Download Mechanism of drug action

Pharmacodynamics
Pharmacodynamics is the study of the
biochemical and physiologic effects of drugs
and their mechanisms of action.
Mechanisms of Drug Action
How does a drug work
drugs and
endogenous
ligands
molecular
target
drugs and endogenous ligands
Molecular
Target
alters
tissue
function
Types of mechanism of drug action
(1) Physical and chemical reaction
Antacids neutralizing gastric acid
Mechanism of drug action
(2)Joining or interfering with cell metabolism
Vitamins, iron preparations and some anticancer
drugs whose chemical structure resemble purine
or pyrimidine are called counterfeit
incorporation or antimetabolite.
Mechanism of drug action
(3) Affecting transportation of physical substances
Reserpine affect the uptake of norepinephrine
Mechanism of drug action
(4) Affecting enzyme activity
Neostigmine exerts its cholinergic effect by
inhibiting activity of AChE
Mechanism of drug action
(5) Affecting ion channels on the cell membrane
Mechanism of drug action
(6) Affecting immunology function
The immunosuppressive and immunomodulating agents
result in efficiency by influencing body immunity
function.
glucocorticoids or
cyclosporin
Active immunity obtained by
using vaccine
Mechanism of drug action
(7) Affecting nucleotide metabolism
Many anticancer drugs exert effective action
on cancer cells by interrupting DNA and
RNA metabolism of cancer cells.
Mechanism of drug action
(8). Receptors
Receptors are specialized target
macromolecules, present on the cell surface
or intracellular; that bind drugs and mediate
their pharmacologic actions.
Receptors have become the central focus of
investigation of drug effects and their
mechanisms of action.
Many drug receptors have been isolated and
characterized in detail, thus opening the way
to precise understanding
of the molecular basis
of drug action.
Receptors
Largely determine the quantitative relations
between dose or concentration of drug and
pharmacologic effects.
Be responsible for selectivity of drug action.
Mediate the actions of pharmacologic
agonists and antagonists.
Development of receptor theory
a.Langley(1878): Intercounter of atropine with
pilocarpine in salivary excretion.
"There is some substance or substances in the
nerve ending or gland cell with which both atropine
and pilocarpine are capable of forming compounds."
b. Langley(1905):Intercounter tubocurarine
with nicotine in skeletal muscle – “receptive
substance”
Development of receptor theory
c. Ehrlich(1905): “ receptor”
trying to develop specific drugs to treat parasitic
infections
trying to understand the basis of selectivity of agents
a drug could have a therapeutic effect only if it has the
“right sort of affinity.”
"... that combining group of the protoplasmic molecule
to which the introduced group is anchored will hereafter
be termed receptor.“
Each cell would have particular characteristics to
recognize particular molecules.
Development of receptor theory
c. Ehrlich(1905): “lock and key”
drug
drug
receptor
Only the
correctly
shaped key
opens a
particular lock.
Interaction between receptor and drug
(receptor theory)
(1) Occupation theory
Simple occupancy theory
-
-
“ Intensity of response to
a drug is proportional to
the number of receptors
occupied by that drug”
Maximal response occurs
when all available
receptors have been
occupied
2. Modified Occupancy Theory
a. Affinity binding- strength of the
attraction between drug and receptor. Drugs
with low affinity require higher concentrations
to bind to receptor
b. Intrinsic activity- ability of a drug to
activate its receptor. High intrinsic activity
relates to high maximal efficacy
Kinetics of Receptor and Drug
Drug + Receptor↔ Drug-receptor complex → Biologic effect
Factors Affecting Drug-Target Interactions
Drug + Receptor
Drug-receptor complex
Affinity
Biologic effect
Intrinsic Activity
Two basic properties of the drug-receptor
interaction contribute to drug responses
the
ability of the drug to bind to its receptor
the ability of the drug to alter the activity of its
receptor

Receptor Binding
Affinity: the ability of a drug to bind to the
receptor (just bind).
Covalent bonds = strong
bonds and long-lasting or
irreversible effects
Hydrogen
Ionic
Weak
Hydrophobic
Reversible
Van der Waals
Receptor Binding and Affinity
Drug + Receptor
The
Affinity Drug-receptor complex
ability of a drug to bind a receptor
 A measure
of how strongly that drug binds to
the receptor

