (e.g. heparin)
2. Drugs unstable in GI (e.g. insulin)
3. Unconscious patients
4. Rapid onset of action
5. High bioavailability
◦ Advantage: no first pass metabolism
◦ Disadvantages: Risk of infection
◦ Can be irreversible
11. Intravenous (IV)
◦ Bolus: Immediate delivery of full amount
◦ Infusion: Delivery over a longer time
Intramuscular
◦ Aqueous solution (Rapid absorption)
◦ Depot preparation in nonaqueous
vehicle
Subcutaneous
◦ Less risk of hemolysis
◦ May provide sustained slow effect
12. Inhalation
◦ Oral or nasal
◦ Rapid delivery across the large surface area of mucous
membranes
Intrathecal/intraventricular
◦ Direct injection into the cerebrospinal fluid
◦ Rapid delivery
◦ To avoid the blood brain barrier
Topical: application
◦ Skin, for local effect.
Transdermal
◦ Sustained delivery of drugs (e.g. nicotine patches)
Rectal
◦ Avoids first pass metabolism
◦ Rapid delivery
◦ Used when oral administration is not possible (antiemetics)
13.
14. Absorption is the transfer of a drug from the site
of administration to the bloodstream via one of
several mechanisms
Rate and efficiency of absorption of a drug
depend on:
◦ The environment where the drug is absorbed
◦ Chemical characteristics of the drug
◦ Route of administration
15. Absorption Rate: how rapidly does the drug get from
its site of administration to the general circulation ?
Absorption Extent: How much of the administered
dose enters the general circulation ? ( %
bioavailability = F)
16. Bioavailability: The fraction of administered drug
that reaches the systemic circulation
Example 100 mg of a drug were administered
orally, 70 mg of the drug were absorbed
unchanged.
◦ The bioavailability of this drug is 0.7 or 70%
For IV drugs, absorption is complete
◦ (100% bioavailability)
Drug administration by other routes may result in
partial absorption and lower bioavailability
17.
18. Factors that influence oral bioavailability
◦ First-pass hepatic metabolism
(Metabolism by liver enzymes prior to reaching the systemic
circulation)
◦ Nature of the drug formulation
◦ Solubility of the drug
◦ Chemical instability
◦ Decomposition in acidic gastric juices
◦ Decomposition by hydrolytic gut enzymes (eg,
proteases, lipases)
◦ Degradation by gut microorganisms
◦ Food in the gut may alter absorption rate and amount
(eg. interact or form a complex)
◦ Metabolism by gut wall enzymes
19. When an oral drug is absorbed
across the GI tract, it first enters
the portal circulation before the
systemic circulation
If the drug is rapidly metabolized,
less of the active ingredient will
reach the systemic circulation
Example: nitroglycerine
(90% is cleared through passage
through the liver)
◦ It is Given sublingually
20. Solubility of the drug
◦ Very hydrophilic drugs can not cross lipid-rich cell
membranes, and so they are poorly absorbed
◦ Extremely hydrophobic drugs are poorly absorbed
because they’re insoluble in aqueous body fluids
◦ For good absorption the drug needs to be
hydrophobic with some water solubility
◦ Most drugs are weak acids or bases
21. Chemical instability
◦ Insulin is destroyed in the stomach by degradative
enzymes
◦ Penicillin G. is instable in gastric pH
Nature of the drug formulation
◦ Presence of excipients alter the rate of absorption
22. Passive diffusion:
Facilitated diffusion
Active transport
Endocytosis and exocytosis
23. Movement of drug molecules
across membranes from a
region of high concentration to
a region of lower concentration
Most drugs are absorbed
through this mechanism
No carrier involved
Non saturable
24. Entry to the cell through specialized
transmembrane carrier proteins
Movement occurs from the area of
the high concentration to the area of
low concentration
Does not require energy
Can be saturated and inhibited by
compounds that compete for the
carrier
25. Involves specific carrier proteins
Requires energy
Moves the drugs against the
concentration gradient
(from low concentration to high
concentration regions)
Selective
Saturable, can be inhibited by
cotransported substances
26. Transport of exceptionally large
drugs
Endocytosis: engulfment of a
molecule by the cell membrane
Exocytosis: the reverse process
that leads to the release of
molecules
Example: Vitamin B12 transport
across the gut wall by endocytosis
27. 1. pH
◦ Most drugs are weak acids or weak bases
HA H+ + A-
BH+ B + H+
◦ Drugs pass through membranes easier
when uncharged
◦ pH < pKa protonated form predominates
◦ pH > pKa deprotonated form predominates
28.
29. 2. Blood flow to the absorption site
◦ Because blood flow is much greater in the intestines
than the stomach, absorption is greater in the
intestines.
