The document discusses drug nomenclature and pharmacokinetics. It explains that drugs have three categories of names - chemical, non-proprietary, and proprietary. It then describes the processes of absorption, distribution, metabolism, and excretion that make up a drug's pharmacokinetics. Absorption can occur through various routes of administration like oral, sublingual, rectal, and parenteral routes. Distribution and metabolism determine the amount of drug that reaches the systemic circulation. Excretion removes the drug from the body.
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Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
A power point presentation on general aspects of Pharmacokinetics suitable for undergraduate medical students beginning to study Pharmacology. Also suitable for Post Graduate students of Pharmacology and Pharmaceutical Sciences.
A power point presentation on Pharmacodynamics (what drug does to the body) suitable for undergraduate medical students beginning to study Pharmacology
This ppt is for pharmacology students of MBBS UG&PG and other healthcare persons who needs basic science like BDS, Nursing Ayurveda unani homeopathy etc.
This is the second part of my presentation. It is all about the review on Routes and rights of drug administration. The slide also covers IP & Drug Laws too.
Pharmacokinetics - drug absorption, drug distribution, drug metabolism, drug ...http://neigrihms.gov.in/
A power point presentation on general aspects of Pharmacokinetics suitable for undergraduate medical students beginning to study Pharmacology. Also suitable for Post Graduate students of Pharmacology and Pharmaceutical Sciences.
A power point presentation on Pharmacodynamics (what drug does to the body) suitable for undergraduate medical students beginning to study Pharmacology
This ppt is for pharmacology students of MBBS UG&PG and other healthcare persons who needs basic science like BDS, Nursing Ayurveda unani homeopathy etc.
This is the second part of my presentation. It is all about the review on Routes and rights of drug administration. The slide also covers IP & Drug Laws too.
Know About Your Drug ,,, Part - II ( Route of Drug Administration) for study purpose pharmaceutical professional such as students and other specialized field. Presentation for "LEARN & EARN KNOWLEDGE" based.
Thanks all of you for your support...Part-I success and your comments.
Multi-source connectivity as the driver of solar wind variability in the heli...Sérgio Sacani
The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
The increased availability of biomedical data, particularly in the public domain, offers the opportunity to better understand human health and to develop effective therapeutics for a wide range of unmet medical needs. However, data scientists remain stymied by the fact that data remain hard to find and to productively reuse because data and their metadata i) are wholly inaccessible, ii) are in non-standard or incompatible representations, iii) do not conform to community standards, and iv) have unclear or highly restricted terms and conditions that preclude legitimate reuse. These limitations require a rethink on data can be made machine and AI-ready - the key motivation behind the FAIR Guiding Principles. Concurrently, while recent efforts have explored the use of deep learning to fuse disparate data into predictive models for a wide range of biomedical applications, these models often fail even when the correct answer is already known, and fail to explain individual predictions in terms that data scientists can appreciate. These limitations suggest that new methods to produce practical artificial intelligence are still needed.
In this talk, I will discuss our work in (1) building an integrative knowledge infrastructure to prepare FAIR and "AI-ready" data and services along with (2) neurosymbolic AI methods to improve the quality of predictions and to generate plausible explanations. Attention is given to standards, platforms, and methods to wrangle knowledge into simple, but effective semantic and latent representations, and to make these available into standards-compliant and discoverable interfaces that can be used in model building, validation, and explanation. Our work, and those of others in the field, creates a baseline for building trustworthy and easy to deploy AI models in biomedicine.
Bio
Dr. Michel Dumontier is the Distinguished Professor of Data Science at Maastricht University, founder and executive director of the Institute of Data Science, and co-founder of the FAIR (Findable, Accessible, Interoperable and Reusable) data principles. His research explores socio-technological approaches for responsible discovery science, which includes collaborative multi-modal knowledge graphs, privacy-preserving distributed data mining, and AI methods for drug discovery and personalized medicine. His work is supported through the Dutch National Research Agenda, the Netherlands Organisation for Scientific Research, Horizon Europe, the European Open Science Cloud, the US National Institutes of Health, and a Marie-Curie Innovative Training Network. He is the editor-in-chief for the journal Data Science and is internationally recognized for his contributions in bioinformatics, biomedical informatics, and semantic technologies including ontologies and linked data.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
2. DRUG NOMENCLATURE
• A drug generally has three categories of names:
(a) Chemical name:
• It describes the substance chemically,
e.g. 1-(Isopropylamino)-3-(1-naphthyloxy) propan-2-ol
for propranolol, and not suitable for prescribing.
