An updated PowerPoint presentation on Pharmacodynamics suitable for UG MBBS level Medical students

1. Pharmacodynamics
Dr. D. K. Brahma
Department of Pharmacology
NEIGRIHMS, Shillong

2. What is Pharmacodynamics?
What drugs do to the body when they enter?
Study of action-effect sequence of drugs and dose-effect
relationship
Defn.: It is the study of biochemical and physiological effects of drugs and
their mechanism of action at organ level as well as cellular level
Also Modification of action of one drug by another drug

3. Drug Action by Physical/Chemical
properties
• Color – Tincture Card co.
• Physical mass – Ispaghula (laxative)
• Physical form – Dimethicone (antifoaming)
• Smell - Volatile Oils
• Taste - Bitters
• Osmotic action – Mannitol, Magsulf
• Adsorption – Activated Charcoal
• Soothing-demulcent – Soothing agents like calamine
• Oxidizing property – Pot. Permanganate
• Chelation – EDTA, dimercaprol
• Radioactivity - Iodine and others
• Radio-opacity – Barium sulfate
• Chemical properties – Chelating agents (EDTA, dimercaprol)
• Scavenging effect – Mesna (with cyclophosphamide)

4. PRINCIPLES OF DRUG ACTION
- Do NOT impart new functions on any system, organ
or cell
- Only alter the PACE of ongoing activity
• STIMULATION
• DEPRESSION
• IRRITATION
• REPLACEMENT
• CYTOTOXIC ACTION

5. PRINCIPLE S OF
ACTION
MODE EXAMPLE
STIMULATION Selective Enhancement of level of
activity of specialised cells
- Excessive stimulation is often followed
by depression of that function
Adr stimulates Heart
Pilocarpine stimulates salivary
glands
Picrotoxin – CNS stimulant 
convulsions  coma  death
DEPRESSION Selective Diminution of activity of
specialised cells
Certain drugs – stimulate one cell type
and depress others
Barbiturates depress CNS
Quinidine depresses Heart
Ach – stimulates smooth
muscle but depresses SA node
IRRITATION Non-selective often noxious effect –
applied to less specialised cells
(epithelium, connective tissue)
-stimulate associated function
Bitters – salivary and gastric
secretion
Counterirritants increase
blood flow to a site
REPLACEMENT Use of natural metabolites, hormones
or their congeners in deficiency states
Levodopa in parkinsonism
Iron in anaemia
CYTOTOXIC ACTION Selective cytotoxic action for invading
parasites or cancer cells – for
attenuating them without affecting the
host cells
Penicillin, chloroquine

6. MECHANISM
OF DRUG
ACTION

7. MECHANISM OF DRUG ACTION
• MAJORITY OF DRUGS INTERACT WITH
TARGET BIOMOLECULES:
Usually a Protein
1. ENZYMES
2. ION CHANNELS
3. TRANSPORTERS
4. RECEPTORS

8. 1. Enzymes – drug targets
• All Biological reactions are carried out under catalytic
influence of enzymes – major drug target
• Drugs – increases/decreases enzyme mediated reactions
• In physiological system enzyme activities are optimally set
• Enzyme stimulation is less common by drugs – common by
endogenous substrates
– Pyridoxine (cofactor in decarboxylase activity)
– Adrenaline stimulates hepatic glycogen phosphorylase
(hyperglycaemia)
• Enzyme inhibition – common mode of DRUG action

9. Enzymes – contd.
• Nonspecific inhibition: Denature of proteins –
strong acids, heavy metals, alkalis, alcohol, phenols
etc.
• Specific Inhibition: Many Drugs Inhibit Specific enzyme
• Competitive Noncompetitive
Equilibrium Nonequilibrium

10. Competitive Enzyme Inhibition
Equilibrium Type:
• Structurally similar
competes with substrate –
binding sites
• Product not formed/non
functional
• New equilibrium – kM
increased, Vmax
unchanged
• Higher conc. of substrate
– ½ maximal reaction
• Sufficiently high conc. –
Equal Vmax

11. Competitive Enzyme Inhibition
• Nonequilibrium type:
• Same catalytic site
• Form strong covalent Bond
• Normal substrate cannot
displace
• Organophosphorous
compounds/Nerve gases
(cholinesterase)
• Methotrexate – 50,000
times DHFR than DHFA
• kM: increased but Vmax
reduced

