Definition
Classification and description of each class.
Description of individual receptor.
Forces affecting the drug receptor binding.
Binding of drug receptor affect drug action.
Agonist and antagonist.
Disease due to malfunctioning of receptors.
New drug design based on structure of receptors
Receptor as target for drug discovery.
Drug action not mediated by receptor.
Definition
Classification and description of each class.
Description of individual receptor.
Forces affecting the drug receptor binding.
Binding of drug receptor affect drug action.
Agonist and antagonist.
Disease due to malfunctioning of receptors.
New drug design based on structure of receptors
Receptor as target for drug discovery.
Drug action not mediated by receptor.
1. Receptors
2. Receptor dynamics
3. Drug receptor binding
4. Agonists & Types of Agonists
5. Antagonists
6. Constants related to antagonists
7. Types of antagonists
8. Mechanisms of actions of receptors
9. Thank you
1. Receptors
2. Receptor dynamics
3. Drug receptor binding
4. Agonists & Types of Agonists
5. Antagonists
6. Constants related to antagonists
7. Types of antagonists
8. Mechanisms of actions of receptors
9. Thank you
Advanced Medicinal Chemistry of GPCR Receptorsaurabh gupta
Contents:-
Introduction
Structure of G-protein
Signal Molecules / Ligands of GPCRs
G- Protein Mediated Pathways
Receptor Site Theories
Forces involved in drug receptor interactions
Mechanism of drug action, Relationship between drug conc & effect, Receptors, Structural & families of receptors, Quantitation of drug receptor interaction & elicited effects
General description about various types of receptor, their classification, mechanism of action and its clinical significance, along with recent advances.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
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.
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.
This pdf is about the Schizophrenia.
For more details visit on YouTube; @SELF-EXPLANATORY;
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Thanks...!
2. PHARMACODYNAMICS
o The study of the biochemical and physiological
effects of drugs and their mechanisms of
action
o Can provide the basis for the rational
therapeutic use of a drug and the design of
new and superior therapeutic agents
2DEPARTMENT OF PHARMACY
3. PHARMACODYNAMICS
o A drug effect is as a result of an interaction
between its molecules and some part of the
tissue cells.
o In some cases the interaction is specific and
others non-specific.
o Chemical or physical properties of the drug
account for the observed effects.
3DEPARTMENT OF PHARMACY
4. HOW DO DRUGS PRODUCE THEIR
EFFECTS?
o Non-specific drug action – act by virtue of their
physicochemical properties e. g general
anaesthetics, osmotic diuretics
o As false substrates (inhibitors) for enzymes or
transport systems
o By acting on specific protein molecules located
on cell membranes called receptors
4DEPARTMENT OF PHARMACY
5. PHARMACODYNAMICS
WHAT IS THE BASIS OF DRUG ACTION
o Drugs do not create new functions
but
o Modify inherent functions of the tissues
or cells or organs concerned.
5DEPARTMENT OF PHARMACY
6. PHARMACODYNAMICS
THERE ARE 5 MAIN DRUG ACTIONS:
o Stimulating or depressing cellular activity.
o Replacing deficient substances.
o Causing irritation.
o Killing invading foreign organisms (bactericidal)
o Weakening invading foreign organisms
(bacteriostatic)
6DEPARTMENT OF PHARMACY
7. PHARMACODYNAMICS
1. Stimulation
Is an increase in the rate of the functional
activity of a cell or tissue, e g caffeine,
amphetamine stimulate the CNS.
2. Depression
Denotes a reduction in such activity e g
barbiturates, alcohol, depress CNS. 7DEPARTMENT OF PHARMACY
8. PHARMACODYNAMICS
3. Replacement
When there is under production of natural substances
e g Insulin for diabetes mellitus.
4. Irritation
Effect of drugs on the nutrition, growth, morphology
and functioning of living tissues e g liniments to
relieve muscle pain, and phenolphthalein an irritant
purgative. 8DEPARTMENT OF PHARMACY
9. PHARMACODYNAMICS
5. Bacteriostatic
Inhibition of bacterial growth and multiplication e g
some antibiotics
6. Bactericidal
Killing of bacteria induced by antibiotics and
chemotherapeutic substances e g. penicillins,
tetracycines
9DEPARTMENT OF PHARMACY
10. RECEPTOR THEORY
o Receptor is a macromolecule with special sites that
serve as targets for ligand action.
o Drugs may be designed to mimic, modify or block
actions of endogenous ligands at a receptor.
o A perfect drug would be the one that binds only to
one type or subtype of receptor and consistently
produces only the desired biological effect.