• A code name, e.g. RO 15-1788 (later named
flumazenil) may be assigned by the manufacturer for
convenience and simplicity before an approved name
is coined.
3. DRUG NOMENCLATURE
b) Non-proprietary name
• It is the name accepted by a competent scientific
body/authority,
• E.g. The United States Adopted Name (USAN) in USA,
• British Approved name (BAN) in Britain
• Commonly, it is termed as generic name
• Now BAN is modified with Recommended International
Non-proprietary Name (rINN)
• The rINN kept the Newer drugs names uniform so as to
follow by all the countries in WHO.
• Untill in the addition of Pharmacopeia it is called Approved
name ,After in official publication it is called Official name.
4. DRUG NOMENCLATURE
(c) Proprietary (Brand) name:
• It is the name assigned by the manufacturer(s) and
his property or trade mark.
• One drug may have multiple proprietary names
e.g. ALTOL, ATCARDIL, ATECOR,
• ATEN, BETACARD, LONOL, TENOLOL, TENORMIN for
atenolol from different manufacturers.
• Brand names = catchy, short, easy to remember and
often suggestive, e.g. LOPRESOR (Low BP)
• Brand names generally differ in different countries,
e.g. timolol maleate eye drops are marketed as
TIMOPTIC in USA but as GLUCOMOL in India
5. PHARMACOLOGY
Drug: “ A drug is any chemical molecule, which can be
administered exogenously into the living system produce
biological response or effect.”
Pharmacology is the science of drugs (Greek :Pharmacon—drug;
logos—discourse in).
Pharmacology
Pharmacodynamics
(Greek: dynamis—power)
—What the drug does to the body.
Pharmacokinetics
(Greek: Kinesis—movement)
—What the body does to the drug.
8. ADME- Drug Absorption
• Absorption is movement of the drug from its site of
administration into the circulation.
• Not only the fraction of the administered dose that gets
absorbed, but also the rate of absorption is important.
Some of the factors affecting the absorption:
• Aqueous solubility : Water soluble drugs = more absorption
Water insoluble drugs = less absorption
• Concentration: Conc. Solutions = faster absorption
Dilute solutions = lesser absorption
• Area of absorbing surface: Larger is the surface area,
faster is the absorption.
9. ADME-Routes of Administration
• Routes of drug administration affects drug absorption,
because each route has its own peculiarities.
10. ADME
Routes can be broadly divided into
(a) Local action
Topical
Deeper tissues
Arterial supply
(b) Systemic action
Oral
Sublingual/ buccal
Rectal
Cutaneous (TTS)
Inhalation
Nasal
Parenteral (sc,iv,im)
11. ADME
Local routes:
Topical: external drug application to the surface for localized action.
It is often more convenient.
• Drugs can be efficiently delivered to the localized lesions on skin,
oropharyngeal/ nasal mucosa, eyes, ear canal, anal canal or vagina
• in the form of lotion, ointment, cream, powder, rinse, paints, drops,
spray, lozenges, suppositories or pesseries.
Deeper tissues : Certain deep areas can be approached by using a
syringe and needle, but the drug should be in such a form that
systemic absorption is slow,
• E.g: intra-articular injection, retro bulbar injection
Arterial supply : Close intra-arterial injection is used for contrast
media in angiography;
• anticancer drugs can be infused in femoral or brachial artery to
localize the effect for limb malignancies.
12. ADME
Systemic routes: ORAL Route
Oldest & commonest method
More convenient
No need assistance
Often painless
not to be sterile so, it is Cheaper
Solid dosage forms :
powders,tablets, capsules,
moulded tablets,
Liquid dosage forms : elixirs,
syrups, emulsions, mixtures
• Limitations:
Action of drugs is slower and thus
not suitable for emergencies.
