The document discusses various aspects of detoxification including:
1. Detoxification is the process by which toxic substances are rendered less harmful and more water soluble through biochemical transformations in the body.
2. Xenobiotics are compounds that are foreign to the body which can be ingested through foods, drugs, or produced endogenously.
3. Biotransformation is the process by which substances are chemically changed in the body, either activating or inactivating them, through phase 1 and phase 2 reactions like oxidation, reduction, and conjugation.
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.
NUCLEIC ACID METABOLISM AND DISORDERS CBME 6.1-6.4 DJT 22.pptxDhiraj Trivedi
Lecture presentation for medical student to under stand nucleic acid metabolism over view. Clinical conditions associated with metabolism of nucleic acid.
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.
NUCLEIC ACID METABOLISM AND DISORDERS CBME 6.1-6.4 DJT 22.pptxDhiraj Trivedi
Lecture presentation for medical student to under stand nucleic acid metabolism over view. Clinical conditions associated with metabolism of nucleic acid.
biotransformation of drug
Biotransformation/Xenobiotic metabolism/ drug metabolism/detoxification.
-Xenobiotics: a wide variety of foreign compounds to which humans get exposed in day to day life.
-It includes unknown compounds, drugs, environmental pollutants, toxins.
-Many xenobiotics can evoke biological responses.
DEFINITION
The biochemical alteration of drug or xenobiotic in the presence of various enzymes that acts as a catalyst which themselves not consumed in the reaction and there by may activate or deactivate the drug is called biotransformation.
Why Biotransformation is necessary?:
To easily eliminate the drug
To terminate drug action by inactivating it
Consequences of Biotransformation
Active to Inactive:
Phenobarbitone---- Hydroxyphenobarbitone
Inactive (prodrug) to Active :
L-Dopa ---- Dopamine
Parathion -- Paraoxon
Talampicillin -- Ampicillin
Active to equally active:
Diazepam -- Oxazepam
Amitriptyline -- Nortriptyline
Imipramine -- Des-imipramine
Codeine -- Morphine
Sites of biotransformation
In the body: Liver, small and large intestines, lungs, skin, kidney, nasal mucosa & brain.
Liver is considered “metabolite clearing house” for both endogenous substances and xenobiotics.
Intestines are considered “initial site of drug metabolism”.
FIRST PASS METABOLISM:
First pass metabolism or presystemic
metabolism or ‘first pass effect’
After oral administeration many drugs are absorbed from the small intestine - transported first via portal system to the liver, where they undergo extensive metabolism before reaching systemic circulation.
fundamental concepts in drug biotransformation
Lipid soluble drugs are poorly excreted in the urine. They tend to store in fat and/or circulate until they are converted (phase I biotransformation) to more water soluble metabolites or metabolites that conjugate (phase II biotransformation) with water soluble substances.
Water soluble drugs are more readily excreted in the urine. They may be metabolized, but generally not by the CYP enzyme systems.
Enzymes catalyzing phase I biotransformation reactions
Enzymes catalyzing phase I biotransformation reactions include:
cytochrome P-450
aldehyde and alcohol dehydrogenase
deaminases
esterases
amidases
epoxide hydratases
Addition of water
Cleavage of R-O or R-N bond accompanied by addition of H2O
CYTOCHROME P450
The cytochrome P-450 families are referred to using an arabic numeral, e.g., CYP1, CYP2, etc.
Each family has a number of subfamilies denoted by an upper case letter, e.g., CYP2A, CYP2B, etc.
The individual enzymes within each subfamily are denoted by another arabic numeral, e.g., CYP3A1, CYP3A2, etc.
This PowerPoint presentation includes all the necessary points regarding xenobiotics in a well organised and concised way which will help students to frameout before before getting into details.
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.
Dr. Dhiraj J. Trivedi presenting Lecture on Carbohydrate metabolism for medical students.
Professor, SDM College of Medical Sciences, Dharwad, Karnataka, India
Dr. Dhiraj J. Trivedi presenting Lecture on Carbohydrate metabolism for medical students.
Professor, SDM College of Medical Sciences, Dharwad, Karnataka, India
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
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!
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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
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.
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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.
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.
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
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
3. Detoxification: Biochemical process whereby the noxious
substances are rendered less harmful and more water
soluble
Xenobiotics: Compounds which may be accidentally
ingested / taken as drugs / produced in the body by the
bacterial action is rendered hydrophilic.