Determined by the dissociation constant (KD)
Dissociation Constant (KD)
KD = [D] x [R]
[DR]
Affinity
is the inverse of the KD (1/KD)
The
smaller the KD, the greater affinity a
drug has for its receptor
Receptor Binding and Affinity
[ D].[ R]
KD 
[ DR ]
Receptor Binding and Affinity
Total number of receptors: Rt = [R] + [DR]
[R] = Rt – [DR]
KD 
[ D].( Rt  [ DR ]) [ D].Rt  [ D].[ DR ]

[ DR ]
[ DR ]
After rearrangement:
[ D ].Rt
[ DR ] 
K D  [ D]
[ DR ]
[ D]

Rt
K D  [ D]
When [D] = KD
[DR]
= 0.5
RT
[ DR ]
[ D]

Rt
K D  [ D]
1.00
[DR]/Rt
0.75
KD is the concentration of drug
when half of the receptor
population is occupied.
0.50
0.25
0.00
0
5
10
15
20
[D]
KD
Receptor Binding and Affinity
high
Receptor Binding and Affinity
KD
high concentration for occupying
half of the receptor


low affinity
low
Every drug/receptor
combination will have
a characteristic KD.
KD
lower
concentrations for occupying
half of the receptor
high
affinity
Two drugs that have equal affinities (binding)
for a specific target but have different
efficacies (degree of response)
Other factors, in addition to
affinity and receptor
occupancy, determine the
strength of response.
Intrinsic activity (Efficacy)
Activation of the Molecular Target
The
ability of drug-receptor complex to
activate the receptor and initiate downstream
events, leading to an effect
Be
not directly related to receptor affinity
Drugs categorized based on their intrinsic activity
at a given receptor
Agonist has affinity plus
full intrinsic activity
Antagonist has affinity
but no intrinsic activity
Agonist
 A compound
that binds to the
receptor and alters the receptor state
resulting in a biological response
 Mimics the response to the
endogenous ligand
 e.g.: Pilocarpine
Receptor
Some Effect
Pilocarpine
A Cell
Agonist
Increasing concentrations
of the agonist will
increase the biological
response until there are
no more receptors for the
agonist to bind or a
maximal response has
been reached.
Types of agonists
Full agonists: high affinity
and high efficacy （ α = 1)
Partial agonists :high
affinity and lower intrinsic
activity (0﹤α﹤1 )
This designation of full vs. partial
agonist is system-dependent
Inverse agonists inhibit
rather than activate the
receptor
Antagonists
to receptors but do not activate them(α = 0)
 Have no effect of their own
 Prevent agonists from binding the receptors
 Block or reverse the effect of an agonist
 eg: Atropine, β-blockers
 Bind
Dude, you’re
in my way!
Atropine
Acetylcholine
Agonists alone
Full
activation
Antagonists alone
No
activation
Agonists +
Antagonists
Less
activation
Partial agonists
 High
affinity and lower intrinsic activity
(0﹤α﹤1).
 Cannot bring about the same maximum
response as full agonists even at very high
doses
Partial agonist
Oh!!!, I should
Have been here
Full agonist
Submaximal
effect
Partial agonists
Possess
some of the properties of both
antagonists and full agonists
When
used alone, a partial agonist will act
like a weak agonist
In
the presence of a full agonist, a partial
agonist will act like an antagonist
Full agonists
alone
Full
activation
Partial agonists
alone
Partial
activation
Full agonists +
Partial agonists
Less
activation
Inverse agonist
 Any
drug that binds to a receptor and
produces an opposite effect as that of an
agonist
 Inverse agonists inhibit rather than activate
the receptor.
Receptor
Effect opposite to
that of
the true agonist
Inverse agonist
A Cell
Drug Receptor Interactions
The two-state model of receptor activation
‘In
the unbound state
a receptor is
functionally silent’
Some
receptor
systems display
constitutive activity in
absence of the ligand
two-state model
The receptor is in two
conformational states, ‘resting’ (R)
and ‘active’ (R*), which exist in
equilibrium.
Normally, when no ligand is
present, the equilibrium lies far to
the left, and a few receptors are
found in the R* state.
For constitutively active
receptors, an appreciable
proportion of receptors adopt the
R* conformation in the absence of
any ligand.
Resting
state
Active
state
two-state model
An agonist has
higher affinity for R*
than for R
A neutral
antagonist has equal
affinity for R and R*
An inverse agonist
has higher affinity for R
than for R*
Resting
state
Active
state
Inverse agonists vs Antagonists
Elicit
similar effects because
both types of drugs will
reverse the effects of
endogenous ligands
Antagonists have no activity
in the absence of agonists or
inverse agonists

