1. Dr. Anoop Kumar discusses different types of drug receptor interactions including agonists, antagonists, partial agonists, and inverse agonists. He explains how these ligands can stimulate, inhibit, or modify cellular functions through receptor binding. 2. Four main classes of receptors are described: intracellular receptors, enzyme-linked receptors, ligand-gated ion channels, and G-protein coupled receptors. Intracellular receptors modify gene transcription in the nucleus. Enzyme-linked receptors dimerize and phosphorylate substrates upon ligand binding. Ligand-gated ion channels open to conduct ions when bound by ligands. 3. Specific examples like nicotinic acetylcholine receptors and GABAA receptors are given.

1. Dr. Anoop Kumar
Assistant Professor
Pharmacology and Toxicology
NIPER-R, Lucknow

2. Pharmacodynamics
WHAT does the drug do
when it gets there at target cells

3. General Principles of Drug Actions
• DRUGS DO NOT CREATE A NEW FUNCTION
IN THE CELL or TISSUES
• They can only  MODIFY or
 SUBSTITUTE for
a function already existing in the cell
WHAT ALL THE DRUGS CAN DO?

4. General Principles of Drug Actions
 In a Host cell / tissue, DRUGS CAN -
• STIMULATE: Selectively a specific function of
a specialized cell;
e.g. Ach Increase the Salivary Secretion
• INHIBIT: Selectively a specific function of a
specialized cell;
e.g. Ach Inhibits the heart
Same Drug may Inhibit a function in one tissue
and Stimulate a function in another tissue
e.g. Adrenaline Stimulates Heart but
Inhibits Intestinal smooth muscles

5. General Principles of Drug Actions
 In the Host cell DRUGS CAN -
• IRRITATE: Nonselectively stimulate many
functions in a Nonspecialized tissue :
Low dose Beneficial effect, but
High dose Harmful effect, e.g. Counterirritants
• REPLACE: A deficient function in a Specialized
cell, e.g. Insulin in Diabetes;
Vit. B12 in Pernicious anemia.
 In a Foreign Invader Cell, DRUGS CAN 
Stimulate / Inhibit / Irritate & thereby Selectively
 the Organism without adversely affecting Host
Cell  called ANTI-INFECTIVE action
e.g. Chemotherapy drugs

6. • Drugs ACT on some Biochemical / Physiological
/ Molecular processes of the cell, (which is Not
Necessarily Visible Ordinarily).
= Drug Action
(Molecular actions are often referred to as
“Mechanism of Action”)
• This molecular / cellular ACTION, through
complex sequences, ultimately causes an
EFFECT (Visible / Explicit) on organ systems
= Drug Effect
Pharmacodynamics is the study of both parts:
i.e. ACTION – EFFECT Sequence
HOW EXACTLY does the drug
do, what it does, when it gets there.

7. Drug Mechanisms
Drugs can act on / through –
• PROTEIN Targets
• RECEPTORS
• ENZYMES
• NON-PROTEIN Targets / mechanisms
Majority of Drugs act through RECEPTORS
 DRUG – RECEPTOR INTERACTIONS

8. RECEPTORS

9. Drug-RECEPTOR Interactions:
RECEPTORS – what are they?
• Langley (1878) suggested presence of specific interaction
mechanisms/sites after observing SPECIFIC antagonistic
interactions between ‘Pilocarpine & Atropine’
• RECEPTORS -
• Macromolecular PROTEIN/PEPTIDE structures
• On the Cell Surface, or Transcellular or Intra-cellular
• Have SPECIFIC 3-D structure & Binding properties
• Regulate critical Cell Functions – e.g.
Enzyme activity
Permeability of cell (wall, membrane, etc)
Ion Channels activity
Carrier functions
Template Function, etc.

