The document discusses xenobiotic metabolism, which involves the biotransformation of foreign chemicals by the body. It notes that phase I reactions like oxidation and hydrolysis expose functional groups on xenobiotics, while phase II conjugation reactions like glucuronidation and sulfation greatly increase water solubility. Cytochrome P450 enzymes play a major role in phase I, catalyzing reactions like hydroxylation and epoxidation. The liver is the primary site of metabolism, but other tissues contribute as well. Proper biotransformation can eliminate toxins, while some intermediates are more toxic and chemically reactive.
Normally, lipophilic xenobiotics that enter an animal’s body are rapidly detoxified. Detoxification
can be divided into phase I (primary) and phase II (secondary) processes (Figure 8.1). Phase I reactions consist of oxidation, hydrolysis, and reduction. The phase I metabolites are sometimes polar
enough to be excreted but are usually further converted by phase II reactions. In phase II reactions,
the polar products are conjugated with a variety of endogenous compounds such as sugars, sulfate,
phosphate, amino acids, or glutathione and subsequently excreted. Phase I reactions are usually
responsible for decreasing biological activity of a toxicant, and, therefore, the enzymes involved
are rate limiting with respect to toxicity. The most important function of biotransformation is to
decrease the lipophilicity of xenobiotics so that ultimately they can be excreted. In insects, the
major tissues involved in the metabolism of xenobiotics are the midgut, fat body, and Malpighian
tubules.
Normally, lipophilic xenobiotics that enter an animal’s body are rapidly detoxified. Detoxification
can be divided into phase I (primary) and phase II (secondary) processes (Figure 8.1). Phase I reactions consist of oxidation, hydrolysis, and reduction. The phase I metabolites are sometimes polar
enough to be excreted but are usually further converted by phase II reactions. In phase II reactions,
the polar products are conjugated with a variety of endogenous compounds such as sugars, sulfate,
phosphate, amino acids, or glutathione and subsequently excreted. Phase I reactions are usually
responsible for decreasing biological activity of a toxicant, and, therefore, the enzymes involved
are rate limiting with respect to toxicity. The most important function of biotransformation is to
decrease the lipophilicity of xenobiotics so that ultimately they can be excreted. In insects, the
major tissues involved in the metabolism of xenobiotics are the midgut, fat body, and Malpighian
tubules.
Xenobiotics are foreign compounds to our body. They are more lipophilic and less hydrophilic . So it is quite tough to excrete them out from the body. Hence metabolism of xenobiotic is important.
Introduction
Drug Metabolizing Enzyme
Chemical Pathway of Drug Biotransformation
Phase I reaction
Phase II Reaction
Isoniazide & Phenacetin Metabolism
Factors Affecting Metabolism
metabolism of xenobiotis, drugs, medicine, carcinogen generation by enzymes like cyt p450 mono oxigenases, prostaglandin synthase ect. alcohol metabolism, toxin metabolism, definition of genobiotics, biotransformation, detoxification. effects on health
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Pharmacokinetics involves absorption, distribution, metabolism and excretion. Metabolism involves a huge range of chemical reactions which occur at body temperature with the help of enzymes
Xenobiotics are foreign compounds to our body. They are more lipophilic and less hydrophilic . So it is quite tough to excrete them out from the body. Hence metabolism of xenobiotic is important.
Introduction
Drug Metabolizing Enzyme
Chemical Pathway of Drug Biotransformation
Phase I reaction
Phase II Reaction
Isoniazide & Phenacetin Metabolism
Factors Affecting Metabolism
metabolism of xenobiotis, drugs, medicine, carcinogen generation by enzymes like cyt p450 mono oxigenases, prostaglandin synthase ect. alcohol metabolism, toxin metabolism, definition of genobiotics, biotransformation, detoxification. effects on health
The all the content in this profile is completed by the teachers, students as well as other health care peoples.
thank you, all the respected peoples, for giving the information to complete this presentation.
this information is free to use by anyone.
