complete information on receptors and their mechanism of actions... briefly discussed about pharmacodynamics and up regulation and desensitization of receptors,

1. Pharmacodynamics:
Mechanism of Drug Action
Presented to:
Dr. Qaiser Jabeen
Presented By:
Saira Aslam
M.Phil Pharmacology
Session 2019-21
Roll # 09
Pharcol-001

2. Content to Discuss
1. Pharmacodynamics
2. Binding of Drug Molecules to Cells (Receptor Mediated Response)
3. Drug Classification (Agonists, Antagonists)
4. Dose Response Relationship
5. Therapeutic Index
6. Drug Receptors and their various types
7. Targets for Drug Action
8. Signal Transduction
• Drug Receptor Complexes
• Receptor States
• Receptor Up and Down Regulation
9. Major Receptor Families

3. Pharmacodynamics
‘Pharmaco Drugs’
‘Dynamics  Power/ Action’
• “What a drug dose to the body”
• Action:
• How and Where the effect is produced
• Effect:
• Type of response produces by the drug
• Sight of Drug Action:
i. Extracellular
• Antacids neutralizing gastric acidity
• Chelating agents forming complexes with heavy metals
• MgSO4 acting as purgative by retaining fluid inside lumen of intestine

4. ii. Intracellular
• Folic acid synthesis inhibitors (folic is intracellular component essential for synthesis
of proteins)
• Trimethoprim and sulpha drugs interfere with synthesis of folic acid.
iii.Cellular
• Ach on nicotinic receptors of motor end plate, leading to contraction of skeletal
muscles.
• Effect of sympathomimetics on heart muscle and blood vessels

5. • Type of Drug Responses:
• Drugs do not impart new functions on any system, organ or cell; they only alter the
pace of ongoing activity
• Major principles of drug responses are:
i. Stimulation
• Drugs act by enhancing the level of activity of specialized cells
• e.g. Catecholamines stimulates the heart and increase heart rate and force of cardiac
contraction
• Pilocarpine stimulates salivary glands
• Excessive stimulation is often followed by depression of that function
• Picrotoxin a CNS stimulant produce convulsions followed by coma and respiratory
depression
ii. Inhibition/ Depression
• Drugs act by diminution of activity of specialized cells
• Alcohol, barbiturates and anesthetics depress CNS.
• Atropine inhibit ACh action.
• Quinidine depress heart
• Certain drugs stimulate one type of cells and but depress others
• ACh stimulates intestinal smooth muscles but depress SA node in heart

6. iii.Replacement
• When there is deficiency of endogenous substance, they can be replaced by the drugs.
• Insulin in diabetes mellitus
• Thyroxine in cretinism and myxedema
• Iron in anemia
• Levodopa in parkinsonism
iv.Cytotoxic
• Treatment of infectious diseases/ cancer with drugs that are selectively toxic for
infecting organisms and cancer cells
• Selective cytotoxic action for invading parasites or cancer cells, attenuating them
without significant effect on host cells is used for cure, palliation of infections and
neoplasms
• Anticancer drugs
• Antibiotics

7. v. Irritation
• Connotes a nonselective, often noxious effect
• Often applied to less specialized cells (epithelium and connective tissues)
• Drugs on topical application cause mild irritation of the skin and adjacent tissues
which stimulates the associated functions
• These drugs are used as counter irritants
• Eucalyptus oil and methyl salicylates are used in sprains, joint pain and myalgia
• Strong irritation results in inflammation, corrosion, morphological damage.
• Factors Affecting Drug Response:
• Age
• Weight
• Gender
• Environment
• Fever
• Shock

8. • Mechanism of Drug Action:
• Drugs act either by receptor or by nonreceptor or by targeting specific genetic changes
• Majority of drugs act (HOW)
i. Receptor mediated
• Drugs produce their effect through interacting with some chemical compartment of
living organism i.e. Receptor.
• Receptors are in dynamic state.
• The affinity of the response to drugs is not fixed. It alters according to situation.
ii. Non receptor mediated
• Voltage gated Ion channels
• Enzymes
• Transporters
• Drug may act by physical properties, chemical properties, modulating body function
regulators, ion channels, enzyme binding or miscellaneous mechanism

9. Binding of Drug Molecules to Cells (Receptor
Mediated Response)
‘Corpora non agunt nisi fixata’
Drug will not work unless it is bound
• Drug molecules can be ‘bound’ to particular constituents of cells and tissues
in order to produce an effect by interacting with some chemical
compartments of living organism c/s receptors
• Receptors:
• “Any target molecule with which the drug molecule has to combine in order
to elicit its specific effect”
• Specialized areas in cell to which drugs get bound
• They are regulatory protein macromolecules present either on cell surface or cytoplasm
or nucleus