10. • LIGAND: (*Latin: Ligare = Bind)
 Is a Molecule that Selectively binds to ‘a Specific’
Receptorthis binding property is called AFFINITY
 Molecule with a different configuration wo’nt fit / bind
 Ligands of different configurations will have AFFINITY
for ONLY their ‘respective’ Receptors
Ligand Receptor
Effective
Ligand-Receptor
Interaction
Works like Lock and Key principle.
“Wrong Shaped” Key doesn’t Fit
Drug-RECEPTOR Interactions - contd:
Other
Molecule

11. Agonist
Molecule
Receptor
Agonist-Receptor
Interaction
Lock and key mechanism;
Only Matching Key Opens (or
Activates) Lock
AGONIST:
• A Ligand molecule, which after binding, to receptor, can
“Activate” a Cell Function & cause MAXIMAL RESPONSE
 property called INTRINSIC ACTIVITY
• AGONIST = AFFINITY + full INTRINSIC ACTIVITY
Drug-RECEPTOR Interactions - contd:

12. Receptor
Induced
Perfect Fit!
Conformational
Change
Drug-RECEPTOR Interactions - contd:
• Ligand may not always fit into pre-ready shaped receptor
• It may cause a ‘Conformational Change’ in receptor and
induce shape-change to ensure a perfect fit with receptor

13. Antagonist Receptor
Antagonist-Receptor
Complex
DENIED!
AgAgAg
Antagonist blocks
Agonist action
ANTAGONIST:
• A Ligand molecule which binds, but can NOT “Activate” a
cell function No Action-effect Sequence (Response)
• But by binding to Receptor, it prevents Agonist-binding
• ANTAGONIST = AFFINITY + NO INTRINSIC ACTIVITY
Drug-RECEPTOR Interactions - contd:

14. Antagonist Receptor
Antagonist-Receptor
Complex
Antagonist can be dislodged
from receptor if Agonist conc.
is sufficiently increased (and
vice versa)  Competitive
Antagonism
COMPETITIVE ANTAGONIST:
• If Antagonist binds with receptor thru weak bonds, higher
conc. of Agonist can over-ride/displace Antagonist
• Such interaction is called Competitive Antagonism
• Such Antagonist & Agonist are usually chemically similar
Drug-RECEPTOR Interactions - contd:
Agonist-Receptor
Interaction

15. Agonist Receptor
Noncompetitive
Antagonist
‘Inhibited’-Receptor
DENIED!
• NON-COMPETITIVE ANTAGONIST:
When Antagonist binds with Receptor thru Strong bonds,
Agonist CAN NOT over-ride the antagonism – Irreversible
 called Non-Competitive Antagonism
Such Antagonist may actually bind at a site different from
the usual agonist-binding site

16. Drug-RECEPTOR Interactions - contd:
PARTIAL AGONIST:
• A Ligand molecule which ONLY PARTIALLY “Activates” a
cell function  cause only Submaximal Response (not a
Full Response) acts as ‘Weak’ agonist when given alone
• But will prevent a FULL AGONIST from binding with the
receptor  Acts as Antagonist to a FULL AGONIST
• PARTIAL AGONIST = AFFINITY + INCOMPLETE /PARTIAL
INTRINSIC ACTIVITY
INVERSE AGONIST:
• Ligand has AFFINITY and “OPPOSITE AGONIST ACTION”
• Intrinsic activity causes Response that is Opposite to the
normally expected response. In fact “Inverse agonists”
can reduce receptor activity below basal levels observed
in the absence of bound ligand
Benzodiazepines -BDZAgonist (Diazepam)Anxiolytic
Beta-Carbolines  Anxiogenic thru BDZ receptors 
Inverse Agonist …….. (See later)

17. UP-REGULATION & DOWN REGULATION OF RECEPTORS:
• Continuous Exposure to the Agonist leads to DOWN-
REGULATION of the receptors. The receptor synthesis by
the cell decreases, and existing receptors are internalized
and presented to lysosomes for destruction.
• Down-Regulation leads to Decreased Response to the
agonists.
• Conversely Prolonged lack of exposure of receptors to
the Agonist leads to UP-REGULATION. More receptors
are synthesised by the cell and expressed on the surface.
• Up-Regulation leads to Restoration of, or an Enhanced,
Response.
• Examples: Clinical Response to Beta2-agonists in Asthma
decreases on continuous use. Response is restored on
discontinuation of drug for some time. Corticosteroids
can help RESTORE (upregulate) Beta2-receptors & the
response in asthmatics.
• Up- / Down-regulation are Gradual processes while a
rapid loss of response is called Desensitization.

