Microsomal enzymes like cytochrome P450 and UDP glucoronosyl transferases are important for drug metabolism in the liver and other tissues. Cytochrome P450 enzymes catalyze oxidation, reduction, and other phase I reactions. UDP glucoronosyl transferases catalyze phase II conjugation reactions like glucoronidation. Drug metabolism can be induced or inhibited by other drugs and environmental factors, leading to potential drug-drug interactions. A better understanding of an individual's genetic polymorphisms and environmental factors can help optimize drug therapy and avoid adverse reactions.
Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides.
Just the type of presentation a top presenter would look for.
The topic is well introduced, the designs of the slides are simple yet the explanation is very powerful.
Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides.
Just the type of presentation a top presenter would look for.
The topic is well introduced, the designs of the slides are simple yet the explanation is very powerful.
Detailed information of all terms like Thyroid gland, Thyroxine, Triidothyronine, Calcitonine, growth and development , propylthiouracil, Calorigenesis, tadpole to frog, Oligomenorrhoea, snehal chakorkar, pharmacology, Cretinism, Myxoedema coma, Graves disease, Thiocynates, Perchlorate, Nitrates.
Radioactive iodine, I131
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
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.
Detailed information of all terms like Thyroid gland, Thyroxine, Triidothyronine, Calcitonine, growth and development , propylthiouracil, Calorigenesis, tadpole to frog, Oligomenorrhoea, snehal chakorkar, pharmacology, Cretinism, Myxoedema coma, Graves disease, Thiocynates, Perchlorate, Nitrates.
Radioactive iodine, I131
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
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.
1. Introduction
2. Phases of metabolism
3. Phase-I Metabolism
4. Cytochrome P family
5. Phase –II Metabolism
6. First pass metabolism
7. Ante Drugs
8. Microsomal Enzymes induction
Role of metabolism in drug discovery
pharmacokinetics- action of body on the drug. includes absorption, dissolution, metabolism and excretion of drug. In this presentation metabolism and excretion of the drug are covered . Includes conversion of lipophilic / non-water soluble compounds into easily removable compounds by the action of hepatic enzymes which can be microsomal or non-microsomal . Excretion is further removal or elimination of compounds or agents from the body. Drug elimination is the sum of the processes of removing an administered drug from the body. In the pharmacokinetic ADME scheme (absorption, distribution, metabolism, and excretion), it is frequently considered to encompass both metabolism and excretion. Hydrophobic drugs, to be excreted, must undergo metabolic modification making them more polar. Hydrophilic drugs, on the other hand, can undergo excretion directly, without the need for metabolic changes to their molecular structures. Introduction
Most drugs are xenobiotics, ie, chemical substances not naturally produced by the body. Xenobiotics undergo various body processes for detoxification, thus reducing their toxicity and allowing them to be readily available for excretion. These processes allow for the chemical modification of drugs into their metabolites and are known as drug metabolism or metabolic biotransformation.
These metabolites are the byproducts of drug metabolism and can be characterized by active, inactive, and toxic metabolites. Active metabolites are biochemically active compounds with therapeutic effects, whereas inactive metabolites are biochemically inactive compounds with neither a therapeutic nor toxic effect. Toxic metabolites are biochemically active compounds similar to active metabolites but have various harmful effects.
Drug metabolism occurs at a specific location in the body, resulting in a low concentration of active metabolites in the systemic circulation. This phenomenon is called first-pass metabolism because it limits drug bioavailability. First-pass metabolism primarily occurs in the liver; however, metabolizing enzymes can be found throughout the body.
Understanding these alterations in chemical activity is crucial in utilizing the optimal pharmacological intervention for any patient. This is a topic of interest to any provider who routinely treats patients with medications. The metabolism of pharmaceutical drugs is an important aspect of pharmacology and medicine. For example, the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. Drug metabolism also affects multidrug resistance in infectious diseases and in chemotherapy for cancer, and the actions of some drugs as substrates or inhibitors of enzymes involved in xenobiotic metabolism are a common reason for hazardous drug interactions. These pathways are also important in environmental science, with the xenobiotic metabolism of microorganisms determining whether a pollutant will be broken down or not is covered.pharmacokinetic
animal toxicity tests are useful in finding the right dose for drugs to be used in humans. this ppt contains the method of toxicity studies and different types of toxicity studies.