10. • Receptors Functions:
• Two essential functions
• Recognition of specific ligand molecule (Ligand Binding Domain)
• Transduction of signals into responses (Effector Domain)

11. • Ligand:
• Ligand means the any substance which binds to receptors.
• Hormones
• Neurotransmitters
• Drugs
• Chemical substances
• Toxins etc.
• Receptor Types:
i. Receptors on the surface of the cell membranes
• Serpentine Receptors (7-pass receptors, GPCR)
• One Pass Receptors (Enzyme Linked Receptors)
• Ions Operated Channels (Ligand Gated Ion Channels)
ii. Receptors within the cell
• Nuclear Receptors

12. • Drug-Receptors Interaction:
• Drug + Receptor  Drug Receptor Complex  Response
i. Selectivity:
• Degree of complementary co-relation between drug and receptor
• Adrenaline selectivity for α and β-receptors
ii. Affinity:
• Ability of drug to get bound to receptor
iii.Intrinsic activity or Efficacy:
• Ability of drug to produce pharmacological response by making drug-receptor
complex

13. Drug Classification
• Association of Drug Molecules to Binding Sites
• On basis of Affinity and Efficacy:
i. Agonists
• Bind to receptor and produce biological response
ii. Antagonists
• Bind to receptor and produce no response
• Bind to receptor decrease or oppose action of other drug

14. Agonists
1. Full agonists
2. Partial agonists
3. Silent antagonists
4. Inverse agonists

15. Agonists
i. Full Agonist
• Drug bind to receptor and produce maximal response that mimics the response of
endogenous ligand
• A full agonist produce complete activation of a receptor at high dose concentration
• Phenylephrine agonist of α1-adrenergic receptor

16. ii. Partial Agonist
• Efficacy/ intrinsic activity greater than zero but less than that of full agonist
• These drugs have partial affinity to receptors but have low intrinsic activity
• If all the receptors are occupied partial agonists cannot produce Emax.
• These have affinity that is greater than, less than, or equivalent to that of full agonist.
• Affinity is less as compared to agonists
• e.g. pindolol, pentazocine

17. iii.Inverse Agonist
• These drugs have full affinity to receptors but intrinsic activity is zero to -1.
• They produce a response below the baseline responses measured in the absence of drug
• They decrease the number of activated receptors to below observed in the absence of
drug
• Exert opposite pharmacological effect of receptor agonist
• e.g. carboline is inverse agonist of benzodiazepines receptors

18. Antagonists
1. Competitive/ reversible
antagonists
2. Irreversible antagonists
3. Functional and
chemical antagonism

19. Antagonists
Definition:
• Drugs that decrease or appose the action of another drug or endogenous ligand
• Antagonist have no effect if agonist is agonist is not present
• Antagonists itself have no intrinsic activity, produce no effect by themselves.
• Antagonists possess strong affinity to bind avidly to target receptors
i. Competitive antagonist
• If both agonist and antagonist bind to the same site on a receptor; said to be
“competitive”
• Competitive antagonist prevent agonist from binding to its receptor and maintain
receptor in its inactive conformational state.
• ED50 of agonist is increased in competitive antagonism.
• Trazosine an antihypertensive drug antagonize the effect of epinephrine at α1-
adrenergic receptor  decreasing the vascular smooth muscles tone and reduce blood
pressure.

20. ii. Irreversible Antagonists:
• Irreversible antagonist causes a downward shift of maximum, with no shift of the
curve on the dose unless spare receptors are present
• Their effect cannot be overcome by adding more agonist
• It cannot increase ED50 of agonist.
i. Mechanism of Action:
a. Antagonist can bind covalently or with high affinity to active site of receptor
b. Antagonist can bind to allosteric site  produce conformational changes 
preventing activation of receptor even agonist attach to active site
iii.Functional and Chemical Antagonism:
• Antagonist act at completely separate receptor, initiating effects that are completely
opposite to those of agonists
• Functional antagonism by epinephrine to histamine induce bronchoconstriction
• Also known as “Psychological Anatogonism”