Unpalatable drugs
(chloramphenicol) are difficult to
administer.
May cause nausea and vomiting
(emetine).Cannot be used for
uncooperative/unconscious/
vomiting patient.
Others are destroyed by digestive
juices (penicillin G,insulin) or in liver
(GTN, testosterone, lidocaine).
13. ADME
First Pass Effect:
• It is the term used for hepatic metabolism of a drug
when it is absorbed from the gut & delivered to the Liver
via portal circulation.
• Greater the First pass effect, lesser the drug reaches the
systemic circulation ( Oral route).
Where it occurs?
o Liver
o Gut wall
o Gut lumen
Results
o Low
Bioavailability
o Short duration
of action(t 1/2)
14. ADME
SUBLINGUAL :
• the drug is placed under the tongue
or crushed in the mouth and
spread over the buccal mucosa (Buccal)
• Absorption is relatively rapid—action in mins.
• The chief advantage is that liver is
bypassed and drugs with high first pass
metabolism can be absorbed directly into systemic
circulation.
• Drugs given sublingually are—GTN, buprenorphine,
desamino-oxytocin.
15. ADME
RECTAL :
Certain irritant and unpleasant drugs
can be used as suppositories
when the patient is having recurrent vomiting or is
unconscious, this route may preferable.
inconvenient and embarrassing; absorption is
Absorption is slower, irregular and often unpredictable
Rectal inflammation can result from irritant drugs.
• Diazepam, indomethacin, paracetamol, ergotamine and few
other drugs are some times given rectally.
16. ADME
CUTANEOUS:
• Highly lipid soluble drugs applied over the skin for slow and
prolonged absorption.
• The liver is also bypassed. The drug can be incorporated in an
ointment and applied over specified area of skin. ( By rubbing
the drug preparation , the absorption may increases.
Transdermal therapeutic
Patches (TTS) :
• In India,
GlycerinTetra Nitryl,
fentanyl,
nicotine and estradiol
Local irritation
Erythema
17. ADME
INHALATION:
• Volatile liquids and gases are given by
inhalation for systemic action,
e.g. general anaesthetics.
• Absorption takes place from the vast surface of alveoli—action
is very rapid.
• When administration is discontinued the drug diffuses back and
is rapidly eliminated in expired air.
Thus, controlled administration is possible with moment to
moment adjustment.
Irritant vapours (ether) cause inflammation of respiratory tract
and increase secretion.
18. ADME
PARENTERAL:
to administration by
injection which takes the
drug directly into the tissue
fluid or systemic circulation.
Drug action is surer and
faster ( Emergencies).
Gastric irritation & vomiting
are not provoked.
unconscious, uncooperative
or vomiting patients.
Liver is bypassed.
No interference of food &
digestive juices.
preparation has to be
sterilized and so costlier,
the technique is invasive
and painful, assistance of
another person is mostly
needed
there are chances of local
tissue injury.
Once the preparation is
administrated , it cant be
withdrawn back.
19. ADME
Subcutaneous:
• Only small volumes of drug can be deposited in the loose
subcutaneous tissue
• Self-injection is possible because deep penetration is not
needed. (Insulin injection)
a) Dermojet: In this method needle is not used; a high
velocity jet of drug solution is projected from a microfine
orifice using a gun like implement.
It is essentially painless and suited for mass inoculations.
b) Pellet implantation: The drug in the form of a solid pellet
is introduced with a trochar and cannula. This provides
sustained release of the drug over weeks and months,
e.g. DOCA, testosterone
20. ADME
Intramuscular (i.m.)
• Can be injected in large skeletal muscles—deltoid,
triceps, gluteus maximus, rectus femoris, etc.
• i.m.injections should be avoided in anticoagulant
treated patients, because it can produce local
haematoma.
Intradermal injection :
• The drug is injected into the
dermis of skin raising a bleb.
(often painful)
• (e.g. BCG vaccine, sensitivity testing)
21. ADME
Intravenous (i.v.)
• Can be injected as a bolus (Greek: bolos–lump) or infused
slowly over hours in one of the superficial veins.
• Drug reaches blood stream immediately and so affects can
produce faster.