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
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
- 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
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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.
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.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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!
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
3. Bio-transformation
• DEFINITION : Chemical alteration of the drug in the body.
Non-polar compounds to polar (lipid-insoluble) compounds.
• SITES :
liver kidney intestine lungs
4. • ACTIONS
1. Inactivation
EG : Ibuprofen, lidocaine, propranolol
2. Active metabolite from active drug
Active drug Active metabolite
Morphine Morphine-6-glucoronide
Codeine Morphine
Amitryptiline Nortriptiline
Spironolactone Canrenone
Imipramine Desimipramine
5. 3. Active metabolite from inactive drug
Prodrug Active form
Levodopa Dopamine
Enalapril Enalaprilat
Prednisone Prednisolone
Sulfasalazine 5-aminosalicylic acid
Acyclovir Acyclovir triphosphate
6. Bio-transformation Phases
Phase 1 Phase 2
• Non-Synthetic/functionalization
reactions
• Metabolite may be active or inactive
1. Oxidation
2. Reduction
3. Hydrolysis
4. Cyclization
5. De-cyclization
(On Race Honda CD)
• Synthetic / conjugation reaction
• Mostly inactive
1. Glucuronide conjugation
2. Acetylation
3. Methylation
4. Sulphate conjugation
5. Glycine conjugation
6. Glutathione conjugation
7. Ribonucleotide/nucleotide synthesis
(Get A Motor Scooter, Go Get Racing)
7.
8. ENZYME INDUCTION
Microsomal Non-microsomal
Smooth endoplasmic reticulum( in liver,
kidney, intestine, lungs)
Cytoplasm and m itochondria (in liver)
Eg : Monooxygenases, CYP450, UGT,
epoxide hydrolases etc.
Esterases, amidases, some flavoprotein,
most conjugases
Catalyzes oxidation, reduction,
glucoronide conjugation etc.
All conjugation except glucoronidation
Inducible Non-inducible
9. Microsomal Enzymes
• Microsomes : ER is isolated by homogenization and fractionation of cells
reform into
Vesicles known as microsomes
10. • They are inducible by drugs and environmental factors and some dietary
constituents.
• For e,g
1. A component of grapefruit juice inhibits drug metabolism (leading to potentially
disastrous consequences, including cardiac dysrhythmias)
2. Brussel sprouts and cigarette smoke induce P450 enzymes.
3. Components of the herbal medicine St John’s wort induces CYP450 isoenzymes as
well as P-glycoprotein (P-gp)
12. Cytochrome P450
• Cytochrome P450 enzymes are heme proteins, comprising a large family (‘superfamily’)
each referred to as CYP followed by a defining set of numbers and a letter.
• P450 because reduced heme protein binds with CO to form a complex that absorbs light
maximally at 450nm.
• Not all 57 human CYPs are involved in drug metabolism.
• CYP enzymes in families 1–3 mediate 70%–80% of all drug metabolism.
• Twelve CYPs accounted for 93.0% of drug metabolism.
14. • CYP Isoforms found in liver are
CYP1A2,
CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1
CYP3A4, CYP3A5
CYP4A11
CYP7
• The most active CYPs for drug metabolism are of CYP2c, CYP2d, and CYP3a
subfamilies.
18. Drug interaction due to enzyme induction
Auto-induction : Because the inducing agent is often itself a substrate for the induced
enzymes, the process can result in slowly developing tolerance
Eg: carbamazepine, rifampicin, nevirapine dose needed to be doubled after 2 weeks.
Enzyme induction can increase toxicity of an active metabolite of paracetamol by its
metabolite N-acetyl-P-benzoquinone imine (NAPQI).
The risk of serious hepatic injury following paracetamol overdose is increased in
patients in whom CYP has been induced, for example, by chronic alcohol Consumption.
Antibiotic rifampicin, given for 3 days, reduces the effectiveness of warfarin as an
anticoagulant.
20. Therapeutic Uses Of Enzyme Induction
• Non-hemolytic anemia : Its due to deficient glucuronidation of bilirubin,
phenobarbitone hastens its clearance.
