The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
Phase I Vs Phase II Drug metabolism and factors affectiing drug metabolism.
Enzyme induction, Enzyme inhibitor, physicochemical properties wthich acan affect the drug metabolism
Phase I Vs Phase II Drug metabolism and factors affectiing drug metabolism.
Enzyme induction, Enzyme inhibitor, physicochemical properties wthich acan affect the drug metabolism
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.
By the end of this lecture, students should:
Explain why drug metabolism is essential
Describe the phases of drug metabolism
Explain the role of cytochrome p 450 enzyme system in drug metabolism
Definition
Chemical reactions which occur in the body to change drugs from nonpolar lipid soluble forms to polar water soluble forms that are easily excreted by the kidney.
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
drug metabolism, phase I metabolism, biotransformation, Xenobiotics- substances foreign to body
Non polar lipid soluble compounds are made polar lipid insoluble, so that they are easily excreted.
Advantages of metabolism
Termination of drug action
↓ toxicity
Reduced lipophilicity.
Renal / biliary excretion ↑
↑ water solubility
↑ polarity
↑ excretion
Loss of phsiological activity
Active drug → more active drug
Non Active drug → active drug
Active drug → inactive drug
BIOTRANSFORMATION REACTIONS - 2 TYPES
Phase I / Non synthetic / Functionalization
A functional group is generated
Metabolite – active or inactive
Phase II / Synthetic / Conjugation
Metabolite is usually inactive
BIOTRANSFORMATION REACTIONS - 2 TYPES
Phase I / Non synthetic / Functionalization
A functional group is generated
Metabolite – active or inactive
Phase II / Synthetic / Conjugation
Metabolite is usually inactive
Depending upon nature and localisation of enzymes which catalyse reaction –
Microsomal enzymes
Non- Microsomal enzymes
Oxidation of alcohol
ethanol→ acetaldehyde → acetic acid →TCA cycle → CO₂
Eg.
chloral hydrate → trichloroacetic acid
mefenamic acid → hydroxy methyl derivative
ALIPHATIC HYDROXYLATION
Hydroxyl group added to drug
RCH2CH3 O RCHOHCH3
Salicylic acid to Gentisic acid
Ibuprofen
Tolbutamide, Chlorpropamide,
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
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
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
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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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
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.
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
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.
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Triangles of Neck and Clinical Correlation by Dr. RIG.pptx
Drug metabolism
1.
2. Drug is any substance or product that is
used or is intended to be used to modify or
explore physiological systems or
pathological states for the benefit of the
recipient.
Biotransformation means chemical alteration
of the drug in the body.
The metabolites formed are less lipid
soluble.
3. What does biotransformation do?
It converts lipid soluble compounds to lipid
insoluble so that they are not reabsorbed.
Role of biotransformation:
› defensive mechanism
› increases polarity of drug molecules,
restricts penetration through cellular
membrane
reduces distribution
promotes elimination
15. Oxidation- This reaction involves addition of
oxygen /negatively charged radical or
removal of hydrogen /positively charged
radical.
Oxidations are the most important drug
metabolizing reactions.
Various oxidation reactions are:
hydroxylation;oxygenation at C,N or S
atoms; N or 0-dealkylation, oxidative
deamination, etc.
16. Oxidative reactions are mostly carried out by
a group of monooxygenases in the liver
which in the final step involve a cytochrome
P-450 haemoprotein, NADPH, cytochrome
P-450 reductase and molecular 02.
More than 100 cytochrome P- 450
isoenzymes differing in their affinity for
various substrates (drugs) have been
identified.
Eg Imipramine, diazepam, codiene,
phenytoin, barbiturates, paracetamol.
17. Reduction- A chemical reaction in which
hydrogen s added to, or oxygen is removed
from a compound.
Alcohols, aldehydes, quinones are reduced.
Drugs -chloralhydrate, chloramphenicol,
halothane, warfarin.
18. Hydrolysis -This is cleavage of drug
molecule by taking up a molecule of water.
Ester + H20 Esterase Acid + Alcohol
Hydrolysis occurs in liver, intestines, plasma
and other tissues.
Examples are choline esters, procaine,
lidocaine, procainamide, aspirin, c
19. Super family of phase I enzymes expressed at high levels
in the liver bound to ER.
Six families of FMOs, FMO3 – most abundant in the liver.
Metabolize nicotine, H2 receptor blocker, antipsychotics
[clozapine], antiemetics [itopride].
Genetic deficiency Fish odor syndrome due to lack of
metabolism of TMAO [ trimethylamine N oxide ] TMA.
Minor contributors to drug metabolism - produce benign
metobolites.
Not involved in drug-drug interactions.
Eg : Itopride metabolized by FMO3
: Cisapride metabolized by CYP3A4
19
20. Phase 2 conjugation enzymes are synthetic in nature –
result in formation of metabolite with increase in
molecular mass.
Terminate biological activity of the drug.
Characteristic feature – dependency on the catalytic
reaction for cofactors such as UDP-GA, & PAPS,for UGT
& SULT, which react with available functional groups on
the substrates.
All reactions are carried out in cytosol of the cell,
exception of glucuronidation.
Catalytic rates of phase 2 reaction are significantly faster
than rates of CYP’s.
So rate of elimination depends on Phase 1.
20
21. Most important phase 2 reaction catalyzed by UDP-
Glucuronosyltransferases (UGTs).
UGT2 – Greater specificity for glucuronidation of steroids.
UGT1A1 – Glucuronidation of bilirubin.
Crigler Najjars syndrome type 1 & type 2
Most common genetic polymorphism – Gilberts
syndrome (10% popuplation) (mutation in UGT1A1
gene).