18. CLASSES (TYPES) OF RECEPTORS:
INTRA-
CELLULAR
TRANSMEMBRANE
ENZYME (KINASE)
LINKED
LIGAND
GATED ION
CHANNEL
G-PROTEIN
COUPLED
Examples:
• STEROIDS
• THYROXIN
•INSULIN •Ach-Nicot
• GABA
• Glutamate
• Aspartate
• Ach-Muscarinic
• Adrenergic
Receptors
Time:
Hours Minutes Milli-Sec Seconds
4321 Drug
Outside
Cell
Inside
Cell
CellMembrane

19. 1: NUCLEAR
RECEPTORS
2: RECEPTOR
KINASES
3: LIGAND-
GATED ION
CHANNELS
4: G-PROTEIN
COUPLED
RECEPTORS
Location Intracellular Membrane Membrane Membrane
Effector Gene
Transcription
Protein Kinases Ion Channel Channel or
Enzyme
Coupling Via DNA Direct Direct G-protein
Examples Steroid
receptors
Insulin, Growth
factors, Cytokine
receptors
N-Ach
receptor,
GABA A
receptor
M-Ach
receptor,
Adrenoceptors
Structure Monomeric -
with separate
receptor- &
DNA-binding
domains
Single -
transmembrane
helix linking
extracellular
receptor domain
to intracellular
kinase domain
Oligomeric
assembly of
subunits
surrounding
central pore
Monomeric,
Dimeric or
structure
comprising
Seven Trans-
membrane
Helices

20. 1.
INTRACELLULAR
(Nuclear)
RECEPTORS for Lipid
Soluble agents

21. 1. INTRACELLULAR RECEPTORS for Lipid Soluble agents
Ligand-Binding
Domain
DNA-binding Domain
(Zn fingers)
Transcription Domain
• Lipid soluble agents
(Corticosteroids, Sex
Steroids, Vitamin D,
Thyroxin etc) cross
into the cell & act on
Intracellular receptors
to activate them.
• Activated Receptors
bind with specific
“Response Elements”
(DNA Sequences) in
the nucleus.

22. INTRACELLULAR (Nuclear) RECEPTORS-contd.
• In the Nucleus, they Stimulate Transcription of
the Corresponding Genes  mRNA synthesis 
Specific Proteins are formed  which lead to
RESPONSES. That is why they cause -
• SLOW-onset Therapeutic Response (0.5-many
hours)
• Effects (Therapeutic or ADRs) lasting LONGER
even after plasma Agonist levels fall to zero
• Recombinant techniques showed that Corticoids
remove “a restraining factor” on Transcription
process by binding to the specific component of
intracytoplasmic steroid receptor protein

23. Molecular M.O.A. of Corticoids
•Inabsence of Steroid, HSP90
(Heat Shock Protein) keeps
DNA-Binding Domain masked
•Steroid enters cytoplasm &
attaches toLigand-Binding
Domain that triggers the
release of HSP90
•This Unmasks DNA-binding &
Transcription-activating
domains of receptor-protein
folds (Zinc fingers)
•Specific mRNA synthesis
causes protein synthesis
whichcause RESPONSES
mRNA 
Response
Proteins
Intracellular
Receptor for
Corticoids