 Antagonists block
the effects
of both the agonists and
inverse agonists
Spare Receptors
A pharmacological
system has spare
receptors if a full agonist can cause a
maximum response when occupying only a
fraction of the total receptor population
Not
all of the receptors in the tissue are
required to achieve a maximal response with
some high efficacy agonists
Spare Receptors
Spare receptors are exhibited by insulin
receptors, where it has been estimated that 99
percent of the receptors are “spare.”
The “spare” receptors are not
nonfunctional.
When they are occupied they can be coupled
to response.
Receptor reserve
Quantifying Drug-Target Interactions:
DOSE-RESPONSE RELATIONSHIPS
A mathematic relationship between
the
dose of a drug and the body's reaction to it.
Can
be illustrated as a graph called a doseresponse curve.
dose-response curve
Effect
Concentration
(in vitro)
Dose
(in vivo)
Two basic types of dose-response curves
Graded
• Continuous scale
• the effect of various doses of a drug
on an individual
• Relates dose to intensity of effect
Quantal
• All-or-none pharmacologic effect
• the effect of various doses of a drug
on a population of individuals
• Relates dose to frequency of effect
Graded dose–response relations
The
response is continuous and gradual
Describe
the effect of various doses of a
drug on an individual
Graded Dose-Response Curve
rectangular hyperbola
Effect
C
Graded Dose-Response Curve
sigmoid curve
(S-shaped curve)
80
Effect %
slope
20
lgC
Advantages of this curve:
Show a much larger range of concentrations
The portion of the curve between 20 and 80%
of Emax is approximately a straight line.
It is more easier to quantitative values
Phase 1: occurs at low doses
Curve is flat because response is too low to measure
Phase 2: increase in doses elicits increase in response
Phase 3: occurs at high dose (maximum response)
Higher dose does not increase extra therapeutic effects,
but increases the risk of adverse effects
100
Maximal effect
Effect %
(efficacy)
50
Minimal Effective
Concentration (MEC)
Slope
EC50
lgC
Half Maximal
Effective Concentration
Minimal Effective Concentration (MEC)
A minimum plasma concentration that will produce
an effect.
Maximal response (efficacy, Emax )
 Maximal response or efficacy of the drug
Slope
(the rise in response with changes in concentration)
 A steep
slope indicates a small increase in drug
dosage produces a large change in responses.
A shallow
slope indicates a much larger increase
in dose is required to cause the same increase in
response.
EC50
(Half Maximal Effective Concentration )
The molar concentration of an agonist that
produces 50% of the maximal possible effect of
that agonist.
ED50 (best reserved for
in vivo use )is
sometimes used
interchangeably with
EC50
EC50
Concentration
Potency
An
expression of the activity of a drug, in
terms of the concentration or amount needed to
produce a defined effect.
A measure
of how much drug is required to
elicit a given response
Commonly
designated as the EC50
Potency
EC50
Concentration
Potency
The
potency of a drug is inversely related to
its EC50.
The
smaller is the EC50, the lower the dose
required to give a response, the more potent is the
drug.
Farther
to the left = more potent
Potency
pEC50 (pD2): The negative decade logarithm of
the EC50 of an agonist
pD2= pEC50 = logEC50
pD2 is taken as the measure of potency
The higher pD2, the higher potency !
Potency vs. Efficacy (Maximal Effect )
Potency
The amount of drug required to
achieve a defined biological effect
Given by the position of the doseresponse curve along the x-axis
Efficacy
 The maximal response a drug
can produce
Given by the peak of the doseresponse curve
Maximal Effect
EFFICACY
POTENCY
ED50
Log [Dose]
Potency vs. Maximal Effect (Efficacy)
Potency
has nothing to do with efficacy
Efficacy is not related to potency
"Relative Pharmacological Potency"
and the "Maximal Efficacy"
In most cases the efficacy is more important than
the potency in drug selection.
Greater potency or
efficacy does not
necessarily mean
that one drug is
preferable to another.
Quantal Dose–Response Relationships
Describes
the distribution of responses to
different doses in a population of individuals
Quantal
responses are all-or-none responses to a
drug
Even
graded responses can be considered to be
quantal if a predetermined level of the graded
response is designated as the point at which a
response occurs or not.
Y-axis is the percentage of individuals experiencing sleep at
any given dose.
Number of Individuals
Many
Sensitive
Individuals
Minimal
Effect
Majority of
Individuals
Resistant
Individuals
Average Effect
Maximal
Effect
Few
Mild
Response to SAME dose
Extreme
Quantal dose-response curves describe the relationship between
drug dosage and the frequency with which a biologic effect occurs.
Quantal Dose–Response Relationships
Cumulative Effect %
sigmoidal curve
lgD
Quantal Dose–Response Relationships
This type of sigmoidal curve yields useful safety
information when the all-or-nothing responses are
defined as therapeutic maximal responses, toxic
responses, or lethal responses.
individuals
individuals
individuals
individuals
ED50 Median effective doses
TD 50 Median toxic doses
LD50 Median lethal doses (in animals)
Two Definitions of ED50
– one for whole animal vs population studies
ED50 (Half maximal effective concentration) :
the dose that produces 50% of the maximal
response to that drug (the response is graded)
ED50 (Median effective dose) : the effective
dose at which 50% of the test subjects produce
effective response (the response is all-or-none)
Drug Safety & the Therapeutic Index
Therapeutic index = LD50/ ED50
A statement
of relative safety of a drug
Large values of TI indicate that the doses
that produce death are much greater than
those that produce a therapeutic effect