21
22. SULT located in cytosol, metabolise various substrates.
13 SULT isoforms identified – role in human homeostasis.
SULT1B1 catalysis of cholesterol .
SULT1A3 selective for catecholamine
SULT1E1 estrogens are sulfated
SULT2A1 DHEA
SULT1 Sulfation of phenolic molecules. Eg:-
acetaminophen and minoxidil.
SULT1A1 Most abundant in human tissue.
22
23. The glutathione-S-transferases (GSTs) catalyze
the transfer of glutathione to reactive
electrophiles, a function that serves to protect
cellular macromolecules from interacting with
electrophiles that contain electrophilic
heteroatoms (-O, -N, and -S) and in turn
protects the cellular environment from damage.
24. Glutathione exists in the cell as oxidized
(GSSG) or reduced (GSH) forms, and the ratio
of GSH:GSSG is critical in maintaining a cellular
environment in the reduced state.
A severe reduction in GSH content can
predispose cells to oxidative damage.
25. Over 20 human GSTs have been identified and
divided into two subfamilies: the cytosolic and
the microsomal forms.
The major differences in function between the
microsomal and cytosolic GSTs reside in the
selection of substrates for conjugation;
The cytosolic forms have more importance in
the metabolism of drugs and xenobiotics,
Whereas the microsomal GSTs are important in
the endogenous metabolism of leukotrienes and
prostaglandins.
26. › The cytosolic N-acetyltransferases (NATs) are responsible
for the metabolism of drugs and environmental agents that
contain an aromatic amine or hydrazine group.
› NATs are among the most polymorphic of all the human
xenobiotic drug-metabolizing enzymes.
› There are two functional NAT genes in humans, NAT1 and
NAT2.
› The therapeutic relevance of NAT polymorphisms is in
avoiding drug-induced toxicities.
26
27. NAT1 is ubiquitously expressed among most
human tissues, whereas NAT2 is found
predominantly in liver and the GI tract.
28. Xenobiotics undergo O-, N-,S- methylation.
N-methyltransferase are COMT, POMT, TPMT.
The common theme among the MTs is the generation
of a methylated product, substrate specificity is high
and distinguishes the individual enzymes.
TPMT – catalysis the S- methylation of aromatic and
cyclic sulfhydryl compounds.
Genetic deficiency of TPMT – severe toxicities of thio
purine drugs.(Azathioprine , 6-mercaptopurine )
28
29. Drugs on repeated administration stimulate the
growth of smooth endoplasmic reticulum.
This induction usually reversible, leads to increased
microsomal enzyme activity.
Therefore, metabolism is increased and
pharmacological response in decreased.
Mostly in liver, but can also occur in intestine, lung,
placenta, kidney.
30. 1. It reduces efficacy and potency of drugs metabolized by these
enzymes.
2. It reduces plasma half-life and duration of action of drugs.
3. It enhances drug tolerance.
4. It increases drug toxicity by enhancing concentration of metabolite, if
metabolite is toxic.
5. It increases chances of drug interactions.
6. Can be used for therapeutic benefits.
Clinical importance of enzyme
induction
30
32. It takes 3-10 days to induce and 1-3 weeks to return to normal
levels after stoppage of inducer
32
Atorvastatin
33. One drug may inhibit the metabolism of another drug
with resultant increase in the circulating levels of the
slowly metabolised drug and prolongation of its
pharmacological effects.
Enzyme inhibition can be of hepatic microsomal MFOs
or of enzymes having specific functions. Eg:xanthine
oxidase, monoamine oxidase.
Rapid and usually reversible process.
35. Adverse consequences
1. Unexpected nausea, vomiting and tremors
may occur when Theophylline is given with
erythromycin.
2. Enhanced bleeding tendency when
Dicumerol is given with cimetidine.
3. Severe respiratory depression may occur
when Morphine is given with MAOs.
36. Therapeutically beneficial consequences
1. Increased accessibility of L-dopa in brain
when given along with carbidopa.
2. Aversion to alcohol after prior administration
of disulfiram.
3. Reversal of skeletal muscle paralysis due to
tubocurarine by neostigmine.
37. Age
Sex
Species
Race
Genetic variations
Nutrition and diet
38. Metabolism normally results in the
inactivation of their therapeutic effectiveness
and facilitates their elimination.
The extent of metabolism can determine the
efficacy and toxicity of a drug by controlling
its biological t1/2.
39. If a drug is metabolized too quickly, it rapidly
loses its therapeutic efficacy.
This can occur if specific enzymes involved
in metabolism are naturally overly active or
are induced by dietary or environmental
factors.
40. If a drug is metabolized too slowly, the drug
can accumulate in the bloodstream; as a
consequence, the pharmacokinetic parameter
AUC (area under the plasma concentration-time
curve) is elevated and the plasma clearance of
the drug is decreased.
This increase in AUC can lead to
overstimulation or excessive inhibition of some
target receptors or undesired binding to other
cellular macromolecules.
41. While environmental factors can alter the
steady-state levels of specific enzymes or
inhibit their catalytic potential.
The phenotypic changes in drug metabolism
are also observed clinically in groups of
individuals that are genetically predisposed
to adverse drug reactions because of
pharmacogenetic differences in the
expression of xenobiotic-metabolizing
enzymes.
42. Before a new drug application (NDA) is filed
with the Food and Drug Administration, the
route of metabolism and the enzymes
involved in the metabolism must be known.
As a result, it is now routine practice in the
pharmaceutical industry to establish which
enzymes are involved in metabolism of a
drug candidate and to identify the
metabolites and determine their potential
toxicity.