21. Dose Response Relationship
Components of Dose Response Relationship:
i. Dose plasma concentration relationship
ii. Plasma concentration response relationship
Dose Response Curve:
• Graph illustrating the relationship of dose of a drug and its quantitative
response
• Intensity of response increases with increase in dose and dose response curve
is rectangular hyperbola
• Dose response curve is required for
i. Deciding dose of drug
ii. Comparing dosage to percentage of people showing different effects

23. Threshold;
• A dose below which there are no adverse effects from exposure to chemicals

24. Types of Dose Response Curves;
i. Graded Dose Response Curve
• Graded dose response curves are constructed for response that are measured on
continuous scale e.g. heart rate
• Curves relates the intensity of response to size of dose hence used in characterizing
actions of drug
• Graded dose response means slight increase of drug brings small increase in response

25. ii. Quantal Dose Response Curve
• Quantal dose response curves are constructed for those drugs that elicit all or none
response.e.g presence or absence of epileptic seizures
• Indicates that given dose of drug has or has not evoked a certain effect in various
subject under investigation that is pharmacological effects are expressed in passive or
negative
• An experiment performed on 100 subjects and the effective dose to produce a quantal
response was determined for each individual

26. Importance of Dose Response Curves;
• Provide information about efficacy, potency, slope and individual variability of a drug
i. Potency and Efficacy:
• Drug potency refers to amount of drug needed to produce a response.
• Relative potency is more meaningful than absolute potency
• e.g. If 10 mg of morphine=100 mg of pethidine, morphine is 10 times more potent
than pethidine
• Drug efficacy refers to ability of drug to elicit a response when it binds to a
receptor
• e.g. Morphine produces a degree of analgesia not obtainable with any dose of aspirin
hence Morphine is more efficacious than aspirin

27. Importance of Dose Response Curves;
• Provide information about efficacy, potency, slope and individual variability of a drug
ii. Slope and Variability:
• Slope Effect of incremental increase dose
• Variability  Variability is reproductivity of data, different for different people

28. Therapeutic Index
Definition:
• Therapeutic index is ratio of Ld50 to Ed50
• Therapeutic Index =
𝐿𝐷50
𝐸𝐷50
• Where
• ED50 – Median effective dose at which 50% of individuals exhibit a specific effect
• LD50 – Median lethal dose required to produce death in 50% individuals
Side Effects:
• Drug effects other than desired effects
• TD50 : toxic dose
• TI for side effects =
𝑇𝐷50
𝐸𝐷50

29. 100
50
0
DRUG DOSE
0 X
ED LD
% Population
Therapeutic Index =
𝐿𝐷50
𝐸𝐷50
Relatively Safe Drugs~

30. 100
50
0
DRUG DOSE
0 X
ED LD
% Population
Therapeutic Index =
𝐿𝐷50
𝐸𝐷50
1. Less Safe Drug ~

31. 100
50
0
DRUG DOSE
0 X
ED
LD
% Population
1. Slope of curve important ~

32. Receptors and Their Various Types
1. Receptors:
• Enzymes
• Carrier Molecules
• Ion Channels
• Receptors
• Structural and Plasma Proteins (i.e. Colchicine binds to Tubulin)
2. Receptor Classification:
i. Cell Surface Receptors:
• Inotropic receptors (ligand gated ion channels)
• Metabotropic receptors (Serpentine receptors)
• Ligand regulated transmembrane receptors
ii. Intracellular Receptors:
• Nuclear receptors

33. Targets for Drug Action
1. Enzymes as receptors
• Acetylcholinesterase
• Cyclo-oxygenase
• Angiotensin-converting Enzyme
• Monoamine Oxidase
• Phosphodiesterase Type V
• Dihydrofolate Reductase
• Thymidine kinase
2. Carrier Molecules/ Transporters
• Noradrenaline Transporter (Membrane)
• Weak Acid Carrier (Renal Tubule)
• Na+
/K+
/2Cl−
• Co-transporter (Loop Of Henle)
• Proton Pump (Gastric Mucosa)
• MDR Transporter

34. 3. Ion Channels
• Voltage-gated Na+
Channels
• Renal Tubule Na+
Channels
• Voltage-gated Ca2+
Channels
• ATP-sensitive K+
Channels
• GABA-gated Cl−
Channels
4. Receptors
• Nicotinic ACh receptor
• β-Adrenoceptor
• Histamine (H1 receptor)
• Opiate (μ-receptor)
• Dopamine (D2 receptor)
• Oestrogen receptor