10DEPARTMENT OF PHARMACY
11. RECEPTOR THEORY
Types of receptors
o Transmembrane ion channels:
o Seven-transmembrane receptors
o Enzyme-linked transmembrane
receptors
o Intracellular receptors 11DEPARTMENT OF PHARMACY
12. RECEPTOR THEORY
Transmembrane ion channels
o Create pores across phospholipid membranes,
allow the transport of ions into and out of cells.
o The two major families are
• Ligand gated ion channels – opened by the
binding of a ligand e. g Ach to an extracellular
part of the channel.
• Voltage gated ion channels – opened at
particular membrane potentials by a voltage
sensing segments of the channel. 12DEPARTMENT OF PHARMACY
13. RECEPTOR THEORY
o Drugs can affect ion channel function by
interacting either with the receptor site of
ligand-gated channels, or with other parts of
the channel molecule.
o The interaction can be indirect, involving a
G-protein and other intermediaries, or
direct, where the drug itself binds to the
channel protein and alters its function. 13DEPARTMENT OF PHARMACY
14. RECEPTOR THEORY
Seven-transmembrane (7TM) receptors
o Ligand binds to extracellular loops and alter
the three-dimensional conformation of the
receptor protein.
o The intracellular loops are involved in coupling
this conformational change to the second
messenger system via a G-protein
o G-protein coupled receptor (GPCR)
14DEPARTMENT OF PHARMACY
15. RECEPTOR THEORY
o Second messengers are key distributors of an
external signal.
• Cyclic nucleotide system i. e cAMP, cGMP
• Phosphotidylinositol system i. e IP3
o Activation affects cellular processes such as
• Enzyme activity
• Contractile proteins
• Ion channels
• Cytokine production
15DEPARTMENT OF PHARMACY
16. RECEPTOR THEORY
Enzyme-linked transmembrane receptors
o Similar to GPCR
• Have ligand binding domain on surface of the cell
membrane
• Traverse the membrane
• They have an intracellular effector region
o However
• Extracellular ligand binding site very large to
accommodate their polypeptide ligands e. g
hormone
• Only one transmembrane helical region 16DEPARTMENT OF PHARMACY
17. RECEPTOR THEORY
Activation of enzyme-linked receptors enables binding
and activation of many intracellular signalling proteins,
leading to changes in gene transcription and other
cellular functions
17DEPARTMENT OF PHARMACY
18. RECEPTOR THEORY
Intracellular receptors
o Includes a highly conserved DNA-binding region with
zinc-containing loops and a variable ligand binding
domain.
o Ligands are hormones, lipophilic.
o Type 1 (cytoplasmic) receptors e. g Oestrogen,
glucocorticoid receptors
o Type 2 (nuclear) receptors e. g thyroid hormone,
vitamin D receptors 18DEPARTMENT OF PHARMACY
19. RECEPTOR THEORY
Naming of Receptors
Pharmacological receptors are named according to
either:
o The principal endogenous agonist that activates
them e. g adrenoceptors, cholinoceptors,
glucocorticoid receptors or
o The first exogenous agonist found to activate them
e. g opioid receptors, benzodiazepine receptors19DEPARTMENT OF PHARMACY
20. RECEPTOR THEORY
Drugs can be divided into two categories:
o Those acting on pharmacological receptors
situated on or within the cells.
o Those in which the receptors are not
involved.
20DEPARTMENT OF PHARMACY
21. RECEPTOR THEORY
Drugs which act via receptors:
o Act at low concentrations e. g
acetylcholine, adrenaline, noradrenaline
and histamine.
o React with specific receptors e. g
cholinergic receptors, adrenergic
receptors
o Show structure-activity relationship.
o Can be antagonized by specific
antagonists. 21DEPARTMENT OF PHARMACY
22. RECEPTOR THEORY
Drugs which do not act via receptors:
o Act at higher concentrations.
o Do not react with specific receptors.
o Do not tend to show structure-activity
relationship.
o Do not have specific antagonists.
e g diethyl ether, halothane, thiazides.
22DEPARTMENT OF PHARMACY
23. RECEPTOR THEORY
Receptor Theory of Drug Action
o It is possible to map out (identify) and
measure the density of receptors for drugs,
hormones and neurotransmitters on various
tissues.
o It has been found that the structure of the
drug is related to the correlative structure of
the receptor.
o In simple terms the receptor is the ‘lock’ and
the drug is the ‘key’. 23DEPARTMENT OF PHARMACY
24. RECEPTOR THEORY
The three essential components for action:
I. the drug has to reach the receptor in
optimal amounts.