Biotransformation: Is a process whereby a substance is
changed from one chemical form to another by a chemical
reaction in the body
• Detoxification is the process of biotransformation of a
xenobiotic
4. Detoxification
Knowledge of how to handle toxic matter at
cellular level is key to learn how to survive in
this adulterated and polluted world
Basic to a rational understanding of
Pharmacology, Toxicology, Cancer research and
DRUG ADDICTION
Why?
5. Few terms for better understanding
• Toxin: Substance with harmful effects on living
systems.
• Detoxification: Removal / neutralization of toxic
quality of toxins.
• Xenobiotic: Chemical substance present within but
not made within a living body – stranger to life
• Toxic load: Sum Total toxins within a given living
system
6. Few terms for better understanding
• Lipophilic Toxin: Low molecular weight, non
polar, fat soluble toxins. Difficult to
eliminate.
• Polyvinyl chloride, Bisphenols, Benzoate
• Hydrophilic toxins: Water soluble, Polar
toxins. Easy to be excreted.
• Urea, uric acid, creatinine, bilirubindiglucuronide
7. Truth:
Ubiquitous,
too many to count,
Complex interactions
• Alter brain function,
• Gut disturbance,
• Reproductive effects,
• Hormonal imbalance
Inflammation,
cancer,
diabetes,
Autoimmune disease,
CVD,
Renal disease
and more…
Consequences R MANY
8. Definition
• Biochemical process to convert toxic
lipophilic substances to less toxic or
nontoxic hydrophilic form.
• Easy to excrete form
9. What are the Source of Toxins?
• Exogenous
• Diet - addative
• Drug - chemical
• Abuse – toxins
• Microbes -
• Occupation – man made
• Endogenous
• Metabolism
• Normal – urea, UA,
Bilirubin
• Abnormal – Acetae,
formate
10. Bio-transformation:
Substance is changed from one substance to other
by a chemical reaction within the body
Bio-activtion
Biotransformation
leading to more
toxic compound
than the parent
-Entoxication
Bio-inactivation
Noxious substances
rendered less harmful
and more water soluble
is called Detoxication
and
Procarcinogen / prodrug
11. What all needs detoxification?
Food additives
Toxins / Poisons
Cosmotics
Drugs
Metabolites
Chemicals / Dyes
Pesticides
Insecticides
Many more…..
12. Who looks after Bio-transformations?
• The liver handles 70% of the bio-transformation
reactions in body.
• Other sites are
• Kidneys
• Lungs
• Skin
• Intestinal cells
• Endothelial cells of BBB
13. Factors that affect biotransformation
• Diet
• Age
• Developmental status
• Hormonal status
• Disease
• Functional status of Liver and Kidney
• Genetics
14. Biotrans formation of lipophilic Toxins
• Phase 1:
• Reaction that add a functional group to a fat
soluble toxin so the new structure can be
conjugated and made hydrophilic, excretory
form.
• Phase 2:
• Reactions that either continue the phase 1 or
independent, create a water soluble compound
suitable for excretion
15. Phase 1 Phase 2
Fat Soluble
Oxidation/
epoxidation
Conjugation with Glucuronic acid
Reduction Conjugation with sulfate
Hydrolysis Conjugation with Glutathione
Acetylation Conjugation with Amino acid
How does it happen ?
17. Phase 1 Oxidation or Hydroxylation
• Large number of foreign substances are
destroyed by oxidation or hydroxylation
• Reaction needs
• Cytochrome P450 / Mono-oxygenase
• Concentrated on smooth ER of liver
• Heme containing enzyme
• Inducible: By Phenobarbitone, Alcohol
18. • P450 because absorb light at 450nm
• It can detoxify exogenous drugs as well
endogenous steroid and eicosanoids
• It is typically mono-oxygenase as it incorporates
one atom of oxygen to form hydroxy derivative,
Second atom is reduced to water
Cytochrome - P450
RH + O2 + NADPH ROH +H2O NADP+
19. Mechanism of mono-oxygenase
NADPH+H
NADP+
NADPH- Cyt P450
Reductase Ox
NADPH- Cyt P450
Reductase Red
Fe+3
Fe+2
Cyt P450
Cyt P450
R-H
R-OH
H2O
O2
50% of the medicinal drugs are metabolised by Cyt P450
OX
Red
21. • CYP3A is important cytochrome P450involved in drug
metabolism, because of its abundance in liver and
intestine it can fluctuate by almost 400-fold due to
inhibition and induction, thus leading to problems with
drug dosage
Iso forms
22. • CYP2E1, which is induced by consumption of
ethanol. This may increase the risk of carcinogenicity
developing from exposure to such compounds
• CYP2A6, involved in the metabolism of nicotine null
alleles, who have impaired metabolism of nicotine,
are apparently protected against becoming tobacco-
dependent smokers
Iso forms
24. Oxidation
Aniline P- Amino Phenol
Acetanilide P- acetyl amino phenol
Ingrediant of analgesic drug which relieves pain
Meprobamate Hydroxy meprobamate
A Tranquilizer use for psychiatric disorder
Chloral (CCl3CHO) Trichloroacetic acid
Used as hypnotic, converted to TCA and excreted
25. Epoxide
An epoxide is a cyclic ether with a three-atom ring.