When a drug’s therapeutic index is less than 10, then the
drug is defined as having a narrow therapeutic window.
when the therapeutic index is
low, it is possible to have a
range of concentrations where
the effective and toxic
responses overlap.
Penicillin is safe and
common to give doses in
excess (often about ten-fold
excess) of that which is
minimally required to
achieve a desired response.
The TI may be misleading as to safety, depending on the slope
of the dose-response curves for therapeutic and lethal effects.
A1
A2
100
Cumulative
Effect %
B1
B2
50
ED50
LD50
lgD
Certain Safety Factor = LD1/ED99
Therapeutic window : the
plasma concentrations
range between minimum
effective concentration
and minimum toxic
concentration
DRUG ANTAGONISM
Types of Antagonism
/1/ Chemical antagonism
2/ Physiological antagonism
/
/3/ Pharmacokinetic antagonism
/4/ Antagonism by receptor block
/1/ Chemical antagonism
Interaction of two substance based on their
chemical properties.

Example : Chelating agents (e.g.,
dimercaprol) that bind heavy metals to form
an inactive complex, and thus reduce their
toxicity.
2/ Physiological antagonism
/
Two drugs act on separate physiological
systems and produce opposite actions.
Example : Histamine acts at H1 receptors on
bronchial smooth muscle to cause
bronchoconstriction, whereas adrenaline is an
agonist at the β2 receptors bronchial smooth
muscle, which causes bronchodilation.
/3/ Pharmacokinetic antagonism
One
drug accelerates the metabolism or
elimination of another.
Example: phenobarbital (enzyme induction)
accelerates the rate of metabolic degradation
of the anticoagulant warfarin.
/4/ Antagonism by receptor block
The antagonists may block the ability of agonists
to bind to the receptor by competing for the
same receptor site or may bind to another site
on the receptor that blocks the action of the
agonist
Pharmacologic Antagonists
Competitive reversible antagonism
(competitive surmountable antagonism)
Binds reversibly with receptors at the
same site as the agonist
Inhibition can be overcome by increasing
agonist concentration (i.e., inhibition is
reversible)
Competitive reversible antagonism
In the competitive presence of the antagonist,
the agonist curve is shifted to the right (parallel
shift) without change in slope or maximum.
Maximal response occurs at a higher agonist
concentration than in the absence of the
antagonist
Primarily affects
agonist potency
= Agonist
= Antagonist
= Agonist
= Antagonist
= Agonist
= Antagonist
pA2
The
negative logarithm of the antagonist
concentration at which it is necessary to double the
concentration of agonists in order to produce the
same response as if there were no antagonists.
Be
used to measures the potency of competitive
antagonists
Competitive irreversible antagonism
(competitive insurmountable antagonism)
Binds to same site on receptor as agonist
Forms covalent bond with the receptor
The antagonist dissociates from the receptors
very slowly, or not at all
Inhibition cannot be overcome by increasing
agonist concentration
Competitive irreversible antagonism
Maximal response (Emax)is depressed
The slope of the curve will be reduced
The agonist dose-response curve will be shifted
to the right
Agonist potency may or may not be affected
= Agonist
= Antagonist
Phenoxybenzamine
(irreversible α–adrenoreceptor antagonist)
If overdose occurs, α–adrenoreceptor blockade cannot be
overcome by agonist. The effects must be antagonized
physiologically by using a pressor agent that does not act via
α–adrenoreceptors
Competitive Irreversible Antagonism
Noncompetitive antagonism
(allotropic or allosteric antagonism)
Does not bind to the same receptor sites as the
agonist.
Impair the ability of an agonist to bind to or
activate the receptor
Inhibition cannot be overcome by increasing
agonist concentration (irreversible)
Noncompetitive antagonism
Maximal response will be depressed
The slope of the curve will be reduced
The agonist dose-response curve will be shifted
to the right
Agonist potency may or may not be affected
Noncompetitive antagonism
Noncompetitive antagonists will exert functional
effects similar to those of competitive irreversible
antagonists in that both types of antagonist will
decrease the Emax or efficacy of the agonist.
Signaling Transduction Mechanism
The cellular process in which a signal is conveyed
to trigger a change in the activity or state of a cell
Agonist binding to a receptor are normally only the first of
many steps required to produce a pharmacological effect.
MAJOR RECEPTOR FAMILIES
1. Ligand-gated ion channels
2. G-protein-coupled receptors (GPCRs)
3. Kinase-linked receptors
4. Nuclear receptors
Ligand-gated ion channels
Receptor-operated channels
Acetylcholine causes the opening of the ion
channel in the nicotinic acetylcholine receptor
G protein-coupled
receptors
Exposed at the extracellular
surface of the plasma membrane,
traverse the membrane, and
possess intracellular regions that
activate a unique class of
signaling molecules