II. the drug is specific to its matching
receptor.
III. the specificity is based on the chemical
structure of the drug (structure-activity–
relationship) (SAR).
24DEPARTMENT OF PHARMACY
26. RECEPTOR THEORY
TYPES OF DRUG ACTION
Drugs can be classified by their receptor action as;
Agonists
Antagonists
Partial agonists
Inverse agonists
Allosteric modulators
Enzyme inhibitors or activators
Physiological antagonist
Non-specific
26DEPARTMENT OF PHARMACY
27. RECEPTOR THEORY
Affinity and Intrinsic Activity
o Affinity - Describes the ability of a drug to
form and subsequently maintain a complex
with a receptor.
o The binding of a drug to a receptor can be
represented as:
Drug (D) + Receptor (R) Complex 27
k1
k2
k3
DEPARTMENT OF PHARMACY
28. RECEPTOR THEORY
o Where k1, k2 and k3 are rate
constants.
o The rate at which the drug molecule
combines with site is k1.
o The rate at which the drug-receptor
complex dissociates is k2.
o The rate at which a response is
generated after drug-receptor
interaction is k3. 28DEPARTMENT OF PHARMACY
29. RECEPTOR THEORY
o Intrinsic Activity describes the ability of a drug to
evoke a pharmacologic response on combining with a
receptor and can be measured by k3.
Thus agonists have both affinity and intrinsic activity.
Antagonists display only affinity i e the k3 for
antagonists is zero.
Partial Antagonists possess less intrinsic activity than a
full agonist but may have full affinity. 29DEPARTMENT OF PHARMACY
31. COMBINATION OF DRUGS
When one drug is given together with a second
drug the effects produced by the first drug may
either be increased or decreased.
The terms employed to describe the combined
effects of drugs are addition, potentiation and
antagonism.
31DEPARTMENT OF PHARMACY
32. COMBINATION OF DRUGS
Addition or Summation
The combined effect of the drugs is equal to the
algebraic sum of their independent effects (2+2=4).
When two drugs act on the same receptors the
combined effect is an additive effect.
In contrast when the two act by different mechanisms
(receptors) producing same response, the combined
effect is summation, e g aspirin and codeine.
32DEPARTMENT OF PHARMACY
33. COMBINATION OF DRUGS
Potentiation or Synergism
• The combined effect of two drugs given at the same
time is greater than the algebraic sum of the
independent effects of each drug (2+2=5 )
• Potentiation – describes combined drug action by two
drugs, only one of which produces a particular action
e g acetylcholine action, by saving it from destruction
by enzyme cholinesterase. The second drug instead
is used as a substrate.
33DEPARTMENT OF PHARMACY
34. COMBINATION OF DRUGS
Synergism - when two drugs produce same type
of effect, but by acting at different sites and by
different mechanisms.
e g combination of hydrochlorthiazide with
methyldopa in the treatment of essential
hypertension.
34DEPARTMENT OF PHARMACY
35. COMBINATION OF DRUGS
Antagonism
o Antagonist prevents the action of an agonist.
o In antagonism, the combined effect of two drugs is
lesser than the algebraic sum of the individual effects
of each drug (2 + 2 = 1).
o The opposing effects of certain drugs has been
utilized in toxicology in the treatment of poisoning as
antidotes or antagonists.
35DEPARTMENT OF PHARMACY
36. COMBINATION OF DRUGS
There are four types of antagonism:
a. Pharmacologic antagonism
o Is observed when an antagonist reduces or blocks the
effect of the agonist by preventing the latter from
combining with its receptor.
36DEPARTMENT OF PHARMACY
37. COMBINATION OF DRUGS
o Competitive antagonism: when the antagonist
combines reversibly with the same receptor sites as the
agonist, and can be displaced from these sites by an
excess of the agonist. e g diphenylhydramine
(antihistamine) and histamine
o Non–competitive antagonism: when the antagonist
combines irreversibly with same receptor sites and
cannot be displaced from site by an excess of agonist.
e g phenoxybenzamine (adrenoceptor blocker) and
37DEPARTMENT OF PHARMACY
38. COMBINATION OF DRUGS
b. Physiologic antagonism
Two agonists acting on different sites, counter
balance each other by producing opposite
effects on the same physiologic function.
e g catabolic action of glucocorticoid hormones
increase blood sugar levels, an act that is
physiologically opposed to insulin.