This ring approximates an equilateral triangle,
which makes it highly strained. The strained ring
makes epoxides more reactive than other ethers.
Oxidation
27. Entoxification
Poly cyclic Aromatic
hydrocarbon (PAH)
Epoxide
Potent carcinogen
•Iso form of Cyt P450 i.e. P448 found in lung of
cigarette smokers
•Cigatette smoke PAH are converted to Tar
Which is procarcinogen
29. Reduction
• Less important than oxidation
Picric acid Picramic acid
NO2
NO2
OH
NO2 NH2
NO2
OH
NO2
Chloral (CCl3CHO) Trichloro ethyl alcohol
Used as sedetive, reduced before excreted
36. Phase 2 Reactions
Conjugation
Number of substances undergo complex formation
– conjugation after phase 1 reaction, this will
make them more hydrophilic and suitable for
excretion
37. Conjugation
1. Conjgation with glucuronic acid
2. Conjugation with glycine
3. Conjugation with Sulfate
4. Conjugation with glutamine
5. Conjugation with Cysteine / Glutathione
6. Acetylation
7. Methylation
42. R –X + GSH GS – R + X –H
Glutathione helps in conjugation reaction
Isoniazide & Sulfanamide are detoxicted by Acetylation
Isoniazide Acetyl-INH
Sulphaniamide Acetyl sulphanilamide
Acetic acid
Foreign compounds like food, drugs, chemical carcinogens, food additives, food preservatives, pollutants, products of micro organism needs biotransformation or detoxication to protect health of an individual.
Though on broad sense make same meaning but they make difference on deeper sense.
Human encounter thousands of toxic chemicals and metabolites which need to be transformed in the water soluble and non-toxic form before they are excreted out of the body.
It is impossible to stay away from toxic chemicals / substances. As they are ubiquitous and uncountable. If they remain it is going to affect on your body and bring toxic effect in the form of abnormal physiology or disease.
Exogenous – Knowingly or unknowingly we are exposed or consuming from external source
Endogenous – many are produced in our body as part of normal metabolic intermediates.
Good diet – exposes less toxic matter
Young age positive factor in detoxication
Balanced hormonal correlation help removal of toxins
Healthy liver and kidney keeps body toxin free
Genetic makeup of person is sometimes responsible for toxicity
Disease may produce toxic or unphysiological product which has to be eliminated
By phase 1 reaction some substances are converted in to less toxic form which then conjugate with other substance. Thus phase 1 reaction make them ready for conjugation.
Phase 2 reaction generally make them water soluble form so that they are easily excreted via urine without getting deposited in lipid fraction of body.
Enzymes of Oxidation are present in microsome and non-microsomal fraction (cytosol, mitochondria)
Microsomal oxidation – cyt P450
Non-microsomal oxidation – dehydrogenase enzymes
Liver contains many P450 isoenzymes, as it is involved in bulk of drug metabolism.
Main compounds required for cyt P450 is NADPH and Molecular oxygen (O2). NADPH transfers electron through FAD and FeS complex. It is also called as mixed function oxygenase as it oxidise two different substrate simultaneously.
Epoxides are acting as free oxygen radical and have carcinogenic property.
Oxidation reaction belongs to phase 1, instead making chemical nontoxic less effective, it increases the activity and toxicity.
Epoxidation reaction belongs to phase 1, instead making chemical nontoxic less effective, it increases toxicity.
Example : Poly Aromatic Hydrocarbon present in cigarette smoke is oxidised by Cyt P488 to black TAR which is responsible for lung cancer.