3. Total surface area available for absorption
◦ Intestines have large surface area
4. Contact time at the absorption surface
◦ Absorption is affected by changes in gastric motility
(e.g. diarrhea)
5. Expression of P-glycoprotein
◦ Drug transporter (reduces absorption)
◦ In liver, kidney, brain, intestines
30. It is expressed throughout the body, and its
functions include:
◦ In the liver: transporting drugs into bile for
elimination
◦ In kidneys: pumping drugs into urine for excretion
◦ In the placenta: transporting drugs back into maternal
blood, thereby reducing fetal exposure to drugs
◦ In the intestines: transporting drugs into the intestinal
lumen and reducing drug absorption into the blood
◦ In the brain capillaries: pumping drugs back into
blood, limiting drug access to the brain
High expression of p-gp reduces absorption
31. Bioequivalence
Two related drug preparations are bioequivalent if they show
◦ Comparable bioavailability
◦ Similar times to achieve peak blood concentrations.
Therapeutic equivalence
Two similar drug products are therapeutically equal if they are
pharmaceutically equivalent with similar clinical and safety
profiles
36. Distribution: the process by which a drug reversibly
leaves the blood stream and enters the interstitium
and then cells
For an IV drug; No absorption occurs
Distribution occurs immediately after administration
37. Distribution depends on
1. Cardiac output and
regional blood flow
2. Capillary permeability
3. Tissue volume
4. Drug-protein binding
in plasma and tissues
5. Hydrophobicity of the
drug
38. Due to unequal distribution of cardiac output,
the rate of blood flow to tissue capillaries is
variable
Blood flow to the brain, liver and kidney is
greater than that to skeletal muscles
Adipose tissue, skin and viscera have lower
rates of blood flow
39. Example: thiopental, highly lipid soluble
◦ Initially rapidly moves into the brain due to high
blood flow and produces anesthesia
◦ A slower distribution into skeletal muscles and
adipose tissues lowers plasma concentration, and
CNS concentration
◦ Consciousness is regained
40. Depends on
◦ Capillary structure
◦ Chemical nature of the drug
41. Binding to plasma proteins
◦ Nonselective
◦ Albumin
◦ Protein bound drug Free drug
Binding to tissue proteins
◦ Drugs can accumulate in tissues due to tissue protein
binding extending their effects or causing local toxicity
Hydrophobicity
◦ Hydrophobic drugs cross cell membranes
◦ Hydrophilic drugs need to pass through the slit junction
Distribution
Metabolism
Excretion
42. Amount of drug in the body
C0
Vd: Apparent volume of distribution
C0:Plasma concentration at time zero
Vd=
43. Vd has no physiologic basis
It can be used to compare the
distribution of a drug in the water
compartments of the body
• Plasma (4L)
large molecular weight or highly protein
bound drugs
e.g. Heparin
• Extracellular fluid (14L)
Low molecular weight but hydrophilic
and can not cross cell membranes
• Total body water (42 L)
Low molecular weight and hydrophobic
44. Apparent volume of distribution (Vd)
◦ A drug rarely associates with one water compartment
◦ Usually drugs are bound to cellular compartments like
Proteins in plasma and cells
Lipids in adipocytes and cell membranes
Nucleic acids in nuclei of cells
Vd is useful for calculating the loading dose of a
drug
45. Example:
If 10 mg of a drug are injected and the plasma
concentration is 1 mg/L what is Vd?
Vd= Dose = 10 = 10 L
C0 1
46. Length of time needed
to decrease drug plasma
concentration by one
half
The greater the half-life
of the drug, the longer it
takes to excrete
Determines frequency
and dosages
47. Elimination depends on the amount of the
drug delivered to the liver or the kidney per
time unit
The greater the Vd the less drug that is
available to the excretory organ
The greater the Vd the higher the half life of
the drug, and the longer the duration of
action
An exceptionally high Vd indicates the
sequestration of the drug in tissues
48.
49. Once the drug enters the body, elimination
begins
Routes of elimination include:
1. Hepatic metabolism
2. Elimination in bile
3. Elimination in urine
Metabolism leads to products with increased
polarity which allows drug elimination
50. Clearance (CL) the amount of drug cleared
from the body per unit time
◦ CL= 0.693 X Vd/t1/2
t1/2: elimination half life for the drug
Vd: apparent volume of distribution
51. 1. First-order kinetics
The rate of drug metabolism
and elimination is directly
proportional to the drug
concentration
2. Zero-order kinetics
(nonlinear kinetics)
e.g. aspirin, ethanol,
phenytoin
The rate of metabolism or
elimination is constant and
does not depend on drug
concentration.