24. 2.
ENZYME LINKED
TRANSMEMBRANE
(KINASE)
RECEPTORS

25. γ γ
Inactive Monomers
Enzyme
Domain
Recog-
nition
Domain
Ligand Domain
α α
β β
Transmembrane Receptor
protein consist of –
• (a) Extracellular Ligand-
Binding domain (α);
• (b) Trans- & Intracellular
‘β’ domain
• Enzyme (Kinases)
Domain aminoacids (‘γ’)
lie in association with ‘β’
domain
• The inactive receptors
existing as MONOMERS
• Agonist binding causes
Monomers to DIMERIZE
Out
In
Cell Membrane
2. ENZYME-LINKED TRANSMEMBRANE (KINASE) RECEPTORS

26. γγγ γ
ENZYME-LINKED KINASE RECEPTORS - contd
Inactive Monomers
Enzyme
Kinases
Recog-
nition
Domain
Ligand Domain
P P
Substrate (s) S-Phos
ATP ADP
Ligand
α α
β β
Active
Dimer
• Ligand binding: ‘Inactive Monomers’‘Dimerize’ (activated)
• Activated Enzymes Phosphorylate specific AA residues ‘γ’ in
the substrate (Tyrosine for Insulin)  Responses
Out
In
Cell Membrane

27. Kinase-linked receptors
•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.

28. Kinase-linked receptors
• Signal transduction generally involves
dimerisation 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.

29. Kinase-linked receptors
•Two important pathways are:
•the Ras/Raf/mitogen-activated protein
(MAP) kinase pathway, which is important
in cell division, growth and differentiation
•the Jak/Stat pathway activated by many
cytokines, which controls the synthesis
and release of many inflammatory
mediators.
•A few hormone receptors (e.g. atrial
natriuretic factor) have a similar architecture
and are linked to guanylate cyclase.

30. Central Role of Kinases in Signal Transduction

31. • CaM kinase = Ca2+/calmodulin-
dependent kinase;
• DAG = diacylglycerol;
• GC = guanylate cyclase;
• GRK = GPCR kinase;
• IP3 = inositol trisphosphate;
• PKA = cAMP-dependent protein
kinase;
• PKC = protein kinase C;
• PKG = cGMP-dependent protein
kinase.

32. 3.
LIGAND GATED
RECEPTOR LINKED
CHANNELS

33. 3. LIGAND GATED RECEPTOR LINKED ION CHANNELS
• Also called Ionotropic Receptors
• 4-5 Transmembrane peptide sequences
• Ligand binds to Extracellular Ag-binding domain
• Transmembrane Domain enclose an Ion Channel
in Center
• Ex: Ach-Nicotinic-Receptors  Na+ Ion
GABAA-Receptors  Cl- Ion

34. • N-Ach-R consists of 5 subunits (2α and 1 each β, γ, δ)
which form a cluster around a Central Trans-membrane
Pore
• There are 2 Ach-binding sites in Extracellular part of
receptor at the interface between the α- δ, and α- γ
adjoining subunits.
α-helices forming gate
Ach-Nicotinic Receptor
Pore 0.7 nm diameter

35. • The lining of PORE is rich in negatively charged
amino -acids, which makes the pore Cation-selective.
• Kinked ‘α’ helices form the GATE
• When Ach binds, KINKS straighten out or swing out
of way
• This opens channel pore for Na+ influx  results in
Depolarization.
α-helices forming gate
Ach-Nicotinic
Receptor
-ve Charged
Aminnoacids

36. B G
Cl-
Cl-
Cl- Cl-
Cl- Cl-
LIGAND GATED GABAA-RECEPTOR- Cl- CHANNELS
• Benzodiazepines (BDZ) [B] are Anxiolytic / Sedatives
Agonists on the BDZ-receptors
• Given alone, however, they do not affect Cl- ion influx
(necessary for Hyperpolarisation)
• GABA [G] acts as Agonists on GABAA-R and opens Cl-
channels  Influx of Cl- ions  Hyperpolarize Cell 
Anxiolytic / Sedative