Pharmacokinetics involves absorption, distribution, metabolism and excretion. Metabolism involves a huge range of chemical reactions which occur at body temperature with the help of enzymes
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.
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
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
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
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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.
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.
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
2. Basic definitions:
1. Xenobiotic
• Chemicals foreign to the body. Can be
manufactured or natural.
– Drugs
– Industrial chemicals
– Pesticides
– Pollutants
– Pyrolysis products in grilled foods
– Secondary plant metabolites
– Toxins produced by molds, plants, animals
3. Elimination of Xenobiotics
• Depends on their lipophilicity
– Lipophilic compounds can be reabsorbed more
easily, therefore they circulate longer.
• Depends on their conversion to water
soluble compounds – biotransformation.
4. Biotransformation
• Definition: Conversion of a xenobiotic to a
more water soluble compound.
• Biotransformation = metabolism
• Biotransformation is catalyzed by enzymes
in the liver and other tissues.
5. Tissue sources of metabolizing
enzymes:
• The liver is the richest source.
• Tissues associated with the major routes of
exposure: skin, lung, nasal mucosa, eye,
gastrointestinal tract.
• Others: Kidney, adrenal, pancreas, spleen, heart,
brain, testis, ovary, placenta, plasma, erythrocytes,
platelets, lymphocytes, aorta.
6. Biotransformation is accomplished by a
small number of enzymes with broad
substrate specificities.
• Some xenobiotic metabolizing enzymes
also metabolize endogenous compounds.
Ex: bile salts, bilirubin.
• Metabolizing enzymes are either:
– 1. Constitutive
– 2. Inducible – enzyme synthesis is induced by
some external stimulus.
8. Age of Enlightenment:
• All substances are poisons; there is none
which is not a poison. The right dose
differentiates a poison from a remedy.
Paracelsus
10. Biotransformation Reactions:
• Phase I: Oxidation, reduction, hydrolysis
– Reactions that expose or introduce a functional
group.
• Phase II: conjugation
– Covalent linkage between the xenobiotic or one
of its metabolites with a water-soluble,
endogenous compound, e.g., glutathione.
11. Biotransformation Reactions:
• Phase I: Oxidation, reduction, hydrolysis
– Imparts small increases in hydrophilicity.
• Phase II: conjugation
– Imparts large increases in hydrophilicity.
12. Phase I Hydrolytic Enzymes:
• Carboxylesterases
– Hydrolyze esters, amides, and thioesters
• Organophosphatases
– Hydrolyze phosphoric acid esters
• Important to insecticide/pesticide metabolism
21. Peroxidases
• Cooxidation reactions: Reactions which
couple the reduction of hydrogen peroxide
or arachidonic acid with the oxidation of a
xenobiotic.
• Do not require NADPH or NADH
• Include many different enzymes in a variety
of tissues.
22. Examples of peroxidase
enzymes:
• Prostaglandin H synthase (cyclooxygenase):
– Kidney, platelets, vasculature, GI tract, brain,
lung, bladder
• Myeloperoxidase
– leukocytes
• Lactoperoxidase
– Mammary tissue
25. Metabolism of benzene to toxic
intermediates
OH
P450 P450
OH
OH
OH
OH
myeloperoxidase
O.
OH
Protein and
DNA binding -
bone marrow
suppression
Liver
Bone marrow
26. Cytochrome P450-mediated
oxidations
• Most important phase I enzyme.
• High concentrations found in the liver in the
endoplasmic reticulum (microsomes).
• Appreciable levels found in just about every tissue
in the body.
• Important role in the duration of action of drugs.
• Plays a pivotal role in both the detoxication of
xenobiotics and their activation to toxic or
tumorigenic intermediates.
27. Cytochrome P450-mediated
oxidations (continued)
• Can metabolize a large number of xenobiotics.
• Various isoforms are present in a variety of
tissues, each with diverse substrate specificities.
• Heme protein that can bind oxygen.
• Requires NADPH for catalytic activity.
• Can also metabolize endogenous compounds, for
example, steroid hormones, bile acids, vitamins,
fatty acids.