• Cushings syndrome: Phenytoin may reduce the manifestation by enhancing
degradation of adrenal steroids.
• Chronic poisoning
• Liver diseases.
23. Drug Interaction Due To Enzyme Inhibition
• Several inhibitors of drug metabolism influence the metabolism of different
stereoisomers selectively.
• Examples of drugs that inhibit the metabolism of the active (S) and less active (R)
isomers of warfarin
Inhibition of metabolism drugs
Stereoselective for ( S ) isomer Phenylbutazone
Metronidazole
Sulfinpyrazone
Trimethoprim–
sulfamethoxazole
Disulfiram
Stereoselective for ( R ) isomer Cimetidine
Omeprazole
Non-stereoselective amiodarone
25. UDP Glucoronosyl Transferases(UGT)
• Catalyse phase II reaction - Glucuronidation
• Glucoronides excreted via – Intestine via bile (majority)
Kidney (minority)
• Glucoronides are cleaved by beta-glucuronidase found in bacteria of lower GIT –
enterohepatic circulation of drugs eg. OCPs
• UGT 1 – drugs metabolism
UGT 2 – endogenous substrate metabolism
26. Flavin Monooxygenases
• Phase I reaction
• 6 families are present
• FMO 3 is most abundant in human liver
• They are not induced or inhibited by any drug
Not involved in drug-drug interaction
27. Epoxide Hydrolases
• Carry out hydrolysis of epoxide, many of which are produced by CYP
• It metabolises very few drugs eg. Carbamazepine
28. Glutathione S Transferases (GST)
• Found in both ER and cytosol
• Microsomal form – metabolism of endogenous leukotrienes and prostaglandins
• Cytosolic form – conjugation, reduction, isomerization reaction of drug metabolism.
29. Factors Affecting Drug Metabolism
Genetic Factors Non-genetic Factors
Genetic polymorphism Commensal Gut Microflora
Diet And Envt Factors
Age And Sex
Concurrent Exposure To Inhibitors or Inducers
Diseases
30. Genetic Polymorphism
• Definition : Occurrence of a variant allele of a gene at a population frequency more
than 1%, resulting in altered expression of functional activity of the gene product, or
both.
• Based on metabolic ratio, individuals are divided into 1- Poor metabolisers
2- Extensive metabolisers
3- Ultra rapid metabolisers
• Metabolic Ratio = Percentage of dose excreted as unchanged drug
Percent of dose excreted as metabolite in urine
31. Conclusion
• Understanding drug metabolism and interaction within the body allows principles of
biotransformation to be applied in better designing and therapeutic uses of drug.
• Increased understanding of biotransformation based on pharmacogenomics will also
render pharmacologic treatment of disease more individualised, efficacious and safe.
Phase 1 reactions often introduce a reactive group, such as hydroxyl, into the molecule, a process known as ‘functionalisation’. This group then serves as the point of attack for the conjugating system to attach a substituent such as glucuronide explaining why phase 1 reactions so often precede phase 2 reactions
Both microsomal and non-microsomal enzymes are deficient in new born ESP PREMATURE, hence making them more susceptible to many drugs.
Each of the pink or blue rectangles represents one single molecule of cytochrome P450 (P450) undergoing a catalytic cycle. Iron in P450 is in either the ferric (pink rectangles) or ferrous (blue rectangles) state. P450 containing ferric iron (fe3+) combines with a molecule of drug (‘DH’), and receives an electron from NADPH– P450 reductase, which reduces the iron to fe2+. This combines with molecular oxygen, a proton and a second electron (either from NADPH–P450 reductase or from cytochrome b5) to form an fe2+ooh–dh complex. This combines with another proton to yield water and a ferric oxene (feo)3+–dh complex. (Feo)3+ extracts a hydrogen atom from DH, with the formation of a pair of short-lived free radicals (see text), liberation from the complex of oxidised drug (‘DOH’), and regeneration of P450 enzyme.
(When starting treatment with the antiepileptic drug carbamazepine. Treatment starts at a low dose to avoid toxicity (because liver enzymes are not induced initially) and is gradually increased over a period of a few weeks, during which it induces its own metabolism)