Bind the guanine
nucleotides GTP and GDP

G protein-coupled
receptors
G protein-coupled
receptors have seven
transmembrane regions
within a single polypeptide
chain
G proteins haveα and βγ
subunits that are noncovalently
linked in the resting state
Stimulation of a GPCR causes its cytoplasmic domain to
bind and activate a nearby G protein → the α subunit of the
G protein exchanges GDP for GTP → the α-GTP subunit
dissociates from the βγ subunit → the α or βγ subunit
diffuses along the inner leaflet of the plasma membrane to
interact with a number of different effectors.
Adenylyl
Cyclase
Effectors
Guanylyl
Cyclase
Cyclic
Adenosine-3′,5′Monophosphate
(cAMP)
Cyclic
Guanosine-3′,5′Monophosphate
(cGMP)
Second Messenger
Diacylglycerol
(DAG)
Effectors
Activates
protein kinase C
Phospholipase C Second Messenger
(PLC)
Inositol-1,4,5-trisphosphate
(IP3)
Increasing the
cytosolic Ca 2+
concentration
β-adrenergic receptor
The receptors are stimulated
by the binding of endogenous
catecholamines→induces a
conformational change in the
receptor → activating G
proteins associated with the
cytoplasmic domain of the
receptor → activates adenylyl
cyclase → increased
intracellular cAMP levels and
downstream cellular effects.
Transmembrane Receptors
with Enzymatic Cytosolic Domains
These receptors transduce an extracellular ligand-binding
interaction into an intracellular action through the activation of
a linked enzymatic domain
Receptors have an intracellular enzymatic domain.
These enzymatic cytosolic domains form dimers or
multisubunit complexes to transduce their signals by adding or
removing phosphate groups to or from specific amino acid
residues.
Receptor Tyrosine Kinases
insulin receptor
Intracellular receptors
 Lipophilic drugs passively cross the
cell membrane
The transcription regulatory factors
are important cytosolic receptors that
are targeted by lipophilic drugs.
Transcription of many genes is
regulated, in part, by the interaction
between lipid-soluble signaling
molecules and transcription regulatory
factors.
Steroid hormones diffuse through the plasma membrane →
bind to transcription factors in the cytoplasm or nucleus
→ activate or inhibit transcription → alter the intracellular or
extracellular concentrations of specific gene products → have
a profound effect on cellular function.
Receptor Regulation
Receptors can undergo dynamic changes with respect
to their density (number per cell) and their affinity for
drugs and other ligands.
Receptor Desensitization
Receptor Hypersensitization
RECEPTOR DESENSITIZATION
Repeated or continuous administration of an
agonist may lead to changes in the
responsiveness of the receptor.
Clinical sketch
A middle-aged man has always
suffered from anxiety and insomnia.
He has been taking diazepam during
the day and temazepam at night for
many year. The doses of both drugs
have gradually been increased (on the
patient’s request) over the years
because of diminishing effectiveness.
Clinical sketch
Comment: this inappropriate long-term
use of sedatives can sometimes be hard
to avoid. However, the drugs have
probably become part of the problem
instead of offering any therapeutic
benefit. The diminishing effectiveness of
the drug is termed ‘tolerance’
Tachyphylaxis or desensitization refers to
the relatively rapid (minutes, hours)
diminishing response caused by repeated drug
administration.
Tolerance generally refers to reductions in
responsiveness that occur over a longer time
frame (days or longer) caused by prolonged
drug administration.
Mechanisms of Desensitization
I.Decreased sensitivity of receptors
The receptors are still present on the cell surface
but are unresponsive to the ligand
The mechanisms protecting a cell from
excessive stimulation.
Mechanisms of Desensitization
II. Down-regulation
The receptor undergoes