• Some isoforms also present in the mitochondria.
28. • Hydroxylation of aliphatic or aromatic carbon.
• Epoxidation of a double bond.
• Heteroatom (S-, N-) oxygenation and N-
hydroxylation.
• Heteroatom dealkylation (Ex. ROR ROH or
SR SH)
• Ester cleavage
• Dehydrogenation
Cytochrome P450 catalyzes
many types of reactions:
33. Chemical Interactions
(Drug-drug interactions)
• Potentiation => one chemical causes a another
chemical to have greater effect than if given
alone
– Example: hepatotoxicity of acetaminophen is
enhanced by ethanol
+
®
34. Chemical Interactions
(Drug-drug interactions)
• Potentiation => one chemical causes a another
chemical to have greater effect than if given
alone
– Example: hepatotoxicity of acetaminophen is
enhanced by ethanol
+
®
Induces CYP2E1
35. Drugs which Modulate P450
Inducers Drug whose metabolism is enhanced
Phenobarbital and other barbiturates Chloramphenicol, digitoxin,
doxorubicin, estradiol, phenytoin,
cortisol
Omeprazole (Prilosec) or cigarette
smoke
Tricyclic antidepressants, propranolol
warfarin, theophylline
Rifampin Digitoxin, glucocorticoids, oral
contraceptives, propanolol
Ethanol acetaminophen
Inhibitors Drug whose metabolism is inhibited
Cimetidine (Tagamet) Diazepam, warfarin
Ketoconazole (antifungals) Cyclosporine, terfenadine
Grapefruit juice Tricyclic antidepressants, propranolol
warfarin, theophylline
36. Phase II
A. Glucuronidation : UDP - glucuronic acid is the
glucuronyl donor, and a variety of
glucuronosyltransferases, present in both the
endoplasmic reticulum and cytosol, are the
catalysts. Molecules such as 2-acetylamino
fluorene ( a carcinogen), aniline, benzoic acid,
memprobamate (a tranquilizer), phenol, and many
steroids are excreted as glucuronides. The
glucuronide may be attached to oxygen, nitrogen ,
or sulfur groups of the substrates. Glucuronidation
is probably the most frequent conjugation reaction
37. B. Sulfation : Some alcohols, arylamines, and
phenols are sulfated. The sulfate donor in
these and other biologic sulfation reactions
(eg : glycosaminoglycans, glycolipids) is
adenosine 3’ - phosphate - 5’ -
phosphosulfate (PAPS)
38. C : Conjugation with glutathione : A number of
potentially toxic electrophilic xenobiotics (such as
certain carcinogens) are conjugated to the nucleophilic
GSH in reactions that can be represented as follows
R + GSH R ---- S ----- G
Where R = an electrophilic xenobiotic. The enzymes
catalyzing these reactions are called glutathione S-
transferases and are present in high amounts in liver
cytosol and in lower amounts in other tissues. A variety
of glutathione S-transferases are present in human
tissue. If the potentially toxic xenobiotics were not
conjugated ato GSH, they would be free to combine
covalently with DNA, RNA, or cell protein and could
thus lead to serious cell damage.
39. D - Other reactions :
• Acetylation - Acetylation is represented by
X + Acetyl-CoA Acetyl-X + CoA
Where X represents a xenobiotic. As for other acetylation
reactions, acetyl-CoA (active acetate) is the acetyl
donor. These reactions are catalyzed by
acetyltransferases present in the cytosol of various
tissues, particularly liver. The drug isoniazid, used in
the treatment of tuberculosis, is subject to acetylation.
Polymorphic types of acetyltransferases exist, resulting
in individuals who are classified as slow or fast
acetylators,and influence the rate of clearance of drugs
such as isoniazid from blood. Slow acetylators are
more subject to certain toxic effects of isoniazid
because the drug persists longer in these individuals.
40. • Methylation : A few xenobiotics are subject
to methylation by methyltransferases,
employing S-adenosylmethionine as the
methyl donor.