12. Competitive Enzyme Inhibition - Examples
• Physostigmine Vs Acetylcholine
(cholinesterase)
• Sulfonamides Vs PABA (folate synthetase)
• Moclobemide Vs Catecholamines (MAO-A)
• Captopril Vs Angiotensin 1 (ACE)
• Finesteride Vs Testosterone (5α-reductase)
• Carbidopa Vs Levodopa (dopa decarboxylase)

13. Noncompetitive Enzyme Inhibition
Inhibitor reacts with an adjacent site
not – catalytic site
• Alters the Enzyme – loses catalytic
property
• kM unchanged and V max reduced
• Examples:
• Acetazolmide – Carbonic
anhydrase
• Aspirin – COX
• Omeprazole (PP) – HKATpase
• Digixin – NaKATPase
• Theophylline –
Phosphodiesterase
• Lovastatin – HMG-CoA
reductase

14. 2. Ion Channel
• Proteins take part in transmembrane signaling and regulates ionic
composition
• Drugs also target these channels: mainly on 3 types
– Ligand gated channels
– G-protein operated channels
– Direct action on channels
• Examples: BZD opens ligand gated GABAA Cl- channel, Histamine binds
GPCR and activates G-protein, local anesthetics – directly blocks channel
• Many drugs modulate opening and closing of channels: Phenytoin,
Ethosuximide, Nifedepine, Quinidine Nicorandil and Amiloride, etc.

15. + +
- -
+ +
--
- -
+ + + +
- -
Na+
+ ++ +
- - - -
Resting
(Closed**)
Open
(brief)
inactivated
Very slow
repolarization in
presence of LA
LA receptor
LA have highest
affinity for the
inactivated form
Refractory period
LA acting on Na+ receptorsLA acting on Na+ receptors

16. 3. Transporters
• Substrates are translocated across membrane by binding to
specific transporters (carriers) – Solute Carrier Proteins (SLC)
• Pump the metabolites/ions in the direction of concentration
gradient or against it
• Drugs can interact with these transport system
• Examples: ANS - Desipramine & cocaine (NET), Fluoxetine
(SSRI), Amphetamine (DAT), Reserpine (vesicular reuptake of
NA), Hemicholinium (choline uptake) and Vesamicol (active
transport of Ach to vesicles); Kidney: Probenecid (penicillin
and uric acid - OAT), Furosmide (blocks Na+K+2Cl-
cotransport), Thiazides block Na+Cl- symporter,
Amphetamine (blocks Dopamine reuptake),

17. Biomacromolecular targets of Drugs action
1. ENZYMES 2. CHANNELS
3. TRANSPORTERS 4. RECEPTORS

18. 4. Receptors
• Many Drugs usually do not bind directly with enzymes,
channels, transporters or structural proteins, but act through
specific macromolecules – RECEPTORS …
• Definition: It is defined as a macromolecule or binding site
located on cell surface or inside the effector cell that serves
to recognize the signal molecule/drug and initiate the
response to it, but itself has no other function, e.g.
Muscarinic (M type) and Nicotinic (N type) receptors of
Cholinergic system

19. Some Common Terms
• Agonist: An agent which activates a receptor to produce an effect similar
to a that of the physiological signal molecule, e.g. Muscarine and Nicotine
• Antagonist: an agent which prevents the action of an agonist on a
receptor or the subsequent response, but does not have an effect of its
own, e.g. atropine and muscarine
• Inverse agonist: an agent which activates receptors to produce an effect
in the opposite direction to that of the agonist, e.g. DMCM in BDZ
receptors (DMCM (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-
carboxylate)
• Partial agonist: An agent which activates a receptor to produce
submaximal effect but antagonizes the action of a full agonist, e.g. opioids
• Ligand: (Latin: ligare – to bind) - any molecule which attaches selectively
to particular receptors or sites (refers only binding or affinity but no
functional change)

20. Evidences of Drug action via receptors
– Historical
1. Drugs exhibit structural specificity of action: example –
Catecholamines (isopropyl substitution on ethylamine
side chain of sympathetic drugs – cardiac and
bronchial)
2. Competitive Antagonism: Between agonists and
antagonists (Atropine - M type receptors) – by Langley
3. Acetylcholine - 1/6000th
of cardiac cell surface –
maximal effect – by Clark