36. Signal Transduction
i. Drug Receptor Complex:
• Cells have different types of receptors, each of which is specific for a particular ligand
and produces a unique response
Drug + Receptor ←→ Drug–receptor complex → Biologic effect
• e.g. heart have receptors that bind and respond to epinephrine or norepinephrine as
well as muscarinic receptors specific for acetylcholine.
• The magnitude of response is proportional to the number of drug-receptor complex
ii. Receptor states
• Inactive (R) sates
• Active R* states (show response)
Receptor (R)←→ Receptor (R*)
• These are in reversible equilibrium with one another.
• Unoccupied receptor does not influence intracellular processes

37. iii. Signal Transduction:
• Receptor with bound ligand is activated
• It has altered physical and chemical properties, which leads to interaction with cellular
molecules to cause a biologic response
• Recognition of a drug by a receptor ,triggers a biologic response called signal
transduction

38. iv. Characteristics of Signal Transduction:
• Signal transduction has two important features:
i. Signal amplification and Up-regulation of Receptors:
a. a single ligand–receptor complex can interact with many G proteins, thereby
multiplying the original signal many fold.
b. Second, the activated G proteins persist for a longer duration than the original ligand–
receptor complex
Prolonged use of antagonist Increase in Receptor sensitivity  Increased Drug
effect
• Ex:- propranolol is stopped after prolong use, produce withdrawal symptoms. Rise BP,
induce of angina.
ii. Desensitization and down-regulation of receptors
• When repeated administration of a drug results in a diminished effect, the phenomenon
is called tachyphylaxis
• Endocytosis and is sequestered
• “refractory” or “unresponsive.”
Prolonged use of agonist  Decrease in Receptor sensitivity  Decreased Drug effect
• Ex: Chronic use of salbutamol down regulates ß2 adrenergic receptors

39. Major Receptor Families
i. Receptor Families:
• Ligand-gated ion channels (Ionotropic Receptors)
• G protein–coupled receptors (Metabotropic Receptors)
• Enzyme–linked receptors (One Pass Receptors)
• Intracellular receptors

40. i. Ligand Gated Ion Channels:
• Ionotropic receptors
• Similar structure to ion channels incorporating a ligand binding site in
extracellular domain
• Ligand binding and channel opening occur in millisecond timescale
• Oligomeric assembling of subunits surrounding central pore
• These are receptors for fast neurotransmitters
 GABA receptors
 Glutamate receptors
 Nicotinic acetylcholine receptors
 5-HT3 receptors

42. • Gating Mechanism in Ligand Gated Ion Channels:
 Receptors control the fastest synaptic events
 Neurotransmitter acts on the postsynaptic membrane and transiently increases
permeability to particular ions (Na+ and K+)
 Na+ influx generates action potential due to cell depolarization reaches to peak in
few milliseconds and also decays in milliseconds
 The sheer speed of this response implies that the coupling between the receptor
and the ionic channel is a direct one
 In contrast to other receptor families no intermediate biochemical steps are
involved in the transduction process.

43. Signal molecules binds as a ligand
at a specific site on the receptor
Conformational changes open the
channel allowing ions to flow into
the cell
The changes in ion concentration
within the cell triggers cellular
responses

44. • Effects due to Concentration Changes in Different Ions:
 Na+ and Ca+ Ions:
• Increase Level  Excitatory
• Decrease Level  Inhibitory
 K+ Ions:
• Increase Level  Inhibitory
• Decrease Level  Excitatory
 Cl- Ions:
• Increase Level  Inhibitory
• Decrease Level  Excitatory

45. • Importance of Ligand Gated Ion Channels:
 Generation and propagation of nerve impulse
 Synaptic transmission of neurons
 Muscle contraction
 Salt balance
 Hormones release
 Muscle relaxants, anti-arrythmatics, anesthetics  act by blocking ions channels

46. ii. G-Protein Coupled Receptors (Serpentine Receptors):
• Metabotropic receptors or 7-transmembrane (7-TM or heptahelical) receptors.
• Membrane receptors coupled to intracellular effector systems via a G-protein
• The largest family include receptors for many hormones and slow transmitters,
 Muscarinic acetylcholine receptor
 Adrenoceptors
 Chemokine receptors

47. • Molecular Structure:
 Four to five subunits (α2, β, γ, δ) form a cluster surrounding a central transmembrane
pore
 Lining is formed by the M2 helical segments of each subunit
 Receptor contains negatively charged amino acids making them cation (+ve) selective

48. • Families of G-Protein Coupled Receptors:
 Rhodopsin Family
• Amines NT
• Purines
• Cannabinoids
 Secretin/Glucagon Receptors Family
• Peptide hormones
 Metabotropic Glutamate Receptors/ Calcium Sensor Family
• GABA
• Glutamate