52. Michaelis-Menten Enzyme Kinetics
V= rate of drug metabolism= Vmax [C]
Km +[C]
◦ First-order kinetics (C is <<<<Km)
V= rate of drug metabolism= Vmax [C]
Km
◦ Zero-order kinetics (C>>>>>Km)
V= rate of drug metabolism= Vmax [C] =
Vmax
[C]
53. Kidney cannot efficiently eliminate lipophilic
drugs as they get reabsorbed in distal
convoluted tubules.
Lipid soluble agents must be metabolized
into more polar (hydrophilic) substances in
the liver
1. Phase I reactions
Oxidation, Reduction, Hydrolysis
2. Phase II reactions
Conjugation
54. Not all drugs undergo Phase I and Phase II
metabolism in that order, sometimes the
order is reversed.
55. Conversion of lipophilic molecules into more
polar molecules by unmasking or adding a polar
group like –OH or –NH2
◦ Involve P450 enzymes
(most frequent for Phase I drug metabolism)
◦ Not involving P450: e.g. Esterases and Hydrolysis
56. Example: CYP3A4
Genetically variable
◦ Altered drug efficacy
◦ Altered toxicity risk
CYP2D6
Inducers (increase metabolism)
(Drug Interactions)
◦ Decrease plasma concentration
◦ Decrease therapeutic effect
◦ Decrease drug activity if metabolite is inactive
◦ Increase drug activity if metabolite is active
Family Isozyme
Subfamily
57. Inhibitors:
◦ P450 inhibitors cause drug interactions
◦ Can cause adverse reactions
◦ Example: Grapefruit and its juice can inhibit CYP3A4
leading to increased levels of drugs metabolized by
this enzyme causing higher therapeutic or toxic
effects
58. Conjugation reactions
If Phase I metabolite are still too lipophilic
then they undergo conjugation reactions with
endogenous substrates like:
◦ Glucuronic acid (most common)
◦ Sulfuric acid
◦ Acetic acid
◦ Amino acid
59.
60. The most important route for drug removal
from the body is through the kidney into the
urine
Drugs need to be polar enough for efficient
excretion
61. Elimination of drugs into the
urine involves 3 processes:
1. Glomerular filtration
2. Proximal tubular secretion
3. Distal tubular reabsorption
62. Drugs enter the kidney through renal arteries
which divide to form a glomerular capillary plexus
Free drug (non-protein bound) flows into
Bowman’s space as part of the glomerular filtrate
Glomerular filtration rate is 125mL/min
Lipid solubility and pH do not influence glomerular
filtration rate
63. Secretion occurs in the proximal tubules by 2
energy requiring active transport systems
◦ One for anions (deprotonated forms of weak acids)
◦ One for cations (protonated forms of weak bases)
Competition between drugs on the transport
systems can occur
64. As a drug moves toward DTC its concentration
becomes higher than in the perivascular space
Uncharged drugs will diffuse out of the nephric
lumen to the systemic circulation
65. Increasing the ionized form of the drug in the
lumen by changing the pH of the urine can
minimize the back-diffusion and increase
clearance
{Ion Trapping}
◦ Elimination of weak acids can be increased by
alkalinization of the urine
e.g. phenobarbital (weak acid) overdose
Alkalinization of urine with bicarbonate keeps the drug ionized
◦ Elimination of weak bases can be enhanced by
acidification of the urine
e.g. overdose of amphetamine (weak base)
Acidification of urine with NH4Cl causes the protonation of the
drug and enhancement of its excretion
66. Most drugs are lipid soluble
Without chemical modification drugs
would diffuse back from the kidney
lumen when their concentration is
higher there
To minimize reabsorption drugs are
modified (mainly in liver) to more
polar compounds
67. Liver
Intestine
Bile
Lungs
Milk in nursing mothers
To a small extent in sweat, tears saliva, hair
and skin
68. Liver
◦ contributes to drug loss through metabolism and/or
excretion into the bile
◦ patients with renal failure may benefit from drugs
excreted through this route
Feces
◦ Elimination of unabsorbed orally ingested drugs
◦ Elimination of drugs that are secreted directly into
the intestines or bile
Lungs
◦ Elimination of anesthetic gases
Breast milk
◦ Source of undesired effects to the infant
69. Total body clearance
t1/2 of drugs can be altered by
o Diminished renal or hepatic flow ( t1/2)
(e.g. cardiogenic shock, heart failure, hemorrhage)
o Decreased ability to extract drug from plasma ( t1/2)
(e.g. renal disease)
o Decreased metabolism ( t1/2)
o Increased hepatic blood flow ( t1/2)
o Decreased protein binding ( t1/2)
o Increased metabolism ( t1/2)