21. Drug – Receptor occupation theory –
Clark`s equation (1937)
• Drugs are small molecular ligands (pace of cellular function
can be altered)
• Drug (D) and receptor (R) interaction governed by “law of
mass action”
• Effect (E) Is the direct function of the Drug-Receptor complex
• But DR complex may not be sufficient to elicit E (response)
• D must be able to bring a conformational change in R to get E
• Affinity and Intrinsic activity (IA)
D + R DR E (direct function of DR complex)
K1
K2

22. Receptor occupation theory – contd.
• Affinity: Ability to bind with a Receptor
• Intrinsic activity (IA): Capacity to induce functional change in
the receptor
• Competitive antagonists have Affinity but no IA
• Therefore, a theoretical quantity (S) – denoting strength of
stimulus imparted to the cell was interposed
D + R DR S E
K1
K2

23. Definitions redefined
If explained in terms of “affinity and IA”:
• Agonist: Affinity + IA (1)
• Antagonist: Affinity + IA (0)
• Partial agonist: Affinity + IA (0-1)
• Inverse agonist: Affinity + IA (0 to -1)

24. Two-state receptor model

25. Nature of
Receptors
• Not hypothesis anymore – proteins and nucleic acids
• Isolated, purified, cloned and amino acid sequencing done
• Cell surface receptors remain floated in cell membrane lipids
• Non-polar hydrophobic portion of the amino acid remain buried in
membrane while polar hydrophilic remain on cell surface
• Binding of small ligand – capable of tripping balance at distance site –
brings conformational changes
• Major classes of receptors have same structural motif – individual
receptors differ in amino acid sequence, length of extra and intracellular
loops etc.
• Most drugs act on Physiological receptors – neurotransmitters,
autacoides, hormones etc.
• True drug receptors - BZD, Sulfonylureas (SUR1)

26. Receptor Subtypes
• Evaluation of receptors and subtypes – lead to discovery of various newer
target molecules
• Example Acetylcholine - Muscarinic and Nicotinic
– M1, M2, M3 etc.
– NM and NN
– α (alpha) and β (beta) ….
• Criteria of Classification:
1. Pharmacological criteria – potencies of selective agonist and
antagonists – Muscarinic, nicotinic, alpha and beta adrenergic etc.
2. Tissue distribution – beta 1 and beta 2
3. Ligand binding – Radiological radio-labelled ligands
4. Transducer pathway: MN and MM
5. Molecular cloning – based on cloning, amino acid sequencing and
three dimensional structure

27. Action – effects !
• Receptors : Two essential functions:
• Recognition of specific ligand molecule
• Transduction of signal into response
• Two Domains:
• Ligand binding domain (coupling proteins)
• Effectors Domain – undergoes functional conformational change
• “Action”: Initial combination of the drug with its receptors
resulting in a conformational change (agonist) in the later, or
prevention of conformational change (antagonist)
• “Effect”: It is the ultimate change in biological function
brought about as a consequence of drug action, through a
series of intermediate steps (transducers)

28. The Transducer mechanism
• Most transmembrane signaling is accomplished by a small
number of different molecular mechanisms (transducer
mechanisms)
• Complex multistep process - amplification and integration of
concurrently received extra /intra cellular signals
• Large number of receptors share these handful of
transducer mechanisms to generate an integrated and
amplified response
• Mainly 4 (four) major categories:
A. G-protein coupled receptors (GPCR)
B. Receptors with intrinsic ion channel
C. Enzyme linked receptors
D. Transcription factors (receptors for gene expression)

29. A. G-protein Coupled
Receptors (GPCR)
• Large family of cell membrane
receptors linked to the effector
enzymes or channel or carrier
proteins through one or more
GTP activated proteins (G-
proteins)
• All receptors has common
pattern of structural organization
• The molecule has 7 α-helical
membrane spanning hydrophobic
amino acid segments – 3 extra
and 3 intracellular loops
• Agonist binding - on extracellular
face and cytosolic segment binds
coupling G-protein
Transducer A ….