37. GB
Cl-
Cl-
Cl-
Cl-
Cl-
LIGAND GATED RECEPTOR LINKED ION CHANNELS-contd
• When Benzodiazepines [B] and GABA [G] act together,
Cl- ion influx is more efficient than that with GABA alone
• Thus BDZ effects (Anxiolytic, Hypnotic …) occur by
Agonist action on BDZ receptors, which FACILITATE
(Potentiate) GABA action on Chloride Channels
• BDZ-R can also bind with ‘Agonists’ like β-Carbolines
which cause Closure of Cl- Channel  INVERSE AGONIST
[IA]  ANXIOGENIC / CONVULSIOGENIC
G
Cl-
Cl-
Cl-
IA

38. G
Cl-
Cl-
Cl-
F
B
• Flumazenil, [F] BDZ-R Antagonist, blocks BDZ-
Receptors and prevents effect of BDZ [B]. Can be
used to Reverse Overdose with Benzodiazepines
• Flumazenil can block BDZ-R in both states of
conformation – Agonist well as Inverse Agonist
conformations  i.e. Can block effects of BDZ as
well as β-Carbolines
G
Cl-
Cl-
Cl-
F
IA
LIGAND GATED RECEPTOR LINKED ION CHANNELS-contd

39. Drug Binding Sites in Voltage Gated Na+ Channels
• Ion Channels have
Muliple sites for Ligand
acting directly on it
• Ion Channels are also
affected INDIRECTLY by
ligands 
GPCRs thru 2nd
Messengers system
e.g. Opioids & β-adr.
affect Ca++ and K+
Channels
Intracellular signals
e.g. Sulfonylureas on
ATP-gated K+
channels

40. 4.
G-PROTEIN COUPLED
RECEPTORS

41. 4. G-PROTEIN COUPLED RECEPTORS (GPCRs)
• Sometimes called Metabotropic
Receptors
• Hepta-helical (7 Transmembrane
loops) Receptors
• G-Proteins are located on the
intracytoplasmic face of cell
membrane along with GDP
• Called G-Proteins as they interact with GDP/GTP
• Agonist binds with specific Extracellular Domain
of GPCReceptor
• G-Prot are GOPHER (Go Between) Proteins which
carry ‘Ligand-R interaction’ signal to EFFECTORS
by diffusing within the cytoplasm
Ag-Binding
Domain
G-Protein
Coupling
Domain

42. Hepta-helical Structure of GPCR

43. G-PROTEIN COUPLED RECEPTORS (GPCR)
• G-Proteins are TRIMERS – consist of α, β and γ
subunits.
• Resting State: Trimer is attached to cell membrane
‘distant from receptor’ & GDP is anchored to α-
subunit.
• When Ag acts on Extracellular R-Domain, GTP
displaces GDP
• This activates “α-subunit+GTP” to diffuse away “to
the Effectors and activate them”. The βγ complex
can also bind with effectors.
• The Effectors are usually Enzymes or Ion Channels
• Many subtypes of G-Proteins – Gs, Gi, Gq etc, exist.
Ligands interact with different receptors thru
different G-Prot subtypes causing different end-
results (responses).

44. SOME TARGETS FOR G-PROTEINS
• Adenylyl cyclase, the enzyme responsible for
cAMP formation
• Phospholipase C, the enzyme responsible for
inositol phosphate and diacylglycerol (DAG)
formation
• Ion channels, particularly calcium and potassium
channels
• Rho A/Rho kinase, a system that controls the
activity of many signalling pathways controlling cell
growth and proliferation, smooth muscle
contraction, etc.