Bioavailability is 100%
One big advantage with this route is—in case response is
accurately measurable
(e.g. BP)
22. ADME- Bioavailability
Bioavailability (BA or F) is the fraction (%) of an
administered drug that reaches the systemic
circulation in a chemically unchanged form.
• For example: 100mg of a drug is administered orally
and 70mg of this drug absorbed unchanged, then the
BA of the is 0.7 or 70%.
Bioavailability Comparison:
Parenteral > Inhalation > Oral (Sublingual > Buccal) >
Rectal > Topical.
23. ADME- DRUG DISTRIBUTION
Drug
Distribution(V):
it refers to reversible
transfer of drugs
between the blood
and extra cellular
fluid & other tissues
of the body.
• Factors affecting drug Distribution:
1. Blood flow
2. Capillary permeability
-> Capillary structure
->Blood Brain Barrier
3. Protein binding of drugs
24. ADME
Penetration into brain and CSF
• The capillary endothelial cells in brain have tight junctions and
lack large paracellular spaces and the neural tissue covers the
capillaries. Together called Blood-Brain Barrier (BBB).
• Similararly, blood-CSF barrier is having tight junctions lined by
choroidal epithelium. Both these barriers are lipoidal (Only
lipid-soluble drugs, therefore, are able to penetrate)
• Drugs, e.g. streptomycin, neostigmine, etc.
25. ADME
Distribution across Placenta:
• Placental membranes are lipoidal and allow free passage
of lipophilic drugs, while restricting hydrophilic drugs.
• As it is an incomplete, any drug taken by the mother can
affect the foetus or the newborn (drug taken just before
delivery, e.g. morphine).
26. ADME
Drugs binding to plasma proteins:
• Most drugs possess physicochemical affinity for plasma
proteins and get reversibly bound to these.
• Bound are pharmacologically inactive, Only the free or
unbound drugs can act on the target sites, produce biological
response and be available for the process of elimination.
• Acidic drugs generally binds to plasma albumin
• basic drugs to α1 acid glycoprotein.
• Albumin has the strongest affinity for anionic and
hydrophobic drugs.
27. ADME- DRUG METABOLISM
• Drug metabolism is the metabolic breakdown of drugs by
living organisms, usually through specialized enzymatic
systems.
• The metabolism of pharmaceutical drugs is an important
aspect of pharmacology and medicine.
• The primary site for drug metabolism is liver; others are—
kidney, intestine, lungs and plasma.
28. ADME
Biotransformation (Metabolism) reactions can be classified
into:
(b) Nonsynthetic/Phase I/
Functionalization reactions:
• Oxidation
• Reduction
• Hydrolysis
• Cyclization
• Decyclization
(a) Synthetic/Conjugation/
Phase II reactions:
• An endogenous radical is
conjugated to the drug—
metabolite is mostly
inactive;
• Glucuronide conjugation
• Methylation
• Acetylation
• Glutathione conjugation
29. ADME
Phase I reactions
1 .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 O-dealkylation, oxidative deamination, etc
2. Reduction: This reaction is the converse of oxidation and
involves cytochrome P-450 enzymes working in the opposite
direction. Alcohols, aldehydes, quinones are reduced.
• Drugs primarily reduced are chloralhydrate, chloramphenicol,
halothane, warfarin.
30. ADME
3.Hydrolysis: This is cleavage of drug molecule by taking
up a molecule of water.
• Similarly, amides and polypeptides are hydrolysed by
amidases and peptidases.
4. Cyclization: This is formation of ring structure from a
straight chain compound, e.g. proguanil.
5. Decyclization: This is opening up of ring structure of the
cyclic drug molecule, e.g. barbiturates, phenytoin.
• This is generally a minor pathway.
31. ADME- Phase II Reactions:
1. Glucuronide Conjugation:
• It is the important synthetic reaction carriedout by a group of
UDP-glucuronosyl transferases (UGTs). Compounds with a
hydroxyl or carboxylic acid group are easily conjugated with
glucuronic acid which is derived from glucose.
• Examples are— chloramphenicol, aspirin, paracetamol,
diazepam,lorazepam, morphine, metronidazole.