30. GPCR - 3 Major Pathways
1. Adenylyl cyclase:cAMP pathway
2. Phospholipase C: IP3-DAG pathway
3. Channel regulation

31. 1. Adenylyl cyclase: cAMP pathway
PKA Phospholamban
Increased
Interaction with
Ca++
Faster relaxation
Troponin
Cardiac
contractility
Other
Functional
proteins
PKA alters the functions of many
Enzymes, ion channels,
transporters
and structural proteins.
Faster sequestration of
Ca++ in SR

32. Adenylyl cyclase: cAMP pathway
• Main Results:
– Increased contractility of heart/impulse generation
– Relaxation of smooth muscles
– Lipolysis
– Glycogenolysis
– Lipolysis
– Modulation of junctional transmission
– Hormone synthesis
– Opens specific type of Ca++ channel – Cyclic nucleotide gated channel
(CNG) - - -heart, brain and kidney
– Responses are opposite in case of AC inhibition

33. 2. Phospholipase C:IP3-DAG pathway
PKc

34. IP3-DAG pathway
• Main Results:
– Mediates /modulates contraction
– Secretion/transmitter release
– Neuronal excitability
– Intracellular movements
– Eicosanoid synthesis
– Cell Proliferation
– Responses are opposite in case of PLc inhibition

35. 3. Channel regulation
• Activated G-proteins can open or close ion channels
– Ca++, Na+ or K+ etc.
• These effects may be without intervention of any of
above mentioned 2nd
messengers – cAMP or IP/DAG
• Bring about depolarization, hyperpolrization or Ca ++
changes etc.
• Gs – Ca++ channels in myocardium and skeletal
muscles
• Go and Gi – open K+ channel in heart and muscle and
close Ca+ in neurones

36. B. Receptors with Intrinsic Ion Channel
• Cell Surface ligand gated ion channels – enclose ion selective
channels – for Na+
, K+
, Ca+
or Cl-
• Agonist binding opens the channel –
depolarization/hyperpolarization etc.
• Most useful drugs in clinical medicine act by mimicking or
blocking the actions of endogenous ligands that regulate the
flow of ions through plasma membrane channels
• The natural ligands include acetylcholine, serotonin,
aminobutyric acid (GABA), and the excitatory amino acids
(e.g, glycine, aspartate, and glutamate)
Transducer B ….

37. Receptors with Intrinsic Ion
Channel (Ligand gated)

38. C. Enzyme Linked
Receptors
• Receptors with enzymatic property
• Extracellular agonist-binding domain and a cytoplasmic
catalytic domain – connected through transmembrane
peptide chain
• 2 (two) types of receptors:
1. Intrinsic enzyme linked receptors
• Protein kinase or guanyl cyclase domain
1. JAK-STAT-kinase binding receptor
Transducer C ….

39. i. Enzyme linked
receptors
• Agonist Binding - Upon binding to the receptor induces
conversion of monomeric state to an active dimeric state
– Activates tyrosine protein kinase (t-Pr-K) - sometimes serine and
threonine Pk
• Auto phosphorylates tyrosine residues on each other – also
phosphorylates other SH2-Pr domain substrate proteins
• Increases affinity for binding substrate proteins
• Ultimately downstream signaling function
• Examples – Insulin, EGF ------- Trastuzumab, antagonist of
a such type receptor – used in breast cancer
• Dimerization – also promotes internalization, degradation
in lysosomes and down regulation

40. ii. JAK-STAT-kinase
Binding Receptor
• Mechanism closely resembles that of receptor tyrosine kinases
• Only difference - protein tyrosine kinase activity is not intrinsic to the
receptor molecule
• Dimerization – activates intracellular domain- affinity to bind Free
cytosolic protein kinase JAK (Janus kinase)
• JAK phosphorylates tyrosine residues – binds to STAT (Signal transducer
and activation of transcription)
• Activated JAK phosphorylates STAT tyrosine residues
• Phosphorylated STAT dimerize, dissociate from receptor and moves to
nucleus
• Examples – cytokines, growth hormones, interferones etc.