49. • Roll of G-Proteins:
 Membrane resident proteins  Recognize activated GPCRs Pass message to
effectors
 Occur in interaction with membrane nucleotides ; freely moving in cytoplasm
 α, β and γ subunits  trimmer in resting states
 Three subunits attached to GPCRs through fatty acid chains  Prenylation

50. • G-Proteins Subtypes:
G- Proteins Receptor For Signaling Pathways
Gs
Beta Adrenergic Amines
Serotonin
Glucagon Histamines
Adenyl cyclase cAMP
Excitatory effects
Gi1, Gi2, Gi3
Alpha2 Adrenergic Amines
Serotonin
Opioids
Adenyl cyclase cAMP
Cardiac K+ channels
Golf Olfactory epithelium Adenyl cyclase cAMP
Go
NT
Opioids
Cannabinoids
Not Clear
Gq
Serotonin
5 HT2
PLC
IP3
DAG
Cytoplasmic Ca
Gt1, Gt2
Rodopsins and color opsins in retinal rods
and cone cells
cGMP
Phosphodiestrase cGMP

51. • Secondary Messenger System involved in Signal Transduction:
 Adenyl cyclase / cAMP system
 cAMP -nucleotide synthesized from ATP- by Adenyl cyclase, metabolized by PDE
 Regulate enzymes of metabolism, growth and contractile muscle proteins
 NT- acts on GPCRs -Gs / Gi activated- produce effects by increase and decrease activity
of Adenyl cyclase / cAMP.
 cAMP activates protein kinase which activates/inactivates enzymes by phosphorylation
 Cellular events
 Phospholipase C / Inositol phosphate system
 Phospholipase C: cleaves membrane phospholipids- Phosphoinositides-
 PLC beta –cleaves phosphatidylinositol (4,5)bis phosphate PIP2 into DAG and IP3
 DAG and IP3 – secondary messenger elicit cellular responses

52. • Action of Gs Coupled Receptors:
Ligand
Bind to
GPCR
α-subunit of Gs proteins become activated
α-subunit leaves the beta and gamma subunit
α-subunit
bind to
Adenylyl
Cyclase
Conversion of ATP to cAMP
Activation
of protein
kinase A
Alteration of cell metabolism
Alteration of genomic expression
Alteration in electric properties of cells via activation of ion channels

53. • Action of Gi Coupled Receptors:
Ligand Bind with the
serpentine receptors
Alpha subunit of Gi
proteins become
activated
Alpha subunit leaves
the beta and gamma
subunit and bind with
the protein called
Adenylyl Cyclase
Now A.C sends signals
to the effector domain
to stop the conversion
of ATP into cAMP
Beta and Gamma unit
binds with the ions
channels and causes the
efflux of potassium
from membrane
Beta and Gamma unit
binds with the ions
channels and causes the
efflux of potassium
from membrane

54. • Action of Gq Coupled Receptors:
Ligand Bind with the
serpentine receptors
Alpha subunit of Gq
proteins become
activated
Alpha subunit leaves
the beta and gamma
subunit and bind with
the Phospholipase C
Phospholipase C
causes the breakdown
of PIP2 and resulting
in IP3 and DAG

55. • Action of Gq Coupled Receptors:PhospholipaseC
IP3
Binds to IP3 sensitive Ca2+
channels
Calcium activates
Calmodulin protein
Activation of enzyme CaM
Kinase
Alteration of cell
metabolism
Alteration of genome=ic
expression
Alteration in electric
properties of cells via
activation of ion channels
DAG
Activate an enzyme called
Protein Kinase
Alteration of cell
metabolism
Alteration of genome=ic
expression
Alteration in electric
properties of cells via
activation of ion channels

56. • Action of Gq Coupled Receptors:

57. • Secondary Messenger System involved in Signal Transduction:
 Ion channels
 GPCR -Directly controls ions channels without secondary messengers-
 e.g. Muscarinic receptors in heart- activates K+ channels

58. iii.Enzyme Linked Receptors:
• Heterogeneous group of membrane receptors respond to protein mediators
• They comprise an extracellular ligand-binding domain linked to an intracellular
domain by a single transmembrane helix.
• The intracellular domain is enzyme in nature
i. Protein kinase activity
ii. Guanylyl cyclase activity