38DEPARTMENT OF PHARMACY
39. COMBINATION OF DRUGS
c. Biochemical antagonism
Observed when one drug indirectly decreases
the amount of the second drug that would be
available in the absence of the first (antagonist)
drug.
e g phenobarbitone induces hepatic enzymes and
increases the metabolism of drugs such as
warfarin, digitoxin, griseofulvin 39DEPARTMENT OF PHARMACY
40. FACTORS INFLUENCING DOSING
d. Chemical antagonism
o Is the reaction between an agonist and
antagonist to form an inactive product.
o Protamine is positively charged at physiologic
pH, and used clinically to counteract heparin,
that is negatively charged at physiologic pH.
o Acts by ionic binding, making heparin
unavailable for interactions with proteins
involved in blood clotting.
40DEPARTMENT OF PHARMACY
41. RECEPTOR THEORY
PROPERTIES OF DRUG ACTION
o Dose-response relationship
o Selectivity
o Potency
o Efficacy
41DEPARTMENT OF PHARMACY
44. RECEPTOR THEORY
Potency and Efficacy
Potency
o Potency is the dose of drug required to
produce a specific effect of given
intensity as compared to a standard
reference.
o A drug is said to be potent when it has
high intrinsic activity at low unit weight
doses.
44DEPARTMENT OF PHARMACY
45. RECEPTOR THEORY
Efficacy
Refers to the maximum or peak response
produced by a drug and is important in
drug selection process i. e whether useful
or not.
45DEPARTMENT OF PHARMACY
46. RECEPTOR THEORY
Drug X more
potent than
Drug Y but
have same
efficacy
DEPARTMENT OF PHARMACY 46
47. RECEPTOR THEORY
o Drug X is more potent than drug Y, because
drug X produces same intensity as drug Y at
smaller doses, but both achieve maximum
response.
o Thus drug potency is useful in deciding what
dose to give.
o But irrelevant in choosing which drug to use, as
long as dose can be conveniently administered47DEPARTMENT OF PHARMACY
48. RECEPTOR THEORY
48
Drug A is more potent than drug B, because drug A
produces same intensity as drug B at smaller doses,
but both achieve maximum response.
DEPARTMENT OF PHARMACY
50. RECEPTOR THEORY
o Drug X is not only potent, but
exhibits more efficacy than drug Y
because it gives more maximum
response.
50DEPARTMENT OF PHARMACY
51. PROPERTIES OF DRUG ACTION
DEPARTMENT OF PHARMACY 51
Drug A exhibits
more efficacy
than drug B
because it
gives a higher
maximum
response.
52. RECEPTOR THEORY
Drugs Acting on Enzymes
o Many drugs inhibit action of enzymes on cell
membranes or inside cells.
o Some drugs compete with the normal
substrate at active site of the enzyme, in a
reversible manner.
o This is known as competitive inhibition e g
allopurinol on enzyme xanthine oxidase.
52DEPARTMENT OF PHARMACY
53. RECEPTOR THEORY
o However some drugs combine with
enzymes in irreversible manner.
o This is known as non-competitive
inhibition.
53DEPARTMENT OF PHARMACY
55. THERAPEUTIC INDEX
o An “Ideal” drug should cure all patients in a
dose that kills none.
o Therapeutic Index gives a measure of the
safety margin of a drug, but does not take
into account abnormal reactions such as
hypersensitivity reaction or allergy.
55DEPARTMENT OF PHARMACY
56. THERAPEUTIC INDEX
o The dose of a drug necessary to produce the desired
effect in one half of all patients in sample is known
as the median effective dose or ED50.
o Dose of a drug that exhibits an undesirable toxic
reaction in one half of all patients is termed the
median toxic dose or TD50.
o The larger the difference between TD50 and ED50
the greater is the safety margin of drug.
56DEPARTMENT OF PHARMACY
58. NON-RECEPTOR MECHANISMS OF
DRUG ACTION
(i) Antimetabolites (substitution)
(ii) Chelation e g drugs in poisoning
(iii) Drugs affecting permeability of cell membranes
(antibiotics).
(iv) Drugs acting as antiseptics (alcohol for swabbing)
(v) Drugs acting by their physical or chemical nature
(bulking agents).
vi. Drugs acting through antibodies (vaccines)
vii. Placebo effects
58DEPARTMENT OF PHARMACY