41. JAK-STAT-kinase Receptors

42. Receptors regulating gene
expression
• Intracellular – cytoplasmic or nuclear –
responds to lipid soluble chemical messenger
• The receptor proteins – specific for each
hormone/regulator – capable of binding to
specific genes – but kept inhibited
• Agonist binding exposes the DNA binding
regulatory segment

43. Receptors of gene expression - Image

44. D. Receptors regulating gene
expression
• Intracellular (cytoplasmic or nuclear) receptors
• Lipid soluble biological signals cross the plasma membrane
and act on intracellular receptors
• Receptors for corticosteroids, mineralocorticoids, thyroid
hormones, sex hormones and Vit. D etc. stimulate the
transcription of genes in the nucleus by binding with specific
DNA sequence – called - “Responsive elements” – to
synthesize new proteins
• Hormones produce their effects after a characteristic lag
period of 30 minutes to several hours – gene active hormonal
drugs take time to be active (Bronchial asthma)
• Beneficial or toxic effects persists even after withdrawal
Transducer D ….

45. Receptor Regulation
• Receptors – exist in Dynamic state – density and
efficacy being regulated by the level of ongoing
activity
• Up regulation of receptors:
– In typically active systems, prolonged deprivation of
agonist (by denervation or antagonist) results in
supersensitivity of the receptor as well as to effector
system to the agonist. Sudden discontinuation of
Propranolol, Clonidine, opioid withdrawal etc.
– 3 mechanisms - Unmasking of receptors or proliferation
(up regulation) or accentuation of signal amplification

46. Receptor Regulation – contd.
• Conversely - continued exposure to an agonist or
intense receptor stimulation causes desensitization
or refractoriness: receptor become less sensitive to
the agonist
• Examples – beta adrenergic agonist and levodopa
• Causes:
1. Masking or internalization of the receptors
2. Decreased synthesis or increased destruction of the
receptors (down regulation) - Tyrosine kinase
receptors

47. Mechanism of Masking or
internalization
ßARK (beta-adrenergic
receptor kinase)
Beta-arrestin

48. Desensitization
• Sometimes response to all agonists which act through different receptors
but produce the same overt effect is decreased by exposure to anyone of
these agonists – heterologous desensitization
• Homologous – when limited to the agonist which is repeatedly activated
• Mechanism: Homologous – BARK-arrestin; Heterologous - In GPCRs (PKA
or PKC) Kinases may also phosphorylate the GPCRs
R+ TransducerHomologous
Ach
Hist
Heterologous

49. Functions of Receptors - Summary
1. To Regulate signals from outside the cell to inside
the effector cell – signals not permeable to cell
membrane
2. To amplify the signal
3. To integrate various intracellular and extracellular
signals
4. To adapt to short term and long term changes and
maintain homeostasis.

50. Dose-Response Relationship
• Drug administered – 2 components of dose- response
– Dose-plasma concentration
– Plasma concentration (dose)-response relationship
– Obeys law of mass action
• E is expressed as
Emax X [D]
Kd + [D]
E is observed effect of drug dose [D], Emax = maximum response,
KD = dissociation constant of dose of drug receptor complex at
which half maximal response is produced
E max

51. Dose-Response Curve
dose in ml of 10 mcg/ml dose
Log dose
%response
%response
100% -
50% -
100% -
50% -
E =
Emax X [D]
Kd + [D]
! ! ! ! ! !
0.2 0.4 0.8 1.6 3.2 6.4

52. Dose-Response Curve
• Advantages:
– Stimuli can be graded by Fractional change in
stimulus intensity
– A wide range of drug doses can easily be displayed
on a graph
– Potency and efficacy can be compared
– Comparison of study of agonists and antagonists
become easier

53. How we get DRC in vitro
Practically??
• Example: Frog rectus muscle and
Acetylcholine response – in millimeters
– Can compare with a drug being studied for having
skeletal muscle contracting property

54. Potency and efficacy
• Potency: It is the amount of drug required to produce a
certain response
• Efficacy: Maximal response that can be elicited by the drug
Response
Drug in log conc.
1 2 3 4

55. Potency and efficacy - Examples
• Aspirin is less potent as well as less efficacious than Morphine
• Pethidine is less potent analgesic than Morphine but eually
efficacious
• Diazepam is more potent but less efficacious CNS depressant
than phenobarbitone
• Furosemide is less potent but more efficacious than
metozolone
• Potency and efficacy are indicators only in different clinical
settings e.g. Diazepam Vs phenobarbitone (overdose) and
furosemide vs thaizide (renal failure)

56. Slope of DRC
• Slope of DRC is also important
• Steep slope – moderate increase in dose markedly increase the response
(individualization)
• Flat DRC – little increase in response occurs in wide range of doses
(standard dose can be given to most ptients)
• Example: Hydralazine and Hydrochlorothiazide DRC in Hypertension
Hydralazine
Thiazide
FallinBP