59. • Role of Enzyme Linked Receptors:
• Involved in growth factors -growth, proliferation, differentiation and survival-
• Mediate action of protein mediators –Growth factors, cytokines, hormones,
insulin and leptin-
• Slow- require expression of new gene
• Single membrane spanning helix- extracellular ligand binding domain-
intracellular domain

60. • Types of Enzyme Linked Receptors:
 Tyrosine Kinase Receptors
 Insulin receptors
 Tyrosine Kinase Associate Receptors
 Serine/ Threonine Kinase Receptors
 Phosphorylate enzymes causing the alteration in cell metabolism.
 Cytokine Receptors
 Guanylyl Cyclase Receptors
 Activated GCR leads to the conversion of GTP into cGMP.
 cGMP will activate the protein kinase G.
 Which will further lead to the phosphorylation of enzyme and genes transcriptional factors.
 Tyrosine Phosphatases
 Once it is activated it causes the dephosphorylation of the other phosphorylated proteins.

61. • Enzyme Linked Receptors Mechanism:
 Receptors for various growth factors incorporate tyrosine kinase in their
intracellular domain.
 Cytokine receptors have an intracellular domain that binds and activates cytosolic
kinases when the receptor is occupied.
 The receptors all share a common architecture, with a large extracellular ligand-
binding domain connected via a single membrane-spanning helix to the
intracellular domain.
 Signal transduction generally involves dimerization of receptors, followed by
autophosphorylation of tyrosine residues.
 The phosphotyrosine residues act as acceptors for the SH2 domains of a variety of
intracellular proteins, thereby allowing control of many cell functions.
 They are involved mainly in events controlling cell growth and differentiation, and
act indirectly by regulating gene transcription.

62. • Transduction Mechanisms of Enzyme-Linked Receptors.:
 Growth Factor Pathway:

63.  Cytokines Pathway:

64. • Protein Phosphorylation in Signal Transduction:
 Many receptor-mediated events involve protein phosphorylation, which controls
the functional and binding properties of intracellular proteins.
 Receptor-linked tyrosine kinases, cyclic nucleotide activated tyrosine kinases and
intracellular serine/ threonine kinases comprise a ‘kinase cascade’ mechanism that
leads to amplification of receptor mediated events.
 There are many kinases, with differing substrate specificities, allowing specificity
in the pathways activated by different hormones.
 Desensitization of G-protein-coupled receptors occurs as a result of
phosphorylation by specific receptor kinases, causing the receptor to become non-
functional and to be internalized.
 There is a large family of phosphatases that act to reverse the effects of kinases.

65. • Central role of Kinase Cascades in Signal Transduction:

66. iv.Intracellular Receptors:
a. Nuclear receptors
• Ligand activated transcription factors
• Present in soluble form -either in cytoplasm or nucleus- freely diffusable.
• Ligand must have lipid solubility to cross membrane
• Transduce signals by modifying gene transcription
• Play vital role in endocrine signaling and metabolic regulations
i. Steroid hormones
ii. Glucocorticoids
iii. Vit. D & A
iv. Orphan receptors (No well defined ligands)
b. Response:
• 30 minutes to days
c. Example:
• Transcription of DNA into RNA
• Translation of RNA into an array of proteins

67. • Receptors that Control Gene Transcription:
 Receptors are intracellular proteins ligand first enter cell
 Receptors consist of a conserved DNA binding domain attached to variable ligand
binding and transcriptional control domains
 DNA binding domains recognize specific base sequences, thus promoting or
repressing particular genes
 Pattern of gene activation depends on both cell type and nature of ligand, so effects
are highly diverse
 Effects are produced as a result of altered protein synthesis and therefore are slow
in onset
 One type of nuclear receptor is responsible for the increased expression of drug
metabolizing enzymes induced by many therapeutic agents.

69. References
1. H. P. Rang, M. M. Dale, J.M. Ritter, P. K. Moore, Rang and Dale
Pharmacology, 7th edition, page 20-45
2. Bertram G. Katzung, Basic and clinical Pharmacology, 10th edition, 2006,
page 197-206.
3. K.D. Tripathi, Essentials of Medical Pharmacology, 6th edition, 2008, page
40-52.
4. Richards Lippincott’s Illustrated Review of Pharmacology, 4th edition, Page
25-34.
5. Leon Shargel, Susanna WU-Pong, Andrew, Applied Biopharmaceutics and
Pharmacokinetics
6. Goodman, L. S. (1996). Goodman and Gilman's the pharmacological basis
of therapeutics (Vol. 1549). New York: McGraw-Hill.