endocytosis and is sequestered
from further agonist interaction.
These receptors may be recycled
to the cell surface, restoring
sensitivity, or may be further
degraded, decreasing the total
number of receptors available.
β2 adrenergic agonists
Receptor Hypersensitization
Continuous or repeated exposure to
antagonists initially can increase the response
of the receptor.
With chronic exposure to antagonists, the
number of receptors on the membrane surface
(density) increases via up-regulation.
Clinical sketch
A 70-year –old man has been taking
beta-blockers for many years for his
angina. He develops intermittent
claudication, and his doctor stops the betablocker suddenly. His angina worsens
within days, and he is admitted to hospital
with a myocardial infarction.
Clinical sketch
 Comments：it
is likely that
receptor numbers are increased
(‘upregulated’) in the presence of
prolonged ‘blocking’. Sudden
withdrawal of the drug can
produce marked effects, as here.
RECEPTOR CLASSIFICATION
Specificity
Specificity of drug action relates to the number
of different mechanisms involved.
Examples : atropine (a muscarinic antagonist), salbutamol (a β2adrenoceptor agonist), phenoxybenzamine (an α-adrenergic
blocking agent), and cimetidine (an H2-receptor antagonist).
Nonspecific drugs result in drug effects through
several mechanisms of action.
Examples : Phenothiazine, which causes blockade of D2dopamine receptors, α-adrenergic receptors, and muscarinic
receptors.
Structure-Activity Relationship
The chemical structure of a drug determines its
affinity for the receptor and ability to elicit a
response
The drug and receptor must be structurally
complementary to recognize each other and initiate an
effect.
The specificity of such interaction raises the concept
of molecular recognition.
Drug receptors or targets must have molecular
domains that are spatially and energetically favorable
for binding specific drug molecules.
Structure-Activity Relationship
Proteins undergo folding to form threedimensional structures so that a minimum three
point attachment of a drug to a receptor site is
required.
 Drug binding to receptors often exhibits
stereoselectivity, in which stereoisomers of a drug
that are chemically identical,
but have different orientations
around a single bond, can have
very different affinities.
RECEPTOR CLASSIFICATION
Receptors are commonly named after the
natural agonist that activates them.
Each receptor family typically contains
multiple subtypes that may be characterized
pharmacologically by the use of selective
agonists, antagonists, or both.
Few drugs are entirely specific for one receptor
Epinephrine
1 Receptors
in Heart
2 Receptors in
Bronchioles
Clinical Selectivity
No drug causes only a
(Selectivity of Drug Responses) single effect
A drug's ability to preferentially produce a
particular effect
Be related to the structural specificity of drug
binding to receptors.
Selectivity of pharmacological effect is not
equal to specificity of drug action
Tissue Distribution of Receptors
Even if a drug binds to only one kind of
receptor, the biochemical processes controlled
by such receptors would take place in many cell
types and would be coupled to many other
biochemical functions.
Only those tissues possessing receptors will
respond to the drug.
Atropine
Muscarinic acetylcholine receptor antagonist
Higher specificity of drug action
Lower selectivity of pharmacological effect
Broad distribution of muscarinic acetylcholine
receptor in the body (gland, eyes, smooth muscle,
heart, blood vessels, and CNS)
Clinical Selectivity
(Selectivity of Drug Responses)
Clinical Connection:
Knowledge of receptor subtypes and their
regional distribution can assist in drug
selection.
In clinic, we often choose a drug with
higher selectivity to decrease side effects of
the drug.