57. Selectivity
• Drugs produce different effects – not single
• DRC of different effects may be different
• Example – Isoprenaline – Bronchodilatation
and cardiac stimulation – same DRC
• Salbutamol – different (selective
bronchodilatation)

58. Therapeutic index (TI)
• It is defined as the gap between therapeutic effect DRC and
maximal acceptable adverse effect DRC (also called margin of
safety)

59. Therapeutic index (TI)
• In experimental animals
• Therapeutic Index =
Median Lethal Dose (LD50)
Median Effective dose (ED50)
Idea of margin of safety Margin of Safety

60. Risk-benefit Ratioo
• Estimated harm (ADRs, Cost, inconvenience)
Vs
• Expected advantages (relief of symptoms,
cure, reduction of complications, mortality,
improvement of life etc.)

61. Combined Effects of Drugs
• Drug Synergism:
– Additive effect (1 + 1 = 2)
• Aspirin + paracetamol, amlodipine + atenolol, nitrous oxide +
halothane
– Supra-additive effect (1 + 1 = 4)
• Sulfamethoxazole + trimethoprim, levodopa + carbidopa,
acetylcholine + physostigmine
• PABA DHFA THFA
Sulfamethoxazole Trimethoprim
Folate
synthase
Dihydrofolate
Reductase

62. Drug Antagonism
1. Physical: Charcoal
2. Chemical: KMnO4, Chelating agent
3. Physiological antagonism: Histamine and
adrenaline in bronchial asthma, Glucagon and
Insulin
4. Receptor antagonism: One drug blocks receptor
action of others, also blocks physiological signal
molecules – relatively selective (Ach Vs Histamine
in SM contraction)
a. Competitive antagonism (equilibrium)
b. Non-competitive
c. Non-equilibrium (competitive)

63. Receptor antagonism - curves
o Competitive:
o Antagonist is chemically similar to agonist and binds to same receptor
molecules
o Affinity (1) but IA (0), Result – no response
o Log DRC shifts to the right
o But, antagonism is reversible – increase in concentration of agonist
overcomes the block
o Parallel shift of curve to the right side
o Non-competitive:
o Allosteric site binding altering receptor not to bind with agonist
o No competition between them – no change of effect even agonist conc. .is
increased
o Flattening of DRC of agonist by increasing the conc. Of antagonist
o Experimental - no clinical basis

64. Receptor antagonism - curves
• Non – equilibrium:
– Antagonists Binds receptor with strong bond
– Dissociation is slow and agonists cannot displace
antagonists (receptor occupancy is unchanged)
– Irreversible antagonism developes
– DRC shifts to the right and Maximal response
lowered

65. Drug antagonism DRC

66. Drug antagonism DRC – competitive
nonequillibrium antagonismResponse
Shift to the right
and lowered response
Drug in log conc.
Agonist
Agonist
+ CA (NE)

67. Spare Receptor
• When only a fraction of the total population
of receptors in a system, are needed to
produce maximal effect, then the particular
system is said to have spare receptors
• Example – Adrenaline (90%)

68. Competitive Vs NC antagonism
Competitive
• Binds to same receptor
• Resembles chemically
• Parallel right shift of DRC in
increasing dose of agonist
• Intensity depends on the conc. Of
agonist and antagonist
• Example – Ach and atropine,
Morphine and Naloxone
Noncompetitive
• Binds to other site
• No resemblance
• Maximal response is
suppressed
• Depends only on
concentration of antagonist
• Diazepam - Bicuculline

69. Summary
• Basic Principles of Pharmacodynamics
• Mechanisms of drug action – Enzymes, Ion channels, Transporters and
Receptors with examples
• Definitions of affinity, efficacy, agonist and antagonists etc.
• Drug transducer mechanisms
• GPCR and different GPCR transducing mechanisms – cAMP, Protein kinase
etc.
• Up regulation and down regulation of receptors and desensitization
• Principles of dose response curves and curves in relation to agonist,
competitive antagonist etc.
• Therapeutic index, margin of safety and risk-benefit ratio concepts
• Combined effects of drugs – synergism etc.
• Dose response curve (DRC) – agonist and antagonist

70. Thank you