45. E1 E2
βγ
Rec
GDP
α
G-Prot
GTP
E1 E2
βγ
Rec
GDP
α
G-Prot
GTP
Resting State
G-Prot Unattached
Ligand Receptor
Activates G-Prot
E1 E2
βγ
Rec
GTP
α
2nd Messengers /
Ion Channels
RESPONSE
E1 E2
Rec
α
GDP
GTP
G-Prot
(Hydrolysis)
βγ
G-Prot Activate
Effectors
Back to Resting State
G-Proteins
Coupled
Receptors
+ P

46. EFFECTS OF G-Protein Receptor-Ag Interaction
G-PROTEIN MEDIATED EFFECTS mostly involve
generation of Chemicals called 2nd Messengers:
(a) Activation of Adenylyl Cyclase - cAMP pathway:
Binding to β-adrenoceptors  adenylyl cyclase
thru the Stimulatory G-Protein (Gs) which causes
dissociation of its ‘αs-subunit’ charged with GTP.
‘Charged αs-subunit’ activates adenylyl cyclase
 synthesis of cAMP.
The  cAMP levels produce –
*  Cardiac contractility
* Smooth muscle relaxation (Bronchi, Blood
Vessels, Gut, Uterus), and
* Glycogenolysis
Ex. of drugs  cAMP  Glucagon;
β-Adrenergic drugs (Adrenaline, Salbutamol);
Adenylyl Cyclase activity is  by Muscarinic
drugs thru Gi-subtype G-Proteins.

47. EFFECTS OF RECEPTOR OCCUPATION BY AGONISTS
G-PROTEIN MEDIATED EFFECTS- 2nd Messengers:
(b) Phospholipase-C: IP3 – DAG Pathway:
Lead to Contraction, Secretion, Transmitter
Release, Neuronal Excitability, etc.
Ex: α1–Adrenergic, H1-Histaminic, M1-Muscarinic
Effects.
A ligand can produce different effects in
different cells by interacting with different
subtypes of G-Proteins:
e.g. Catecholamines respond to Stress by
Increasing Heart Rate thru Gs-coupled
β-receptors & Vasoconstriction in skin
thru Gq-coupled α1-receptors
(c) Channel Regulation:
Ca++, Na+, K+ channels Open / Close .

48. G-Proteins Mediated Effects – 2nd messengers

49. βM3
Gq Gs
Aden
Cycl M2
Gi
ATP cAMP
+ _
_
DAG IP3
Ca++
PLC-β
Contraction of Sm. M.
_
G-Proteins mediated 2nd Messengers in Smooth Muscles
Cardiac , Sm.
M. Relaxation,
Glycogenolysis
Protein Kinase C
G-Proteins subtypes 
Gs – Stimulates Target enzymes
Gi – Inhibitory effects
Gq – Activates Phospholipase-C  release
IP3  Ca++ release & PKC 

50. SPARE RECEPTORS
Clark (1930s) observed that –
• Adrenaline / Acetylcholine / Histamine can still produce
Maximal Response when most receptors have been blocked
by Irreversible Antagonist.
• Receptors are said to be "spare" if maximal biologic
response can be elicited at Ag-concentration that does not
occupancy the full complement of available receptors.
• It really indicates that very small % of available receptors are
needed to produce maximal response.
• Spareness of receptors determines the sensitivity of tissue.
• Experimentally, spare receptors may be demonstrated by
using “Irreversible Antagonist” to prevent binding of Agonist
to a proportion of available receptors and showing that high
concentrations of agonist can still produce an undiminished
maximal response.

51. RECEPTOR HETROGENEITY & SUBTYPES
• Receptors within a given family generally occur in several
molecular varieties, or subtypes, with similar architecture but
significant differences in their AMINOACID sequences.
• This results in variation in their pharmacological properties.
• Examples: Ach-N  Nicotinic-N (nervous tissue) &
Nicotinic-M (skeletal muscles)
Beta-adrenoceptors  β1, β2, β3
Alpha-adrenoceptors  α1 & α2 and their further
subtypes α1A, α1C, etc
• Different subtypes / isoforms allow more selective agonists &
antagonists for use in specific disorders
• New subtypes are being discovered regularly, specially after
gene-splicing technology and cloning of receptors