• Not onlydrugs but endogenous substrates like bilirubin,
steroidal hormones and thyroxine utilize this pathway
2. Methylation: The amines and phenols can be methylated by
methyl transferases (MT); methionine and cysteine acting as
methyl donors,
• e.g. adrenaline, histamine, nicotinic acid, methyldopa, captopril,
mercaptopurine.
32. ADME
3. Acetylation: Compounds having amino or hydrazine residues
are conjugated with the help of acetyl coenzyme-A.
E.g. sulfonamides, Isoniazid, PAS, Dapsone, Hydralazine,
Clonazepam, Procainamide.
4. Glutathione conjugation: This is carried out by glutathione-S-
transferase (GST) forming a mercapturate.
• However, it serves to inactivate highly reactive quinone or
epoxide intermediates formed during metabolism of certain
drugs, e.g. paracetamol.
• When large amount of such intermediates are formed (in
poisoning or after enzyme induction),
• glutathione supply falls short—toxic adducts are formed with
tissue constituents → tissue damage.
33. ADME- DRUG ELIMINATION/ EXCRETION
• Excretion is the passage out of systemically absorbed drug.
Drugs and their metabolites are excreted in:
-> Urine
->Faeces
-> Exhaled air
->Saliva & Sweat
-> Milk
Renal Excreation:
• Glomerular filtration
• Tubular reabsorption
• Tubular secretion
34. ADME
Clearance (CL) :
• The clearance of a drug is the theoretical volume of plasma
from which the drug is completely removed in unit time
(analogy creatinine clearance)
• It can be calculated
CL = Rate of elimination/C where C= Plasma concentration
35. PHARMACODYNAMICS
Pharmacodynamics is the study of drug effects.
• It describes, what the drugs do and how they do.
“what the drug does to the body when they enter”
• Drugs (except those gene based) do not impart new
functions to any system, organ or cell; they only alter
the pace of ongoing activity.
• Principles of Drug Action:
Stimulation
Depression
Irritation
Replacement
Cytotoxic action
36. PHARMACODYNAMICS
Stimulation:
• It refers to selective enhancement of the level of activity
of specialized cells,
• E.g. adrenaline stimulates heart, pilocarpine stimulates
salivary glands.
• However, excessive stimulation is often followed by
depression.
Depression:
• It means selective diminution of activity of specialized
cells,
• E.g. barbiturates depress CNS, quinidine depresses
heart, omeprazole depresses gastric acid secretion
37. PHARMACODYNAMICS
Irritation:
• Strong irritation results in inflammation, corrosion,
necrosis and morphological damage.
• This may result in diminution or loss of function.
Replacement
• This refers to the use of natural metabolites, hormones
or their congeners in deficiency states,
• E.g. levodopa in parkinsonism, insulin in diabetes
mellitus, iron in anaemia.
38. PHARMACODYNAMICS
Cytotoxic action :
• Selective cytotoxic action on invading parasites or
cancer cells, attenuating them without significantly
affecting the host cells is utilized for the cure/ palliation
of infections and neoplasms.
• E.g. penicillin, chloroquine, cyclophosphamide,
zidovudine, etc.
39. PHARMACODYNAMICS
Mechanism of Drug Actions:
• Bulk laxatives (ispaghula)—physical mass
• Dimethicone, petroleum jelly—physical form, opacity
• Paraamino benzoic acid—absorption of UV rays
• Activated charcoal—adsorptive property
• Mannitol, mag. sulfate—osmotic activity
• 131I and other radioisotopes—radioactivity
• Antacids—neutralization of gastric HCl
• Pot. permanganate—oxidizing property
• Chelating agents (EDTA, dimercaprol)—chelation heavy
metals.
• Cholestyramine—sequestration of bile acids and
cholesterol in the gut
45. PHARMACODYNAMICS
There are many theories to understand the concept of
Receptors :
Receptor occupation
theory - Clark in 1937
The two-state receptor
model:
46. Bibliography
• K.D. Tripati ; Section 1, 1,2,3 & 4 Chapters
• Rang & Dale; 1st & 2nd Chapters
• Internet sources : Google