52. SILENT RECEPTORS
• Drugs can bind to molecules that have no direct relation with
the action-effect sequence.
• These binding sites are indeed termed as “Sites of Loss” as
this fraction is not available for action.
• These sites are also called Drug Acceptors
• Most important example is “Binding to Plasma Proteins”
• Other sites can be Tissue Binding sites in those tissues
where the primary action of drug is not expected
• These sites have been called as “SILENT RECEPTORS”
• Indirectly these bindings affect drug response as bound
fraction acts as Storage Site from where drug is released into
active free form as the free fraction levels decline
• Highly plasma protein bound drugs show features like Slow
Onset & Prolonged Duration of action, more displacement
Drug-Drug Interactions, etc.

53. ORPHAN RECEPTORS
• In 1970s, the-then theoretical receptors began emerging as
biochemical realities with “labeling of receptors”.
• This led to extraction & purification of receptor material – first
of them was N-Ach receptors from Electric Organs of Rayfish
& Electric eels.
• Simultaneously venoms of snakes of cobra family were
found to have polypeptides that bound avidly with the N-Ach
receptors.
• After isolation / purification of receptor proteins, their
aminoacid sequence was deciphered.
• Gene cloning allowed hundreds of subtypes of receptors to
be prepared – so much so that the ligands for many gene-
cloned receptors are yet to be found - & their role remains
unknown.
• Such receptors are called ORPHAN RECEPTORS. Some
day their specific ligands are found & used in medicine.

54. SPARE RECEPTORS

55. Non-receptor Mechanisms - Enzymes
• Actions on Enzymes
• Enzymes = Biological catalysts
• Speed chemical reactions
• Are not changed themselves
• Drugs altering enzyme activity alter processes
catalyzed by the enzymes
• Examples
• Cholinesterase inhibitors
• Monoamine oxidase inhibitors

56. Non-receptor Mechanisms –Physical actions
• Changing Physical Properties
• Mannitol
• Changes osmotic balance across
membranes
• Causes urine production (osmotic
diuresis)

57. Non-receptor Mechanisms -Permeability
• Changing Cell Membrane Permeability
• Lidocaine
• Blocks sodium channels
• Verapamil, nefedipine
• Block calcium channels
• Bretylium
• Blocks potassium channels
• Adenosine
• Opens potassium channels

58. Non-receptor Mechanisms – Chemical actions
• Combining With Other Chemicals
• Antacids
• Antiseptic effects of alcohol, phenol
• Chelation of heavy metals

59. Non-receptor Mechanisms-Antimetabolites
• Anti-metabolites
• Enter biochemical reactions in place
of normal substrate “competitors”
• Result in biologically inactive
product
• Examples
• Some anti-neoplastics
• Some anti-infectives

60. Drug Response Relationships
• Time Response
• Dose Response

61. Latency Duration of Response
Maximal (Peak) Effect
Effect/
Response
Time
Time Response Relationships

62. Effect/
Response
Time
IV
SC
IM
Time Response Relationships

63. Dose Response Relationships
• Potency
• Absolute amount of drug required to
produce an effect
• More potent drug is the one that
requires lower dose to cause same
effect

64. Potency
Effect
Dose
A B
Which drug is more potent?
A!Why?
Therapeutic
Effect

65. Dose Response
Relationships
• Threshold (minimal) dose
• Least amount needed to produce
desired effects
• Maximum effect
• Greatest response produced
regardless of dose used

66. Dose Response Relationships
Which drug has the lower threshold dose?
Effect
Dose
A
B
Which has the greater maximum effect?
A
B
Therapeutic
Effect

67. Dose Response Relationships
• Loading dose
• Bolus of drug given initially to
rapidly reach therapeutic levels
• Maintenance dose
• Lower dose of drug given
continuously or at regular intervals
to maintain therapeutic levels